Drug-related emergency department visits in Qatar: a prospective cohort study.

This was a prospective cohort study that was conducted in the EDs of Hamad Medical Corporation (HMC). HMC is the principal provider of secondary and tertiary healthcare in Qatar. The HMC network manages 15 hospitals and centers with over 2,100 beds. This study was carried out at the ED of two of the major HMC hospitals [i.e. Hamad General Hospital (HGH) and Al-Wakra Hospital (AWH)]. HGH is a 600-bed tertiary hospital that provides care in different clinical areas and specialties, including emergency medicine and internal medicine. AWH has a bed capacity of 330 beds with areas of varying expertise, including internal medicine, endocrinology, obstetrics and gynecology, emergency care, and other specialties [ 15 ]. All adult patients (aged 18 years or above) presenting to the ED of HGH and AWH between November 2020 to January 2022 were eligible for inclusion in the study. A systematic random sampling technique was applied for subjects’ selection. Patients who left or were transferred from ED before treatment were excluded from the study. The daily number of ED visits in both hospitals was estimated at approximately 2000 cases per day at the time of conducting the study. A list of all eligible patients was prepared using the hospitals’ registries on a daily basis. Each patient was assigned a unique code. A random starting point of 4 was selected. Starting from patient coded number 4, every 2 nd patient was selected. Participants’ selection was done before assessing the reason for their ED visit. Prior to start of the study, the attending ED physicians and pharmacists who assessed the reason for the ER visit received training on the identification, and classification of ADEs and DTPs by the study team and a group of professionals who are experts in the field of medication safety. The demographic and clinical information of the selected participants were collected prospectively from the HMC electronic health record system (Cerner © ) and directly from the patients through face-to-face interviews for data validation purposes. Data collected included medical history, medication history, history of allergies, chief complaint, physical examination, laboratory tests and diagnostic tests performed in the ED, and the consequence of the visit. The selected visits were independently reviewed by an ED pharmacist and an ED physician. To minimize subjectivity and bias, the pharmacists and physicians conducting the assessments and determining the reasons for the ER visits were different from those who provided direct patient care. Whenever needed, they also searched drug information resources and primary literature to determine the strength of the evidence on the relation between the symptoms and the drug. A visit was considered drug-related if the pharmacist’s and the physician’s judgement of a patient’s ADE were in agreement. In case of any discrepancies in judgement between the ED pharmacist and the ED physician or if there were any uncertainties in their judgement, the patient case was reviewed by a panel of physicians and pharmacists using a structured and systematic approach. The study team conducted a systematic and thorough review of the literature for identifying tools that can be used to assess drug-related emergency visits. The selected tools were evaluated for their validity and reliability before adaption. A pilot of 30 patients in the ED was randomly selected. In the initial piloting phase, three ED pharmacists independently assessed each of the 30 patient cases in order to determine the presence of an ADE. The reliability of the tools was measured through assessing the interrater reliability between the three pharmacists. In addition, tools were reviewed for face and content validity by an expert panel of experienced academic pharmacy faculty and clinicians at Qatar University (QU) College of Pharmacy (CPH) and HMC before final adaptation. Adapted tools included: the World Health Organization - Uppsala Monitoring Center (WHO-UMC) system for standardized case causality assessment, Naranjo algorithm for assessing the causality of an ADR and other tools used at HMC such as Hartwig’s Severity Assessment Scale [ 16 – 18 ]. The WHO-UMC system is a structured tool for determining the causality of adverse drug reactions [ 16 ]. The Naranjo algorithm, a 10-item questionnaire, is employed to evaluate the likelihood that an adverse drug reaction is attributable to a specific medication [ 17 ]. In contrast, the Hartwig’s Severity Assessment Scale is utilized to classify the severity of adverse events as mild, moderate, or severe [ 19 ]. ADEs were categorized into one of eight drug therapy problems (DTPs). We adapted the DTP definition and seven categories as per Hepler, Strand and Morley in their pharmaceutical care model [ 2 ]. These categories included: 1) the drug is not needed as the patient does not have any existing medical indication, 2) additional drug therapy is needed to treat or prevent a medical condition in the patient, 3) the drug is not effective at achieving the required response in the patient.,4) the dosage is too low to attain the required response in the patient, 5) the drug is causing an ADR in the patient, 6) the dosage is too high, leading to undesirable effects in the patient and, 7) the patient is not compliant with his or her prescribed drug therapy [ 2 ]. An eighth category not indicated by Hepler, Strand and Morley was added which is adverse drug-drug interactions, defined as any noxious or unintended effects caused by the coadministration of two or more medications [ 19 ]. ADEs were also classified according to their severity into: mild (not requiring treatment), moderate (requiring treatment, admission to the hospital or resulting in non-permanent disability), severe (life threatening or resulting in permanent disability), or fatal [ 20 , 21 ]. Furthermore, the preventability of the ADEs was classified as: nonpreventable, preventable, or ameliorable. ADEs were considered preventable if they were due to errors or DTPs that could have been totally avoided [ 20 , 21 ]. Ameliorable events are those whose severity or duration could have been considerably reduced if different actions had been taken [ 20 , 21 ]. All other events were considered non-preventable [ 20 , 21 ]. Moreover, the preventability of ADEs was also assessed as per the National Coordinating Council for Medication Error Reporting and Prevention (NCCMERP) [ 22 ]. Finally, the consequences of the ADEs were recorded, including, death, hospitalization, discharge after consultation in the ED, referral to other clinics or health institutions, and hospital length of stay in case of hospitalization. The medications implicated in the event were categorized as per the 2023 WHO Anatomical Therapeutic Chemical (ATC) classification system and the defined daily dose (DDD) [ 23 ]. The primary study outcomes were the incidence, the severity, and the preventability of ED drug-related visits. Based on the results of studies conducted outside Qatar [ 11 , 16 – 20 ], the incidence rate of drug-related ED visits can range between 5 and 20%. Therefore with a priori sample size of 1000 cases, the margin of error will range between ±1.4% and ±2.5%. Demographic and clinical characteristics of the patients were summarized using means and standard deviations for numerical variables such as age and frequency distributions for categorical variables such as gender, implicated drug class, etc. The incidence of ED drug-related visits was computed along with its 95% confidence intervals. Moreover, the prevalence of severity and preventability of such incidences were also computed along with their 95% confidence intervals. Bivariate and then multivariate logistic regression models were used to assess the predictors of ED visits for ADEs. Unadjusted and adjusted odds ratios along with their corresponding 95% confidence intervals and p-values were presented. The final logistic regression model included variables that had a p-value of at least 0.25 (except for nationality that we decided to keep even though the p-value was 0.313 since it has a confounding effect on the other variables in the model. Some variables were not included in the final model as they have collinearity with other variables in the model, for example comorbidities with number of medications (correlation coefficient 0.60 with p  < 0.001). All data analyses were conducted using IBM-SPSS (version 24, IBM Corporation, Armonk, NY, USA). P-value was considered significant if it was less than 0.05.

Based on the 1000 randomly selected cases in the ED, there were 178 ADEs during a 14-month duration. The sociodemographic and clinical characteristics of the 1000 selected cases are presented in Table 1 . The incidence of ADEs was 178 per 1000 individuals (95% CI: 15.6–20.3). Over 60% of ED visits due to ADEs were in male patients ( n  = 109, 61.2%) and patients aged between 18 and 59 years old ( n  = 151, 84.8%). Of the 104 ED visitors aged ≥60 years, 27 had an ADE; while among the 896 visitors younger than 60 years, 151 had an ADE. As a result, the incidence rate of ED visits for ADEs among older adults (aged ≥60 years) was 260 (95% CI: 18.5- 35.2) visits per 1000 individuals compared with 169 (95% CI: 14.5–19.5) visits per 1000 individuals for those younger than 60 years. Table 1 Patients’ Characteristics and Emergency Department (ED) Visits ED visits for ADEs ED visits for other causes p-value Patient Characteristic Number of cases % (95% CI) Number of cases % (95% CI) Gender N = 178 N = 822 0.030** Male 109 61.2(53.9–68.1) 430 52.3 (48.9–55.7) Female 69 38.8(31.9–46.1) 392 47.7 (44.3–51.1) Age N = 178 N = 822 0.022** 18–59 years 151 84.8 (78.8–89.4) 745 90.6 (88.4–92.4) ≥60 years 27 15.2 (10.6–21.2) 77 9.4 (7.6%-11.6) Nationality N = 176 N = 814 0.313† Bilad Al Sham 22 12.5(8.3–18.3) 105 12.9 (10.8–15.4) European countries 5 2.8(1.0–6.7) 13 1.6 (0.9–2.7) Gulf Cooperation Council (GCC) 25 14.2(9.7–20.2) 141 17.3 (14.9–20.0) North African countries 29 16.5(11.7–22.7) 147 18.1 (15.6–20.9) North and Central American countries 3 1.7(0.3–4.9) 8 1.0 (0.5–2.0) Other African countries 7 4.0(1.8–8.1) 25 3.1 (2.1–4.5) Other Middle Eastern countries 5 2.8(1.0–6.7) 30 3.7 (2.6–5.2) Southeast Asian countries 1 0.6(0.01–3.1) 344 42.3 (38.9–45.7) South Asian countries 79 44.9(37.7–52.3) 1 0.1 (0.0–0.7) Education level N = 177 N = 811 0.126†† Primary school only 20 11.3(7.4–16.9) 54 6.7 (5.1–8.6) Secondary school only 56 31.6(25.2–38.8) 255 31.4 (28.3–34.7) Diploma 17 9.6(6.0–14.9) 74 9.1 (7.3–11.3) Undergraduate degree 69 39.0(32.1–46.3) 325 40.1 (36.8–43.5) Postgraduate degree 9 5.1(2.6–9.5) 69 8.5 (6.8–10.6) None 5 2.8(1.0–6.6) 31 3.8 (2.7–5.4) Other 1 0.6(0.0–3.1) 3 0.4 (0.1–1.1) Medical conditions N = 178 N = 822  < 0.001**‡ Hypertension 77 43.2(36.2–50.6) 166 20.2 (17.6–23.1) Diabetes 47 26.4(20.5–33.4) 146 17.8 (15.3–20.5) Hyperlipidemia 20 11.2(7.3–16.8) 76 9.2 (7.4–11.4) Coronary artery disease 19 10.7(6.9–16.1) 46 5.6 (4.2–7.4) Anemia 12 6.7(3.8–11.5) 41 5.0 (3.7–6.7) Renal dysfunction 11 6.2(3.4–10.8) 35 4.3 (3.1–5.9) Asthma 10 5.6(3.0–10.2) 47 5.7 (4.3–7.5) Arrhythmias 9 5.1(2.6–9.5) 15 1.8 (1.1–3.0) Epilepsy 8 4.5(2.2–8.8) 4 0.5 (0.1–1.2) Thyroid disorders 7 3.9 (1.8–8.1) 39 4.7 (3.5–6.4) Depression/bipolar disease 6 3.8(1.4–7.3) 8 1.0 (0.5–1.9) Stroke 5 2.8(1.02–6.6) 4 0.5 (0.1–1.2) Heart failure 4 2.2(0.6–5.7) 9 1.1 (0.5–2.1) Cancer 4 2.2(0.6–5.7) 13 1.6 (0.9–2.7) Migraine 4 2.2(0.6–5.7) 8 1.0 (0.5–1.9) Inflammatory Bowel Disease 3 1.7(0.4–4.9) 6 0.7 (0.3–1.6) Other heart problems 3 1.7(0.4–4.9) 3 0.36 (0.1–1.1) Obesity 4 2.2(0.6–5.7) 19 2.3 (1.5–3.6) Polycystic Ovary Syndrome/Endometriosis 2 1.1 (0.1–4) 10 1.2 (0.6–2.3) Smoking status N = 176 N = 822 0.150 Non-smoker 121 68.7(61.6–75.2) 612 74.5 (71.4–77.3) Past smoker 23 13.1(8.8–18.9) 78 9.5 (7.7–11.7) Current smoker 32 18.2(13.1–24.6) 115 14.0 (11.8–16.5) Number of Medications on admission Mean ±SD = 3.28 ± 3.06 Median = 3.0 Range: 0–15 Mean ± SD = 2.42 ± 3.22 Median = 1 Range: 0–19  < 0.001** Primary reason of visiting emergency department * N = 178 N = 822 Nervous system disorders 53 29.8 (23.5–36.9) 146 17.8 (15.3–20.5)  < 0.001** Cardiac disorders 51 28.7 (22.5–35.7) 155 18.9 (16.3–21.7) 0.003** Gastrointestinal disorders 30 16.9 (12.0–23.1) 284 34.5 (31.4–37.9)  < 0.001** Vascular disorders 27 15.2 (10.6–21.2) 14 1.7 (1.0–2.9)  < 0.001** Musculoskeletal and connective tissue disorders 12 6.7 (3.8–11.5) 64 7.8 (6.1–9.8) 0.634 Urinary, renal and gynecologic disorders 9 5.1 (2.6–9.5) 80 9.7(7.9–12.0) 0.047** Respiratory, thoracic and mediastinal disorders 9 5.1 (2.6–9.5) 62 7.5 (5.9–9.6) 0.285 Endocrine disorders 9 5.1 (2.6–9.5) 12 1.5 (0.8–2.6) 0.006** Psychiatry disorders 8 4.5 (2.2–8.8) 3 0.4 (0.1–1.1)  < 0.001** Constitutional 8 4.5 (2.2–8.8) 70 8.5 (6.8–10.6) 0.088 Laboratory, metabolism and nutrition disorders 6 3.4 (1.4–7.3) 1 0.1 (0.0–0.7)  < 0.001** Injury, poisoning and procedural complications 5 2.8 (1.0–6.6) 40 4.9 (3.6–6.6) 0.230 Infections and infestations 4 2.2 (0.6–5.7) 17 2.1 (1.3–3.3) 0.778 Skin and subcutaneous tissue disorders 4 2.2 (0.6–5.7) 21 2.6 (1.7–3.9) 0.999 Eye disorders 3 1.7 (0.4–5.1) 8 1.0 (0.5–1.9) 0.424 Hepatobiliary disorders 2 1.1 (0.1–4.0) 23 2.8 (1.9–4.2) 0.289 Blood and lymphatic system disorders 2 1.1 (0.1–4.0) 6 0.7 (0.3–1.6) 0.638 ENT (Ear, nose and throat) 1 0.6 (0.0–3.1) 9 1.1 (0.5–2.1) 0.999 Surgical complications 0 0 (0.0–1.7) 0 0 (0–0.4) 1.000 * Categorization is made as per MedDRA Introductory Guide [ 24 , 25 ] ** p-value < 0.05 †† p-value for comparing the outcome between Gulf Cooperation Council (GCC) vs. non GCC countries † p-value for comparing the outcome between those with postgraduate vs. lower than postgraduate education ‡Comparing distribution of comorbidities any vs. more than one comorbidity between the two groups Patients’ Characteristics and Emergency Department (ED) Visits Mean ±SD = 3.28 ± 3.06 Median = 3.0 Range: 0–15 Mean ± SD = 2.42 ± 3.22 Median = 1 Range: 0–19 * Categorization is made as per MedDRA Introductory Guide [ 24 , 25 ] ** p-value < 0.05 †† p-value for comparing the outcome between Gulf Cooperation Council (GCC) vs. non GCC countries † p-value for comparing the outcome between those with postgraduate vs. lower than postgraduate education ‡Comparing distribution of comorbidities any vs. more than one comorbidity between the two groups The most common reasons for visiting the ED due to an ADE were nervous system disorders ( n  = 53, 29.8%), cardiac disorders ( n  = 51, 28.7%) gastrointestinal disorders ( n  = 30, 16.9%), and vascular disorders ( n  = 27, 15.2%). The majority of ADEs were caused by one DTP ( n  = 170/178, 95.5%), Seven ADEs were caused by two DTPs ( n  = 7/178, 4.0%) and one ADE was caused by three DTPs ( n  = 1/178, 0.5%). The total number of DTPs responsible for the 178 cases of ADEs was 187. The distribution of DTPs was as follows: the “non-compliance to drug therapy ( n  = 77, 41.2%)”, followed by “additional drug therapy is needed”( n  = 38, 20.3%), “ineffective drug therapy” ( n  = 35, 18.7%), “the drug is causing an ADR” ( n  = 21, 11.2%), “dose too high” ( n  = 8, 4.3%), “dose to low” ( n  = 7, 3.7%), and “drug-drug interaction” ( n  = 1, 0.5%) The mean ± SD number of drugs implicated in DTPs was 1.16 ± 0.92 with a range of 0 to 6 drugs. Zero number of drugs implicated was linked to the DTP category of “additional drug therapy is needed” ( n  = 27). Medication systems implicated in the 178 cases of ADEs were: cardiovascular system ( n  = 83, 46.6%), alimentary tract and metabolism ( n  = 32, 18.0%), blood and blood forming agents ( n  = 24, 13.5%), nervous system ( n  = 19, 10.7%), musculoskeletal system ( n  = 15,8.4%), respiratory system ( n  = 8, 4.5%), anti-infectives for systemic use ( n  = 5, 2.8%), systemic hormonal preparations excluding insulin and sex hormones ( n  = 5, 2.8%), antineoplastic and immunomodulating agents ( n  = 3, 1.7%), and anti-parasitic products, insecticides and repellants ( n  = 1, 0.5%). The medication classes responsible for the 178 cases of ADEs were: calcium channel blockers ( n  = 28, 15.7%), antidiabetic drugs ( n  = 25, 14.0%), beta blockers ( n  = 21, 11.8%), drugs affecting renin angiotensin system ( n  = 18, 10.1%) anti-inflammatory and anti-rheumatic drugs ( n  = 13, 7.3%), anti-thrombotic agents ( n  = 12, 6.7%), diuretics ( n  = 11, 6.2%), anti-anemic agents ( n  = 11, 6.2%), anti-epileptics ( n  = 8, 4.5%) drugs for chronic obstructive pulmonary disease ( n  = 7, 3.9%), cardiac therapy ( n  = 6, 3.4%), lipid agents ( n  = 6, 3.4%), anti-bacterial agents ( n  = 5, 2.8%), and other medications (Fig. 1 . Medication Classes Implicated in Adverse Drug Events) Fig. 1 Medication Classes Implicated in Adverse Drug Events Medication Classes Implicated in Adverse Drug Events More than half of the ADEs were of moderate severity ( n  = 98, 55.1%) (95% CI: 47.72–62.18), followed by mild in severity ( n  = 76, 42.7%) (95% CI: 35.66–50.04) (Fig. 2 . Severity of Identified Adverse Drug Events). Fig. 2 Severity of Identified Adverse Drug Events Severity of Identified Adverse Drug Events In addition, the majority of the ADEs were preventable based on the NCC MERP and the definition stated in the methods [( n  = 154, 86.5%) (95% CI: 80.7–90.8) and ( n  = 150, 84.35% (95%CI:78.2–88.9), respectively] (Fig. 3 . Preventability of Identified Adverse Drug Events [ 20 , 21 ] and Fig. 4 . Preventability of Identified Adverse Drug Events as per the NCCMERP [ 22 ]). Furthermore, greater than half of the ADEs cases were discharged with no further action ( n  = 97, 54.5%), while a substantial proportion of the cases were hospitalized ( n  = 75, 42.1%) (Table 2 ). The mean ± SD number of days for hospitalized cases was 4.2 ± 2.8 with a range of 1 to 17 days. Fig. 3 Preventability of Identified Adverse Drug Events Fig. 4 Preventability of Identified Adverse Drug Events as per the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) Table 2 Consequences of Emergency Department (ED) Visits Due to Adverse Drug Events or Other Causes ED visits for ADEs ED visits for other causes Consequences of the ED visit N = 178 % N = 822 % Hospitalization 75 42.1 311 37.8 Discharge 97 54.5 499 60.7 Refer to another hospital 6 3.4 9 1.1 Death 0 0 3 0.4 Number of days in case of hospitalization Mean ±SD:4.2 ± 2.8 Median = 3.0 Range:1–17 Mean ±SD:4.7 ± 5.9 Median = 3.0 Range:1–60 Preventability of Identified Adverse Drug Events Preventability of Identified Adverse Drug Events as per the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) Consequences of Emergency Department (ED) Visits Due to Adverse Drug Events or Other Causes Mean ±SD:4.2 ± 2.8 Median = 3.0 Range:1–17 Mean ±SD:4.7 ± 5.9 Median = 3.0 Range:1–60 The unadjusted and adjusted odd ratios (ORs) for ADEs are presented in Table 3 . At the bivariate level, the odds of ADE incidence were significantly higher among the patients older than 60 years (OR 1.73; 95% CI 1.079–2.774, p  = 0.023) as compared to patients less than 60 years of age. Moreover, for every additional medication the patient was receiving at admission, the odds of ADE increased by 7.7% (OR 1.077; 95% CI 1.029–1.126, p  = 0.001). On the other hand, the odds of ADE incidence were lower in female patients versus male patients (OR 0.694; 95% CI 0.499–0.967, p  = 0.031). When the data were adjusted for covariates using multivariate logistic regression analyses, similar trends were observed. However, the only significant differences were observed between male and female patients and with the number of medications on admission. Table 3 Unadjusted and Adjusted Odds Ratios for the Incidence of Adverse Drug Events (ADEs) as Per DifferentFactors OR (95% CI) P value aOR † (95% CI) P value Age ≥60 years vs. < 60 years 1.730 (1.079,2.774) 0.023* 1.289 (0.763,2.178) 0.343 Female vs. male 0.694 (0.499,0.967) 0.031* 0.682 (0.483,0.964) 0.030* Nationality: Gulf Cooperation Council (GCC) vs. non-GCC 0.789 (0.498,1.250) 0.313 0.774 (0.477,1.255) 0.299 Total number of medications on admission 1.077 (1.029,1.126) 0.001* 1.074 (1.022,1.129) 0.005* Postgraduate education vs. not-postgraduate education 0.576 (0.282,1.177) 0.130 0.551 (0.268,1.131) 0.104 † Adjusted Odds Ratio *p-value < 0.05 Unadjusted and Adjusted Odds Ratios for the Incidence of Adverse Drug Events (ADEs) as Per DifferentFactors † Adjusted Odds Ratio *p-value < 0.05

Adverse drug events have been recognized as significant contributors to ED visits and admissions in Qatar. The study revealed that the majority of DTP related ED visits were preventable, with 46.6% of them attributed to cardiovascular medications. The most common DTP was patient non-compliance. Therefore, it is essential to design interventions to improve patient adherence. Additionally, more studies are needed in Qatar assessing emergency room visits related to specific medication classes, as well as proposing solutions to minimize specific DTPs.

To our knowledge, this study is the first in Qatar to assess the incidence, severity, and preventability of drug-related ED visits in two of the largest governmental hospitals in the country. The study involved categorizing ADEs based on the type of DTP, identifying the medications related to these problems, and determining the patient sociodemographic and clinical factors associated with these visits. Numerous studies have investigated the association between DTPs and ED visits and admissions. In the current study, the overall incidence rate of ED visits due to ADEs was 178 per 1000 individuals, accounting for 17.8% of all ED visits. Among these, 86.5% were deemed preventable with 46.6% attributed to cardiovascular medications, 18% related to alimentary tract and metabolism medications, 13.5% connected to blood and blood forming agents, and 10.7% linked to the nervous system. In comparison, a 2008 Canadian study showed a 12% drug-related ED visit rate, with 68% preventable incidents [ 11 ]. Moreover, an Italian and an Australian study reported prevalence rates of 3.4% and 9.2% for medication-related ED visits, with 70.7% and 79% of them being possibly or certainly preventable, respectively [ 26 , 27 ]. The Australian study reported that only 4.7% of the cases resulted in death or likely permanent harm [ 27 ]. Furthermore, a 2022 study conducted in Norway found that 19.7% of ED visits were drug-related, with about 19% linked to antithrombotic agents [ 28 ]. Similarly, a 2021 multi-center study carried out in Spain identified that 7.4% of ED patients sought assistance for ADEs, with anti-thrombotic agents being the most common cause [ 29 ]. Another study in Finland has also identified an incidence rate of 7.8%, which was greater among elderly, with anti-thrombotic agents and docetaxel being the most common causative agents [ 30 ]. Moreover, another Spanish study reported that 37.6% of ED cases were due to ADEs, with 71% being preventable [ 31 ]. On the other hand, central nervous system agents were the primary contributors for ADEs, accounting for 22.1% of all cases [ 31 ]. In contrast, the Italian study mentioned above identified antibiotics and anti-inflammatory drugs as the most common implicated drug classes in ADE-related ED visits [ 26 ]. The differences in results in ADE incidents, preventability, and contributing medications between these studies and the current study may be due to variations in definitions of outcomes, methodology, and sample size of the studies. Moreover, pharmacy practice in Qatar and Arab countries is different from that in other countries [ 32 ]. For instance, many prescription medications are readily available for patients in community pharmacies without a prescription, as opposed to other Western and European countries such as Canada and the US, where generally a prescription is needed to purchase prescription medications, and a community pharmacist assesses the appropriateness of prescriptions and educates patients before dispensing [ 32 , 33 ]. Self-medication practices are also common in Arab countries [ 32 ]. In addition, Qatar lacks pharmacovigilance system, while other countries such as Canada, the US, and the UK include a pharmacovigilance responsible body within their healthcare systems for reporting ADEs [ 32 , 34 ]. In the current study, the incidence rate of ED visits due to ADEs among elderly patients was high compared to younger patients. In comparison, in an investigation that was recently carried out in the US, it was found that older adult patients had higher ED visits related to ADEs, compared to those younger than 65 years [ 35 ]. Within the same study, the most common medication classes associated with ED visits in older adults were anticoagulants and anti-diabetic agents [ 35 ]. Similarly, a Chinese study concluded that patients over 60 years contributed to more than 80% of the emergency drug-related hospitalizations, with oral antiplatelet agents, anti-hyperglycemic agents, and antihypertensive agents being the most frequent causative agents [ 36 ]. Furthermore, a study conducted in Taiwan revealed that ED visits due to ADEs in older adults were significantly higher (14.3 per 1000) than in younger adults aged below 65 years (4.1 per 1000) [ 37 ]. Studies reported that the medication use exhibits an increase with aging populations and that polypharmacy was proven to be an influencing factor for the incidence of serious and certainly preventable ADEs [ 26 , 38 ]. A 2013 study conducted among patients older than 65 years showed that patients who developed ADRs on emergency admission were significantly older and took more medications compared to patients who did not develop ADRs [ 39 ]. Moreover, a Canadian study revealed that over 50% of elderly patients presenting to the ED were taking more than 11 distinct medications a year [ 40 ]. Moreover, severe ADRs occurred more in older, sicker patients with many coexisting conditions, in addition to patients who were more likely to take greater than 11 medications [ 40 ]. In Qatar, a 2020 retrospective cross-sectional investigation conducted in Primary Health Care Corporation (PHCC) concluded that among Qatari population, the prevalence of polypharmacy among elderly attending PHCC centers was very high [ 41 ] which explains some of the current study results. Data collected in this study shows that the most common DTP was “patient is not compliant with his/her therapy” accounting for 41.2% of total DTPs. The Canadian study discussed above revealed that the most common ADEs were ADRs (39.3%), followed by nonadherence, accounting for 27.9% of all visits [ 11 ]. In contrast, the Italian study revealed that allergic reactions were the most frequent cause of ADE-related ED visits, followed by neurological effects [ 26 ]. This difference might be attributed to the differences in causative agents for ADE-related ED visits. Medication non-adherence is a huge contributor for ADEs and consequently, negative outcomes of therapy. Research has shown that in developed countries, nearly 50% of individuals do not take their medications as prescribed [ 42 , 43 ]. Medication non-adherence is multi-factorial, as factors contributing to poor medication adherence can be either related to patients, physicians, or healthcare systems [ 42 ]. Patient-related factors include lack of understanding of the disease and involvement in the treatment plan [ 42 , 44 ]. In addition, patients’ beliefs, attitudes, and previous failed experiences with pharmacological treatment contribute to poor medication adherence [ 42 , 45 , 46 ]. Patients with low socioeconomic status specifically may be burdened by high medication costs [ 42 , 47 ]. Physicians prescribing complex regimens can also contribute to low medication adherence [ 45 , 47 ]. Furthermore, failure to explain the benefits and adverse effects of medications, and lack of effective communication between the patient and physician are examples of physician related factors to nonadherence [ 42 , 45 , 47 , 48 ]. There are a few studies conducted in the Middle East region on ADE related ED visits, with the majority being conducted in the Kingdom of Saudi Arabia (KSA) [ 49 – 52 ]. Two studies were published in 2014 and in 2015 aiming to measure the incidence of ED visits and admissions due to DTPs at Riyadh Military Hospital and King Fahd Hospital respectively. The results of the first study were consistent with our findings, as it indicated that 18.7% of patients were presented to the ED due to DTPs. Of those, 92.9% of were admitted to the hospital, representing 17.3% of all ED visits [ 49 ]. However, although our study showed that 17.8% of ED visits were related to ADEs, only 45.5% were admitted or referred to another hospital. The difference in hospital admissions between the two studies can be explained by the fact that only 2.2% of cases in our study were severe, compared with 14.3% of severe cases in the previous study [ 49 ]. One of the predominant DTPs identified in both studies was non-compliance representing 30.4% and 41.2% in the prior investigation and our current study, respectively [ 49 ]. The most prevalent medication group associated with DTPs in the Saudi study was anti-hypertensives, constituting 21.5% of all cases [ 49 ]. In comparison, the primary medication class identified in our present investigation was determined to be calcium channel blockers constituting 15.7% of observed DTPs. This is probably due to similar healthcare systems in the region, and due to the increased prevalence of hypertension in both countries, where 25% of Saudis suffer from hypertension, compared to 33% of the population in Qatar [ 53 , 54 ]. The second Saudi study showed that only 4.5% of ED admissions were caused by DTPs due to differences in the methods [ 50 ]. However, similar to other studies, the most common DTP was found to be non-compliance, accounting for 44.3% of all cases [ 50 ]. Moreover, in 2008, a prospective observational study was conducted in KSA to measure the prevalence of ED admissions rather than visits, due to DTPs [ 51 ]. The rate of admissions due to DTPs was 14.7% of all admitted cases in which 86.8% of them were definitely or possibly preventable, compared to a rate of ED admissions of around 8.1% in the current study. Medications mostly associated with definite DTPs were insulins, covering for 18.86%, compared to a percentage of 14.0% for drugs used in diabetes in the current study. This can also be explained by the increased incidence of diabetes in the region. In Qatar, studies have reported an increased prevalence of diabetic complications, which are strongly associated with low medication adherence [ 55 , 56 ]. In a 2018 study conducted on patients with uncontrolled diabetes, it was reported that patients who were non-adherent to their anti-diabetic medications had higher HbA1C, higher fasting glucose, and experienced more complications compared to adherent patients. In the same study, it was found that 73.5% of patients recruited self-reported non-adherence to their anti-diabetic medications, noting that forgetfulness was the most common barrier for non-adherence. Moreover, in a 2018 qualitative study that was conducted on patients with uncontrolled diabetes in Qatar, three themes emerged describing a number of barriers to medication adherence including patient-related factors, patient-provider factors, and societal and environmental factors [ 57 ]. Overall, our results were consistent with regional and international studies, suggesting an increase in the incidence of ED visits and admissions due to DTPs which are mostly preventable in nature. This brings attention to the importance of patient counselling and education on medication proper use. Aligning with previous studies, the current study concluded non-compliance as the predominant DTP. This emphasizes the importance of implementing programs for medication management and monitoring to improve patient compliance, aiming to lessen ED visits and admissions. For instance, the Medication Use Review (MUR) is a strategy that aims to increase patient adherence and optimize drug therapy outcomes. MURs benefits have been increasingly recognized worldwide, where a patient undergoes a private consultation with a pharmacist aiming to improve patient’s knowledge on medication use, concordance, and ability to detect any DTP [ 58 , 59 ]. Although studies reported that MUR was introduced to some healthcare facilities in Qatar, no data was reported on the nature or extent of MUR services or their implementation in the outpatient sector [ 58 ]. It is anticipated that MUR in the primary care setting would improve medication safety by minimizing drug-related DTPs [ 58 ]. Moreover, campaigns and educational interventions can improve patients’ awareness and adherence [ 43 ]. A systematic Review published in 2017 indicated that public health campaigns can help in raising awareness on the importance of appropriate medicine intake [ 43 , 60 ]. Additionally, it is imperative to revise and enhance existing policies and procedures in Qatar to ensure the limited accessibility of medications by the public. It is crucial to establish a framework where prescription medications are dispensed exclusively to patients with a prescription, thereby minimizing the risk of ADEs. This entails a comprehensive evaluation and potential restructuring of current regulations to align with best practices, guaranteeing a safer and more controlled distribution of prescription medications. In addition, the study findings emphasize the need for a more robust and defined role for ED pharmacists in mitigating ADE-related visits. One innovative approach could be to set up discharge clinics in the ED. [ 61 ] These clinics could be managed by Doctor of Pharmacy (PharmD) pharmacists who would offer to each patient personalized therapeutic advice on how to use their medications, how to adhere to their treatment plan, and how to prevent any potential unsafe drug use. [ 62 ] Moreover, provision of structured pharmacist-led discharge counseling programs in the ED could ensure that patients who have high risk to be readmitted due to ADEs get the necessary monitoring and follow-up care [ 63 ]. ED pharmacists could also perform medication reconciliation at discharge to detect and resolve any drug therapy problems. And they can collaborate with primary care providers to ensure seamless transitions of care, reduce medication errors, and ultimately minimize the risk of preventable ED revisits and hospital readmissions [ 64 , 65 ]. The study had several strengths. It contributed to the published literature on drug related emergency visits and allowed comparing the profile of these visits in Qatar to other countries. This study was designed prospectively with a relatively large predetermined sample size. Additionally, pharmacists and physicians received training and education to reduce subjectivity and discrepancies in ADE identification and classification. Furthermore, they independently assessed the visits, enhancing the internal validity of the study. It is also noteworthy to mention that a pharmacoeconomic analysis aimed to understand the economic impact of drug-related ED visits in Qatar is conducted and will be published in another publication Despite the fact that our study participants are representative of Qatar’s population, only two government hospitals were included in the study. The study results may not be generalizable to other governmental or private hospitals. To improve the external validity of the findings, future studies should include other hospitals. Moreover, similar future studies should assess ER visits due to specific medication classes, and formulate solutions in order to minimize ED admissions as a result of specific DTPs.

Medication therapy is the most common intervention used in healthcare for the prevention and treatment of medical conditions and illnesses [ 1 ]. Medication use has undergone important changes in the last few decades, including an increased availability and variety of medications, more complex regimens, a rising number of prescription and non-prescription medications, and a growing number of patients on polypharmacy [ 2 ]. Factors contributing to these changes include ageing population, high prevalence of chronic diseases, and increase in the number and types of practitioners with prescribing privileges. This increased use of medications and their complexity is associated with avoidable harms, risks, and adverse effects [ 2 ]. An adverse drug event (ADE) is defined as “an injury or harm resulting from the use or inappropriate use of a drug” [ 3 ] including, but not limited to medication errors, adverse drug reactions (ADRs), allergic reactions, and drug overdose [ 4 ]. ADEs impose a huge burden on healthcare systems and represent a challenging public health problem. They are associated with increased rates of hospitalization, emergency department (ED) visits, prolongation of hospital stays, morbidity, and mortality [ 5 – 8 ]. As per the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance (NEISS-CADES) Project, ADEs accounted for 42,585 actual ED visits in 2013–2014 in the United States (US) as compared to 23,798 visits in 2005–2006, with 27.3% of these visits resulting in hospitalization [ 9 ]. Baena et al., reported that the overall prevalence of drug-related ED visits in nine Spanish hospitals was 35.7%, of which 81% were judged as preventable [ 10 ]. A systematic review of the literature concerning drug-related problems that result in ED visits was conducted by Patel et al., [ 7 ]. The results from eight retrospective and four prospective studies indicated that 28% of all ED visits were drug-related [ 7 ]. Of these, 70% were preventable, while 24% resulted in hospital admissions [ 7 ]. Furthermore, Zed et al., identified that 12% of ED visits at a large tertiary care hospital in British Columbia were drug-related [ 11 ]. The most frequent reasons for the visits were ADRs (39.3%), nonadherence (27.9%), and use of wrong or suboptimal drug (11.5%) [ 11 ]. Another study in Australia reported that 16% of cases presenting to the ED of a tertiary referral hospital had confirmed drug-related admissions, with 4.1% presenting with a serious ADE [ 12 ]. Medication use in Qatar is largely regulated by the Pharmacy and Drug Control Department of the Ministry of Public Health. Despite the policies and procedures in place in hospitals in Qatar for reporting ADRs that occur in hospitals, there is no dedicated monitoring system or a national pharmacovigilance center that documents outpatient ADEs and that captures ED or hospital visits that are ADE-related [ 13 ]. Furthermore, research studies investigating drug-related visits in EDs in Qatar are lacking. Extrapolating results from studies conducted elsewhere is not valid for several reasons. First, there exists significant variability across studies and countries regarding emergency visits related to drugs, making it challenging to extrapolate these findings to the local context. Second, Qatar is characterized by its multiculturalism, with the majority of the population originating from diverse countries around the world. Religion, and cultural beliefs can affect how patients understand health and thus can influence their medication use experience and medication taking behavior, which in turn can affect the incidence of ADEs [ 2 ]. In addition, the pharmacy regulations that govern prescription and dispensing of medications in Qatar are different from those in Western and European countries. For example, in Qatar the majority of medications with the exception of antibiotics, steroids, and controlled substances, are readily available to the public over-the-counter without the need for a prescription [ 14 ]. This ease of accessibility to prescription medications has serious implications on appropriateness of medication use and medication safety in Qatar, including predisposing many people to preventable ADEs. Therefore, investigating the incidence of ADEs, ED visits due to ADEs, and estimating the multidimensional burden of these events on Qatar’s healthcare system, is of paramount importance. The primary objective of the study was to determine the incidence, severity, and preventability of ED visits due to ADEs in Qatar. The study also aimed to categorize the visits by type of drug therapy problems (DTPs), identify the medications involved in these problems and determine the sociodemographic and clinical factors associated with these visits.