924373 research-article20202020 SGOXXX10.1177/2158244020924373SAGE OpenRuiz Ramos et al. Original Research SAGE Open Elderly People With Drug-Related April-June 2020: 1­–7 © The Author(s) 2020 DOI: 10.1177/2158244020924373 https://doi.org/10.1177/2158244020924373 Problems Identified in the Emergency journals.sagepub.com/home/sgo Department: Impact of Therapeutic Complexity on Consultations to the Health System Jesus Ruiz Ramos1 , Ana María Juanes Borrego1, Marta Blazquez Andion1, Maria Antonia Mangues Bafalluy1, and Mireia Puig Campmany1 Abstract Different scales have been validated to assess the medication regimen complexity. However, the effect of this complexity on the risk of health care center consultations in patients with drug-related problems is unknown. This study’s objective is to evaluate the association between the Medication Regimen Complexity Index (MCRI) and the number of drugs prescribed and new consultations to the health care system in patients who visit an emergency service due to drug-related problems. This is a retrospective observational study. We included patients >65 years who attended in an emergency service for drug-related problems. To identify variables associated with health care center reconsultation, a multivariate analysis was performed, including demographic and comorbidity variables, number of drugs prescribed, and MCRI value. Two hundred and one patients were included. A significant association was found between the prescription of more than five drugs (odds ratio [OR] = 2.50, 95% confidence interval [CI] = [1.08, 5.79]), an MCRI > 20 (2.98 [1.46–6.09]), and an increase in the number of drugs prescribed (2.87 [1.57–5.21]) and its MCRI (2.06 [1.13–3.77]) at discharge and a new visit to the emergency department. An association was found between the prescription of more than five drugs, an MCRI > 20, an increase in the number of drugs, and in MCRI value at discharge and a new visit to any other health care center. The number of prescribed drugs and the medication complexity of patients who visit the emergency department for drug-related problems was associated with an increase in the number of revisits to the emergency department and to other health care centers. Keywords drug safety, emergency medicine, medication safety, drug-related pharmacy, geriatrics Introduction and 50%, with it being higher in those patients who suffer any adverse event associated with their treatment, as well as Over the last 40 years, developed countries have experienced in those with more complex treatment regimens (Marcum & a progressive aging of their population, with an increase in Gellad, 2012). the number of patients with multiple chronic conditions and, Different scales have been validated over the past few years consequently, the number of patients receiving multiple to assess the pharmacotherapeutic complexity in these patients medications (Colchero et al., 2016; Salive, 2013). on multiple medications (Paquin et al., 2013), highlighting It is known that multiple medications are associated with among them, the scale published by George et al. (2004). an increase in hospital admissions and visits to emergency However, the information is limited as regards the relationship departments, as well as an increase in costs for the health of these scales with the likelihood of suffering a drug-related system (Burnier, 2017; Gellad et al., 2011; Peterson et al., 2003; Simpson et al., 2006). Several studies have associated a high therapeutic complexity with a lack of adherence to the 1 Hospital de la Santa Creu i Sant Pau, Barcelona, Spain treatment, as well as an increase in adverse effects (Mansur Corresponding Author: et al., 2012; Salvi et al., 2017), especially in elderly patients Jesus Ruiz Ramos, Pharmacy Department, Hospital de la Santa Creu i Sant (Onder et al., 2002). The lack of adherence to the long-term Pau. C/San Quintín 89, Barcelona 08041, Spain. treatment by the patient has been estimated between 10% Email: jrzrms@gmail.com Creative Commons CC BY: This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). 2 SAGE Open problem (DRP), defined as a situation that causes the appear- electronic primary care prescription system, which includes ance of a negative effect associated with the drug (Research regular medications and those used only if necessary, in accor- Group in Pharmaceutical Care [University of Granada], dance with the criteria established by George et al. (2004). Research Group in Pharmacology [University of Granada], This index calculates the complexity of the treatment based on 2007), including problems associated with the indication (the the number of drugs prescribed and other factors, such as dos- patient does not use the medicines that s/he needs or uses med- age form, route of administration, dose frequency, or addi- icines that s/he does not need), the effectiveness (the patient tional instructions given for their use. uses an erroneously chosen medicine or uses a lower dosage To analyze the impact of the complexity of the treatments and/or a different dosage schedule than required and/or does on the repeat visits of the patients with DRP, a number of not continue therapy for the full duration of the treatment indi- steps were followed; these included the effect of the number cated), or its safety (the patient uses a higher dosage or a dif- of drugs, the MCRI at discharge from the emergency depart- ferent dosage schedule than required and/or exceeds the full ment on hospital readmissions, and the number of unsched- duration of treatment indicated or uses a medicine that causes uled visits to public health care centers in Catalonia (including an adverse drug reaction). Furthermore, the effect of polyphar- hospitals, long-term healthcare facilities and primary care macy, defined as five or more medications daily (Masnoon centers) at 30 days from hospital discharge, based on the data et al., 2017), as well as its complexity on the patients who are obtained from the clinical notes computer system shared seen in hospital emergency departments due to a DRP, has still with the Catalan Health Institute. not been established. For all these reasons, this research study was conducted with the aim of evaluating the association of the complexity Statistical Analysis of the treatment on repeat visits to the health care system in The data analysis was performed using the Stata 13.0 statis- those patients who visit emergency departments due to a tics program (StataCorp LLC, College Station, TX, USA). DRP. The quantitative variables were obtained as mean values and standard deviation (SD) or median and interquartile range (IQR), whereas the qualitative variables were expressed as Material and Method percentages. The variables between the different groups were A retrospective, observational study was designed. It included compared using parametric (Fisher’s exact test, Student’s patients over 65 years old who visited an emergency depart- t-test) or nonparametric (χ2 test, Mann–Whitney U test) tests ment of a tertiary hospital in Spain for any DRP, in accordance depending on the normality analysis of the sample. with diagnosis made by the physician during the period from To assess the impact of the number of drugs prescribed at June 2017 to June 2018. Those patients who went to emer- discharge and the MCRI on the repeat visits to the emer- gency department with a DRP secondary to treatment with che- gency department, as well as to the health system, a multi- motherapy or hospital dispensed medication were excluded. variate logistic regression analysis was performed, with The hospital has 644 beds, dealing with around 140,000 emer- those variables with a value of p < .2 in the previous univari- gencies annually. The Spanish health care system during this ate analysis being included. The following factors were eval- period was based on a co-payments system of both pensioners uated: age > 80 years, prescribed multiple drugs (defined as and working-population, depending on income intervals and more than five drugs, Masnoon et al., 2017), diabetes, heart with a maximum contribution per month. The identification of failure, chronic kidney failure, chronic obstructive pulmo- patients was made prospectively as a usual activity by a phar- nary disease (COPD), cirrhosis, destination of the patient at macist attached to the emergency department, based on the discharge (residence or home), and a DRP caused by the information included in the emergency admission and dis- most common anatomical therapeutic chemical classifica- charge reports obtained at 8 a.m. in the morning from Monday tion system (ATC) therapeutic groups (A: digestive tract and to Friday. The DRPs were classified as necessity, safety, or effi- metabolism; B: blood and hematopoietic derivatives; C: car- cacy by the emergency department pharmacist, based on the diovascular system and N: central nervous system) (World criteria established in the Third Consensus of Granada Health Organization Collaborating Centre for Drug Statistics (Research Group in Pharmaceutical Care [University of Methodology, n.d.). Given the strong association between Granada], Research Group in Pharmacology [University of the number of drugs and the treatment complexity, both vari- Granada], 2007). ables were introduced separately into the model. For this From the patients included, the reasons for consulting in propose, patients included were divided into two groups emergency department were recorded, as well as the number based on the following variables: polypharmacy, >5 drugs of chronic diseases based on the information obtained from (Masnoon et al., 2017), greater treatment complexity (MCRI electronic primary care records at the moment of admission, value higher than the median value of all included patients), the length of the stay, and the destination on discharge from and an increase in the number of drugs and the MCRI value the emergency department. The number of drugs on admission at discharge. The study had the approval of the Research and at discharge were recorded, as well as the Medication Ethics Committee of the Hospital (reference no. IIBSP- Regimen Complexity Index (MCRI) obtained from the COD-2018-25). Ruiz Ramos et al. 3 Table 1. Characteristics of Patients Included in the Study (n = Table 2. Drugs Involved in Drug-Related Problems of the 201). Patients Included in the Study. Age > 80 years 83 (41.3) Variable n = 201 (%) Female (%) 112 (56.1) Origin (%) Group A ATC 37 (17.5) Home/Primary health care 172 (85.6) Insulin 19 (9.0) Elderly residence 29 (14.4) Oral hypoglycemic 11 (5.2) Number of drugs at admission (median; IQR) 9 (5–10) Laxatives 5 (2.3) MCRI at admission (median; IQR) 21 (14–30.5) Group B ATC 72 (34.1) Number of drugs at discharge (median; IQR) 9 (6–12) Heparins 6 (2.8) MCRI at discharge (median; IQR) 25 (17.5–33) Oral anticoagulants 64 (30.3) >5 Chronic pathologies (%) 193 (91.6) Antiplatelets 2 (9.5) Hypertension 142 (70.6) Group C ATC 25 (12.4) Chronic renal failure 66 (31.2) B-Blockers 5 (2.4) Diabetes 82 (40.8) IECA/ARA-II 7 (3.3) COPD 52 (25.9) Diuretics 9 (4.3) Chronic heart failure 56 (27.9) Group J ATC 6 (2.8) Cirrhosis 14 (7.0) Group N ATC 45 (22.4) Cognitive deterioration 89 (44.3) Benzodiazepines 10 (4.7) Destination at discharge (%) Opioids 8 (3.8) Home 40 (19.9) Antidepressants 8 (3.8) Elderly residence/long-term care facility 87 (43.3) Antiepileptic 16 (7.6) Hospitalization 74 (36.8) Other ATC groups 16 (7.6) Note. IQR = interquartile range; MCRI = Medication Complexity Note. ATC = anatomical therapeutic chemical classification system. Regimen Index; COPD = chronic obstructive pulmonary disease. as well as an MCRI greater than 20 points, is associated with a Results greater number of visits to emergency department and health A total of 201 patients were included (112 females [56.1%]; clinics (Figures 1 and 2). The increase in the number of pre- mean age [SD] = 77.6 [15.3]), identified by the emergency scribed drugs, as well as their complexity, is also associated department specialist or the pharmacist in emergency depart- with a higher number of repeat visits to emergency department ment with a DRP as primary (79.0%) or secondary (21.0%) (drugs = 48.3% vs. 24.6%, p < .001; MCRI = 42.2% vs. diagnosis. Their characteristics are shown in Table 1. Twenty- 26.1%, p = .017) and health clinics (drugs = 69.0% vs. 40.4%, five patients consulted the emergency department due to an p < .001; MCRI = 62.4% vs. 41.3%, p < .001) at 30 days effectiveness DRP, 55 (12.4%) due to a necessity DRP, and from discharge. 131 (65.2%) due to a safety DRP. The main DRP of the The results of the univariate analysis are shown in Table 3. patients included were thromboembolic events (15.4%), In the multivariate analysis, a significant relationship is changes in blood glucose (14.4%), hemorrhagic events observed between the prescription of more than five drugs at (13.9%), sedation confusion (10.9%), and cardiovascular discharge (odds ratio [OR] = 2.50, 95% confidence interval changes (10.9%). The principal therapeutic groups involved [CI] = [1.08, 5.79]), an MCRI > 20 (2.98 [1.46, 6.09]), and in the DRPs included Group A (digestive tract metabolism; the increase in the number of drugs (2.87 [1.57, 5.21]) and in 37; 18.4%), Group B (blood and hematopoietic derivatives; the MCRI (2.06 [1.13, 3.77]) and repeat admission in emer- 72; 35.8%), Group C (cardiovascular system; 30; 14.9%), gency department (Table 4). As regards the number of con- and Group N (nervous system; 50; 24.9%) (Table 2). sultations in any health center, the multivariate analysis An increase in the number of drugs prescribed at dis- found a relationship between these and the prescription of charge was observed in 82 (38.6%) patients (median = 1 more than five drugs at discharge (2.74 [2.95, 12.23]), an drug [IQR = 1–2]), as well as an increase in their MCRI in MCRI > 20 (4.56 [1.36, 15.24]), and the increase in the 106 (52.8%) patients (mean percentage increase = 27.0% number of drugs (3.78 [1.58, 9.00]) and in the MCRI value [SD = 21.4%]), with a significant overall increase being (3.01 [1.72, 5.92]). observed in the group of patients included, 21.5 (13.1) versus 24.3 (14.3), p = .043. A total of 70 (34.8%) patients made a repeat visit to the Discussion emergency department, and 106 (55.6%) patients required According to the results of this study, the increase in the unscheduled visit to health care centers in the 30 days after hos- number of drugs, as well as in the therapeutic complexity of pital discharge. Treatment with five or more drugs at discharge, those patients who go to emergency departments due to a 4 SAGE Open Figure 1. Percentage of patients who visit the emergency department 30 days after discharge according to the MCRI value and the number of prescribed drugs. Note. MCRI = Medication Complexity Regimen Index. Figure 2. Percentage of patients who visit health care centers 30 days after discharge according to the MCRI value and the number of prescribed drugs. Note. MCRI = Medication Complexity Regimen Index. DRP, is associated with an increase in the number of repeat 2017; Tesfaye et al., 2019; Wimmer et al., 2014). However, it visits to the health system. should be noted that our results show, for the first time, the DRPs are a very prevalent health issue. Different studies impact of pharmacotherapeutic complexity on those patients have shown that they are implicated in between 20% and who consult emergency department due to a DRP. 40% of the visits to emergency departments, and that around It should also be noted that a high percentage of patients 70% of the cases are considered avoidable (Baena et al., of our study, after consulting due to a DRP, paradoxically 2006; Castro et al., 2013). experienced an increase in the number of prescribed drugs In our study, the majority of patients who consulted due to and in the complexity of their treatment at discharge, despite a DRP were elderly, with a mean of nine drugs, an MCRI of that the inappropriate use of a drug was a direct or indirect 21, and 91% had more than five chronic conditions, being a factor that caused their emergency department visit. patient population with significant comorbidity and multiple Patients who had already suffered a DRP leading to a visit medication and, therefore, highly vulnerable to have a DRP. to the emergency department may be considered as high risk Polypharmacy has been widely associated with an for new DRPs. Given that the increased risk of suffering increased risk in suffering a DRP, and the MCRI has been adverse events occurs in the first days or months after a new associated with an increased number of admissions in prescription, a rapid medication review is needed for the patients receiving multiple medications (Oscanoa et al., long-term treatments in patients who visit emergency Ruiz Ramos et al. 5 Table 3. Results of the Univariate Analysis. 30-day Health system consultation 30-day Emergency department admission Variable OR [95% CI] p OR [95% CI] p Age > 80 years 1.21 [0.54, 2.72] .644 1.74 [0.81, 3.74] .156 >5 Drugs at discharge 2.50 [1.08, 5.79] .032* 4.63 [2.10, 10.23] <.001* MCRI>20 at discharge 2.98 [1.46, 6.09] .003* 2.73 [1.52, 4.92] .001* Increase in the number of drugs 2.87 [1.57, 5.21] .001* 1.74 [1.34, 2.27] <.001* Increase in the MCRI 2.06 [1.13, 3.77] .099 2.74 [1.52, 4.92] .001* >5 Chronic pathologies 3.95 [0.87, 9.91] .075 4.05 [1.25, 13.07] .019* Chronic renal failure 1.33 [0.76, 2.33] .323 1.29 [0.68, 3.54] .455 Diabetes 1.47 [0.72, 3.00] .290 1.91 [0.92, 3.91] .081 COPD 4.23 [1.89, 9.48] <.001* 3.65 [1.51, 8.89] .004* Chronic heart failure 1.25 [0.58, 2.68] .567 2.80 [1.21, 6.44] .016* Cirrhosis 1.57 [0.65, 3.72] .335 2.06 [0.89, 5.75] .294 Destination at discharge Elderly residence/long-term care facility 1.54 [0.68, 3.47] .298 1.31 [0.96, 1.79] .431 Group ATC A 0.63 [0.09, 4.53] .648 0.85 [0.12, 5.98] .869 B 1.53 [0.21, 6.54] .751 1.29 [0.17, 4.55] .877 C 0.46 [0.06, 3.26] .439 1.11 [0.16, 7.63] .915 N 1.24 [0.23, 2.26] .519 1.17 [0.19, 5.63] .672 Note. OR = odds ratio; CI = confidence interval; MCRI = Medication Complexity Regimen Index; COPD = chronic obstructive pulmonary disease; ATC = anatomical therapeutic chemical classification system. p < .20 included in the multivariate analysis. Table 4. Results of the Multivariate Analysis. 30-day Health system consultation 30-day Emergency department admission Variable OR [95% CI] p OR [95% CI] p Age > 80 years — — 3.10 [0.81, 3.74] .043* >5 Drugs at discharge 2.50 [1.08, 5.79] .032* 2.74 [2.95, 12.23] .021* MCRI > 20 at discharge 2.98 [1.46, 6.09] .003* 4.56 [1.36, 15.26] .014* Increase in the number of drugs 2.87 [1.57, 5.21] .001* 3.78 [1.58, 9.00] .003* Increase in the MCRI 2.06 [1.13, 3.77] .041* 3.01 [1.72, 5.92] <.001* > 5 Chronic pathologies 3.95 [0.87, 9.91] .075 3.83 [0.60, 16.07] .153 Diabetes — — 0.57 [0.21, 1.59] .284 COPD 4.23 [1.89, 9.48] <.001* 5.70 [1.92, 16.81] .004* Heart failure — — 0.56 [0.21, 1.45] .234 Note. OR = odds ratio; CI = confidence interval; MCRI = Medication Complexity Regimen Index; COPD = chronic obstructive pulmonary disease. *p < .05 is statistically significant. departments due to a DRP, as well as education on the new Ulley et al., 2019). Identification of sequential drug prescrib- treatments prescribed, to minimize the appearance of new ing that could represent a prescribing cascade (Rochon & complications. Gurwitz, 2017) and adjust the treatment to the new clinical According to the results obtained in this study, an increase situation of the patient after the consultation must form part of in the number of drugs prescribed is associated with an the strategies to improve the quality of life of patients with increased risk of readmission. Treatment simplification may multiple conditions (Brath et al., 2018). In this sense, the be an option to prevent new consultation to health care centers. guidelines published to help in the de-prescription are a useful Several studies have found a relationship between treatment tool, and in addition, they advocate taking into account the simplification and the increased adherence to it, despite that opinions of the patients in this process (National Institute for the results in terms of clinical variables and quality of life are Clinical Excellence, 2015; Scottish Government Model of still controversial (Iskedjian et al., 2002; Reeve et al., 2017; Care Polypharmacy Working Group, 2015). 6 SAGE Open It should be pointed out that the patients included in our Ethical Approval study were of advanced age, with a high percentage with The study had the approval of the Research Ethics Committee of cognitive impairment, although an appropriate evaluation of Hospital de la Santa Creu i Sant Pau (reference no. IIBSP- the degree of disability could not be obtained from medical COD-2018-25). records. In this patient group, the establishing of an effective communication with the doctors responsible for the patients Funding outside the hospital environment would ensure a rapid opti- The author(s) disclosed receipt of the following financial support mization of treatment on an essential factor to avoid repeat for the research, authorship, and/or publication of this article: This consultations. It has been demonstrated that a significant research was funded by the Spanish Ministry of Health (Carlos III percentage of patients receive insufficient information on Health Institute, ISCIII) FONDOS FEDER through the Fondo de their new treatment at hospital discharge (Glintborg et al., Investigación para la Salud (FIS) (PI18/00889). 2007; Hesselink et al., 2013). Good communication with the different care levels has a positive impact on the control of ORCID iD chronic diseases (Coll-Vinent et al., 2007; Polnaszek et al., Jesus Ruiz Ramos https://orcid.org/0000-0003-1233-1539 2015), thus being a key element to prevent new decompen- sations in patients with chronic conditions after hospital References discharge. Baena, M. I., Faus, M. J., Fajardo, P. C., Luque, F. M., Sierra, F., Among the limitations of our study, is its single-center Martinez-Olmos, J., . . .Zarzuelo, A. (2006). Medicine-related retrospective character. We have not evaluated other param- problems resulting in emergency department visits. European eters that have been associated with adherence to the treat- Journal of Clinical Pharmacology, 62, 387–393. ment, such as the educational and socioeconomic factors of Brath, H., Mehta, N., Savage, R. D., Gill, S. S., Wu, W., Bronskill, the patients included (Kardas et al., 2013). However, the S. E., . . .Rochon, P. A. (2018). 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