Risk of Cardiovascular Events and Medical Cost of Dapagliflozin and Dipeptidyl Peptidase-4 Inhibitors.

This study compared dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, and dipeptidyl peptidase-4 inhibitors (DPP-4i) with regard to cardiovascular (CV) event incidence and direct medical costs during type 2 diabetes treatment. A retrospective cohort study was conducted using national health insurance claims data from September 1, 2014, to June 30, 2018, of patients in Korea. Patients who were prescribed dapagliflozin and DPP-4i for the first time were included. The primary outcome was the incidence of a composite of major adverse CV events (MACEs)-nonfatal myocardial infarction, nonfatal stroke, or in-hospital CV death. Proportional hazard models after propensity score weighting were used to determine hazard ratios (HRs) and 95% confidence intervals (CIs) for MACE in the dapagliflozin and DPP-4i groups. A decision analytic model was used to compare direct medical costs between the two treatment groups from a healthcare provider's perspective. Of the 260,336 patients in the cohort, 23,147 and 237,189 received dapagliflozin and DPP-4i, respectively. During the follow-up, 184 patients receiving dapagliflozin and 3,674 receiving DPP-4i (incidence, 6.47 and 11.33 events/1,000 person-years, respectively) had MACE. The adjusted HR of MACE for dapagliflozin compared with that for DPP-4i was 0.69 (95% CI 0.57-0.83). The corresponding HRs were consistent among patients with and without underlying CV disease. The estimated direct medical cost appeared to be lower by $68,452 in the dapagliflozin group than that in the DPP-4i group for 3 years, in 1,000 hypothetical patients. In this population-based cohort study, the use of dapagliflozin instead of DPP-4i was associated with a reduced risk of MACE, which subsequently reduced direct medical costs. These data provide valuable information to patients, practitioners, and authorities regarding the risk of CV events associated with dapagliflozin versus DPP-4i use in clinical practice.

Assessment of a medication management program targeting hypertension and diabetes patients: Impact on medication adherence.

BACKGROUND: The National Health Insurance Service in South Korea has conducted a telephone outreach program to improve medication adherence for hypertension and diabetes patients since 2014. OBJECTIVES: To evaluate the direct outcomes of the program. METHODS: Patients were identified among those who visited an outpatient clinic at least twice or used an inpatient service at least once for hypertension or diabetes during 6-month intervals and who were nonadherent based on the proportion of days covered (PDC) calculated. As a preliminary intervention, participants were mailed an information leaflet on their own medication adherence and other tips for effective self-management of chronic diseases. For the intervention, two phone calls and three phone messages were made to patients by 24 participating regional offices. Ultimately, 2,428 hypertension patients and 884 diabetes patients received the intervention. Propensity matching was used based on age, sex, and the Charlson Comorbidity Index to select 12,140 hypertension and 4,420 diabetes patients as controls in the non-participating regions. The outcome was PDC. Multivariate ordinary least squares or logistic regression analysis were used with difference-in-difference specification. RESULTS: The adjusted quarterly PDC increased by 1.96%p for hypertension (p = 0.023) and by 7.79%p for diabetes patients (p < 0.001). Approximately 40.6% and 51.7% of hypertension and diabetes patients in the treatment arm (p = 0.0069) became adherent after the intervention, whereas the corresponding proportions were 37.7% and 41.4% (p < 0.001) in the control group. Both treatment groups showed a higher likelihood of good medication adherence (hypertension: odds ratio = 1.157, 95% CI [1.058, 1.265]; diabetes: odds ratio = 1.532, 95% CI [1.323, 1.774]). The control group, who received only a print intervention with a mailed leaflet, also showed a dramatic increase in medication adherence. CONCLUSIONS: An insurer-coordinated telephone-administered program resulted in improvement of medication adherence among patients with hypertension and diabetes.

Correction to: Gap between patient expectation and perception during pharmacist-patient communication at community pharmacy.

In the original publication of the article the order of authors has been interchanged and now the same has been provided correctly in this correction.

Association between proton pump inhibitor use and risk of fracture: A population-based case-control study.

OBJECTIVES: The purpose of this study was to reconfirm the association between the risk of fracture and proton pump inhibitor use and to establish evidence for defining a high-risk group of patients among proton pump inhibitor users. METHODS: A nested case-control study was performed using data from the National Health Insurance Sharing Service database from the period January 2007 to December 2017. The study population included elderly women aged ≥65 years with claims for peptic ulcer or gastro-esophageal reflux disease. The cases were all incidental osteoporotic fractures, and up to two controls were matched to each case by age, osteoporosis, and Charlson comorbidity index. Conditional logistic regression was used to calculate the adjusted odds ratio and 95% confidence interval (CI). RESULTS: A total of 21,754 cases were identified, and 43,508 controls were matched to the cases. The adjusted odds ratio of osteoporotic fractures related to the use of proton pump inhibitors was 1.15 (95% CI: 1.11-1.20). There was a statistically significant interaction between proton pump inhibitor and bisphosphonate use (p<0.01). The risk of fracture in patients using proton pump inhibitors was 1.15 (95% CI: 1.08-1.92) in bisphosphonate users and 1.11 (95% CI: 1.03-1.20) in bisphosphonate non-users. CONCLUSION: Concomitant use of bisphosphonates and proton pump inhibitors will likely increase the risk of osteoporotic fractures in women aged 65 and over, and caution should be exercised in this high-risk group of patients.

Comparison of heart failure risk and medical costs between patients with type 2 diabetes mellitus treated with dapagliflozin and dipeptidyl peptidase-4 inhibitors: a nationwide population-based cohort study.

BACKGROUND: Dapagliflozin is one of the novel glucose-lowering agents, which has recently been reported to reduce the risk of hospitalization for heart failure (hHF). The present study aimed to compare the differences between the risk of hHF after using dapagliflozin and dipeptidyl peptidase-4 inhibitors (DPP-4i) as second-line drugs for the treatment of type 2 diabetes mellitus using the latest nationwide population data in Korea. Additionally, we aimed to examine the impact of clinical outcomes on direct medical costs in the two groups. METHODS: The present population-based, retrospective cohort study was conducted using the nationwide claims data between September 01, 2014 and June 30, 2018. New users of dapagliflozin and DPP-4i were identified from the database and the differences in patients' characteristics between the two groups were analyzed using propensity score-weighted analysis. Cox proportional hazards regression analysis was used to estimate the risk of hHF. A simple model was used for the estimation of direct medical costs for 3 years. RESULTS: In total, 23,147 patients in the dapagliflozin group and 237,187 patients in the DPP-4i group were selected for the analysis. The incidence rates of hHF were 3.86 and 6.79 per 1000 person-years in the dapagliflozin and DPP-4i groups, respectively. In the entire study population, the hazard ratio for hHF in the dapagliflozin group compared to the DPP-4i group was 0.58 (95% confidence interval 0.46-0.74), with 0.55 (95% confidence interval 0.41-0.74) among patients with underlying cardiovascular disease and 0.66 (95% confidence interval 0.46-0.95) among patients without underlying cardiovascular disease. The direct medical costs were $57,787 lower in the dapagliflozin group than in the DPP-4i group for 3 years. CONCLUSIONS: This study showed that dapagliflozin lowers the risk for hHF and subsequently reduces direct medical costs compared to DPP-4i. The protective effect against hHF was more evident among patients with underlying cardiovascular disease.

Gap between patient expectation and perception during pharmacist-patient communication at community pharmacy.

Background Assessing and satisfying patient expectation are essential in successful patient-centered communication. Recognizing the gap between patient expectation and perception during pharmacist-patient communication can help to identify communication problems and suggest ways to improve communication. Objective To evaluate the gap between patient expectation and perception of sharing information and communications skills during pharmacist-patient communication. Setting Community pharmacies in South Korea. Method A questionnaire was developed to collect expectation and perception of sharing information and communication skills. Items for sharing information included drug effect, dosage/route of administration, adverse drug reactions, storage, drug-drug interactions, drug-food interactions, managing a missed dose or overdose, co-medication, and past drug allergies. Communication skills included friendliness, expertise, easy language, emphasis on main content, confirmation of understanding, enough time, calm environment, and private space. A cross-sectional survey was conducted in 500 convenience sample using an online or written questionnaire in May 2018. Responses about patient expectation and perception were scored using 4-point Likert scales. Gap between patient expectation and perception was calculated as the differences among 4-point Likert scores. Factors associated with patient expectation and gap scores were evaluated using a multivariable regression method. Main outcome measure Patient expectation and perception of sharing information, as well as perception of communication skills during pharmacist-patient communication (questionnaire consisting 35 items). Results This study analyzed responses of 460 participants who answered all items on the questionnaire. Most respondents agreed or strongly agreed that they want to share information with pharmacists. All items had significant gap between patient expectation and perception (p < 0.01). Gap scores were highest for adverse drug reaction, drug-drug interaction, and past drug allergies (all, median 2). Gap scores were negatively associated with age 50-59 years, ≥ 60 years, and presence of ≥ 1 chronic illness. Patient perception of communication skills, especially regarding private space, were poor. Conclusions The information shared with pharmacists was significantly less than that expected by participants, and most pharmacist communication skills were evaluated as poor. Understanding the expectation of each patient and communicating accordingly with appropriate communication skills are necessary to improve patient-centered communication in community pharmacies.

Real-world prescribing and switching patterns of non-calcium containing phosphate binders in dialysis patients in South Korea
.

OBJECTIVE: Non-calcium containing phosphate binders (non-CPBs) are useful for the treatment of hyperphosphatemia without a concern of hypercalcemia in patients undergoing dialysis. However, due to their relatively high cost, prescribing non-CPBs is restricted in South Korea. This study was conducted to investigate prescribing patterns, especially switching between CPBs and non-CPBs, in dialysis patients in a real-world setting. MATERIALS AND METHODS: This is an observational study using the National Health Insurance Service claim data. The study population included patients who initiated dialysis between July 2012 and June 2013 and were prescribed phosphate binders at least once during the observation period (2012 - 2016) (n = 10,073). Medication costs and prescribing patterns including switching of phosphate binders were investigated. RESULTS: Compared with the first year of dialysis, the costs of phosphate binders more than doubled during the 4th year of dialysis (from US$ 28.4 to US$ 60.1), largely due to an increase in the cost of non-CPBs (from US$ 117.5 to US$ 237.8). Many patients continued to change drugs between CPBs and non-CPBs. The continuous prescription period of CPBs was shortened each time a drug was changed. A total of 551 patients (13.4%) changed their medication three times between CPBs and non-CPBs. CONCLUSION: Over time on dialysis, use of non-CPB increased and medication costs increased accordingly. Many patients continued to change drugs between CPBs and non-CPBs due to the restricted criteria of the health insurance. Further outcome research is necessary to evaluate the appropriateness of the clinical practice in which CPBs and non-CPBs are alternately used.

A Real-World Analysis of Prescribing Patterns and Non-persistence of Anti-TNFα Therapy for Inflammatory Bowel Disease.

BACKGROUND AND OBJECTIVES: Anti-tumor necrosis factor alpha (anti-TNFα) therapy is key to the treatment of inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD). The objective of this study was to investigate prescribing patterns and non-persistence of anti-TNFα therapy for the treatment of IBD in a real-world scenario. METHODS: Data from the Korean National Health Insurance claims database obtained between 2010 and 2014 were evaluated to identify patients with IBD who had received anti-TNFα therapy (infliximab or adalimumab). Patient characteristics and prescribing patterns were investigated. The non-persistence rate and associated reasons were determined in patients who initiated therapy between 2010 and 2012. RESULTS: A total of 131,158 patients with UC and 57,286 with CD were identified. Of these 1747 UC (1.3%) and 3731 (6.5%) CD patients had received anti-TNFα therapy and were included in the analysis. Infliximab was prescribed more frequently than adalimumab (84.6% vs 15.4% in UC and 80.7% vs 19.4% in CD); 81.0% of UC and 72.0% of CD patients received anti-TNFα alone or in combination with 5-aminosalicylic acid. The non-persistence rate of anti-TNFα therapy was 72.6% and 80.4% in the UC and CD groups, respectively, with discontinuation of medication being the most common reason in both the UC and CD groups (63.9% and 73.3%, respectively). CONCLUSION: The use of anti-TNFα therapy was seen to be low, with a high rate of non-persistence. Further research efforts are required to improve the response rate and, therefore, improve persistence in patients with IBD.

The Association between Polypharmacy and Hip Fracture in Osteoporotic Women: A Nested Case-Control Study in South Korea.

BACKGROUND AND OBJECTIVE: Polypharmacy, regarded as an indicator of potentially inappropriate medications (PIMs), may lead to a higher risk of serious health consequences in elderly patients with osteoporosis. Thus, this study aimed to analyze the association between polypharmacy and hip fracture in patients with osteoporosis because only a limited number of studies have reported on this association, with inconsistent results to date. METHODS: In this nested case-control study using a population-based sample cohort, the target cases were female patients with hip fracture diagnosed with osteoporosis and aged ≥ 50 years. Polypharmacy (prescription of an average of five or more daily drugs), PIMs for hip fracture (such as benzodiazepines and glucocorticoids), Charlson Comorbidity Index (CCI) score, and other comorbidities were analyzed during the year preceding the diagnosis of hip fracture. Adjusted odds ratios (ORs) for hip fracture for the variables were also analyzed. RESULTS: The cases (n = 1003) showed higher exposure rates to polypharmacy, glucocorticoids, and benzodiazepines, and had more severe comorbidity statuses compared with the controls. The ORs for hip fracture adjusted for confounders increased with polypharmacy level, with persistent statistical significance in most analyses. The ORs (95% confidence intervals), with reference to the 0 to < 1 drug group, were 1.65 (1.31-2.08) and 2.11 (1.12-3.96) for the 5 to < 10 and 10 + drug groups, respectively, with adjustment for PIMs, and 1.34 (1.04-1.72) and 1.45 (0.76-2.80) for the 5 to < 10 and 10 + drug groups, respectively, with adjustment for PIMs and CCI score. CONCLUSIONS: The results suggest that polypharmacy is associated with an increased risk of hip fracture after adjustment for confounders in patients with osteoporosis. These results highlight the importance of polypharmacy management in preventing hip fractures in patients with osteoporosis.

Association of Parkinsonism or Parkinson Disease with Polypharmacy in the Year Preceding Diagnosis: A Nested Case-Control Study in South Korea.

INTRODUCTION: Published studies on the association between polypharmacy and parkinsonism or Parkinson disease are very limited. OBJECTIVE: The objective of this study was to investigate whether polypharmacy is associated with parkinsonism or Parkinson disease in elderly patients. METHODS: From a South Korean national health insurance sample cohort database for 2002-2013, we matched parkinsonism cases (defined by diagnosis codes for parkinsonism/Parkinson disease) and Parkinson disease cases (patients who had records for both Parkinson disease diagnosis and anti-Parkinson disease drug prescriptions) with controls. Logistic regression analysis evaluated the associations of parkinsonism/Parkinson disease with polypharmacy (i.e., five or more prescribed daily drugs) during the year preceding parkinsonism/Parkinson disease diagnosis, medications potentially associated with parkinsonism, and comorbidity status (using the Charlson Comorbidity Index score and hospitalization records). RESULTS: The study population included 6209 cases and 24,836 controls for parkinsonism and 1331 cases and 5324 controls for Parkinson disease. In univariate logistic regression, odds ratios for parkinsonism/Parkinson disease increased significantly with increased polypharmacy, medications potentially associated with parkinsonism, Charlson Comorbidity Index score, or prior hospitalizations. In multiple logistic regression, odds ratios for parkinsonism/Parkinson disease (adjusted for medications potentially associated with parkinsonism and comorbidities) also increased with increased polypharmacy. Odds ratios (95% confidence interval) for Parkinson disease were higher than those for parkinsonism with stronger statistical significance: 1.41 (1.28-1.55) and 2.17 (1.84-2.57) for parkinsonism and 2.87 (2.30-3.58) and 4.75 (3.39-6.66) for Parkinson disease for between five and ten prescribed daily drugs and ten or more drugs, respectively. CONCLUSIONS: Polypharmacy in the year preceding diagnosis may be associated with an increased risk for parkinsonism/Parkinson disease. Medications potentially associated with parkinsonism were assumed to increase the risk for parkinsonism/Parkinson disease, but more studies are required to confirm this relationship.

The Association between Polypharmacy and Dementia: A Nested Case-Control Study Based on a 12-Year Longitudinal Cohort Database in South Korea.

Dementia is a major concern among growing chronic diseases in the aging society and its association with polypharmacy has not been adequately assessed. The objective of this study was to determine the association between polypharmacy and dementia through multiple statistical approaches. We conducted a nested case-control study for newly diagnosed dementia cases using the South Korean National Health Insurance Service sample cohort database (2002-2013, n = 1,025,340). Interactions between polypharmacy (an average use of ≥5 prescription drugs daily) and comorbidities or potentially inappropriate medications (PIMs) were tested. The odds ratios (ORs) for dementia were analyzed according to the presence of comorbidities, PIM uses, the average number of prescribed daily drugs, and significant interactions with polypharmacy using univariate and multiple logistic regression analyses. A higher prevalence of comorbidities, history of PIM use, higher PIM exposure, and higher proportion of polypharmacy were noted among cases than in controls. In the univariate analysis, the OR for dementia increased significantly with the increase in the number of prescribed drugs [1-<5 drugs: 1.72, 95% confidence interval (CI): 1.56-1.88; 5-<10 drugs: 2.64, 95% CI: 2.32-3.05; ≥10 drugs: 3.35, 95% CI: 2.38-4.71; <1 drug used as reference]. Polypharmacy was correlated with comorbidities and PIM use, and significant interactions were observed between polypharmacy and anticholinergics; H2-receptor antagonists; and comorbidities such as hypertension, peripheral or cerebrovascular disease, congestive heart failure, hemiplegia, diabetes, depression, all other mental disorders, chronic obstructive pulmonary disease, peptic ulcer disease, and chronic liver disease (p<0.001). In the multiple regression analysis, most cases exhibited increasing ORs for dementia with increasing polypharmacy levels. Moreover, the increase in OR was more evident in the absence of drugs or comorbidities that showed significant interactions with polypharmacy than in their presence. Polypharmacy increases the risk of PIM administration, and as some PIMs may have cognition-impairing effects, prolonged polypharmacy may result in dementia. Therefore, efforts are needed to limit or decrease the prescription of medications that have been associated with risk of dementia in the elderly.

A national pharmacoepidemiological study of antibiotic use in Korean paediatric outpatients.

BACKGROUND: Information on the use of antibiotics in Eastern Asian children is limited. The objectives of this study were to evaluate in Korean paediatric outpatients (1) the nationwide pattern of prescribing antibiotics according to age group and medical institution and (2) the adherence of antibiotic use for acute respiratory tract infections to both national guidelines and European antibiotic prescribing quality indicators. METHOD: This population-based study used the national insurance reimbursement database for 2011. The study subjects were outpatients younger than 18 years old prescribed systemic antibiotics. Patterns of antibiotic prescription were compared according to diagnostic conditions, age group and medical institution. The disease-specific proportion of recommended antibiotic or quinolone use for acute respiratory tract infections was evaluated on the basis of clinical practice guidelines and European quality indicators. RESULTS: The data consisted of 70.7 million prescription records for 7.9 million paediatric outpatients, which means that 79.3% of the whole paediatric population used antibiotics. Broad-spectrum antibiotics made up 78.5% of the prescriptions, with broad-spectrum penicillins such as amoxicillin/clavulanate being the most commonly prescribed (50.2%). They were prescribed more commonly in younger paediatric patients (∼80%) than in adolescents (66.6%). The leading diagnosis accounting for antibiotic prescription was bronchitis (35.9%). The prescription proportion of recommended antibiotics in the European quality indicators was extremely low compared with the national guidelines: <0.1% for pharyngotonsillitis and 13.4% for acute otitis media. CONCLUSIONS: Antibiotic use in children in Korea is inappropriately high. In addition, broad-spectrum antibiotics are used excessively.

Health Behaviors and Medication Adherence in Elderly Patients.

PURPOSE: To explore the relationships of selected health behaviors to medication adherence. DESIGN: A retrospective cohort study. SETTING: Data from Korean national health insurance claims between January 2010 and June 2011. SUBJECTS: Patients aged 65 years and older with hypertension (N = 662,170), hyperlipidemia (N = 244,702), or diabetes (N = 179,285). MEASURES: Medication adherence as a medication possession ratio from January to June 2011 as a dependent variable. The waist circumference (cm) and the body mass index (weight in kilogram divided by height in meter squared) as a marker for obesity. Smoking, drinking, and physical activity as main independent variables. ANALYSIS: A multivariate logistic regression. RESULTS: Nonobese patients, as based on the waist circumference, were more likely to adhere to their medication (by 8.9% for hypertension, 6.2% for diabetes, and 3.5% for hyperlipidemia). Current smokers were less likely to adhere to their medication (by 8.7% for hypertension and 6.8% for diabetes), and moderate and heavy drinkers were also less likely to show medication adherence for diabetes (by 12.9% and 6.4%). Mild physical activity was related to a 1.1% to 1.8% increase in the likelihood of medication adherence across the three disease groups. CONCLUSION: Health promotion programs for self-care health behaviors of elderly patients should emphasize good medication adherence to achieve successful self-management of diseases.

Prescribed drugs and polypharmacy in healthcare service users in South Korea: an analysis based on National Health Insurance Claims data.

OBJECTIVE: This study was conducted to analyze and compare the exposure to individually prescribed drugs and the prevalence of polypharmacy according to age group and concomitant disease in South Korea. METHODS: The use of prescribed drugs was evaluated according to average numbers of prescription drugs used daily during a year or month, using the Korean Health Insurance Claims Database, which is representative of over 90% of citizens, in 2010 and 2011. The use of prescribed drugs was also analyzed according to concomitant diseases and age. Polypharmacy was defined as the use of 5 or more drugs daily during a specific observation period, and proportions of polypharmacy users were calculated according to comorbidity and age group. RESULTS: The annual average numbers of daily used prescription drugs in 2010 and 2011 were 0.3 (SD = 0.5), 0.4 (SD = 0.7), 1.2 (SD = 1.5), and 2.3 (SD = 2.0) for people aged < 20 years, 20-49 years, 50-64 years, and ≥ 65 years, respectively. Proportions of individuals demonstrating polypharmacy increased with age and were 9.5% and 44.1% for elderly individuals in the year- and month-based analyses, respectively. The annual average number of daily medications used increased by ~2 drugs in the concomitant disease group, and the higher mortality group used a higher number of prescribed drugs than the lower mortality group. CONCLUSIONS: The results highlight the elevated burden of multi-medication in elderly patients, and the study found that prescribed drug use increased with age and the number of concomitant diseases.

Oral Bisphosphonates and Upper Gastrointestinal Cancer Risks in Asians with Osteoporosis: A Nested Case-Control Study Using National Retrospective Cohort Sample Data from Korea.

BACKGROUND: Bisphosphonate can irritate the gastrointestinal mucosa and increase the risk of esophageal or gastric cancer. The relatively high prevalence of upper gastrointestinal cancers and the widespread use of bisphosphonate in Korea call for further investigation. We conducted a case-control study to evaluate the risk of esophageal or gastric cancer after exposure to oral bisphosphonates in Korean patients with osteoporosis. METHODS: We used the National Health Insurance Service-National Sample Cohort database of Korea from 2002 to 2013. Among osteoporotic patients (>40 years), cases were defined as incident diagnosis of esophageal or gastric cancer between 2006 and 2013. For each case, four controls were matched for age, sex, and income level by type of insurance. We categorized bisphosphonate use as non-user, recent user, past user, and past and recent user, depending on prescription in two periods (1 to 2 years and 2 to 4 years prior to the index date). We also assessed the duration of bisphosphonate use by measuring cumulative duration of exposure (CDE). To examine the association between oral bisphosphonates and esophageal or gastric cancer, we estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) using conditional logistic regression analysis, adjusting for concomitant diseases. RESULTS: A total of 1,708 cases and 6,832 controls were identified. The aORs (95% CIs) of recent, past, and continuous bisphosphonate use compared to non-users were 1.18 (0.93-1.51), 1.04 (0.83-1.29), and 1.25 (0.95-1.58)), respectively. In addition, no significant association was observed by CDE, even when different outcome definitions were applied. CONCLUSIONS: This study did not prove an increased risk of esophageal or gastric cancer risk associated with bisphosphonate use, with respect to both risk windows and duration of exposure, in an Asian population-based, real-world setting.

Cost-effectiveness of Bedaquiline for the Treatment of Multidrug-resistant Tuberculosis in the Republic of Korea.

PURPOSE: Bedaquiline is a new drug used for the treatment of multidrug-resistant tuberculosis (MDR-TB). This study aimed to evaluate the cost-effectiveness of adding bedaquiline to a standard regimen (SR) for treating patients with MDR-TB, including extensively drug-resistant (XDR)-TB, in the Republic of Korea. METHODS: A cohort-based decision-analytic model developed in a previously published study from the United Kingdom was used, with a 20-year time horizon and a 5% discount rate for cost and effectiveness, to evaluate the incremental cost-effectiveness ratios of bedaquiline + SR and SR only. The key parameters regarding the clinical data were available via the published Phase II trial of bedaquiline. Additional parameters for recurrence, cure status, loss to follow-up, surgery, death, cost, and health utility were based on Korean data if available; otherwise the international literature data were applied. Univariate and probabilistic sensitivity analyses were conducted. FINDINGS: Based on the analysis, a patient on bedaquiline + SR would gain 1.20 quality-adjusted life-years (QALYs) at 13,961,659 Korean won (KRW) (1100 KRW = US $1) of additional cost compared with a patient administered SR only, with an incremental cost/utility ratio of 11,638,656 KRW/QALY. Bedaquiline + SR had an 80% probability of being cost-effective, at a willingness-to-pay threshold of 26 million KRW, compared with SR only. IMPLICATIONS: The results of this study suggest that, in the Republic of Korea, bedaquiline, as a part of combination therapy with SR, is a cost-effective option for the treatment of MDR-TB (including XDR-TB) compared with SR only.

Patient response to insurer-led intervention for medication adherence - a pilot study based on claims data in Korea.

OBJECTIVE: This study was designed to investigate patient responses to a medication counseling intervention program piloted by the National Health Insurance Service (NHIS), the national health insurer in Korea, to improve medication management in patients with hypertension, hyperlipidemia, or diabetes. METHODS AND MATERIALS: Interventions were conducted from July to September 2013 through direct mailing followed by two telephone-initiated counseling sessions for the medication discontinuation group (< 80% medication possession ratio (MPR) and ≥ 2 months of discontinuation) and the medication over-possession group (≥ 150% MPR). The telephone intervention was applied through two models: model 1 (counseling by NHIS staff only) and model 2 (counseling by NHIS staff with contract-based working pharmacists in community pharmacies). Multivariate logistic regression analysis was performed to identify factors affecting favorable responses of patients to the telephone-initiated intervention. Patient responses to the telephone-initiated intervention were evaluated by a counselor. RESULTS: In all, 891 patients were counseledvia telephone. Patient responses to the telephone-initiated intervention were favorablein 57.6%, neutral in 17.4% and not favorable in 24.9% overall. Counseling by NHIS staff together with pharmacists (model 2) produced more favorable responses from patients than counseling by NHIS staff alone (model 1) (OR 2.73, 95% CI 1.97 - 3.77). CONCLUSION: Our findings of favorable responses to interventions support a personalized approach by the NHIS to improve patient behavior for medication adherence.

Evidence supporting the need for considering the effects of smoking on drug disposition and effectiveness in medication practices: a systematic narrative review.

This study was conducted to provide a narrative overview of interactions between smoking and drug effectiveness/ pharmacokinetics. Database searches were performed to identify review articles published prior to March 10, 2013. Eligible articles reporting altered pharmacokinetic profiles, drug response, or adverse drug effects due to drug-smoking interactions were selected. Information on mechanism of action and clinical effects from the selected articles (n = 83) were summarized by therapeutic drug class. For cardiovascular drugs, smoking effects were variable. Smoking reduced aspirin response but increased clopidogrel response by increasing active metabolites. Warfarin, which has a narrow therapeutic range, required dosage adjustment in smokers due to its rapid clearance. Smoking is a risk factor for respiratory disease, leading to a lower response to corticosteroid and requiring increased doses or additional drugs. Higher doses of theophylline and some antipsychotics, which are mainly metabolized by CYP1A2, are required to reach an optimal plasma concentration in smokers. Smoking is also a risk factor for cancer, especially for lung cancer. Erlotinib or gefitinib are epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for lung cancer and showed lower anticancer effects in smokers. This summary of the interactions between smoking and drug pharmacological properties will aid healthcare professionals in providing patients with appropriate drug therapies, and emphasizes the need for considering smoking status as a patient factor in the clinical setting.

Patient factors affecting frequent potential unnecessary injection use in outpatient care setting.

This study aimed to investigate the prevalence of potential unnecessary injection (PUNI) and to identify factors associated with frequent PUNI uses. Population-based National Health Insurance claims data for outpatient health care settings during the six month period from July to December 2011 were retrospectively reviewed. Patients aged 18-80 without severe diseases and visited healthcare centers more than 25 times during study period were included. PUNI was defined as injection used where substitutable oral agents were available and where injection uses are not warranted. A total of 801,532 patients were included for this analysis. Among them, 29.0 % were frequent PUNI user defined as ≥10 PUNI used during the study period. In multivariate logistic regression results revealed significant associations between frequent PUNI use and several patient and healthcare utilization factors. Women than men, elderly than younger people, residents in rural areas than in big cities, and more frequent visitors to healthcare centers than less frequent visitors were more likely to be frequent PUNI users. Larger number of healthcare center utilized and higher out-of-pocket expense level showed significant lower risks of frequent PUNI uses. Identified factors associated with frequent PUNI use in this study could be the targets to develop programs for reducing injection overuse.

Living arrangements, chronic diseases, and prescription drug expenditures among Korean elderly: vulnerability to potential medication underuse.

BACKGROUND: Insufficient social security combined with family structure changes has resulted in a poverty of the elderly. The objective of this study was to examine an association of living arrangements of the elderly with chronic disease prevalence and prescription drug use. METHODS: 2008 Korea Health Panel Survey (KHPS) data were used in this study. Information on living arrangements, socio-demographics, health behaviors, chronic disease prevalence and healthcare expenditures including out-of-pocket (OOP) prescription drug expenditures for elderly aged 65 or older were collected from self-reported diaries and receipts. OOP prescription drug expenditure as a total cost that subject paid to a pharmacy for prescription drugs was examined. Logistic regression was used to identify differences in major chronic disease prevalence by living arrangements. The association of living arrangements with prescription drug use was analyzed using generalized linear model with a log link and a gamma variance distribution. RESULTS: Proportions of elderly living alone, elderly living with a spouse only, and elderly living with adults aged 20-64 were 14.5%, 48.3%, and 37.2%, respectively. Elderly living alone showed 2.43 odds ratio (OR) (95% confidence interval (CI) = 1.66-3.56) for having major chronic diseases prevalence compared to elderly living with adults. Despite a higher major chronic disease prevalence, elderly living alone showed lower OOP prescription drug expenditures (Cost Ratio = 0.80, 95% CI = 0.67-0.97) after adjusting for the number of major chronic diseases. Total OOP prescription drug expenditures were significantly lower in patients with a low income level versus high income level. CONCLUSIONS: Even though elderly living alone had a higher risk of chronic disease, they spent less on OOP prescription drug expenditures. Optimal drug use is important for elderly with chronic diseases to achieve good health outcomes and quality of life. Public health policies should be supplemented to optimize medical treatment for vulnerable elderly living alone.