Drug-Related Problems and Clinical Pharmacist-Led Medication Therapy Management; Three-Year Survey in an Educational Pharmacotherapy Clinic

Drug-Related Problems and Clinical Pharmacist-Led Medication Therapy Management; Three-Year Survey in an Educational Pharmacotherapy Clinic | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Drug-Related Problems and Clinical Pharmacist-Led Medication Therapy Management; Three-Year Survey in an Educational Pharmacotherapy Clinic Nastaran Valitabar, Hadi Esmaily, Mohammad Sistanizad, Soheil Roshanzamiri, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3812800/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Objectives Drug-related problems (DRPs) are adverse events or circumstances that interfere with favorable health outcomes. Medication therapy management (MTM) was developed to detect and manage DRP. This study set out to identify DRP-associated factors and reporting of subsequent interventions in a university-affiliated educational pharmacy. Methods This study was conducted from January 2020 to December 2022 at Shahid Kazemi Pharmacy, a large referral community pharmacy in Tehran, Iran. After medication review and complete medical history collection, DRPs were identified classified, and necessary interventions were performed. Medication adherence and satisfaction were evaluated before and 2–4 weeks after providing the MTM services. Results Within 1432 admissions, 838 patients were included and received 1116 interventions. Among the 1116 DRPs detected, the most common were drug information (27.4%), difficulty using dosage forms (26.3%), and any toxicity, allergic reaction, or adverse effects related to medications (12.8%). A significant association was detected between the number of DRPs and the age, the number of medications, and underlying chronic diseases ( P < 0.05). Adjusting the age association of the number of medications and the number of underlying chronic diseases remained significant. The use of medications related to the alimentary tract and metabolism, medications affecting the blood and hematopoietic organs, medications affecting the cardiovascular system, antineoplastic and immunomodulatory medications, and medications affecting the nervous system were significantly associated with a higher risk for the occurrence of DRPs ( P < 0.05). Conclusions Community pharmacy-led MTM services have a significant impact on DRP detection, management, medication adherence, and pharmacotherapy satisfaction. Pharmacists Medication Therapy Management Pharmaceutical Services Drug-Related Problems Medication Adherence Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Community pharmacies are among the most accessible components of the healthcare system. Over the past 40 years, the role of pharmacists has shifted from dispensing medications to providing pharmaceutical care ( 1 ). In 1994, the World Health Organization submitted the Good Pharmacy Practice (GPP) standard to optimize pharmacists’ services. In this standard, medication therapy management (MTM) service, is introduced as one of the most important aspects of the pharmacist role, which is independent of, but can occur in conjunction with, the provision of patient’s medications ( 2 ). MTM services have been developed to optimize medication adherence and treatment compliance to detect and manage DRPs. MTM is a promising service to proactively identify DRPs, support evidence-based medication use, and provide individualized counseling to at-risk patients. This includes identifying DRPs and recommending interventions ( 3 ). Clinical pharmacists provide this service as a face-to-face visit in a private setting ( 1 , 4 – 7 ). Readapted clinical services provided by community pharmacists can improve patient health outcomes ( 8 ). Several studies have demonstrated pharmaceutical care's effectiveness in all settings ( 9 – 11 ). In particular, research shows that pharmacist medication review can positively impact adherence, improve prescription appropriateness, and potentially reduce emergency department visits. Most of the pharmacists' missions assigned to them in the GPP standard are in the area of DRP prevention and management, such as prescribing medicines when 1) Proper dose regimens and dosage forms are performed, 2) Instructions for use are clear, 3) Interactions are prevented, 4) Known and predictable ADR, including allergies and other contraindications, are avoided, 5) Unnecessary treatments are minimized, 6) The cost of medicines is considered, assisting patients to understand the importance of taking medicines properly, 7) Monitoring treatment to verify the effectiveness and adverse medicine events. DRPs are defined as "preventable or predictable events or circumstances that actually or potentially interfere with favorable health outcomes'' ( 12 ). They can lead to hospitalization and increase the length of hospital stays ( 13 ). Several systems have been developed to identify and classify the DRPs in a standard manner ( 1 , 14 ). One of these systems was set and validated by the Pharmaceutical Society of Australia which classifies DRPs and subsequent interventions in detail ( 15 ). Studies examining the predisposing factors for DRP occurrence have been performed mostly in hospitalized patients. Factors, such as co-occurrence of chronic diseases, advanced age, polypharmacy ( 16 ), and the use of high-risk medications, for instance, those with a narrow therapeutic index, are reported ( 17 ). Multimorbidity, or the simultaneous occurrence of several conditions, is a clinical and therapeutic challenge for health systems ( 18 ). In this case, because the patient is receiving some pharmacotherapy regimens from different physicians, they will need a service that aligns the different regimens to prevent and manage DRPs if they occur. Despite the negative impact of DRPs on clinical and economic healthcare outcomes in the outpatient setting, few studies have examined the frequency of DRPs occurrence and identified the predisposing factors and subsequent interventions in this setting. Therefore, this study aims to identify DRPs and associated factors such as the occurrence, classification, and reporting of subsequent interventions by clinical pharmacists, and to follow the acceptance rate of physicians in an outpatient setting. Methods Study Design This was performed at the MTM clinic of Shahid Kazemi Pharmacy affiliated with Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran from January 2020 to December 2022. Shahid Kazemi MTM clinic is an ambulatory academic pharmacy and has almost all drugs in the official Iranian drugs list (IDL), such as chemotherapy agents and medications for orphan and rare diseases. Hence, a wide range of patients refer to. Ethical Consideration The study protocol was approved by the Ethics Committee of SBMU with the registered code IR.SBMU.PHARMACY.REC.1399.054. The survey process thoroughly, performed in accordance with Helsinki declaration and patient-centered regulations and the details of recriutment, survey, dara extraction, and reporting were accepted by the Ethic Committee of SBMU. Patients were informed of the study's aims and were assured that their data would be kept confidential. Their participation in the study was voluntary and confirmed with the patients’ informed written consent. Participants Patients were enrolled in the MTM clinic at the pharmacist’s discretion in charge of the community pharmacy or their request for a pharmacotherapy visit. The inclusion criteria for this study included the participants' referral to the MTM clinic with at least one chronic condition. Chronic conditions were defined as those requiring ongoing medical care +/or associated with limitation of daily activities for at least one year. Patients who did not have sufficient information about their medical and medication history and patients who were unwilling to participate in the study were excluded. Outcome Measurements & Data Collection The primary outcome of this study was to identify the association between the incidence of DRPs the number of patients’ medicines, and the number of chronic conditions. The secondary outcome of this study was the effect of pharmacist-led MTM services on medication adherence and medication satisfaction. The third outcome was to evaluate the rate of agreement of physicians to the pharmacist's suggestion for DRP correction. Medication Therapy Management (MTM) & Drug Related Problems (DRP) Identification Patients were evaluated at the MTM clinic by a team consisting of a pharmacy intern and a clinical pharmacy resident under the supervision of a clinical pharmacist. Pharmacists in the MTM clinic received an education program, including how to conduct MTM services and prioritize DRPs to ensure the quality of the MTM services and detection of DRPs. Patient demographics, chief complaints, and medical histories were obtained either from the patients themselves or their caregivers. DRP Classification The WHO disease classification system was used to categorize the underlying chronic diseases ( 23 ). The Anatomical Therapeutic Chemical (ATC) classification system was also used for medication history ( 24 ). To categorize DRPs and subsequent interventions, we used the Pharmaceutical Society of Australia (PSA) ( 12 ). This classification consists of eight categories for DRPs (drug selection, over- or under-prescribing, compliance, under-treatment, monitoring, education or information, unclassifiable, and toxicity or adverse reaction) and five categories for interventions (change in therapy, referral required, provision of information, monitoring, and no recommendation required). In cases where patients needed to be followed up, patients were followed up by telephone or clinic. Medication Adherence Patients' adherence to the treatment regimen was the assessed by Persian language version of the Morisky medication adherence scale-8 ( 19 ), which includes eight questions. To quantify the adherence, questions 1 to 7 (excluding question 5) were given one point for each negative answer and zero points for each positive response. For the last question, 0.25, 0.5, 0.75, and 1 were equivalent to the options "All the time/Usually/Sometimes/Rarely/Never,” and the final score can be classified as those with high adherence ≥ 8, average adherence 6–8 and poor adherence ≤ 6. Patient Satisfaction All patients were assessed regarding their medication satisfaction based on a self-reporting question, “Taking all things into account, how satisfied or dissatisfied are you with this medication?” with a 7-point Likert scale consisting; of 1) Extremely dissatisfied, 2) Very dissatisfied, 3) Dissatisfied, 4) Somewhat satisfied, 5) Satisfied, 6) Very satisfied and 7) Extremely satisfied. Follow-ups In this study, the participants were evaluated at least two times before the intervention, and two to four weeks after the MTM services. Sample Size to calculate the minimum sample size required to establish a relationship between the variables in the study, a pilot study was conducted with 50 patients. The result of the pilot study showed a significant association between the number of medicines and the number of DRPs (Pearson coefficient: 0.125, P = 0.041) and chronic conditions (Pearson coefficient: 0.143, P = 0.038). With an alpha coefficient of 0.05, a power of 80%, and a correlation coefficient of 0.125, the calculated sample size was 826. Data Analysis The Kolmogorov-Smirnov test was used to test the normality assumption of the variables. Parametric variables were presented using mean ± standard deviation (SD); we used median and interquartile range (IQR) for nonparametric variables. One-way analysis of variance (ANOVA) was used to compare the number of DRPs between groups. An independent sample T-test was performed to compare the frequency of drug classes across the number of DRPs. In addition, the linear regression model was used to evaluate the association between the number of DRPs and the number of underlying chronic diseases or medications taken. Finally, a multivariable regression model was constructed and adjusted for age. All analyses were performed in IBM SPSS statistics for Windows (version 22.0 IBM, Armonk. NY). The statement of strengthening the reporting of observational studies in epidemiology (STROBE) was followed in reporting ( 20 ). Results Participant Characteristics Sampling was performed over three years to reach the sample size required to achieve the study objective; during this period, 1432 admissions were recorded in the MTM clinic, among whom 359 cases did not meet the inclusion criteria, 143 cases had exclusion criteria, and 19 cases declined to participate in the study; finally, 911 patients meet the requirements of participation. Awhom 73 did not complete all questionnaires and feedback per protocol. Eventually, the results of 838 patients were included in this study. The mean age of participants was 50.2 ± 12.4. Among the participants, 49 were ≤ 14 years old, and 235 were ≥ 65, and the age of 33% of patients were in the range of 24–65 years, and 51.4% of the study population were females. A summary of patients' demographic and clinical data is available in Table 1 . Table 1 Demographic and clinical characteristics of the study population. Variables Total number of participants: 838 Descriptive statistics (n*, %) (mean ± SD**) Gender Female 431 (51.4%) Male 407 (48.6%) Source of information Patient 582 (69.5%) Patients caregiver 256 (30.5%) Age range (y) 45–64 282 (33.7%) 25–44 253 (30.2%) > 65 235 (28.0%) Duration of consultation 13.05 ± 6.32 Number of baseline chronic condition 1.14 ± 0.75 Number of DRP 1.33 ± 0.68 Number of medication 1.26 ± 1.41 Number of interventions 1.33 ± 0.84 *: absolute frequency **: standard deviation The first three common diseases among the participants were endocrine, nutritional, and metabolic diseases (25.2%), neoplasms (10.7%), and musculoskeletal or connective tissue diseases (10.4%). Figure 1 illustrates the frequency of the underlying chronic conditions in detail. In addition, the first three categories of medications taken by the patients were nutritional and metabolic agents (32.5%), antineoplastic and immunomodulatory agents (31.1%), and musculoskeletal (12.9%) (Fig. 2 ). The most common chief complaints of the patients were related to drug administration (32.7%), requests for drug information (21.5%), and complications of adverse effects (12.6%) (Fig. 3 ). Outcome Reports Description of DRPs : We identified 1116 (median: 1; IQR 1st, third: 1,2) DRPs in the study population. The most common DRPs were patients' requests for information about their medications (27.4%), difficulty using dosage forms (26.3%), and any toxicity, allergic reaction, or adverse effects related to medications (12.8%). Table 3 shows the frequency of major categories and subcategories of DRPs in detail. Only 11 (1.3%) patients did not experience any DRP. Pharmacists performed 1118 interventions during the study period (median: 1; IQR 1st, 3rd: 1,1). Patient education and counseling were the most common interventions (67.9%), followed by referral to a physician (16.7%) and recommendation for dose administration (11%). The detailed distribution of interventions is shown in Fig. 4 . Among the admitted patients, 628 were identified as requiring more follow-ups and were contacted by telephone, and in 334 cases, the patient identified as requiring face-to-face follow-up. Physician Approval Rate To inform the patient's physician about the actions taken by the clinic for DRP management, or to request a decision, 641 correspondences were made, of which 354 (55.2%) correspondences were made for the physician's information, in 287 (44.7%) cases a change in the patient's medication was suggested, of which 276 (96.1%) physicians agreed with the proposal, in 11 other cases the physician suggested another management to the detected DRP. Medication Adherence The average total adherence to the treatment regimen before the intervention was 4.21 ± 1.22, and it improved to 7.53 ± 0.30 ( P < 0.0001). Table 2 illustrates the results in more detail. There is a significant difference between the before and after intervention results in all cases except question 5. Also, the results showed that before the intervention, 775 (92.48%) patients were in the poor adherence level, and only 63 (7.51%) were patients are an average level, while after the intervention, the adherence score of all (100%) patients were in the middle range (P < 0.0001). Analysis of the mean difference in the score obtained from the medication adherence score showed that patients’ average score has increased by 3.31 ± 1.26. Table 2 Adherence to treatment regimen and patient satisfaction before and after the MTM services Item Answer Patients’ Responses # (%) Before After P-Value Medication Adherence Question 1 No 301 (63.96) 385 (45.94) 0.003 Question 2 No 511 (60.98) 720 (85.92) 0.001 Question 3 No 544 (64.92) 731 (87.23) < 0.0001 Question 4 No 419 (64.92) 636 (87.23) < 0.0001 Question 5 Yes 804 (95.94) 833 (99.40) 0.181 Question 6 No 604 (72.08) 804 (95.94) < 0.0001 Question 7 No 343 (40.93) 502 (59.90) < 0.0001 Question 8 Never 160 (19.09) 178 (21.24) < 0.0001 Rarely 192 (22.91) 486 (58.00) Sometimes 453 (54.06) 166 (19.81) Usually 33 (3.94) 8 (0.95) All the time 0 (0) 0 (0) Patient Satisfaction Extremely Dissatisfied 58 (6.92) 0 (0) < 0.0001 Very Dissatisfied 182 (21.72) 0 (0) Dissatisfied 323 (38.54) 61 (7.28) Somewhat Satisfied 210 (25.06) 158 (18.85) Satisfied 59 (7.04) 202 (24.11) Very Satisfied 6 (0.72) 234 (27.92) Extremely Satisfied 0 (0) 183 (21.84) Table 3 Frequency of categories and subcategories of DRPs Categories of DRPs Drug selection (n, %) (69, 6.2%) Compliance (n, %) (366, 32.8%) Over or underdose-prescribed (n, %) (34, 3.0%) Undertreated (n, %) (38, 3.4%) Monitoring (n, %) (31, 2.8%) Education or information (n, %) (401, 35.9%) Not classifiable (n, %) (69, 6.2%) Toxicity or adverse reaction (n, %) (108, 9.7%) Subcategories of DRPs Wrong drug (18, 1.6%) Difficulty using the dosage form (294, 26.3%) The prescribed dose too low (11, 1.0%) Condition undertreated (15, 1.3%) Laboratory monitoring (22, 2.0%) The patient requests drug information (306, 27.4%) Drug interaction (14, 1.2%) Under-use by patient (20, 1.8%) Prescribed dose is too high (6, 0.5%) Condition untreated (11, 1.0%) Non-laboratory monitoring (6, 0.5%) The patient requests disease management advice (95, 8.5%) No indication apparent (13, 1.2%) Erratic use of medications (20, 1.8%) Incorrect or unclear dosing instruction (15, 1.3%) Preventive therapy required (12, 1.1%) Other monitoring problem (3, 0.25%) Other educational information problem (0, 0%) Contraindication apparent (9, 0.8%) Other compliance problem (15, 1.3%) Other dose problem (2, 0.2%) Other undertreated indication problem (0, 0%) Duplication (7, 0.6%) Over-use by patient (15, 1.3%) Other drug selection problem (7, 0.6%) Intentional drug misuse (2, 0.2%) Inappropriate dosage form (1, 0.1%) Incorrect strength (0, 0%) Medication Satisfaction The results of patient satisfaction with their treatment regimen showed that before providing the MTM services, 275 (32.82%) patients were satisfied with their treatment regimen, while after providing services, 777 (92.72%) patients were satisfied (P < 0.0001). Table 2 presents the results in more detail. Factors Associated with DRP Occurrence A significant association was found between the number of DRPs and the age ( P = 0.003, Pearson correlation coefficient = 0.103) the number of medications ( P < 0.001, Pearson correlation coefficient = 0.206) and the number of underlying chronic diseases ( P < 0.001, Pearson correlation coefficient = 0.225). Adjusting the age in the multivariable linear regression model showed that both the number of medications and the number of underlying chronic diseases remained significant (unstandardized B = 0.055 and 0.140, P = 0.006 and < 0.001, respectively). Some chronic diseases resulted in a significantly higher number of DRPs. Table 4 . illustrates in detail the discrepancies in DRP frequency among all diseases. Table 4 Distribution of DRP frequency in different disease categories. Disorders N Number of DRPS Mean ± SD P-Value Endocrine, Nutritional or Metabolic Diseases With 211 1.43 ± 0.82 0.019* Without 627 1.30 ± 0.62 Neoplasms With 90 1.35 ± 0.66 0.724 Without 748 1.33 ± 0.68 Disease of the Musculoskeletal System or Connective Tissue With 87 1.22 ± 0.56 0.138 Without 751 1.34 ± 0.69 Diseases of the Nervous System With 81 1.28 ± 0.57 0.504 Without 757 1.34 ± 0.68 Disease of the Circulatory System With 81 1.51 ± 085 0.015* Without 757 1.31 ± 0.65 Diseases of the Digestive System With 68 1.41 ± 0.67 0.310 Without 770 1.32 ± 0.68 Disease of the Genitourinary System With 61 1.36 ± 0.75 0.729 Without 777 1.33 ± 0.67 Factors Influencing Health Status or Contact with Health Services With 54 1.68 ± 0.99 0.000* Without 784 1.31 ± 0.64 Diseases of Blood or Blood-forming Organs With 47 1.30 ± 0.59 0.724 Without 791 1.33 ± 0.68 Disease of the Respiratory With 31 1.45 ± 0.67 0.315 Without 807 1.32 ± 0.68 Mental & Behavioral or Neurodevelopmental Disorders With 27 1.59 ± 0.75 0.042* Without 811 1.32 ± 0.67 Disease of the Visual System With 4 2.00 ± 1.15 0.048* Without 834 1.33 ± 0.67 Diseases of the Skin With 21 1.43 ± 0.67 0.507 Without 817 1.33 ± 0.68 Certain Infectious or Parasitic Diseases With 7 1.00 ± 0.00 0.193 Without 831 1.33 ± 0.68 Symptoms, Signs or Clinical Findings, Not Elsewhere Classified With 7 1.43 ± 0.53 0.704 Without 831 1.33 ± 0.68 Conditions Related to Sexual Health With 6 1.33 ± 0.52 0.995 Without 832 1.33 ± 0.68 Sleep-wake Disorders With 5 1.60 ± 1.34 0.375 Without 833 1.33 ± 0.67 Disease of the Immune System With 3 0.67 ± 0.58 0.088 Without 835 1.33 ± 0.68 Injury, Poisoning, or Certain other Consequences of External Causes With 3 1.33 ± 0.58 0.997 Without 835 1.33 ± 0.68 Disease of the Ear or Mastoid Process With 1 1.00 0.624 Without 837 1.33 ± 0.68 * With significant difference Among the drug categories in the multivariable regression model, alimentary tract and metabolism (standardized coefficient B = 0.219; P < 0.001), blood and hematopoietic organs (standardized coefficient B = 0.075; P < 0.038), cardiovascular system (standardized coefficient B = 0.076; P < 0.039), antineoplastic and immunomodulatory agents (standardized coefficient B = 0.084; P < 0.025), and nervous system (standardized coefficient B = 0.084; P < 0.016) remained significant in the final model and showed a positive correlation with the number of DRPs. Discussion In the present study, DRPs and subsequent interventions were evaluated at the MTM clinic of a community pharmacy over three years. The significant impact of clinical pharmacy-based MTM services on identifying DRPs and recommendations of interventions was evident. Of all the 838 patients, 1116 DRPs were identified, with difficulty using dosage forms, desire for more information about medications, and any toxicity, allergic reaction, or adverse effect related to medications topping the list. The most common interventions included education and counseling, referral to the prescriber, and dosage recommendation. Interestingly, higher numbers of medications and underlying chronic conditions were associated with more DRPs. Finally, a specific category of diseases contributed to a higher number of DRPs. The results showed that only 11 (1.3%) patients had no DRPs. However, even these patients benefited from MTM services provided by clinical pharmacists, such as education. Additionally, both medication adherence and satisfaction regimens improved after MTM services. Several studies have previously examined DRPs in hospitalized patients ( 11 , 21 – 23 ); however, few data are available from regular community pharmacies ( 24 ). While we found our most common DRPs, studies with predominantly inpatient settings have shown that DRPs such as the need for a new medication or dose increase ( 9 ), suboptimal drug effect ( 22 ), and lack of therapy ( 25 ) are significant problems in inpatients. On the other hand, the most common DRPs in community pharmacies included information problems, therapeutic errors ( 26 ), drug interactions, contraindications ( 27 ), need for additional therapy, unnecessary drug therapy, and poor adherence ( 28 ). The different outcomes may be due to differences in the healthcare system, deficiencies in data documentation, and a lack of appropriate infrastructure. The finding that "seeking more information about medications" is the most common DRP indicates that many patients are not informed about their medications and treatment, underscoring the importance of pharmacists' MTM services. Regarding the drug classes associated with the occurrence of DRPs, the results of previous studies conducted in the outpatient setting are similar. For example, the results for the alimentary tract and metabolism ( 29 , 30 ), blood and hematopoietic organs, cardiovascular system, nervous system ( 29 ), and antineoplastic and immunomodulatory agents were the same. In the inpatient setting, in chronic kidney disease (CKD) clinics, cardiovascular drugs, gastrointestinal agents, and analgesics are more likely to be responsible for DRPs. In an intensive care unit, systemic antimicrobial agents are more likely to be accountable for DRPs ( 7 , 12 , 31 ). Both the number of drugs and underlying chronic diseases were critical factors contributing to the rate of DRPs. Previous studies have shown that the number of medications in both outpatient and inpatient settings could significantly determine the incidence of DRPs ( 32 ). In this regard, polypharmacy is a critical factor leading to a higher risk of DRPs, necessitating a move away from the classic thresholds of 4 + or 5 + medications to a realistic linear approach ( 29 ). To address this issue and reduce the rate of preventable adverse drug events, studies have suggested the use of advanced computerized drug prescribing systems ( 33 ). In addition, the current study results showed that the presence of some diseases was significantly related to the increased risk of DRPs, which is discussed below. In the category of endocrine disorders, more patients had diabetes mellitus who used insulin pens. They had difficulty in using their medication due to inadequate education. A prospective study showed that patients with circulatory diseases were taking more than five medications, which is a risk predictor for developing DRPs. The number of chronic diseases per patient was almost four, indicating obvious multiple morbidities ( 33 ). Visual impairment may also affect patients' taking prescribed medications ( 34 ). This is mainly because they have difficulty reading prescription labels, recognizing expiration dates, understanding the name of the drug, and keeping their medications. Of the group factors affecting health status or contact with health services for illness, most patients were those who had undergone organ transplantation. It seems that these patients are more prone to DRPs due to their polypharmacy and use of immunosuppressive drugs ( 35 ). Patients with severe mental illnesses are less likely to receive standard treatment for their comorbidities, making them more susceptible to DRPs ( 36 ). As we showed that pharmacist-led MTM services could improve patient adherence to the treatment regimen, Daniel A. Ercu et al. also demonstrated that MTM services provided by pharmacists markedly increased medication adherence in patients with type 2 diabetes mellitus by 9.2% at baseline to 61% at six months in a prospective randomized controlled study ( 37 ). This may be because patients with chronic conditions like diabetes mellitus have complex treatment regimens, so educating and clarifying the treatment regimen can make them more adherent. This study found that patients were more satisfied with their treatment regimen after MTM services than before. In a study conducted in a large, integrated healthcare system, 95.3% of patients agreed or strongly agreed that their overall health and well-being had improved due to pharmacist-led MTM services ( 8 ). This may be because pharmacists assume responsibility for patients’ medication therapy outcomes and collaborate with other healthcare providers to facilitate high-quality patient care ( 38 ). This study has some limitations. First, as the data were not collected longitudinally, it does not allow us to identify causal relationships. Second, our results may differ from those of other geographic areas with different healthcare characteristics, particularly concerning domestic pharmaceutical care. Third, the diversity of patients referred to the pharmacy of the study site was high. Although this diversity was an advantage, this amount of variety in patients may not be seen in the usual community pharmacies and affect the generalizability of our results. The following limitation of the study is the non-detection of DRP by the pharmacist, especially in the case of uncommon DRPs that are also related to the pharmacist's professional experience. A standard validated DRP classification system was used in this study to minimize this. Conclusion This study suggests that MTM services lead to the detection and resolution of many DRPs with appropriate interventions and improvement in medication adherence and satisfaction. The mean probability of DRP detection in included patients was 1.33, and the most common were drug information and difficulty using dosage forms. The use of medications related to the alimentary tract and metabolism, medications affecting the blood and hematopoietic organs, medications affecting the cardiovascular system, antineoplastic and immunomodulatory medications, and medications affecting the nervous system were significantly associated with a higher risk for the occurrence of DRPs. A significant association was detected between the number of drug-related problems and the age, number of medications, and underlying chronic diseases. This study represents a promising approach to MTM services in community pharmacies delivered by clinical pharmacists, which could have significant health implications. The findings will be used for developing evidence-based eligibility criteria for MTM services in community pharmacies. Declarations Conflict of interest: There is no conflict of interest of any of the authors with the results of this study. Data availability statement: The data that support the findings of this study are available from the corresponding author, upon reasonable request. Acknowledgments We thank and appreciate the efforts of Dr. Roozbeh Pourziaei Manesh, the director of Shahid Kazemi Pharmacy, and Professor Jamshid Salamzadeh, the head of SBMU pharmacies, who played a significant role in conducting this research. We appreciate the efforts of Morisky Medication Adherence Research group for giving us the license to use the MMAS scale (Certificate Number: 7799-8371-5354-4091-1040). Ethical approval and consent: The study protocol was approved by the Ethics Committee of SBMU with the registered code IR.SBMU.PHARMACY.REC.1399.054. The survey process thoroughly, performed in accordance with Helsinki declaration and patient-centered regulations and the details of recriutment, survey, dara extraction, and reporting were accepted by the Ethic Committee of SBMU. Patients were informed of the study's aims and were assured that their data would be kept confidential. Informed written consent was obtained from all subjects. Consent for publication: N.A Declaration of Interest : The authors declare there is no conflict of interest in this study. Funding : This work was supported by the Medical Research Council of SBMU [Grant NO: 22527]. Data Availability Statement: The data supporting this study’s findings are available from the corresponding author on request. 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BMJ Open. 2020;10(4):1–8. Holland R, Desborough J, Goodyer L, Hall S, Wright D, Loke YK. Does pharmacist-led medication review help to reduce hospital admissions and deaths in older people? A systematic review and meta-analysis. Br J Clin Pharmacol. 2008;65(3):303–16. Ruths S, Viktil KK, Blix HS. [Classification of drug-related problems]. Tidsskr Nor Laegeforen [Internet]. 2007;127(23):3073–6. x. Pharmaceutical Society of Australia. Guidelines for pharmacists performing clinical interventions. 2018. Bloomfield HE, Greer N, Linsky AM, Bolduc J, Naidl T, Vardeny O, et al. Deprescribing for Community-Dwelling Older Adults: a Systematic Review and Meta-analysis. J Gen Intern Med. 2020;35(11):3323–32. Mansur JM. Medication Safety Systems and the Important Role of Pharmacists. Drugs Aging. 2016;33(3):213–21. Parekh AK, Barton MB. The challenge of multiple comorbidity for the US health care system. JAMA. 2010;303(13):1303–4. Moharamzad Y, Saadat H, Nakhjavan Shahraki B, Rai A, Saadat Z, Aerab-Sheibani H, et al. Validation of the Persian Version of the 8-Item Morisky Medication Adherence Scale (MMAS-8) in Iranian Hypertensive Patients. Glob J Health Sci. 2015;7(4):173–83. Checklists - STROBE [Internet]. [cited 2022 Feb 11]. Available from: https://www.strobe-statement.org/checklists/ . Saldanha V, de Araújo IB, Vieira Cunha Lima SI, Randall Martins R, Oliveira AG. Risk factors for drug-related problems in a general hospital: A large prospective cohort. PLoS ONE. 2020;15(5):1–16. Pellegrin KL, Krenk L, Oakes J, Ciarleglio A, Lynn J, Mcinnis T, et al. Reductions in Medication-Related Hospitalizations in Older Adults with Medication Management by Hospital and Community Pharmacists. A Quasi-Experimental Study; 2016. Chisholm-Burns MA, Kim Lee J, Spivey CA, Slack M, Herrier RN, Hall-Lipsy E, et al. US pharmacists’ effect as team members on patient care: Systematic review and meta-analyses. Med Care. 2010;48(10):923–33. Tasaka Y, Tanaka A, Yasunaga D, Asakawa T, Araki H, Tanaka M. Potential drug-related problems detected by routine pharmaceutical interventions: safety and economic contributions made by hospital pharmacists in Japan. J Pharm Heal Care Sci. 2018;4(1). Lewinski D, Wind S, Belgardt C, Plate V. Prevalence and safety-relevance of drug-related problems in German. 2010;(September 2009):141–9. Rhalimi M, Rauss A, Housieaux E. Drug-related problems identified during geriatric medication review in the community pharmacy. Int J Clin Pharm. 2018;40(1). Salmasi S, Tsao NW, Li K, Shaske JN, Marra CA, Lynd LD. Characterization of pharmacist-based medication management services in a community pharmacy. Res Soc Adm Pharm [Internet]. 2020;16(2):178–82. https://doi.org/10.1016/j.sapharm.2019.04.051 . Chau SH, Jansen APD, van de Ven PM, Hoogland P, Elders PJM, Hugtenburg JG. Clinical medication reviews in elderly patients with polypharmacy: a cross-sectional study on drug-related problems in the Netherlands. Int J Clin Pharm. 2016;38(1):46–53. Garin N, Sole N, Lucas B, Matas L, Moras D, Rodrigo-Troyano A et al. Drug related problems in clinical practice: a cross-sectional study on their prevalence, risk factors and associated pharmaceutical interventions. Sci Rep [Internet]. 2021;11(1):1–11. https://doi.org/10.1038/s41598-020-80560-2 . Garedow AW, Mulisa Bobasa E, Desalegn Wolide A, Kerga Dibaba F, Gashe Fufa F, Idilu Tufa B et al. Drug-Related Problems and Associated Factors among Patients Admitted with Chronic Kidney Disease at Jimma University Medical Center, Jimma Zone, Jimma, Southwest Ethiopia: A Hospital-Based Prospective Observational Study. Int J Nephrol. 2019;2019. Martins RR, Silva LT, Lopes FM. Impact of medication therapy management on pharmacotherapy safety in an intensive care unit. Int J Clin Pharm [Internet]. 2019;41(1):179–88. https://doi.org/10.1007/s11096-018-0763-0 . Gandhi TK, Hussar DA, Minsk AG. Adverse drug events in ambulatory care prescriptions for improvement. Med Crossfire. 2003;5(7):21–4. Abdi AA. Introducing clinical pharmacy services to cardiovascular clinics at a university hospital in Northern Cyprus. 2017. Zhi-Han L, Hui-Yin Y, Makmor-Bakry M. Medication-handling challenges among visually impaired population. Arch Pharm Pract. 2017;8(1):8. Stemer G, Lemmens-Gruber R. Clinical pharmacy services and solid organ transplantation: A literature review. Pharm World Sci. 2010;32(1):7–18. Zolezzi M, Abdulrhim S, Isleem N, Zahrah F, Eltorki Y. Medical comorbidities in patients with serious mental illness: A retrospective study of mental health patients attending an outpatient clinic in Qatar. Neuropsychiatr Dis Treat. 2017;13:2411–8. Erku DA, Ayele AA, Mekuria AB, Belachew SA, Hailemeskel B, Tegegn HG. The impact of pharmacist-led medication therapy management on medication adherence in patients with type 2 diabetes mellitus: A randomized controlled study. Pharm Pract (Granada). 2017;15(3):1–7. Cardosi L, Hohmeier KC, Fisher C, Wasson M. Patient Satisfaction With a Comprehensive Medication Review Provided by a Community Pharmacist. J Pharm Technol. 2018;34(2):48–53. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 01 Jan, 2024 Editor assigned by journal 29 Dec, 2023 Submission checks completed at journal 29 Dec, 2023 First submitted to journal 27 Dec, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3812800","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":264590882,"identity":"08e53185-ed48-4243-9c27-03fb47c98043","order_by":0,"name":"Nastaran Valitabar","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Nastaran","middleName":"","lastName":"Valitabar","suffix":""},{"id":264590883,"identity":"245a4921-1073-4528-b42e-dad9c0ce6bc5","order_by":1,"name":"Hadi Esmaily","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIiWNgGAWjYBAC+wYgkVDAwGAARAc+MByAihvg1gKWSjCAaDk4g2gtDFAtzDxwLXiAAf/pxA8PDA4zmLMf3njY5s+daIMDzA8/MBTcw+0XidzNEglALZY9aQWHc9ue5W44wGYswWBQjNsWCd4NYC0GB3IMDuc2HAZqYTADiifgcdjZzT/AWs6/MThs8Qekhf0bfi0MudsgttwA2sLABtLCQ8AWidxtFgkG6UAtzwoO9gL9MvMwTzHQENxa7PvPbr75o8Ia6LDkzR9+/LmT23e8feOHD39wa4GC5voGOJsZiAlqYGCoI6xkFIyCUTAKRi4AAJb7XNBiAFlXAAAAAElFTkSuQmCC","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Hadi","middleName":"","lastName":"Esmaily","suffix":""},{"id":264590884,"identity":"df4adbef-3052-4057-905d-cc8334671d27","order_by":2,"name":"Mohammad Sistanizad","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Mohammad","middleName":"","lastName":"Sistanizad","suffix":""},{"id":264590885,"identity":"e4f431f5-3e2e-42ec-979b-2c0182f6b800","order_by":3,"name":"Soheil Roshanzamiri","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Soheil","middleName":"","lastName":"Roshanzamiri","suffix":""},{"id":264590886,"identity":"f6ea612c-fe7d-42c0-891f-0bb04823fcba","order_by":4,"name":"Amir Farrokhian","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Amir","middleName":"","lastName":"Farrokhian","suffix":""},{"id":264590887,"identity":"a913fdd9-00fb-45ec-9360-0dc455765eac","order_by":5,"name":"Ghader Mohammadnezhad","email":"","orcid":"","institution":"Shahid Beheshti University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Ghader","middleName":"","lastName":"Mohammadnezhad","suffix":""}],"badges":[],"createdAt":"2023-12-27 15:14:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3812800/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3812800/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49129293,"identity":"f8d66acc-b48a-48a5-bce2-77a28b423ff3","added_by":"auto","created_at":"2024-01-03 15:14:04","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":73562,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of baseline chronic conditions.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3812800/v1/27adc6bded673eeaa4dfb900.png"},{"id":49126837,"identity":"4980ab48-bcc6-4937-98bf-93d459882526","added_by":"auto","created_at":"2024-01-03 14:58:04","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":80007,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of the classes of medications used.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3812800/v1/ad754eae1afb86adaeaa35ff.png"},{"id":49128334,"identity":"54869d3a-12f9-4b86-8902-fd75139736f1","added_by":"auto","created_at":"2024-01-03 15:06:04","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":59727,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of the classes of chief complaints.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3812800/v1/a3c288f7bdbda4f0a260ac2d.png"},{"id":49126835,"identity":"8cea2f9a-c1aa-43ee-bb44-b47dff37e8d9","added_by":"auto","created_at":"2024-01-03 14:58:04","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":19287,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of interventions provided by clinical pharmacist.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-3812800/v1/74b61c58f8a6e8204043e981.png"},{"id":49129954,"identity":"1b0bf98e-d2c3-44ad-963e-95b3e93b87c4","added_by":"auto","created_at":"2024-01-03 15:22:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":865496,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3812800/v1/9c0075c6-e724-4748-80c9-c4b6be6360f7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Drug-Related Problems and Clinical Pharmacist-Led Medication Therapy Management; Three-Year Survey in an Educational Pharmacotherapy Clinic","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCommunity pharmacies are among the most accessible components of the healthcare system. Over the past 40 years, the role of pharmacists has shifted from dispensing medications to providing pharmaceutical care (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). In 1994, the World Health Organization submitted the Good Pharmacy Practice (GPP) standard to optimize pharmacists\u0026rsquo; services. In this standard, medication therapy management (MTM) service, is introduced as one of the most important aspects of the pharmacist role, which is independent of, but can occur in conjunction with, the provision of patient\u0026rsquo;s medications (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMTM services have been developed to optimize medication adherence and treatment compliance to detect and manage DRPs. MTM is a promising service to proactively identify DRPs, support evidence-based medication use, and provide individualized counseling to at-risk patients. This includes identifying DRPs and recommending interventions (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Clinical pharmacists provide this service as a face-to-face visit in a private setting (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Readapted clinical services provided by community pharmacists can improve patient health outcomes (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Several studies have demonstrated pharmaceutical care's effectiveness in all settings (\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). In particular, research shows that pharmacist medication review can positively impact adherence, improve prescription appropriateness, and potentially reduce emergency department visits.\u003c/p\u003e \u003cp\u003eMost of the pharmacists' missions assigned to them in the GPP standard are in the area of DRP prevention and management, such as prescribing medicines when 1) Proper dose regimens and dosage forms are performed, 2) Instructions for use are clear, 3) Interactions are prevented, 4) Known and predictable ADR, including allergies and other contraindications, are avoided, 5) Unnecessary treatments are minimized, 6) The cost of medicines is considered, assisting patients to understand the importance of taking medicines properly, 7) Monitoring treatment to verify the effectiveness and adverse medicine events.\u003c/p\u003e \u003cp\u003eDRPs are defined as \"preventable or predictable events or circumstances that actually or potentially interfere with favorable health outcomes'' (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). They can lead to hospitalization and increase the length of hospital stays (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Several systems have been developed to identify and classify the DRPs in a standard manner (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). One of these systems was set and validated by the Pharmaceutical Society of Australia which classifies DRPs and subsequent interventions in detail (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eStudies examining the predisposing factors for DRP occurrence have been performed mostly in hospitalized patients. Factors, such as co-occurrence of chronic diseases, advanced age, polypharmacy (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), and the use of high-risk medications, for instance, those with a narrow therapeutic index, are reported (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Multimorbidity, or the simultaneous occurrence of several conditions, is a clinical and therapeutic challenge for health systems (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). In this case, because the patient is receiving some pharmacotherapy regimens from different physicians, they will need a service that aligns the different regimens to prevent and manage DRPs if they occur.\u003c/p\u003e \u003cp\u003eDespite the negative impact of DRPs on clinical and economic healthcare outcomes in the outpatient setting, few studies have examined the frequency of DRPs occurrence and identified the predisposing factors and subsequent interventions in this setting. Therefore, this study aims to identify DRPs and associated factors such as the occurrence, classification, and reporting of subsequent interventions by clinical pharmacists, and to follow the acceptance rate of physicians in an outpatient setting.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eThis was performed at the MTM clinic of Shahid Kazemi Pharmacy affiliated with Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran from January 2020 to December 2022. Shahid Kazemi MTM clinic is an ambulatory academic pharmacy and has almost all drugs in the official Iranian drugs list (IDL), such as chemotherapy agents and medications for orphan and rare diseases. Hence, a wide range of patients refer to.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eEthical Consideration\u003c/h2\u003e \u003cp\u003e The study protocol was approved by the Ethics Committee of SBMU with the registered code IR.SBMU.PHARMACY.REC.1399.054. The survey process thoroughly, performed in accordance with Helsinki declaration and patient-centered regulations and the details of recriutment, survey, dara extraction, and reporting were accepted by the Ethic Committee of SBMU. Patients were informed of the study's aims and were assured that their data would be kept confidential. Their participation in the study was voluntary and confirmed with the patients\u0026rsquo; informed written consent.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eParticipants\u003c/h2\u003e \u003cp\u003ePatients were enrolled in the MTM clinic at the pharmacist\u0026rsquo;s discretion in charge of the community pharmacy or their request for a pharmacotherapy visit. The inclusion criteria for this study included the participants' referral to the MTM clinic with at least one chronic condition. Chronic conditions were defined as those requiring ongoing medical care +/or associated with limitation of daily activities for at least one year. Patients who did not have sufficient information about their medical and medication history and patients who were unwilling to participate in the study were excluded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eOutcome Measurements \u0026amp; Data Collection\u003c/h2\u003e \u003cp\u003eThe primary outcome of this study was to identify the association between the incidence of DRPs the number of patients\u0026rsquo; medicines, and the number of chronic conditions. The secondary outcome of this study was the effect of pharmacist-led MTM services on medication adherence and medication satisfaction. The third outcome was to evaluate the rate of agreement of physicians to the pharmacist's suggestion for DRP correction.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003eMedication Therapy Management (MTM) \u0026amp; Drug Related Problems (DRP) Identification\u003c/h2\u003e \u003cp\u003ePatients were evaluated at the MTM clinic by a team consisting of a pharmacy intern and a clinical pharmacy resident under the supervision of a clinical pharmacist. Pharmacists in the MTM clinic received an education program, including how to conduct MTM services and prioritize DRPs to ensure the quality of the MTM services and detection of DRPs. Patient demographics, chief complaints, and medical histories were obtained either from the patients themselves or their caregivers.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section3\"\u003e \u003ch2\u003eDRP Classification\u003c/h2\u003e \u003cp\u003eThe WHO disease classification system was used to categorize the underlying chronic diseases (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). The Anatomical Therapeutic Chemical (ATC) classification system was also used for medication history (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). To categorize DRPs and subsequent interventions, we used the Pharmaceutical Society of Australia (PSA) (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). This classification consists of eight categories for DRPs (drug selection, over- or under-prescribing, compliance, under-treatment, monitoring, education or information, unclassifiable, and toxicity or adverse reaction) and five categories for interventions (change in therapy, referral required, provision of information, monitoring, and no recommendation required). In cases where patients needed to be followed up, patients were followed up by telephone or clinic.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section3\"\u003e \u003ch2\u003eMedication Adherence\u003c/h2\u003e \u003cp\u003ePatients' adherence to the treatment regimen was the assessed by Persian language version of the Morisky medication adherence scale-8 (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), which includes eight questions. To quantify the adherence, questions 1 to 7 (excluding question 5) were given one point for each negative answer and zero points for each positive response. For the last question, 0.25, 0.5, 0.75, and 1 were equivalent to the options \"All the time/Usually/Sometimes/Rarely/Never,\u0026rdquo; and the final score can be classified as those with high adherence\u0026thinsp;\u0026ge;\u0026thinsp;8, average adherence 6\u0026ndash;8 and poor adherence\u0026thinsp;\u0026le;\u0026thinsp;6.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section3\"\u003e \u003ch2\u003ePatient Satisfaction\u003c/h2\u003e \u003cp\u003eAll patients were assessed regarding their medication satisfaction based on a self-reporting question, \u0026ldquo;Taking all things into account, how satisfied or dissatisfied are you with this medication?\u0026rdquo; with a 7-point Likert scale consisting; of 1) Extremely dissatisfied, 2) Very dissatisfied, 3) Dissatisfied, 4) Somewhat satisfied, 5) Satisfied, 6) Very satisfied and 7) Extremely satisfied.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eFollow-ups\u003c/h2\u003e \u003cp\u003eIn this study, the participants were evaluated at least two times before the intervention, and two to four weeks after the MTM services.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eSample Size\u003c/h2\u003e \u003cp\u003eto calculate the minimum sample size required to establish a relationship between the variables in the study, a pilot study was conducted with 50 patients. The result of the pilot study showed a significant association between the number of medicines and the number of DRPs (Pearson coefficient: 0.125, P\u0026thinsp;=\u0026thinsp;0.041) and chronic conditions (Pearson coefficient: 0.143, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.038). With an alpha coefficient of 0.05, a power of 80%, and a correlation coefficient of 0.125, the calculated sample size was 826.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eData Analysis\u003c/h2\u003e \u003cp\u003eThe Kolmogorov-Smirnov test was used to test the normality assumption of the variables. Parametric variables were presented using mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD); we used median and interquartile range (IQR) for nonparametric variables. One-way analysis of variance (ANOVA) was used to compare the number of DRPs between groups. An independent sample T-test was performed to compare the frequency of drug classes across the number of DRPs. In addition, the linear regression model was used to evaluate the association between the number of DRPs and the number of underlying chronic diseases or medications taken. Finally, a multivariable regression model was constructed and adjusted for age. All analyses were performed in IBM SPSS statistics for Windows (version 22.0 IBM, Armonk. NY). The statement of strengthening the reporting of observational studies in epidemiology (STROBE) was followed in reporting (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\n \u003ch2\u003eParticipant Characteristics\u003c/h2\u003e\n \u003cp\u003eSampling was performed over three years to reach the sample size required to achieve the study objective; during this period, 1432 admissions were recorded in the MTM clinic, among whom 359 cases did not meet the inclusion criteria, 143 cases had exclusion criteria, and 19 cases declined to participate in the study; finally, 911 patients meet the requirements of participation. Awhom 73 did not complete all questionnaires and feedback per protocol. Eventually, the results of 838 patients were included in this study. The mean age of participants was 50.2\u0026thinsp;\u0026plusmn;\u0026thinsp;12.4. Among the participants, 49 were \u0026le;\u0026thinsp;14 years old, and 235 were \u0026ge;\u0026thinsp;65, and the age of 33% of patients were in the range of 24\u0026ndash;65 years, and 51.4% of the study population were females. A summary of patients\u0026apos; demographic and clinical data is available in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDemographic and clinical characteristics of the study population.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003cp\u003eTotal number of participants: 838\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDescriptive statistics\u003c/p\u003e\n \u003cp\u003e(n*, %)\u003c/p\u003e\n \u003cp\u003e(mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD**)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e431 (51.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e407 (48.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eSource of information\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePatient\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e582 (69.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePatients caregiver\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e256 (30.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" align=\"left\"\u003e\n \u003cp\u003eAge range (y)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45\u0026ndash;64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e282 (33.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25\u0026ndash;44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e253 (30.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e235 (28.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eDuration of consultation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.05\u0026thinsp;\u0026plusmn;\u0026thinsp;6.32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eNumber of baseline chronic condition\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.14\u0026thinsp;\u0026plusmn;\u0026thinsp;0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eNumber of DRP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eNumber of medication\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.26\u0026thinsp;\u0026plusmn;\u0026thinsp;1.41\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eNumber of interventions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\"\u003e*: absolute frequency\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\"\u003e**: standard deviation\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eThe first three common diseases among the participants were endocrine, nutritional, and metabolic diseases (25.2%), neoplasms (10.7%), and musculoskeletal or connective tissue diseases (10.4%). Figure\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e illustrates the frequency of the underlying chronic conditions in detail.\u003c/p\u003e\n \u003cp\u003eIn addition, the first three categories of medications taken by the patients were nutritional and metabolic agents (32.5%), antineoplastic and immunomodulatory agents (31.1%), and musculoskeletal (12.9%) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). The most common chief complaints of the patients were related to drug administration (32.7%), requests for drug information (21.5%), and complications of adverse effects (12.6%) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\n \u003ch2\u003eOutcome Reports\u003c/h2\u003e\n \u003cp\u003e\u003cstrong\u003eDescription of DRPs\u003c/strong\u003e: We identified 1116 (median: 1; IQR 1st, third: 1,2) DRPs in the study population. The most common DRPs were patients\u0026apos; requests for information about their medications (27.4%), difficulty using dosage forms (26.3%), and any toxicity, allergic reaction, or adverse effects related to medications (12.8%). Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e shows the frequency of major categories and subcategories of DRPs in detail. Only 11 (1.3%) patients did not experience any DRP.\u003c/p\u003e\n \u003cp\u003ePharmacists performed 1118 interventions during the study period (median: 1; IQR 1st, 3rd: 1,1). Patient education and counseling were the most common interventions (67.9%), followed by referral to a physician (16.7%) and recommendation for dose administration (11%). The detailed distribution of interventions is shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\n \u003cp\u003eAmong the admitted patients, 628 were identified as requiring more follow-ups and were contacted by telephone, and in 334 cases, the patient identified as requiring face-to-face follow-up.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003ePhysician Approval Rate\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eTo inform the patient\u0026apos;s physician about the actions taken by the clinic for DRP management, or to request a decision, 641 correspondences were made, of which 354 (55.2%) correspondences were made for the physician\u0026apos;s information, in 287 (44.7%) cases a change in the patient\u0026apos;s medication was suggested, of which 276 (96.1%) physicians agreed with the proposal, in 11 other cases the physician suggested another management to the detected DRP.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMedication Adherence\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe average total adherence to the treatment regimen before the intervention was 4.21\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22, and it improved to 7.53\u0026thinsp;\u0026plusmn;\u0026thinsp;0.30 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e illustrates the results in more detail. There is a significant difference between the before and after intervention results in all cases except question 5. Also, the results showed that before the intervention, 775 (92.48%) patients were in the poor adherence level, and only 63 (7.51%) were patients are an average level, while after the intervention, the adherence score of all (100%) patients were in the middle range (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Analysis of the mean difference in the score obtained from the medication adherence score showed that patients\u0026rsquo; average score has increased by 3.31\u0026thinsp;\u0026plusmn;\u0026thinsp;1.26.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eAdherence to treatment regimen and patient satisfaction before and after the MTM services\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eItem\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eAnswer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" align=\"left\"\u003e\n \u003cp\u003ePatients\u0026rsquo; Responses\u003c/p\u003e\n \u003cp\u003e# (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBefore\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAfter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP-Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"12\" align=\"left\"\u003e\n \u003cp\u003eMedication Adherence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuestion 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e301 (63.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e385 (45.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuestion 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e511 (60.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e720 (85.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuestion 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e544 (64.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e731 (87.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuestion 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e419 (64.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e636 (87.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuestion 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e804 (95.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e833 (99.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.181\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuestion 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e604 (72.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e804 (95.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQuestion 7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e343 (40.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e502 (59.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" align=\"left\"\u003e\n \u003cp\u003eQuestion 8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNever\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e160 (19.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e178 (21.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"5\" align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRarely\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e192 (22.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e486 (58.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSometimes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e453 (54.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e166 (19.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUsually\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33 (3.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (0.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAll the time\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"7\" align=\"left\"\u003e\n \u003cp\u003ePatient Satisfaction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExtremely Dissatisfied\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58 (6.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"7\" align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVery Dissatisfied\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e182 (21.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDissatisfied\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e323 (38.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61 (7.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSomewhat Satisfied\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e210 (25.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e158 (18.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSatisfied\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59 (7.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e202 (24.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVery Satisfied\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (0.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e234 (27.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExtremely Satisfied\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e183 (21.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eFrequency of categories and subcategories of DRPs\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCategories of DRPs\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDrug selection\u003c/p\u003e\n \u003cp\u003e(n, %)\u003c/p\u003e\n \u003cp\u003e(69, 6.2%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCompliance\u003c/p\u003e\n \u003cp\u003e(n, %)\u003c/p\u003e\n \u003cp\u003e(366, 32.8%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOver or underdose-prescribed\u003c/p\u003e\n \u003cp\u003e(n, %)\u003c/p\u003e\n \u003cp\u003e(34, 3.0%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eUndertreated\u003c/p\u003e\n \u003cp\u003e(n, %)\u003c/p\u003e\n \u003cp\u003e(38, 3.4%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMonitoring\u003c/p\u003e\n \u003cp\u003e(n, %)\u003c/p\u003e\n \u003cp\u003e(31, 2.8%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEducation or information\u003c/p\u003e\n \u003cp\u003e(n, %)\u003c/p\u003e\n \u003cp\u003e(401, 35.9%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNot classifiable\u003c/p\u003e\n \u003cp\u003e(n, %)\u003c/p\u003e\n \u003cp\u003e(69, 6.2%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eToxicity or adverse reaction\u003c/p\u003e\n \u003cp\u003e(n, %)\u003c/p\u003e\n \u003cp\u003e(108, 9.7%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"8\" align=\"left\"\u003e\n \u003cp\u003eSubcategories of DRPs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWrong drug\u003c/p\u003e\n \u003cp\u003e(18, 1.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDifficulty using the dosage form\u003c/p\u003e\n \u003cp\u003e(294, 26.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThe prescribed dose too low\u003c/p\u003e\n \u003cp\u003e(11, 1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCondition undertreated\u003c/p\u003e\n \u003cp\u003e(15, 1.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLaboratory monitoring\u003c/p\u003e\n \u003cp\u003e(22, 2.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThe patient requests drug information\u003c/p\u003e\n \u003cp\u003e(306, 27.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDrug interaction\u003c/p\u003e\n \u003cp\u003e(14, 1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnder-use by patient\u003c/p\u003e\n \u003cp\u003e(20, 1.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrescribed dose is too high\u003c/p\u003e\n \u003cp\u003e(6, 0.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCondition untreated\u003c/p\u003e\n \u003cp\u003e(11, 1.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNon-laboratory monitoring\u003c/p\u003e\n \u003cp\u003e(6, 0.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThe patient requests disease management advice\u003c/p\u003e\n \u003cp\u003e(95, 8.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo indication apparent\u003c/p\u003e\n \u003cp\u003e(13, 1.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eErratic use of medications\u003c/p\u003e\n \u003cp\u003e(20, 1.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIncorrect or unclear dosing instruction\u003c/p\u003e\n \u003cp\u003e(15, 1.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePreventive therapy required\u003c/p\u003e\n \u003cp\u003e(12, 1.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOther monitoring problem\u003c/p\u003e\n \u003cp\u003e(3, 0.25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOther educational information problem\u003c/p\u003e\n \u003cp\u003e(0, 0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eContraindication apparent\u003c/p\u003e\n \u003cp\u003e(9, 0.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOther compliance problem\u003c/p\u003e\n \u003cp\u003e(15, 1.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOther dose problem\u003c/p\u003e\n \u003cp\u003e(2, 0.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOther undertreated indication problem\u003c/p\u003e\n \u003cp\u003e(0, 0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDuplication\u003c/p\u003e\n \u003cp\u003e(7, 0.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOver-use by patient\u003c/p\u003e\n \u003cp\u003e(15, 1.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"6\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOther drug selection problem\u003c/p\u003e\n \u003cp\u003e(7, 0.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntentional drug misuse\u003c/p\u003e\n \u003cp\u003e(2, 0.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"6\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInappropriate dosage form\u003c/p\u003e\n \u003cp\u003e(1, 0.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"7\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIncorrect strength\u003c/p\u003e\n \u003cp\u003e(0, 0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"7\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cstrong\u003eMedication Satisfaction\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe results of patient satisfaction with their treatment regimen showed that before providing the MTM services, 275 (32.82%) patients were satisfied with their treatment regimen, while after providing services, 777 (92.72%) patients were satisfied (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e presents the results in more detail.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eFactors Associated with DRP Occurrence\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eA significant association was found between the number of DRPs and the age (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003, Pearson correlation coefficient\u0026thinsp;=\u0026thinsp;0.103) the number of medications (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Pearson correlation coefficient\u0026thinsp;=\u0026thinsp;0.206) and the number of underlying chronic diseases (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Pearson correlation coefficient\u0026thinsp;=\u0026thinsp;0.225). Adjusting the age in the multivariable linear regression model showed that both the number of medications and the number of underlying chronic diseases remained significant (unstandardized B\u0026thinsp;=\u0026thinsp;0.055 and 0.140, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006 and \u0026lt;\u0026thinsp;0.001, respectively). Some chronic diseases resulted in a significantly higher number of DRPs. Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e. illustrates in detail the discrepancies in DRP frequency among all diseases.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDistribution of DRP frequency in different disease categories.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth colspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eDisorders\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNumber of DRPS Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP-Value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eEndocrine, Nutritional or Metabolic Diseases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWith\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e211\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.019*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e627\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eNeoplasms\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWith\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.35\u0026thinsp;\u0026plusmn;\u0026thinsp;0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.724\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e748\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eDisease of the Musculoskeletal System or Connective Tissue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWith\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.22\u0026thinsp;\u0026plusmn;\u0026thinsp;0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.138\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e751\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eDiseases of the Nervous System\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWith\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.504\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e757\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eDisease of the Circulatory System\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWith\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.51\u0026thinsp;\u0026plusmn;\u0026thinsp;085\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.015*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e757\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eDiseases of the Digestive System\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWith\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.41\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.310\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e770\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eDisease of the Genitourinary System\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWith\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.36\u0026thinsp;\u0026plusmn;\u0026thinsp;0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.729\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e777\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eFactors Influencing Health Status or Contact with Health Services\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWith\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.000*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e784\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eDiseases of Blood or Blood-forming Organs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWith\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.724\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e791\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eDisease of the Respiratory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWith\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.315\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e807\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eMental \u0026amp; Behavioral or Neurodevelopmental Disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWith\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.59\u0026thinsp;\u0026plusmn;\u0026thinsp;0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.042*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e811\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eDisease of the Visual System\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWith\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.048*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e834\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eDiseases of the Skin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWith\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.507\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e817\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eCertain Infectious or Parasitic Diseases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWith\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.193\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e831\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eSymptoms, Signs or Clinical Findings, Not Elsewhere Classified\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWith\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.704\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e831\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eConditions Related to Sexual Health\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWith\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.995\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e832\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eSleep-wake Disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWith\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.60\u0026thinsp;\u0026plusmn;\u0026thinsp;1.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.375\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e833\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eDisease of the Immune System\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWith\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.088\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e835\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eInjury, Poisoning, or Certain other Consequences of External Causes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWith\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.997\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e835\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eDisease of the Ear or Mastoid Process\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWith\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003e0.624\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWithout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e837\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" align=\"left\"\u003e\n \u003cp\u003e* With significant difference\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eAmong the drug categories in the multivariable regression model, alimentary tract and metabolism (standardized coefficient B\u0026thinsp;=\u0026thinsp;0.219; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), blood and hematopoietic organs (standardized coefficient B\u0026thinsp;=\u0026thinsp;0.075; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.038), cardiovascular system (standardized coefficient B\u0026thinsp;=\u0026thinsp;0.076; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.039), antineoplastic and immunomodulatory agents (standardized coefficient B\u0026thinsp;=\u0026thinsp;0.084; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.025), and nervous system (standardized coefficient B\u0026thinsp;=\u0026thinsp;0.084; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.016) remained significant in the final model and showed a positive correlation with the number of DRPs.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the present study, DRPs and subsequent interventions were evaluated at the MTM clinic of a community pharmacy over three years. The significant impact of clinical pharmacy-based MTM services on identifying DRPs and recommendations of interventions was evident. Of all the 838 patients, 1116 DRPs were identified, with difficulty using dosage forms, desire for more information about medications, and any toxicity, allergic reaction, or adverse effect related to medications topping the list. The most common interventions included education and counseling, referral to the prescriber, and dosage recommendation. Interestingly, higher numbers of medications and underlying chronic conditions were associated with more DRPs. Finally, a specific category of diseases contributed to a higher number of DRPs. The results showed that only 11 (1.3%) patients had no DRPs. However, even these patients benefited from MTM services provided by clinical pharmacists, such as education. Additionally, both medication adherence and satisfaction regimens improved after MTM services.\u003c/p\u003e \u003cp\u003eSeveral studies have previously examined DRPs in hospitalized patients (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e); however, few data are available from regular community pharmacies (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). While we found our most common DRPs, studies with predominantly inpatient settings have shown that DRPs such as the need for a new medication or dose increase (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), suboptimal drug effect (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e), and lack of therapy (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) are significant problems in inpatients. On the other hand, the most common DRPs in community pharmacies included information problems, therapeutic errors (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e), drug interactions, contraindications (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e), need for additional therapy, unnecessary drug therapy, and poor adherence (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). The different outcomes may be due to differences in the healthcare system, deficiencies in data documentation, and a lack of appropriate infrastructure. The finding that \"seeking more information about medications\" is the most common DRP indicates that many patients are not informed about their medications and treatment, underscoring the importance of pharmacists' MTM services.\u003c/p\u003e \u003cp\u003eRegarding the drug classes associated with the occurrence of DRPs, the results of previous studies conducted in the outpatient setting are similar. For example, the results for the alimentary tract and metabolism (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e), blood and hematopoietic organs, cardiovascular system, nervous system (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e), and antineoplastic and immunomodulatory agents were the same. In the inpatient setting, in chronic kidney disease (CKD) clinics, cardiovascular drugs, gastrointestinal agents, and analgesics are more likely to be responsible for DRPs. In an intensive care unit, systemic antimicrobial agents are more likely to be accountable for DRPs (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBoth the number of drugs and underlying chronic diseases were critical factors contributing to the rate of DRPs. Previous studies have shown that the number of medications in both outpatient and inpatient settings could significantly determine the incidence of DRPs (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). In this regard, polypharmacy is a critical factor leading to a higher risk of DRPs, necessitating a move away from the classic thresholds of 4\u0026thinsp;+\u0026thinsp;or 5\u0026thinsp;+\u0026thinsp;medications to a realistic linear approach (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). To address this issue and reduce the rate of preventable adverse drug events, studies have suggested the use of advanced computerized drug prescribing systems (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn addition, the current study results showed that the presence of some diseases was significantly related to the increased risk of DRPs, which is discussed below. In the category of endocrine disorders, more patients had diabetes mellitus who used insulin pens. They had difficulty in using their medication due to inadequate education. A prospective study showed that patients with circulatory diseases were taking more than five medications, which is a risk predictor for developing DRPs. The number of chronic diseases per patient was almost four, indicating obvious multiple morbidities (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). Visual impairment may also affect patients' taking prescribed medications (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). This is mainly because they have difficulty reading prescription labels, recognizing expiration dates, understanding the name of the drug, and keeping their medications. Of the group factors affecting health status or contact with health services for illness, most patients were those who had undergone organ transplantation. It seems that these patients are more prone to DRPs due to their polypharmacy and use of immunosuppressive drugs (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). Patients with severe mental illnesses are less likely to receive standard treatment for their comorbidities, making them more susceptible to DRPs (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAs we showed that pharmacist-led MTM services could improve patient adherence to the treatment regimen, Daniel A. Ercu et al. also demonstrated that MTM services provided by pharmacists markedly increased medication adherence in patients with type 2 diabetes mellitus by 9.2% at baseline to 61% at six months in a prospective randomized controlled study (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). This may be because patients with chronic conditions like diabetes mellitus have complex treatment regimens, so educating and clarifying the treatment regimen can make them more adherent.\u003c/p\u003e \u003cp\u003eThis study found that patients were more satisfied with their treatment regimen after MTM services than before. In a study conducted in a large, integrated healthcare system, 95.3% of patients agreed or strongly agreed that their overall health and well-being had improved due to pharmacist-led MTM services (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). This may be because pharmacists assume responsibility for patients\u0026rsquo; medication therapy outcomes and collaborate with other healthcare providers to facilitate high-quality patient care (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis study has some limitations. First, as the data were not collected longitudinally, it does not allow us to identify causal relationships. Second, our results may differ from those of other geographic areas with different healthcare characteristics, particularly concerning domestic pharmaceutical care. Third, the diversity of patients referred to the pharmacy of the study site was high. Although this diversity was an advantage, this amount of variety in patients may not be seen in the usual community pharmacies and affect the generalizability of our results. The following limitation of the study is the non-detection of DRP by the pharmacist, especially in the case of uncommon DRPs that are also related to the pharmacist's professional experience. A standard validated DRP classification system was used in this study to minimize this.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study suggests that MTM services lead to the detection and resolution of many DRPs with appropriate interventions and improvement in medication adherence and satisfaction. The mean probability of DRP detection in included patients was 1.33, and the most common were drug information and difficulty using dosage forms. The use of medications related to the alimentary tract and metabolism, medications affecting the blood and hematopoietic organs, medications affecting the cardiovascular system, antineoplastic and immunomodulatory medications, and medications affecting the nervous system were significantly associated with a higher risk for the occurrence of DRPs. A significant association was detected between the number of drug-related problems and the age, number of medications, and underlying chronic diseases. This study represents a promising approach to MTM services in community pharmacies delivered by clinical pharmacists, which could have significant health implications. The findings will be used for developing evidence-based eligibility criteria for MTM services in community pharmacies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of interest:\u0026nbsp;\u003c/strong\u003eThere is no conflict of interest of any of the authors with the results of this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement:\u0026nbsp;\u003c/strong\u003eThe data that support the findings of this study are available from the corresponding author, upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank and appreciate the efforts of Dr. Roozbeh Pourziaei Manesh, the director of Shahid Kazemi Pharmacy, and Professor Jamshid Salamzadeh, the head of SBMU pharmacies, who played a significant role in conducting this research. We appreciate the efforts of Morisky Medication Adherence Research group for giving us the license to use the MMAS scale (Certificate Number: 7799-8371-5354-4091-1040).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval and consent:\u003c/strong\u003e The study protocol was approved by the Ethics Committee of SBMU with the registered code IR.SBMU.PHARMACY.REC.1399.054. The survey process thoroughly, performed in accordance with Helsinki declaration and patient-centered regulations and the details of recriutment, survey, dara extraction, and reporting were accepted by the Ethic Committee of SBMU. Patients were informed of the study\u0026apos;s aims and were assured that their data would be kept confidential. Informed written consent was obtained from all subjects.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eN.A\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of Interest\u003c/strong\u003e: The authors declare there is no conflict of interest in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: This work was supported by the Medical Research Council of SBMU [Grant NO: 22527].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement:\u0026nbsp;\u003c/strong\u003eThe data supporting this study\u0026rsquo;s findings are available from the corresponding author on request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution:\u0026nbsp;\u003c/strong\u003eH.E. and S.R. developed the idea and clinical gap, H.E. and G.M. designed the study, N.V. and A.F. extracted the epidemiologic data, H.E. and M.S. conducted the data analyses and interpretation, N.V. wrote the initial manuscript and edited by H.E., M.S., and N.V.. All authors reviewed the manuscript and consented to the submission.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eStrand LM, Cipolle RJ, Morley PC, Frakes MJ. The Impact of Pharmaceutical Care Practice on the Practitioner and the Patient i n the Ambulatory Practice Setting: T wenty-five Years of Experience. 2004;3987\u0026ndash;4001.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGood pharmacy. practice (\u0026lrm;GPP)\u0026lrm; in community and hospital settings [Internet]. [cited 2022 Feb 11]. 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J Pharm Technol. 2018;34(2):48\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-health-services-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bhsr","sideBox":"Learn more about [BMC Health Services Research](http://bmchealthservres.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/BHSR/default.aspx","title":"BMC Health Services Research","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Pharmacists, Medication Therapy Management, Pharmaceutical Services, Drug-Related Problems, Medication Adherence","lastPublishedDoi":"10.21203/rs.3.rs-3812800/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3812800/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eDrug-related problems (DRPs) are adverse events or circumstances that interfere with favorable health outcomes. Medication therapy management (MTM) was developed to detect and manage DRP. This study set out to identify DRP-associated factors and reporting of subsequent interventions in a university-affiliated educational pharmacy.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis study was conducted from January 2020 to December 2022 at Shahid Kazemi Pharmacy, a large referral community pharmacy in Tehran, Iran. After medication review and complete medical history collection, DRPs were identified classified, and necessary interventions were performed. Medication adherence and satisfaction were evaluated before and 2\u0026ndash;4 weeks after providing the MTM services.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eWithin 1432 admissions, 838 patients were included and received 1116 interventions. Among the 1116 DRPs detected, the most common were drug information (27.4%), difficulty using dosage forms (26.3%), and any toxicity, allergic reaction, or adverse effects related to medications (12.8%). A significant association was detected between the number of DRPs and the age, the number of medications, and underlying chronic diseases (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Adjusting the age association of the number of medications and the number of underlying chronic diseases remained significant. The use of medications related to the alimentary tract and metabolism, medications affecting the blood and hematopoietic organs, medications affecting the cardiovascular system, antineoplastic and immunomodulatory medications, and medications affecting the nervous system were significantly associated with a higher risk for the occurrence of DRPs (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eCommunity pharmacy-led MTM services have a significant impact on DRP detection, management, medication adherence, and pharmacotherapy satisfaction.\u003c/p\u003e","manuscriptTitle":"Drug-Related Problems and Clinical Pharmacist-Led Medication Therapy Management; Three-Year Survey in an Educational Pharmacotherapy Clinic","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-03 14:57:59","doi":"10.21203/rs.3.rs-3812800/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-01-01T05:25:55+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-12-29T09:58:44+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-12-29T09:58:43+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Health Services Research","date":"2023-12-27T15:00:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-health-services-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bhsr","sideBox":"Learn more about [BMC Health Services Research](http://bmchealthservres.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/BHSR/default.aspx","title":"BMC Health Services Research","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1fee68d4-2e71-4fec-8720-31e0b861153c","owner":[],"postedDate":"January 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-12-01T16:23:12+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-03 14:57:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3812800","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3812800","identity":"rs-3812800","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}