Factors associated with the use of traditional doses of amitriptyline for chronic pain management: A cross-sectional study.

There are studies on the effect of low-dose amitriptyline on pain control, but there is a lack of studies on the use of amitriptyline for chronic pain and the factors associated with the prescription of traditional doses. We used a national sample cohort of patients aged ≥ 18 years who were prescribed amitriptyline along with chronic pain, without psychiatric disorders, between 2002 to 2015. We categorized the prescriptions into 2 groups according to the daily dose: low doses (≤25 mg) and traditional doses (>25 mg). Multivariable logistic regression models were used to identify factors associated with traditional dose prescriptions. Among 177,769 prescriptions for amitriptyline, 15,119 (8.5%) were prescribed for chronic pain. The prevalence of prescriptions and proportion of traditional doses of amitriptyline tended to decrease during the study period. Male sex (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.05-1.13); age 65-80 years (OR 1.12, 95% CI 1.08-1.16), especially ≥ 80 years (OR 1.55, 95% CI 1.45-1.65); headaches (OR 1.18, 95% CI 1.10-1.27), receiving medical aids (OR 2.58, 95% CI 2.46-2.71); and being prescribed benzodiazepines or zolpidem concomitantly (OR 1.10, 95% CI 1.06-1.15) were significantly associated with traditional dose prescriptions of amitriptyline. Although traditional dose prescriptions of amitriptyline have been declining, close monitoring is still required in the presence of the above-mentioned factors.

Association between culture and the preference for, and perceptions of, 11 routes of medicine administration: A survey in 21 countries and regions.

Medicines can be taken by various routes of administration. These can impact the effects and perceptions of medicines. The literature about individuals' preferences for and perceptions of the different routes of administration is sparse, but indicates a potential influence of culture. Our aim was to determine: (i) any association between one's culture and one's preferred route of medicine administration and (ii) individual perceptions of pain, efficacy, speed of action and acceptability when medicines are swallowed or placed in the mouth, under the tongue, in the nose, eye, ear, lungs, rectum, vagina, on the skin, or areinjected. A cross-sectional, questionnaire-based survey of adults was conducted in 21 countries and regions of the world, namely, Tunisia, Ghana, Nigeria, Turkey, Ethiopia, Lebanon, Malta, Brazil, Great Britain, United States, India, Serbia, Romania, Portugal, France, Netherlands, Japan, South Korea, Hong Kong, mainland China and Estonia, using the Inglehart-Welzel cultural map to ensure coverage across all cultures. Participants scored the pain/discomfort, efficacy, speed of onset and acceptability of the different routes of medicine administration and stated their preferred route. Demographic information was collected. A total of 4435 participants took part in the survey. Overall, the oral route was the most preferred route, followed by injection, while the rectal route was the least preferred. While the oral route was the most preferred in all cultures, the percentage of participants selecting this route varied, from 98% in Protestant Europe to 50% in the African-Islamic culture. A multinomial logistic regression model revealed a number of predictors for the preferred route. Injections were favoured in the Baltic, South Asia, Latin America and African-Islamic cultures while dermal administration was favoured in Catholic Europe, Baltic and Latin America cultures. A marked association was found between culture and the preference for, and perceptions of the different routes by which medicines are taken. This applied to even the least favoured routes (vaginal and rectal). Only women were asked about the vaginal route, and our data shows that the vaginal route was slightly more popular than the rectal one.

Risk of cardiovascular events according to the tricyclic antidepressant dosage in patients with chronic pain: a retrospective cohort study.

PURPOSE: We aimed to examine the risk of cardiovascular adverse events by tricyclic antidepressant (TCA) dosage among patients with chronic pain. METHODS: A retrospective cohort study was conducted using a nationwide sample cohort. Among patients aged ≥ 18 years with a chronic pain diagnosis and no history of cardiovascular events, we extracted users and non-users of TCAs through 1:1 propensity score matching. TCA users were categorized into three groups according to the mean defined daily dose (DDD): very low doses (< 0.15 DDD), low doses (0.15-0.34 DDD), and traditional doses (≥ 0.34 DDD). A 6-month follow-up was conducted with an intention-to-treat approach. We examined the hazard ratio of cardiovascular adverse events using Cox proportional hazards analysis. RESULTS: In total, 16,660 matched patients were followed up (8330 TCA users and 8330 non-users). TCA use did not significantly increase cardiovascular adverse events (hazard ratio [HR] 1.12, 95% confidence interval [CI] 0.94-1.33). Low-dose (0.15-0.34 DDD) TCAs (HR 1.37, 95% CI 1.08-1.74), particularly low-dose (0.15-0.34 DDD) nortriptyline (HR 2.11, 95% CI 1.44-3.08), was associated with an increased risk of cardiovascular adverse events. Administration of TCAs at the traditional dose (≥ 0.34 DDD) increased the risk of ischemic stroke (HR 2.08, 95% CI 1.11-3.88). CONCLUSION: Close monitoring of patients on long-term, low-dose use of TCAs should be conducted to avoid an increase in the cumulative dose, which increases the risk of cardiovascular adverse events.

A nationwide survey of the perception of the APPE by community pharmacy preceptors in South Korea.

BACKGROUND: Considering that approximately 75% of active pharmacists work in a community pharmacy globally, experiential practice in community pharmacies is a crucial part of pharmacy education. Skilled preceptors and their perceptions are integral to experiential practice. However, the perception of community pharmacy preceptors on a nationwide level is rarely studied. OBJECTIVES: To examine the perception of community pharmacy preceptors who had undertaken the newly implemented community pharmacy experiential practice in South Korea. METHODS: This study was based on a self-administered, nationwide, online cross-sectional survey performed by the Korean Pharmaceutical Association in 2017. Active community pharmacy preceptors undertaking experiential practice in South Korea were enrolled. The preceptor's competence, satisfaction, stress, achievement, and the likelihood of continuing preceptorship were evaluated using a 4-point Likert scale. In addition, the determinants of perception were evaluated using multivariate logistic regression analysis. RESULTS: Of the 681 active preceptors, 390 (response rate: 57.3%) participated in this study, and the data of 385 participants were used for the final analysis. The majority of the preceptors were satisfied (83.1%), felt high achievement (85.8%), and were likely to continue with the preceptorship (85.7%). However, 52.8% reported increased stress due to the increased workload and lack of personal time. Preceptors who participated voluntarily had higher competence (odds ratio [OR] 2.050, 1.265-3.322) and exhibited lower stress (OR 0.560, 0.368-0.852). The academic degrees of preceptors and the number of preceptees trained by them were significantly related to competence. Preceptor age (>50 years) was negatively associated with stress (OR 0.635, 0.419-0.962). CONCLUSION: Because competence is a key element associated with community pharmacy preceptors, it is necessary to create an environment in which preceptors can consider themselves competent. This nationwide study with community pharmacy preceptors will provide a basis for improving the quality of training at community pharmacies and may aid experiential practice administrators in revising the current program.

Trimetazidine Use and the Risk of Parkinsonism: A Nationwide Population-Based Study.

An association between trimetazidine (TMZ), an anti-anginal drug, and parkinsonism has been reported in a number of studies. However, evidence from studies with long-term follow-up and better validity is lacking. We investigated the risk of TMZ-associated parkinsonism, specifically the incidence rate, cumulative dose-response relationship, and combined effects with other parkinsonism-inducing medications. This propensity score-matched retrospective cohort study was conducted using 14-year health insurance claims data in South Korea. The risk of parkinsonism was evaluated using multivariate Cox proportional hazard regression analysis, adjusted for comorbidities and concurrent medications. A total of 9712 TMZ users and 29,116 matched non-TMZ users were included. TMZ users had a significantly higher incidence rate of parkinsonism than non-TMZ users (9.34 vs. 6.71 per 1000 person-years; p < 0.0001). TMZ use significantly increased the risk of parkinsonism (adjusted hazard ratio = 1.38; 95% confidence interval = 1.26-1.51). Increased risks were observed with accumulated doses of TMZ, as well as concurrent use of other parkinsonism-inducing medications. The findings indicate that TMZ use significantly increases the risk of parkinsonism in the South Korean population. Closer monitoring should be considered for TMZ users, especially for those who are older, using TMZ at high cumulative doses and other parkinsonism-inducing medications.

A cross-sectional survey of knowledge, attitude, and willingness to engage in spontaneous reporting of adverse drug reactions by Korean consumers.

BACKGROUND: Spontaneous reporting (SR) of adverse drug reactions (ADRs) from patients can be considered as a valuable activity providing both objective and subjective data. However, improving the rate of under-reporting has been a major challenge to ensure successful operation of the SR system. This study aimed to assess knowledge, attitude, and intent to report ADRs and explore the factors contributing to consumers' reporting intent in South Korea. METHODS: Self-administered questionnaire was collected from a sex-, age-, and regionally stratified nationwide convenience sample of consumers using a commercial panel in December 2018. Univariate and multivariate logistic regression analyses were used to explore the factors contributing to the intent to report ADRs by consumers. RESULTS: A total of 1000 respondents were enrolled in the survey; 50.9% were males and the mean age was 44.4 (standard deviation, 13.3) years. While less than 15% of the respondents were aware of the SR system and even fewer (3.4%) had actual experience of SR, however, 59.2% expressed their intent to report ADRs. The positive attitude (adjusted odds ratio [aOR] 3.972, p < 0.001), awareness of the SR system (aOR 2.102, p < 0.01), self-efficacy for SR (aOR 1.956, p < 0.001), and experiences related to ADR counselling with healthcare professionals (OR 2.318, p < 0.001) are the significant factors contributing to reporting intent. CONCLUSIONS: Findings of this study highlight the need for increasing the awareness of the SR system among consumers and empowering them to report ADRs by themselves, which would ultimately improve the drug-safety environment.

Duplicated tramadol use in chronic low back pain: A nationwide cross-sectional study.

Tramadol is a weak opioid that is commonly used for chronic low back pain (LBP). Despite its effectiveness, duplicated use of tramadol, which may indicate abuse or dependence, may exacerbate potential adverse reactions. This population-based, cross-sectional study aimed to investigate the prevalence of duplication of tramadol and its associated factors among patients with LBP. From a Korean nationwide claims database, non-hospitalized patients aged 40-99 years with LBP without malignancy were prescribed tramadol during 2014-2016. Duplication of tramadol was defined as overlapping of prescription days. Among them, we defined "extensive duplication (ED)" when days of tramadol duplication cover 10% or more of the days prescribed tramadol. Patient and healthcare utilization factors associated with ED were examined using a logistic regression model. The study population was 6 417 503 patients. Of these, 13.7% were ED users. The age- and sex-standardized prevalence of using tramadol twice or more a year was 14.06 per 100 people in 2014, 13.74 per 100 people in 2015 and 13.52 per 100 people in 2016. ED occurred more in those in the group aged 70-79 years (OR 1.12, 95% CI 1.11-1.13) than 40-49 years and in those with comorbidities, such as drug abuse (OR 2.99, 95% CI 2.05-4.36) or depression (OR 1.75, 95% CI 1.72-1.77). Based on the results of this study, a proper management system is needed to avoid tramadol duplication among older people and patients with drug abuse or depression.

A nationwide cross-sectional survey of student experiential practice at community pharmacies in South Korea.

BACKGROUND: In South Korea, community pharmacy experiential practice (CPEP) is very important because most pharmacists (71.8%) work in community pharmacies, which also employ the majority of students after graduation. The present study investigated student responses to the current CPEP status, suggestions for improvement, and advancement in their competency after practice based on evaluation of Community Pharmacy Experiential Practice Model (CPEPM) outcomes. METHODS: A nationwide cross-sectional, self-administered online survey was conducted in 2017 for the sixth-year pharmacy students who completed CPEP, using 50 item questionnaire. The answers were evaluated using the 4-point Likert scale, used a scoring system from 1 (strongly disagree) to 4 (strongly agree). Responses of 1 and 2 were considered negative, and 3 and 4 were considered positive. To identify factors affecting CPEPM outcomes, multivariate linear regression analysis was performed. RESULTS: Initially, 1138 students participated in the survey. Of these, responses from 492 students were excluded due to missing data and eventually, data from 646 students were included in the analysis. In total, 95% of students responded in the affirmative that practical training influenced their future career decision. In addition, 78.5% of students were satisfied with the training. Further, they responded that their ability improved based on CPEPM outcomes. The most positive capability change was in the subdomain "personal and professional development", followed by "inter professional collaboration". CONCLUSIONS: Students responded with the higher rating for satisfaction factor, who regarded CPEP as helpful in future career decision making, and those who wanted to practice elective Advanced Pharmacy Practice Education at a community pharmacy had a positive CPEPM outcome, while age was found to be a negative factor in terms of the regression analysis. These are valuable findings as they represent the current student perception of CPEP nationwide. They provide a basis to improve the quality of CPEP-based education not only in Korea, but in other countries as well.

Association between Trimetazidine and Parkinsonism: A Population-Based Study.

BACKGROUND: The prevalence of drug-induced parkinsonism (DIP) has been reported with the use of trimetazidine (TMZ), an antianginal medication available in Asian and European countries. Very few studies have evaluated the association between DIP and TMZ use, and studies using population-based data from national databases are lacking. OBJECTIVES: To investigate the association between DIP and use of TMZ in patients with angina using data from a national healthcare claims database and to determine the predictive factors of DIP in TMZ use. METHODS: A cross-sectional study was conducted on patients aged 40 years or more diagnosed with angina, using the Korean National Healthcare claims 2014 database. The association between TMZ use and DIP was evaluated using multivariate logistic regression analysis, adjusting for confounders, including age; sex; insurance type; comorbidities; and concurrent medications known to be commonly associated with DIP, such as typical and atypical antipsychotics. RESULTS: Of the patients included in the study, 19% were prescribed TMZ. In addition, 2.5% of TMZ users had preexisting extrapyramidal and movement disorders. TMZ use was found to be a significant predictor of a new diagnosis of parkinsonism (adjusted OR [aOR] 1.39; 95% CI 1.06-1.81; p = 0.016). Age ≥65 years (aOR 2.07; 95% CI 1.13- 3.74; p = 0.017) and stroke as comorbid disease (aOR 3.23; 95% CI 1.87-5.61; p < 0.001) were also significantly associated with a new diagnosis of parkinsonism in TMZ users. CONCLUSIONS: Treatment with TMZ was a statistically significant predictor of a new diagnosis of parkinsonism. Efforts should focus on close monitoring of, and education on, TMZ use in relation to DIP in all patients who are prescribed TMZ, including those with preexisting extrapyramidal and movement disorders.

Impact of knowledge, attitude and preceptor behaviour in pharmacovigilance education.

This study aimed to determine the level of pharmacovigilance (PV) education in pharmacy programmes and to evaluate the predictive factors for the intent to report adverse drug reactions (ADRs) by pharmacy students in South Korea. Self-administered questionnaires were collected from a regionally stratified nationwide convenience sample of pharmacy students in September 2017. The association between students' intent to report ADRs and their knowledge and attitude was evaluated by using multivariate logistic regression analysis. In total, 303 pharmacy students participated in the survey; the average age of students was 26.7 (standard deviation 2.9) years and 40.6% were males. Eighty-eight students (29%) marked the degree of their intent as "strongly high." Increased knowledge of ADR reporting methods and positive attitude towards the need for ADR reporting were significant predictors of the intent to report ADRs. Further, witnessing reporting by the preceptor (adjusted odds ratio, 2.37; 95% confidence interval, 1.26-4.46; P < 0.01) was significantly correlated with the knowledge on and attitude towards ADR reporting of pharmacy students. The findings of our study indicated the need for improvements in PV curriculum, such as educational content focused on ADR reporting methods and demonstration of a preceptor's reporting in pharmacy practice experiential rotation, within Korean college of pharmacy curriculum.

Predictive Factors of Spontaneous Reporting of Adverse Drug Reactions among Community Pharmacists.

PURPOSE: To evaluate the association between spontaneous reporting (SR) and the knowledge, attitude, and needs of community pharmacists (CPs), using a questionnaire following a conceptual model known as the mixed model of knowledge-attitude-practices and the satisfaction of needs. METHODS: Self-administered questionnaires were used with a nationwide convenience sample of CPs between September 1, 2014 and November 25, 2014 in Korea. The association between SR and the predictive factors was evaluated using multivariate logistic regression analysis. RESULTS: In total, 1,001 questionnaires were analyzed. The mean age of the respondents and the number of years spent in community pharmacy practice were 45.6 years and 15.3 years, respectively. CPs with experience of SR was 29.4%. Being older than 60 (ORadj, 0.16; 95% CI, 0.06-0.42), having prior experience with adverse drug reactions (ADR) (ORadj, 6.46; 95% CI, 2.46-16.98), having higher specific knowledge of SR (ORadj, 3.58; 95% CI, 1.96-6.56), and having less concern about the obstacles to SR (ORadj, 0.36; 95% CI, 0.23-0.57) were significant contributing factors to SR. The main obstacles to SR included perception of ADRs as 'not serious ADR' (77.9%), 'already well known ADR' (81.5%), and 'uncertain about causality' (73.3%). CPs without reporting experience had greater concerns related to the reporting method and the liability of the pharmacy than those with reporting experience (p<0.05). CONCLUSIONS: Findings from our study showed around one in three CPs had ADR reporting experience in Korea, while 87.1% had prior experience with ADR cases. The knowledge of SR, prior experience of ADR, and less concern about the obstacles to SR were contributing factors for reporting levels.

The efficacy and safety of liraglutide.

AIM OF THE REVIEW: To systematically analyze the efficacy and safety of liraglutide for the treatment of diabetes mellitus in comparison to other mono- and combination therapies. METHOD: PubMed (any date) and EMBASE (all years) search was conducted with liraglutide as a search term. Phase III clinical trials retrieved by the two databases and resources posted in Drug@FDA website were evaluated with regard to outcomes of efficacy and safety. RESULTS: Eight Phase III clinical studies compared the efficacy and safety of liraglutide to other monotherapies or combinations. Liraglutide as monotherapy in doses of 0.9 mg or above showed a significantly superior reduction in HbA1C compared to monotherapies with glimepiride or glyburide. When liraglutide was used as add-on therapy to glimepiride in doses of 1.2 mg or above, the reduction of HbA1C was greater than that in the combination therapy of glimepiride and rosiglitazone. However, liraglutide as add-on therapy to metformin failed to show benefit over combination of metformin and glimepiride. Triple therapy of using liraglutide in addition to metformin plus either glimepiride or rosiglitazone resulted in additional benefit in HbA1C reduction. Most common adverse events were gastrointestinal disturbance such as nausea, vomit, diarrhea, and constipation. During the eight clinical studies, six cases of pancreatitis and five cases of cancer were reported in liraglutide arm, whereas there was one case of each of pancreatitis in exenatide and glimepiride arms, respectively, and one case of cancer in metformin plus sitagliptin arm. CONCLUSION: Liraglutide is a new therapeutic option to improve glycemic control in patients with type 2 diabetes. However, the present lack of evidence of durability of efficacy and long-term safety appear to limit its utility in the general treatment of type 2 diabetes at this time.