The effectiveness of medication reconciliation to prevent medication error: A systematic review and meta-analysis

Research in Social and Administrative Pharmacy xxx (xxxx) xxx–xxx

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The effectiveness of medication reconciliation to prevent medication error: A systematic review and meta-analysis Daranee Chiewchantanakita,∗∗, Anupong Meakchaia, Natdanai Pituchaturonta, Piyameth Dilokthornsakula,b, Teerapon Dhippayoma,∗ a b

Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand Center of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand

ARTICLE INFO

ABSTRACT

Keywords: Medication reconciliation Medication error Hospital care Thailand Systematic review

Background: The impact of medication reconciliation (MR) in low-middle-income countries, including Thailand, may differ from other developed countries. Objective: To evaluate the effect of medication reconciliation (MR) on the reduction of medication error in Thailand. Methods: A systematic search was conducted in the following databases: PubMed, CENTRAL, CINAHL, Scopus, Thai Journals Online, Thai index Medicus, Thai Medical Index, and Health Science Journal in Thailand from inception to January 2018. Studies that evaluated the effect of MR compared to usual care within hospitals in Thailand and reported the occurrence of medication error were included. Meta-analyses were performed using random-effects model. Results: Of the 107 articles retrieved, 7 articles involving 1581 patients were included in quantitative synthesis. Three of the included studies were randomized controlled trials (RCT). Overall, the risk of medication error in patients who received MR in all transitions of care was 75% lower than those receiving usual care (RR 0.25; 95%CI 0.15–0.43). The effect on the reduction of medication error appeared higher when MR was provided to ambulatory patients (RR 0.17 [95%CI 0.04–0.80] compared with hospitalized patients during admission (RR 0.37 [95%CI 0.20–0.65]) and discharge (RR 0.27 [95%CI 0.17–0.43]). Effects on reducing medication error was greater when MR was provided in secondary care hospitals compared with primary care hospitals both during admission (RR 0.49 [95%CI, 0.34–0.69] vs RR 0.25 [95%CI, 0.05–1.26]), and discharge transition (RR 0.19 [95%CI, 0.09–0.39] vs RR 0.30 [95%CI, 0.12–0.79]). Conclusion: Overall, current evidence indicates that the provision of MR in Thailand is effective in reducing medication errors in all transitions of care. However, to promote patient safety, appropriate strategies should be developed to support MR in specific transition of care and hospital setting so patients can benefit most from this service.

Introduction Medication error is a preventable event that may cause or lead to patient harm.1 According to a previous systematic review, at least one medication error was observed in up to 67% of patents at hospital admission and nearly 60% of these errors were clinically important.2 Adverse drug event associated with medication error can prolong hospital stays, lead to emergency visits and hospital readmissions, and increase use of healthcare resources.3 Medication error can occur as a result of medication discrepancy due to poor medication history taking between transitions of care.4 Obtaining accurate patients’ medication ∗

histories is therefore crucial to prevent medication error associated adverse health outcomes and improve patient safety. Medication reconciliation (MR) is a formal process for creating the most complete and accurate list possible of a patient's current medications and comparing the list to those in patient records or medication orders.5 The aims of MR are to avoid errors of omission, duplication, incorrect doses or timing, and adverse drug-drug or drug-disease interactions. One of the well-recognized MR practices suggested four steps as follows: 1) verify (collect a current medication list); 2) clarify (make sure the medications and doses are appropriate); 3) reconcile (compare new medications with the list and document changes in the

Corresponding author. Naresuan University, Phitsanulok, 65000, Thailand. Corresponding author. Naresuan University, Phitsanulok, 65000, Thailand. E-mail addresses: [email protected] (D. Chiewchantanakit), [email protected] (T. Dhippayom).

∗∗

https://doi.org/10.1016/j.sapharm.2019.10.004 Received 7 March 2019; Received in revised form 20 September 2019; Accepted 6 October 2019 1551-7411/ © 2019 Published by Elsevier Inc.

Please cite this article as: Daranee Chiewchantanakit, et al., Research in Social and Administrative Pharmacy, https://doi.org/10.1016/j.sapharm.2019.10.004

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orders), and 4) transmit (communicate the updated and verified list to the appropriate caregivers).6 A number of patient safety organizations has adopted and promoted MR as a medication safety strategy in their guidelines and recommendations.7 Several studies have showed beneficial effects of MR on a wide range of outcomes. Specifically, findings from a recent systematic review and meta-analysis indicated that MR reduced the risk of patients with medication discrepancies by 42%.8 In addition, reduction of 67%, 28% and 19% in adverse drug event-related hospital revisits, emergency department (ED) visits, and hospital readmissions were observed in patients who received MR service.9 However, the existing evidence was mainly derived from developed countries where medication information sharing are feasible or electronic medication records are accessible with an aid of information technology.10 Like many other low-middle-income countries (LMIC), access to electronic medication records and shared medication information especially across healthcare settings in Thailand is limited. Therefore, findings from other developed countries might not be applicable to Thai context. In addition, a variation of MR effects on medication error was observed in relevant Thai literature.11–13 These warrant the need to have a conclusive evidence to support the implementation of MR in Thailand, which could be generalized to other LMIC whose contexts are similar to Thailand. The aim of this study is therefore to systematically review and evaluate the effect of MR on medication error in Thailand.

measured and its findings. Data extraction was performed independently by two reviewers (AM and NP) and verified by DC and TD. Quality assessment

This systematic review and meta-analysis was aligned with the Preferred Reporting Items for Systemic Review and Meta-Analyses (PRISMA) guideline.14 A systematic search was performed in electronic databases including PubMed, CENTRAL, CINAHL, Scopus, Thai Journals Online, Thai Index Medicus, Thai Medical Index, and Health Science Journal in Thailand from the inception of database to January 2018. Grey literature was also searched via the following databases: Thai Thesis Database, Thai Library Integrated System (ThaiLIS), ThaiJournal Citation Index Centre (TCI). Keywords for searching relevant research included three domains: “Medication Reconciliation” AND [“Medication Discrepancy” OR “Medication Discrepancy” OR Rehospitalization OR Readmission OR Hospitalization OR Admission OR “Unplan visit”] AND Thailand.

The EPOC tool15 was used to assess the risk of bias of each included study. The EPOC consists of 9 domains including 1) sequence generation, 2) allocation concealment, 3) similar baseline outcome measurements, 4) similar baseline characteristics, 5) incomplete outcome data, 6) prevent knowledge allocation, 7) protect against contaminating, 8) free from selective outcome reporting, and 9) free from other risks of bias. Studies that reported differences in qualification/competency of pharmacist between study groups were considered as having high risk for the domain of ‘other risks of bias’. Each topic was classified into three levels of potential risk of bias: high, low and unclear risk. The following risk of bias domains were justified as key domains for the summary assessment of the risk of bias within a study: “similar baseline characteristics” and “free from other risks of bias”. Since EPOC can be used to assess risk of bias for RCT, non-RCT, and controlled before-after studies. This means studies other than RCT would score high risk of bias for sequence generation and allocation concealment domains by default. However, the main purpose of these processes were to avoid bias in allocating subjects into different study groups so that both groups would have similar characteristics and less confounders. Therefore, to overcome the problem of high risk of bias in non-RCT studies during allocation process, “similar baseline characteristics” was chosen as one of the key domains to determine the overall risk of bias of individual study. According to the nature of service intervention study, it is unlikely to “blind” or prevent knowledge of allocation for service providers and subjects. This domain could be scored as having low risk of bias if the outcome of interest is measured objectively or there is a method to assure that the assessor could reliably measure the outcome. To offset the potential risk of not be able to prevent knowledge allocation, the qualification/competency of pharmacist were assessed if they were capable to measure the outcome in a reliable manner. This domain was added into “other risk of bias” domain and made one of the key domains to evaluate the overall risk of bias in the present study. The risk of bias summary for each study was classified as low risk (low risk of bias for all key domains), high risk (high risk of bias for one or more key domains), or unclear risk (unclear risk of bias for one or more key domains). Quality assessment was undertaken by two reviewers (AM and NP) and verified by the third reviewer (PD).

Study selection

Outcomes and statistical analysis

Full text studies of randomized controlled trials (RCT), non-RCT, and controlled before-after studies (CBA) were included if they met the following inclusion criteria: 1) assessed the effect of MR, either inpatient or outpatient care, in Thai hospitals; 2) compared MR service with usual care; and 3) reported the occurrence of medication error. Both inpatient and outpatient studies were included in order to capture a comprehensive evidence of MR in Thailand. Studies conducted using MR as part of other services were excluded. Study selection was done independently by two reviewers (AM and NP). Any disagreements were discussed and resolved by the third reviewer (DC).

The study outcome was the number of patients with medication error. Meta-analyses were performed under a random-effects model to determine the effect of MR on medication error compared to usual care and stratified by care transitions. The relative risk (RR) and its corresponding 95% confidence interval (CI) were reported. Heterogeneity across studies was assessed with I2- statistic which was expressed as % of the variance of the overall analysis. Thresholds of I2 were interpreted in accordance with the magnitude and direction of effects and strength of evidence of heterogeneity (i.e. p-value) as follows: might not be important (0%–40%); moderate heterogeneity (30%–60%); substantial heterogeneity (50%–90%); and considerable heterogeneity (75%–100%).16 A sensitivity analysis by including only RCT was performed to explore the robustness of main findings. Subgroup analyses, stratified by different transitions of care, were also performed to explore the effect modifiers of different baseline, which included hospital types and number of drug items. Hospitals in Thailand are classified into four groups: 1) sub-district health promoting hospitals, which are capable of providing primary care with outpatient service in village and sub-district level, and generally have no doctor on duty for the entire time; 2) primary care hospitals, also known as community hospitals, which are located in districts and are usually limited to providing

Methods Study search

Data extraction Data from the included studies were extracted based on the recommendation of the modified Cochrane Effective Practice and Organization of Care Group (EPOC) guideline15 using a modified data record form. Extracted data included study design; study centers and location; length of follow-up; randomization process; number of patients; age of patients; gender; inclusion and exclusion criteria; number of drug items; components of MR process; characteristics of usual care; outcomes of interest such as scope of medication error, how it was 2

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Fig. 1. PRISMA flow diagram of selected articles.

primary care treatment with a capacity of 10–120 beds; 3) secondary care hospitals, also known as general hospitals, which are located in province capitals or major districts, and are capable of providing secondary care treatment with a capacity of 120–500 beds; and 4) tertiary care hospitals, also known as regional hospitals, which are located in province centers or major cities, and are capable of tertiary care provided by a comprehensive set of specialists with a capacity of at least 500 beds. All hospital types, except sub-district health promoting hospitals, have facilities to provide emergency, outpatient, and inpatient services. All meta-analyses were conducted using STATA® version 15.0

(STATA Corp, College Station, TX, USA). Results Identification and selection of studies The search of published and grey literature in various databases yielded 107 articles after duplicates were removed (Fig. 1). The remaining articles were screened through titles and abstracts, of which 70 were removed because of the irrelevance to MR in Thailand. This 3

4

OPD

Female internal medicine, surgery, and emergency medicine wards

Female surgery ward and OPD

IPD

OPD

Male surgery ward

Internal medicine ward

Setting

97

117

45

239

150

45

100

Int

96

117

45

235

150

45

100

Ctrl

Sample size

60.2 ± 13.1

66b

62.7 ± 0.7

61.5 ± 14.5

69.3 ± 9.7

64.19 ± 14.1

62.9 ± 15.7

Age (years)a

Aged ≥20 years old with one of the following medical conditions (with no psychiatric disease): diabetes, HTN, asthma and COPD and required continuous medication

Aged ≥20 years old with no psychiatric disease

Had chronic disease (but not psychiatric disease) that required continuous medication

Had at least one chronic disease and used ≥1 continuous medication

Had at least one chronic disease (but not psychiatric disease) that admitted to the medical or surgical ward

Admitted in surgical ward and had chronic diseases that required continuous medication

Admitted and discharged at internal medicine wards with underlying disease and required continuous medication

Patients' conditions according to the inclusion criteria

5b

6.5

6.5 ± 3.1

11.2 ± 4.5

7.7 ± 2.8

13.1 ± 5.7

4.6 ± 2.4 (Int), 4.7 ± 2.2 (Ctrl)

No. of drug items

Non-specified HC provider collected medication record but not attached to patient record

Similar to intervention group without MR form attached to patient record

Similar to intervention group without DMR form attached to patient record

Similar to intervention group without MR form attached to patient record

Similar to intervention group without OMR form attached to patient record

Nurse copied previous medication record to medical chart/informed doctor

Non-specified HC provider collected medication record

Comparators

3 mo

4 mo

9 mo

12 mo

5 mo

6 mo

1 mo

Study period

Allergy to drug ordered; commission error; duplication; omission error; potential drug interaction; unintentional changed of medication; wrong dose or frequency; wrong drug; and wrong time

Allergy to drug ordered; omission error; wrong dose or frequency; wrong drug; and wrong time

Allergy to drug ordered; illegible writing; omission error; potential drug interaction; wrong dose; wrong drug; wrong frequency; and wrong time

Allergy to drug ordered; omission error; wrong dose or frequency; wrong drug; wrong route; and wrong time

Allergy to drug ordered; drug-drug interaction; duplication; omission error; wrong dose or frequency; and wrong drug

Allergy to drug ordered; illegible writing; missing information; omission error; potential drug interaction; wrong dose; wrong drug; and wrong time

Allergy to drug ordered; commission error; duplication; omission error; wrong dose or frequency; wrong drug; and wrong time

Scope of medication error

DMR: Discharge medication reconcile; HC: Health care; IPD: Inpatient Department; ME: medication error; OMR: Outpatient medication reconcile; OPD: Outpatient Department; pt: patient; RCT: Randomized controlled trial. a Presented as mean ± SD. b Presented as median.

Quasiexperiment

Thorchoo (2016)20

RCT

Siwichi (2008)17

RCT

Quasiexperiment

Mungmee (2010)13

Suetrong (2005)19

RCT

Mensin (2010)12

Quasiexperiment

Quasiexperiment

Kitjaorapin (2009)11

Srisupanwitaya (2010)18

Study design

Study

Table 1 Characteristics of included studies.

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resulted in 37 articles being full text reviewed for eligibility. Of those, 30 articles were excluded for the reasons stated in Fig. 1. Finally, a total of 7 studies11–13,17–20 was included in this systematic review for qualitative synthesis.

scoring unclear risk of bias in this domain had turned the summary risk of bias to unclear risk for all included studies.

Characteristics of included studies

The overall effect was a pooled estimate of relative risk from studies that reported the total number of patients who were presented with medication error following MR intervention at the end of study period from all care transitions. Of the seven included studies, one study11 only presented the number of patients who were classified as having medication error during MR at admission and discharge. The total number of patient at the end of study period that can be used to justify the overall effect of MR during hospitalization was not reported. This study was therefore not included in the main analysis (Fig. 2). Overall, pooled estimate of findings from six studies (1381 patients) showed that those who received MR were less likely to encounter medication error compared to those who had usual care (RR 0.25; 95%CI, 0.15–0.43) with substantial heterogeneity (I2 = 71.9%, p = 0.003). A sensitivity analysis that included only three RCT studies (798 patients)12,17,19 showed similar findings with the main analysis as the RR of having medication error in patients receiving MR was 0.30 (95%CI, 0.16–0.56) compared with usual care groups.

Overall effect

There were a total of 1581 patients included in the 7 studies with the mean age ranging from 60.2 to 69.3 years (Table 1). Three studies12,17,19 were RCTs and the other four studies11,13,18,20 were nonRCTs with quasi experimental design. A wide range of study period was observed, ranging from one to twelve months. Four studies11,12,17,19 explored the effects of MR in hospitalized patients, whilst two studies13,20 delivered MR to patients at outpatient department (OPD) and the remaining study18 expanded MR service from inpatient department (IPD) to OPD follow-up visit. The study setting can be classified into two groups based on hospital types, i.e. primary care hospital (3 studies)11,17,20 and secondary care hospitals (4 studies).12,13,18,19 Almost all (6 out of 7) studies11–13,17,18,20 recruited patients with at least one chronic medical condition or required continuous medication. The average number of drug items incurred by participants among the included studies ranged from 4.6 to 13.1. The following criteria were used in all included studies to justify medication error: allergy to drug ordered, omission error, wrong dose and wrong drug.11–13,17–20 Drug interaction and duplication were used to denoted medication error in four12,13,18,20 and three studies,11,13,20 respectively. Only two studies reported that commission error11,20 and illegible writing12,18 were classified as medication error.

Effects on hospitalized patients Findings from 5 studies11,12,17–19 involving 1088 hospitalized patients showed that MR at IPD admission reduced the risk of medication error by 63% (RR 0.37, 95%CI, 0.20–0.65) of usual care service with substantial heterogeneity (I2 = 78.8%, p = 0.001) (Table 4). Similarly, patients receiving MR at IPD discharge were less likely to have medication error (RR 0.27, 95%CI, 0.17–0.43) compared to those who received usual care with low heterogeneity (I2 = 13.0%, p = 0.331). Effect on medication error was greater when MR was provided in secondary care hospitals compared with primary care hospitals both during admission (RR 0.49 [95%CI, 0.34–0.69] vs RR 0.25 [95%CI, 0.05–1.26]), and discharge transition (RR 0.19 [95%CI, 0.09–0.39] vs RR 0.30 [95%CI, 0.12–0.79]). However, inconsistent findings were presented at different transitions when studies were classified based on number of drug items. Specifically, the RR of medication error following MR during admission among studies on patients who possessed ≥10 drug items (0.23 [95%CI 0.06–0.95]) was lower than the RR from studies on patients with less than 10 drug items (0.52 [95%CI 0.38–0.71]). On the other hand, when MR was provided during discharge, studies on patients who were prescribed with ≥10 drug items showed higher RR compared with their counterparts, i.e. 0.33 [95%CI, 0.15–0.73] vs 0.18 [95%CI, 0.09–0.37].

Detail of MR service Pharmacist was the main healthcare provider that delivered MR service in all included studies, with an exception of two studies11,18 that had doctor and/or nurse took part in providing this intervention (Table 2). In verification step, almost all studies collect a current medication list from hospital medical record and medicines brought to hospital by participating patients as well as interview patients or carers. Clarification step was reported in five11,13,17–19 out of seven studies. All five studies11,12,17–19 that were conducted in hospitalized patients had MR provided in multi-transitions of both admission and discharge. Moreover, two studies11,19 also reported additional reconciliation during hospitalization. During MR transmission step, all included studies attached MR form with patient record. Patients in the usual care either have their medication record collected by healthcare provider (three studies) or received service similar to the intervention group without having MR form attached to patient record (four studies) (Table 1).

Effects on ambulatory patients

Quality of included studies

The benefit of MR in reducing medication error by 83% has been observed when it was provided to ambulatory patients (RR 0.17 [95%CI, 0.04–0.80]), which was accompanied by moderate heterogeneity (I2 = 59.2%, p = 0.086). Unlike the effects found in hospitalized patients, the reduction in medication error following MR to ambulatory patients was only profound in primary care hospitals (RR 0.06 [95%CI, 0.01–0.24]) whereas this effect was not significant in secondary care hospitals (RR 0.34 [95%CI, 0.07–1.58]). It was not possible to perform a subgroup analysis based on number of drug items for studies in OPD setting as no studies was conducted in patients who used ≥10 drug items.

All three RCTs12,17,19 reported appropriate sequence generation, but did not give enough information on allocation concealment process, hence scored unclear risk of bias in this domain (Table 3). The remaining four non-RCTs11,13,18,20 were justified as having high risk of bias in sequence generation and allocation concealments domains. Bias for baseline outcome measurements could not be evaluated as none of the seven studies reported baseline outcome measured. All four nonRCTs11,13,18,20 were deemed as having low risk from contamination as it is unlikely that the control groups received the intervention because they were patients who received usual care before the introduction of MR intervention in the study settings. No studies reported the competency of healthcare practitioners who delivered MR services or provided detail of any given training course to ensure the quality and consistency of service intervention. Therefore, all seven studies were scored unclear risk in “other risk of bias” domain. Since this domain was set as one of the key domains to estimate the summary risk of bias within each study,

Discussion Results from this study reiterate findings from others,8–10,21 which were mainly derived from high income countries, and strengthen the beneficial effects of MR in reducing the risk of medication error. It 5

6

Pharmacist

Pharmacist

Suetrong (2005)19

Thorchoo (2016)20

Yes

Yes

Yes

NR

Yes

Yes

Yes

Yes

NR

Yes

Medicines brought to hospital

Yes

Yes

Yes

Yes

Yes

NR

Yes

Interview pt or carer

NR

NR

NR

HC practitioner from other HC settings; patients' medical booklet

NR

NR

Referring form; patients' medical booklet

Others

NR

Physician reviewed MR form before prescribing

Compared AMR form with order on admission

Compared AMR form with order on admission

Pharmacistb clarified AMR taken by nurse at admission Clarified with pt and/or their relatives

Compared AMR form with order on admission

Compared OMR form with prescribing order

Two times (after doctor ordered and before dispensed)d

Compared MR form with order on admission

Admission/OPD

Reconciliation

Clarified by pharmacist (no detail given)

Clarified by pharmacistb (no detail given)

NR

Clarified by pharmacist (no detail given)

Clarification

NA

Compared TMR form with order in the transferred ward

No

No

NA

No

Compared MR form with doctor order

Hospitalization

NA

Compared DMR form with DC order

Compared DMR form with DC order

Compared DMR form with DC order

NA

Two times (after doctor ordered and before dispensed)d

Two times (before doctor ordered and before dispensed)c

DC

MR form attached to patient record

AMR and TMR form attached to the front page of IPD patient record

AMR form attached to patient record

AMR form attached to patient record

OMR form attached on the front page of patient record

AMR form attached to patient record

MR form (in pink paper) attached on the front page of patient record

Hospitalization/OPD

Transmission

NA

DMR form attached to patient record

DMR form attached to patient record and DC medication list form inserted in OPD patient record

DMR form attached to patient record

NA

DMR form attached to patient record

MR form and drug profile given to patient when discharge

DC

AMR: Admission medication reconcile; DC: Discharge; DMR: Discharge medication reconcile; IPD: Inpatient department; MR: Medication reconcile; NA: Not available; NR: Not report; OMR: Outpatient medication reconcile; OPD: Outpatient department; TMR: Transferred medication reconcile. a Including hospital computer database and records from pharmacy department. b The investigator act as a pharmacist to provided MR intervention. c Two times by doctor before prescribed and pharmacist at pharmacy room before dispensed. d Two times by the pharmacist investigator after doctor ordered and pharmacist at pharmacy room before dispensed.

Nurse (admission) and pharmacist (before DC)

Pharmacist

Siwichi (2008)17

Srisupanwitaya (2010)18

Yes

Pharmacistb

Mungmee (2010)13

Yes

NR

Pharmacistb

Mensin (2010)12

Yes

Hospital medical recorda

Doctor, nurse and pharmacist

HC provider

Verification – information source

Kitjaorapin (2009)11

Study

Table 2 Characteristic of medication reconciliation among the included studies.

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Table 3 Risk of bias of included studies.

*Highlighted columns represent key domains; †High risk if missing data between intervention and control group > 5%; ‡Other sources of bias included qualification/ competency of pharmacist or training before conducting intervention; H=High risk of bias; L = Low risk of bias; U=Unclear risk of bias.

Fig. 2. Overall effects of medication reconcilation on reported medication errors.

According to a previous systematic review on MR process,7 it is difficult to identify best practice for MR as current evidence show heterogeneity between MR interventions and how they were evaluated. However, it is suggested that MR should encompass four main steps: verify, clarify, reconcile and transmit.6 These four steps have been covered by almost all included studies, indicating that MR in Thailand is well aligned with international concept and practice of MR. Medication discrepancies, deemed to be one type of medication error, has been used interchangeably with medication error in several studies.7 As there are limited number of meta-analysis study on the effect of MR on medication error, evidence on medication discrepancies is used to compare with findings from the present study. The positive effect of MR on the reduction of medication error coincided with findings from previous meta-analysis studies. However, when compare with usual care, the risk of having mediation error among patients in MR group showed in this study (RR 0.25) is lower than those reported in previous meta-analysis studies (RR 0.3421 and 0.588). One possible

should be noted, however, that the pooled estimate of overall effects of MR from all care transitions should be interpreted with caution as it was presented with a substantial heterogeneity from studies with unclear risk of bias. Nonetheless, what this study adds to the current literature is that the benefit of MR is well established in setting like Thailand where access to shared patient information is limited. As hospital care practice varies across countries, whether the effects of MR in reducing medication error are prominent in other LMIC requires further exploration. In addition, when stratified by transition of care, this study revealed that the highest magnitude of risk reduction was achieved when MR was performed to ambulatory patients. Subgroup analyses also showed that the effect of MR in reducing risk of ME in hospitalized patients was prominent in secondary care hospitals rather than primary care hospitals. On the other hand, the effect on ME in ambulatory patients was only evident in primary care hospitals, not secondary care hospitals. However, the effect of MR on patients who used 10 or more drug items is still inconclusive. 7

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Table 4 Effects of medication reconcilation on medication errors in subgroup meta-analysis stratified by different transitions of care. Outcomes Hospitalized – Admission Hospitals types Primary care hospitals Secondary care hospitalsa Number of drug items Drug items ≥10 Drug items < 10 Hospitalized – Discharge Hospitals types Primary care hospitals Secondary care hospitalsa Number of drug items Drug items ≥10 Drug items < 10 Ambulatory Hospitals types Primary care hospitals Secondary care hospitalsa Number of drug items Drug items ≥10 Drug items < 10 a

Pooled RR (95%CI)

Heterogeneity, I2%, p-value

No. of studies 11,12,17–19

No. of studied population

0.37 (0.20–0.65)

78.8%, p = 0.001

5

1088

0.25 (0.05–1.26) 0.49 (0.34–0.69)

93.6%, p = 0.000 0.0%, p = 0.801

211,17 312,18,19

674 414

0.23 (0.06–0.95) 0.52 (0.38–0.71)

89.7%, p = 0.002 0.0%, p = 0.806

212,17 311,18,19

564 524

0.27 (0.17–0.43)

13.0%, p = 0.331

511,12,17–19

1088

0.30 (0.12–0.79) 0.19 (0.09–0.39)

61.9%, p = 0.105 0.0%, p = 0.863

211,17 312,18,19

674 414

0.33 (0.15–0.73) 0.18 (0.09–0.37)

47.4%, p = 0.168 0.0%, p = 0.861

212,17 311,18,19

564 524

0.17 (0.04–0.80)

59.2%, 0.086

313,18,20

583

0.06 (0.01–0.24) 0.34 (0.07–1.58)

N/A 22.8%, p = 0.255

120 213,18

193 390

N/A 0.17 (0.04–0.80)

N/A 59.2%, 0.086

N/A 313,18,20

N/A 583

Included general and regional hospitals.

explanation for the higher impact of MR showed in this review is that the provision of MR in all fours studies in hospitalized patients was at multi-transitions, i.e. admission and discharge. Findings from Mekonnen et al.,21 on the other hand, was derived from studies on single transitions whereas Cheema et al. study8 did not clearly define whether the estimate effect was pooled from studies on MR at single or multiple hospital transitions. In addition, the MR interventions in all of the included studies in the present review have transmitted the verified medication list to healthcare providers by attaching a dedicated unique MR form on patient records. This may attract attention from clinicians and prevent medication errors in the next hospital transition such as at discharge. The effect of MR in reducing medication error among studies in ambulatory patients was slightly higher than those studies in hospitalized patients both at admission and discharge transitions. This is probably due to the scope of medication error measured by studies in ambulatory patients which was wider than the scope used among studies in hospitalized patients. Specifically, all three studies in ambulatory patients13,18,20 identified drug interaction as medication error, whereas only one12 out of five studies in IPD reported drug interaction in the scope of their medication error measures. In addition, duplication was counted as medication error in two13,20 out of three studies in ambulatory patients compared to one11 out of five studies in hospitalized patients. It should be noted, however, that the scope and definition of medication error is still inconclusive.22 A goal standard criteria and definition of medication error is needed to better compare effects on medication error among studies. In general, patients admitted in secondary care settings are characterized with more complex medical conditions than those admitted in primary care hospitals. Accordingly, it is expected that the risk of medication error is higher among patients admitted in secondary care setting which indicates more room of improvement than primary care premises. This could explain the reasons why the effect of MR was prominent in secondary care rather than primary care hospitals as shown in this study. Conversely, findings in ambulatory patients showed that MR in primary care hospitals could lessen the risk of medication error than in secondary care hospitals. Perhaps, pharmacists would have more time to conduct effective MR in primary care

hospitals as they generally have smaller number of visiting patients compared to secondary care hospitals. This conjecture, however, requires further investigation. One of the strengths of this study is that it stratified findings based on hospital transitions, i.e. IPD-admission, IPD-discharge, and OPD to better illustrate the effects of MR at different transition care. Subgroup analysis was also conducted which could help decision makers to target specific transition and hospital setting where patients could get the most benefit from MR. Although a test for publication bias could not be conducted due to limited number of included studies, a comprehensive search to cover relevant grey literature was performed to alleviate the concern over the risk of publication bias. There are some limitations that should be mentioned for this study. First, a substantial heterogeneity was witnessed in the main analysis which may be due to differences in study design, setting, level of hospital, and scope of medication errors used among the included studies. However, the magnitude of effect size was similar among main and sensitivity analysis, which confirmed that the primary finding was valid and credible. Second, the generalizability of findings from this study should be limited to patients with chronic diseases who visit primary or secondary care hospitals. This is because the majority of studies recruited patients with at least one chronic medical condition; hence, findings in this study could not be generalized to patients without chronic diseases. Studies conducted in tertiary care hospitals, which may respond to MR with different magnitude, were also not included. Third, the evidence generated came from studies with unclear risk of bias since the competency of service providers could not be justified. Lastly, although there are strong associations between medication error and detrimental clinical outcomes,2,7 the impact of MR on clinical indicators could not be determined in the present study due to limited availability of relevant literature. Future studies should overcome these limitations by exploring the effect of MR at tertiary care hospitals using high standard approach with RCT design, providing a comprehensive description of the competency of service providers, and measuring clinical outcome such as mortality, length of hospital stay, and readmission.

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8. Cheema E, Alhomoud FK, Kinsara ASA, Alsiddik J, Barnawi MH, Al-Muwallad MA, et al. The impact of pharmacists-led medicines reconciliation on healthcare outcomes in secondary care: a systematic review and meta-analysis of randomized controlled trials. PLoS One. 2018;13:e0193510. 9. Mekonnen AB, McLachlan AJ, Jo-anne EB. Effectiveness of pharmacist-led medication reconciliation programmes on clinical outcomes at hospital transitions: a systematic review and meta-analysis. BMJ Open. 2016;6:e010003. 10. Mekonnen AB, Abebe TB, McLachlan AJ, Brien JA. Impact of electronic medication reconciliation interventions on medication discrepancies at hospital transitions: a systematic review and meta-analysis. BMC Med Inf Decis Mak. 2016;16:112. 11. Kitjaorapin B. Outcome of Medication Reconciliation at Medicine Wards in Kabinburi Hospital master's thesis Bangkok: Chulalongkorn University; 2009 111 p. 12. Mensin P. Cost-Effectiveness of Pharmacist-Participation in Medication Reconciliation Process in Surgical Inpatient at Samuprakarn Hospital master's thesis Bangkok: Chulalongkorn University; 2010 113 p. 13. Mungmee S. Medication Reconciliation in Outpatient Visiting Medicine and Surgery Clinics at H.M. Queen Sirikit Hospital master's thesis Bangkok: Chulalongkorn University; 2010 100 p. 14. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151:264–269. 15. Staresinic AG, Sorkness CA, Goodman BM, Pigarelli DW. Comparison of outcomes using 2 delivery models of anticoagulation care. Arch Intern Med. 2006;166:997–1002. 16. Higgins JPT, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]: The Cochrane Collaboration. 2011; 2011. [cited 2019 Mar 15]. Available from: http://handbook-5-1.cochrane.org/. 17. Siwichi W. Outcomes of Medication Reconciliation on Medicatuon Error in the Inpatient Setting at Maetha Hospital, Maetha District, Lamphun Province master's thesis Chiang Mai: Chiang Mai University; 2008 116 p. 18. Srisupanwitaya S. Outcomes of Medication Reconciliation Complete Process in Surgical Chronic Disease Patients at Samutprakarn Hospitalt Samutprakarn Hospital master's thesis Bangkok: Chulalongkorn University; 2010 95 p. 19. Sue-trong C. Developing and Implementing Medication Reconciliation Process Following Transition Points in Inpatient Medication System. Bangkok: Chulalongkorn University; 2005 136 p. 20. Thorchoo S, Upakdee N. Clinical and economic outcomes of medication reconciliation at outcome department, Nongki hospital, Burirum. FDA Journal. 2016;28:34–44. 21. Mekonnen AB, McLachlan AJ, Brien JA. Pharmacy-led medication reconciliation programmes at hospital transitions: a systematic review and meta-analysis. J Clin Pharm Ther. 2016;41:128–144. 22. Ferner RE, Aronson JK. Clarification of terminology in medication errors: definitions and classification. Drug Saf. 2006;29:1011–1022.

The current evidence indicates that MR reduces the number of patients experiencing medication error in both outpatient and inpatient settings in Thailand. Appropriate strategies should be developed to support the provision of MR with priority given to ambulatory patients. The uptake of MR to hospitalized patients should also be promoted, especially in secondary care hospitals. Funding This work was supported by Naresuan University's Faculty of Pharmaceutical Sciences Research Fund. Appendix A. Supplementary data Supplementary data to this article can be found online at https:// doi.org/10.1016/j.sapharm.2019.10.004. References 1. Knez L, Suskovic S, Rezonja R, Laaksonen R, Mrhar A. The need for medication reconciliation: a cross-sectional observational study in adult patients. Respir Med. 2011;105:S60–S66. 2. Tam VC, Knowles SR, Cornish PL, Fine N, Marchesano R, Etchells EE. Frequency, type and clinical importance of medication history errors at admission to hospital: a systematic review. CMAJ (Can Med Assoc J). 2005;173:510–515. 3. Mueller SK, Sponsler KC, Kripalani S, Schnipper JL. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172:1057–1069. 4. Vira T, Colquhoun M, Etchells E. Reconcilable differences: correcting medication errors at hospital admission and discharge. Qual Saf Health Care. 2006;15:122–126. 5. Barnsteiner JH. Medication reconciliation. In: Hughes RG, ed. Patient Safety and Quality: An Evidence-Based Handbook for Nurses [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2008. [cited 2018 Jun 6]. Available from:. https://www.ncbi.nlm.nih.gov/books/NBK2648/. 6. Ptasinski C. Develop a medication reconciliation process. Nurs Manag. 2007;38:18. 7. Almanasreh E, Moles R, Chen TF. The medication reconciliation process and classification of discrepancies: a systematic review. Br J Clin Pharmacol. 2016;82:645–658.

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