Continuity of care between dyslipidemia patients and multiple providers: A cohort study.

OBJECTIVE: This study aimed to investigate the impacts of continuity of care (COC) between patients and multiple providers, i.e., doctors and community pharmacists, on clinical and economic outcomes. METHODS: This is a retrospective cohort study and analyzed Korean national claims data for ambulatory care setting between 2007 and 2018. Patients with dyslipidemia newly diagnosed in 2008 were identified. COC between providers and patients was computed using the continuity of care index (COCI). Based on COCIs, the study patients were allocated to four groups: HM/HP, HM/LP, LM/HP, and LM/LP. Each symbol represents H for high, L for low, M for doctor, and P for pharmacist. The primary study outcome was the incidence of atherosclerotic cardiovascular disease (ASCVD). RESULTS: 126,710 patients were included. Percentages of patients in the four study groups were as follows: HM/HP 35%, HM/LP 19%, LM/HP 12%, and LM/LP 34%. During the seven-year outcome period, 8,337 patients (6.6%) developed an ASCVD, and percentages in the study groups were as follows; HM/HP 6.2%, HM/LP 6.3%, LM/HP 6.8%, and LM/LP 7.1%. After adjusting for confounding covariates, only the LM/LP group had a significantly higher risk of ASCVD than the reference group, HM/HP (aHR = 1.16 [95% confidence interval = 1.10~1.22]). The risk of inappropriate medication adherence gradually increased 1.03-fold in the HM/LP group, 1.67-fold in the LM/HP, and 2.26-fold in the LM/LP group versus the HM/HP group after adjusting for covariates. Disease-related costs were lower in the HM/HP and LM/HP groups. CONCLUSIONS: The study shows that patients with high relational care continuity with doctors and pharmacists achieved better clinical results and utilized health care less, resulting in reduced expenses. Further exploration for the group that exhibits an ongoing relationship solely with pharmacists is warranted.

Impact of the Narcotics Information Management System on Opioid Use Among Outpatients With Musculoskeletal and Connective Tissue Disorders: Quasi-Experimental Study Using Interrupted Time Series.

BACKGROUND: Opioids have traditionally been used to manage acute or terminal pain. However, their prolonged use has the potential for abuse, misuse, and addiction. South Korea introduced a new health care IT system named the Narcotics Information Management System (NIMS) with the objective of managing all aspects of opioid use, including manufacturing, distribution, sales, disposal, etc. OBJECTIVE: This study aimed to assess the impact of NIMS on opioid use. METHODS: We conducted an analysis using national claims data from 45,582 patients diagnosed with musculoskeletal and connective tissue disorders between 2016 and 2020. Our approach included using an interrupted time-series analysis and constructing segmented regression models. Within these models, we considered the primary intervention to be the implementation of NIMS, while we treated the COVID-19 outbreak as the secondary event. To comprehensively assess inappropriate opioid use, we examined 4 key indicators, as established in previous studies: (1) the proportion of patients on high-dose opioid treatment, (2) the proportion of patients receiving opioid prescriptions from multiple providers, (3) the overlap rate of opioid prescriptions per patient, and (4) the naloxone use rate among opioid users. RESULTS: During the study period, there was a general trend of increasing opioid use. After the implementation of NIMS, significant increases were observed in the trend of the proportion of patients on high-dose opioid treatment (coefficient=0.0271; P=.01) and in the level of the proportion of patients receiving opioid prescriptions from multiple providers (coefficient=0.6252; P=.004). An abrupt decline was seen in the level of the naloxone use rate among opioid users (coefficient=-0.2968; P=.04). While these changes were statistically significant, their clinical significance appears to be minor. No significant changes were observed after both the implementation of NIMS and the COVID-19 outbreak. CONCLUSIONS: This study suggests that, in its current form, the NIMS may not have brought significant improvements to the identified indicators of opioid overuse and misuse. Additionally, the COVID-19 outbreak exhibited no significant influence on opioid use patterns. The absence of real-time monitoring feature within the NIMS could be a key contributing factor. Further exploration and enhancements are needed to maximize the NIMS' impact on curbing inappropriate opioid use.

Current Antibiotic Use Among Hospitals in the sub-Saharan Africa Region; Findings and Implications.

Background: The rapid rise in antimicrobial resistance (AMR) globally, impacting on morbidity, mortality and costs with sub-Saharan African countries reporting the greatest burden is a concern. Instigation of antimicrobial stewardship programs (ASPs) can improve antibiotic use in hospitals and reduce AMR. Implementing ASPs requires knowledge of antibiotic utilization against agreed quality indicators with the data obtained from point prevalence surveys (PPS), hence the need to document antibiotic utilization patterns in sub-Saharan Africa. Methods: A narrative review to document current utilization patterns, challenges, indicators and ASPs across sub-Saharan Africa based on previous reviews by the authors, supplemented by the considerable knowledge and experience of the co-authors. Results: Results from multiple PPS studies showed a high prevalence of antibiotic use among hospitals, mostly over 50%. Prevalence rates ranged from as low as 37.7% in South Africa to as high as 80.1% in Nigeria. There was also considerable prescribing of broad-spectrum antibiotics which could be due to lack of facilities within hospitals, alongside concerns with co-payments to perform microbiological tests, resulting in empiric prescribing. This is a concern alongside lack of guidelines or adherence to guidelines, which was as low as 4% in one study. Another concern was the high rates of extended prophylaxis to prevent surgical site infections (SSIs), with antibiotics often prescribed for longer than 24 hours, usually multiple doses. Several quality indicators have been used to evaluate antibiotic utilization providing exemplars for the future. Among the initiatives being instigated to improve antibiotic use, ASPs have proved effective. For ASPs to be successful objectives and indicators must be agreed, and regular audits undertaken. Conclusion: Antibiotic prescribing across Africa is characterised by high prevalence, usually empirical. Various prescribing and quality indicators are being employed to assess antibiotic use, and ASPs have shown to improve antibiotic prescribing providing direction to reduce AMR.

A Comparative Analysis of Anticancer Drug Appraisals Including Managed Entry Agreements in South Korea and England.

OBJECTIVES: This study aimed to compare appraisal decisions about anticancer drugs between the health technology assessment (HTA) agencies in Korea and England, and investigate whether the decisions and supporting evidence are comparable. METHODS: This study identified 49 anticancer drugs listed by the Korean Ministry of Health and Welfare between January 2014 and December 2019. Of those, 46 anticancer drugs for 58 indications were included for analysis. Official appraisal documents from both countries for 58 drug-indication pairs were compared and assessed in terms of clinical and economic evidence. Evidence items and their groups for analysis were predefined. RESULTS: Three-quarters of cases were recommended with managed entry agreements (MEAs) in England and three-fifths in Korea. Finance-based MEA types were most common in both countries. Korean and English authorities made consistent decisions in 48 cases (83%) when classifying decisions as 'recommended' and 'not recommended', while the degree of agreement lowered to 16 cases (28%) when subdividing decisions according to MEA types. When the evidence base was identical, their decisions were more likely to be consistent. Regarding clinical evidence, while the majority of cases referred to the same pivotal studies, differences between the committees' recognized comparators and the appraisal date caused discrepancies in decisions. Economic evidence, including incremental cost-effectiveness ratio (ICER) estimates, was identical in only 12 cases (21%), which contributed to discrepancies. CONCLUSION: England relies on economic evaluation, with increasing use of data collection agreements, in contrast with Korea's new procedure exempting companies from providing economic evaluation. While there is possibility for international cooperation in the assessment of clinical evidence, transferability issues exist, particularly with regard to economic evidence.

Association between cost-sharing and drug prescribing in Korean elderly veterans with chronic diseases: A real-world claims data study.

This study aimed to investigate the relationship between cost-sharing and drug prescribing and its appropriateness in Korean elderly veterans with chronic conditions. This is a cross-sectional study using real-world claims data. Veterans with primary hypertension or dyslipidemia were compared with two controls with higher levels of cost-sharing. Study subjects (age ≥65 years) were selected through stratified random sampling and matching the individual attributes. The primary outcome was the annual amount of drugs prescribed per patient, and the secondary outcomes included several other measures investigating multifaceted aspects of drug prescribing, medical institution utilization behavior, and prescribing appropriateness. Gamma regression models or logistic regression models were employed. Veterans were prescribed 59%~74% more drugs (exp (ß) = 1.59 [95% confidence interval [CI] = 1.55-1.64] ~ 1.74 [1.70-1.79]) compared to the National Health Insurance (NHI) patients. This was attributed mainly to longer prescribing days (44%) and slightly more prescriptions (6%~7%) than NHI patients. Veterans spent 14%~15% higher medication costs. Veterans were less likely to visit multiple medical institutions by estimates of 0.77 (0.76-0.79) ~ 0.80 (0.79-0.82). Similar but smaller differences were observed between veterans and medical aid (MedAid) patients. The veteran patients showed a more than 50% increased risk of therapeutic duplication than the other two controls (adjusted odds ratio [ORs] = 1.47 [1.37-1.57] ~ 1.61 [1.50-1.72]). Inappropriate drug prescribing was also more common in veterans than the two controls (adjusted ORs = 1.20 [1.11-1.31] ~ 1.32 [1.22-1.43]). In Korean elderly veterans with chronic illnesses, a level of cost-sharing was associated with having more prescribed medicines, and increased inappropriate prescribing.

Relationship between continuity of care and clinical outcomes in patients with dyslipidemia in Korea: a real world claims database study.

Dyslipidemia is a risk factor for atherosclerotic cardiovascular disease and requires proactive management. This study aimed to investigate the association between care continuity and the outcomes of patients with dyslipidemia. We conducted a retrospective cohort study on patients with dyslipidemia by employing the Korea National Health Insurance claims database during the period 2007-2018. The Continuity of Care Index (COCI) was used to measure continuity of care. We considered incidence of atherosclerotic cardiovascular disease as a primary outcome. A Cox's proportional hazards regression model was used to quantify risks of primary outcome. There were 236,486 patients newly diagnosed with dyslipidemia in 2008 who were categorized into the high and low COC groups depending on their COCI. The adjusted hazard ratio for the primary outcome was 1.09 times higher (95% confidence interval: 1.06-1.12) in the low COC group than in the high COC group. The study shows that improved continuity of care for newly-diagnosed dyslipidemic patients might reduce the risk of atherosclerotic cardiovascular disease.

Relational continuity of care in community pharmacy: A systematic review.

Relational continuity of care (COC) is becoming an important concept related to improving healthcare quality, reducing medical costs and increasing patient satisfaction with primary care. While community pharmacy (CP) has a considerable role in primary care, there are few reports dedicated to the role of relational COC in CP. This study reviewed the existing evidence of relational COC in CP and its effect on patients. PubMed, Embase, CINAHL, Cochrane Library CENTRAL and Google Scholar were used to search for relevant studies from the date of database inception through to January 2021, which were appraised according to eligibility criteria. There were no limitations on the primary outcome or language. Case reports and studies without control groups were excluded. The Newcastle-Ottawa quality assessment scale was used to assess the quality of the studies. Database searches identified 13 records. Relational COC measures in the included studies were grouped in three kinds; pharmacy-visiting pattern, Continuity of Care Index and loyalty. The assessed outcomes were medication adherence behaviour (e.g., the proportion of days covered, medication possession ratio), adverse drug reactions, potentially inappropriate drug prescribing and clinical outcomes. The odds of patients adhering to their medication regimen were about 1.1~2.5 times higher among those who consistently visited a single pharmacy compared to patients visiting multiple pharmacies. Additionally, the care provision with a high level of relational continuity could lower inappropriate drug use by 21~32 per cent and the use of other costly services by 12~29 per cent. This study suggests that a high degree of relational COC in CP could improve safe use of medications among patients. Future research is needed to employ more rigorous methods to reduce heterogeneity and to measure effects on clinical outcomes.

Synthesis and activity of N-(5-hydroxy-3,4,6-trimethylpyridin-2-yl)acetamide analogues as anticolitis agents via dual inhibition of TNF-α- and IL-6-induced cell adhesions.

Tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) are the critical pro-inflammatory cytokines involved in the pathogenesis of inflammatory bowel disease (IBD). Inhibition of these cytokines and related signaling pathways has been a target for the development of IBD therapeutics. In the current study, 6-acetamido-2,4,5-trimethylpyridin-3-ol (1) and various analogues with the amido scaffold were synthesized and examined for their inhibitory activities in in vitro and in vivo IBD models. The parent compound 1 (1 µM) showed an inhibitory activity against TNF-α- and IL-6-induced adhesion of monocytes to colon epithelial cells, which was similar to tofacitinib (1 µM), a JAK inhibitor, but much better than mesalazine (1,000 µM). All the analogues showed a positive relationship (R2 = 0.8943 in a linear regression model) between the inhibitory activities against TNF-α-induced and those against IL-6-induced adhesion. Compound 2-19 turned out to be the best analogue and showed much better inhibitory activity against TNF-α- and IL-6-induced adhesion of the cells than tofacitinib. In addition, oral administration of compound 1 and 2-19 resulted in a significant suppression of clinical signs of TNBS-induced rat colitis, including weight loss, colon tissue edema, and myeloperoxidase activity, a marker for inflammatory cell infiltration in colon tissues. More importantly, compound 2-19 (1 mg/kg) was more efficacious in ameliorating colitis than compound 1 and sulfasalazine (300 mg/kg), the commonly prescribed oral IBD drug. Taken together, the results suggest that compound 2-19 can be a novel platform for dual-acting IBD drug discovery targeting both TNF-α and IL-6 signaling.

Assessment of the effects of methodological choice in continuity of care research: a real-world example with dyslipidaemia cohort.

OBJECTIVE: To determine if the choice of methodological elements affects the results in continuity of care studies. DESIGN: This is a retrospective cohort study. The association between continuity of care and clinical outcome was investigated using the Continuity of Care Index. The association was explored in 12 scenarios based on four definitions of the relative timing of continuity and outcome measurements in three populations (three Ps × four Ts). SETTING: National Health Insurance claims from all primary and secondary care facilities in South Korea between 2007 and 2015. PARTICIPANTS: Participants were patients diagnosed with dyslipidaemia, made ≥2 ambulatory visits and were newly prescribed with ≥1 antihyperlipidaemic agent at an ambulatory setting in 2008. Three study populations were defined based on the number of ambulatory visits: 10 084 patients in population 1 (P1), 8454 in population 2 (P2) and 4754 in population 3 (P3). MAIN OUTCOME MEASURE: Hospitalisation related to one of the four atherosclerotic cardiovascular diseases, including myocardial infarction, stable or unstable angina, ischaemic stroke and transient ischaemic attack. RESULTS: Concurrent measure of continuity and outcome (T1) showed a significantly higher risk of hospitalisation (adjusted HRs: 2.73-3.07, p<0.0001) in the low continuity of care group, whereas T2, which measured continuity until the outcome occurred, showed no risk difference between the continuity of care groups. T3, which measured continuity as a time-varying variable, had adjusted HRs of 1.31-1.55 (p<0.05), and T4, measuring continuity for a predefined period and measuring outcomes in the remaining period, had adjusted HRs of 1.34-1.46 (p<0.05) in the low continuity of care. Within each temporal relationship, the effect estimates became more substantial as the inclusion criteria became stricter. CONCLUSIONS: The study design in continuity of care studies should be planned carefully because the results are sensitive to the temporal relationship between continuity and outcome and the population selection criteria.

Challenges in informed consent decision-making in Korean clinical research: A participant perspective.

OBJECTIVES: This study investigated how the essential elements of informed consent are realised during the consent process and examined the challenges in obtaining genuine informed consent in Korea. METHODS: Through purposive sampling, we recruited 21 subjects from those participating in anticancer drug research since 2013. We undertook 1:1 in-depth interviews and analysed the data by framework analysis. RESULTS: Themes raised throughout the interviews were categorised into 'disclosure' and 'understanding' of clinical information and 'decision'. Provider-centred information, both verbal and written, was delivered to each participant. There were few tools that the research staff might evaluate study participants' level of understanding of the provided information during the clinical trial. Although participants did not understand basic clinical trial concepts as much as desired, they may not seek to solve difficulties through communication with trial researchers. Doubts were raised about whether participants had sufficient capacity and free will to provide informed consent. CONCLUSION: There is a concern that informed consent can fall short of genuine in Korea. To ensure informed consent meets the international standard, greater efforts should be made to establish an explicit standard operational protocol for obtaining informed consent.

Antitumor activity of BJ-1207, a 6-amino-2,4,5-trimethylpyridin-3-ol derivative, in human lung cancer.

Enhanced expression of NADPH oxidase (NOX) and the subsequent production of reactive oxygen species (ROS) are associated with lung cancer. In the present study, fifty 6-amino-2,4,5-trimethylpyridin-3-ol derivatives were screened for anticancer activity by targeting NOX2-derived ROS. The compounds suppressed ROS production and decreased cancer cell viability (R2 = 0.79). Among the derivatives, the compound coded BJ-1207, which contained a 4-(hydroxydiphenylmethyl)piperidine moiety, exhibited the most effective anticancer activity against A549 lung cancer cell line and eight other cancer cell lines, including H1299, MCF-7, MDA-MB-231, HT-29, SW620, Mia PaCa-2, PANC-1, and U937. BJ-1207 also showed significantly lower inhibitory effects on kinase insert domain receptor (KDR) and c-KIT tyrosine kinase but higher inhibitory activity on NOX than those of sunitinib, a multi-receptor tyrosine kinase (RTK) inhibitor. In addition, BJ-1207-induced inhibition of RTK-downstream signaling pathways, such as ROS production, and expression of target genes, such as stem cell factor and transforming growth factor-α, were similar to those induced by sunitinib. In the xenograft chick tumor model, BJ-1207 inhibited lung tumor growth to a similar or much greater extent than that of sunitinib or cisplatin, respectively. Overall, the present study showed that BJ-1207, a vitamin B6-derived 2,4,5-trimethylpyridin-3-ol compound with azacyclonol moiety at C (6)-position of the pyridine ring, inhibited NOX activity and that it is a promising lead compound for developing anticancer drugs against lung cancer.

Effects of a price cut reform on the cost and utilization of antidiabetic drugs in Korea: a national health insurance database study.

BACKGROUND: Despite the potential widespread application and a significant need, the policy effectiveness of prescribed medications price controls has not been studied extensively. We aimed to explore the effects of a price cut introduced in April 1st of 2012 on the cost and utilization of antidiabetics in South Korea. METHODS: We identified approximately four million outpatients who filed at least one diabetes-related claim during the index period (January 2010 to December 2012) using the National Health Insurance claims data. We performed interrupted time series analyses for cost and utilization of "overall," "reduced price," and "constant price" antidiabetics between January 2009 and June 2013, and measured the growth rate for incidents of medical and surgical procedures for diabetes-induced complications. RESULTS: The segmented regression suggests that spending on overall and reduced price antidiabetics would drop by 6 and 23%, respectively; spending on constant price antidiabetics would rise by 16% in a year after the new pricing compared to if the policy were not in existence. There were a few immediate changes in utilization, and its trend indicated a significant decrease in reduced price antidiabetics and an increase in constant price antidiabetics. Incidents of medical and surgical procedures relating to diabetic complications were unaffected. CONCLUSIONS: The Korean price cut program contained costs by immediately reducing the cost of pharmaceuticals without any major signals associated with compromised clinical conditions in diabetic patients.

Correction: Awareness and attitude of the public toward personalized medicine in Korea.

[This corrects the article DOI: 10.1371/journal.pone.0192856.].

Awareness and attitude of the public toward personalized medicine in Korea.

OBJECTIVES: As personalized medicine (PM) is expected to greatly improve health outcomes, efforts have recently been made for its clinical implementation in Korea. We aimed to evaluate public awareness and attitude regarding PM. METHODS: We performed a self-administered questionnaire survey to 703 adults, who participated in the survey on a voluntary basis. The primary outcome measures included public knowledge, attitude, and acceptance of PM. We conducted multinomial multivariate logistic analysis for outcome variables with three response categories and performed multivariate logistic regression analyses for dichotomous outcome variables. RESULTS: Only 28% of participants had knowledge that genetic factors can contribute to inter-individual variations in drug response and the definition of PM (199 out of 702). Higher family income was correlated with greater knowledge concerning PM (OR = 3.76, p = 0.034). A majority of respondents preferred integrated pharmacogenomic testing over drug-specific testing and agreed to inclusion of pharmacogenomic testing in the national health examination (64% and 77%, respectively), but only 51% were willing to pay for it. DISCUSSION: Our results identify the urgent need for public education as well as the potential health disparities in access to PM. This study helps to frame policies for implementing PM in clinical practice.

Protective effects of 6-ureido/thioureido-2,4,5-trimethylpyridin-3-ols against 4-hydroxynonenal-induced cell death in adult retinal pigment epithelial-19 cells.

Dysfunction or progressive degeneration of retinal pigment epithelium (RPE) contributes in the initial pathogenesis of age-related macular degeneration (AMD) causing irreversible vision loss, which makes RPE the prime target of the disease. The present study aimed to identify compounds to protect 4-hydroxynonenal (4-HNE)-induced RPE cell death by inhibiting NADPH oxidase 4 (NOX4) activity, not just as free radical scavengers, using ARPE-19, a human adult retinal pigment epithelial cell line, as a RPE representative. Novel thirty-two 6-ureido/thioureido-2,4,5-trimethylpyridin-3-ol derivatives 17 were synthesized and tested. We found that there was a strong correlation between level of protective effect of compounds 17 against 4-HNE-induced APRE-19 cell death and that of inhibitory activity against 4-HNE-induced superoxide production, and that most of the compounds 17 showed minimal DPPH radical scavenging activity. Compound 17-28 showed the best protective activity against 4-HNE-induced superoxide production (79.5% inhibition) and cell death (85.1% recovery) at 10 µM concentration, which was better than that of VAS2870, a NOX2/4 inhibitor. In addition, compound 17-28 blocked 4-HNE-induced apoptosis of ARPE-19 cells in a concentration-dependent manner. The results indicate that compound 17-28 may be a lead compound to develop AMD therapeutics.

Satisfaction and expressed needs of pharmaceutical care services and challenges recognized by patients in South Korea.

PURPOSE: To assess the degree of satisfaction and expressed needs of pharmaceutical care services in patients with chronic diseases and explore the factors related to the needs from patients' perspectives for the further development of pharmaceutical care service models. PATIENTS AND METHODS: A cross-sectional survey of 220 patients (mean age ± SD: 61.3±13.1, male:female: 104:116) was conducted. The questionnaire was structured to measure patients' degree of satisfaction and expressed needs using a 5-point Likert scale. Additionally, preferred duration, methods of service delivery, and willingness to pay were surveyed. Responses were analyzed using an ordinal regression method to predict factors that were related to pharmaceutical care services. RESULTS: Sixty-seven patients had experienced pharmaceutical care services. Their satisfaction levels were high in all categories; however, there were no significant differences between categories. The levels of expressed needs were similar among categories without significant differences. The preferred delivery method was a face-to-face conversation combined with being provided with written information (53.2%). The preferred duration was ≤10 min (70.5%). About 48% of the patients showed willingness to pay for the service. Education level and region influenced patients' needs. CONCLUSION: The satisfaction and needs of pharmaceutical care services was very positive; however, noticing only a third of patients experienced pharmaceutical care services, this may indicate a lack of awareness and less appreciation of pharmacists by patients. Details concerning patients' awareness and the value of pharmaceutical care services require further investigation.

Perceived needs of pharmaceutical care services among healthcare professionals in South Korea: a qualitative study.

Purpose To explore the need for pharmaceutical care services, key features of desirable pharmacy services, and perceived barriers for advancing the services in hospital environments with doctors and nurses who are key co-workers of the interdisciplinary team care services.Methods Semi-structured, in-depth interviews with eighteen doctors and fifteen nurses employing purposive and snowballing sampling strategies were conducted in ten hospitals in South Korea. Results The level of pharmaceutical care was varied across regions or institutions in South Korea. The concept of pharmaceutical care was insufficiently defined, and tended to be limited to some parts of medication counseling. Through pharmaceutical care services, doctors desired to acquire comprehensive drug information from and to share clinical responsibilities with pharmacists. Nurses wished to lower their burdens of medication counseling services from their daily practices. Doctors and nurses asked for pharmacists providing essential and carefully selected medication information to their patients in a patient-centered manner. The listed barriers to pharmaceutical care included the lack of appropriate systems for reward, insufficient accessibility to patient records by pharmacists, ambiguous role descriptions of pharmacist, and absence of effective communication among professionals. Conclusion A successful pharmaceutical care service model should allow efficient exchange of information among healthcare professionals to build inter-professional trust and to provide a continuity of care both in terms of time and setting. As prerequisites of such system, it was warranted to develop clinical evidence and an appropriate reward system for pharmaceutical care services.

Inadequate stroke prevention in Korean atrial fibrillation patients in the post-warfarin era.

BACKGROUND: Anticoagulation therapy with warfarin or direct oral anticoagulants (DOACs) is recommended for atrial fibrillation (AF) patients who are at a high risk for stroke. This study aimed to investigate the utilization of anticoagulants since the introduction of DOACs in South Korea. METHODS: This was a cross-sectional study using claim-based national data from 2011 to 2014 derived from the Aged Patient Sample (APS) compiled by the Health Insurance Review & Assessment Service (HIRA). Patients with a high risk for thromboembolism were identified as those having a CHA2DS2-VASc (congestive heart failure, hypertension, age≥75, diabetes mellitus, stroke (or transient ischemic attack), vascular disease, sex) score of ≥2. Patients at a high risk for bleeding with an ATRIA (anticoagulation and risk factors in atrial fibrillation) bleeding score of >4 were excluded. Anticoagulant underutilization was estimated in these high-risk patients. Demographic and clinical factors associated with warfarin and DOAC underutilization were explored using a logistic regression model. RESULTS: Anticoagulant underutilization among high-risk patients for stroke decreased from 68% to 62.5% between 2011 and 2014; however, there was further scope for improvement. The risk factors for underutilization were identified as follows: female sex, old age, having medical aid insurance, presence of vascular disease, and limited anticoagulant options. CONCLUSIONS: Our study demonstrates that a large population of AF patients in South Korea failed to obtain adequate stroke prevention treatment, even in the era of DOAC usage. A more aggressive approach to provide optimal antithrombotic therapy is warranted.

Underutilization of warfarin for stroke prophylaxis in patients with atrial fibrillation or atrial flutter in Korea.

OBJECTIVE: Anticoagulation therapy with warfarin is recommended for stroke prevention in patients with atrial fibrillation (AF) or atrial flutter (AFL) whose risks for stroke are high. However, previous studies suggest that warfarin is markedly underused. This study aims to investigate the incidence and risk factors of warfarin underutilization in patients with high risk of stroke in Korea. METHODS: This was a cross-sectional study using the data of 2009 from National Patients Sample compiled by the Health Insurance Review and Assessment Service. Patients with high risk of thromboembolism were identified with congestive heart failure, hypertension, age ≥75 years, diabetes, and prior stroke (CHADS2) score ≥2. High-risk patients of bleeding were excluded using Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) score >4. Warfarin and antithrombotic therapy underutilization were defined and estimated in high-risk patients. Any demographic and clinical factors associated with warfarin and antithrombotic therapy underutilization were explored using a logistic regression model. RESULTS: Of the national patient sample, 15,885 patients were identified with AF or AFL. Among them, a total of 8475 patients who had an admission history, CHADS2 ≥2, and ATRIA score ≤4 were included in the analysis. From the study sample, warfarin underutilization and antithrombotic therapy underutilization were estimated to be 64.0% and 20.4%, respectively. Predictors of warfarin underutilization include female sex, age ≥80 years, lower CHADS2 score, and insurance type (Medical Aid program). CONCLUSIONS: A high portion of AF/AFL patients with CHADS2 score ≥2 were undertreated with warfarin. As ischemic stroke is one of the leading causes of death in Korea, a more aggressive approach to prevent stroke in patients with AF/AFL is required.

International experience in controlling pharmaceutical expenditure: influencing patients and providers and regulating industry - a systematic review.

OBJECTIVE: To review international policies to control expenditure on pharmaceuticals by influencing the behaviour of patients and providers and regulating the pharmaceutical industry. METHOD: Systematic review of experimental and quasi-experimental studies. Published studies were identified with an electronic search strategy using MEDLINE and EMBASE from 1980 to May 2012. Studies were eligible if they assessed the effect of policies aimed at influencing the behaviour of patients and providers, and regulating the pharmaceutical industry. Outcome measures included pharmaceutical expenditure, prices or utilization; other resource use relating to pharmaceuticals; and health outcomes and patients' or providers' behaviour relating to pharmaceutical use. Quality assessment criteria for each study design were developed based on the standard criteria recommended by the Cochrane Effective Practice and Organisation of Care (EPOC) group. The review includes studies based on randomized controlled trials and rigorous quasi-experimental designs (interrupted time-series and controlled before-and-after studies). Studies were excluded if they were conducted within a single hospital or practice; related to pharmaceutical care services or disease management; had less than 6 months of follow-up period (or less than 12 months overall for interrupted time series); if data in controlled before-and-after studies were not collected contemporaneously or if no rationale was stated for the choice of control group; or if relevant and interpretable data were not presented. RESULTS: A total of 255 studies met the inclusion criteria for this review. The majority of the studies relating to patients evaluated cost sharing interventions such as user charges (52 studies). User charges do reduce utilization of pharmaceuticals, and reduce public expenditure by shifting costs to patients. But they reduce the use of essential as well as non-essential drugs, and without adequate exemptions they affect vulnerable groups disproportionately. The majority of studies relating to doctors evaluated the effects of educational approaches (78 studies), reimbursement restrictions (48 studies) and incentive systems (22 studies). Evidence on these policies is of mixed quality. It appears possible to influence prescribing modestly, through various means, but it is essential that messages to prescribers are based on good evidence of effectiveness and cost-effectiveness. Twenty-nine studies related to industry regulation, and they were of mixed quality. Evidence from studies of reference pricing suggests that this may result in cost savings. These are, however, achieved not by companies reducing or restraining prices, or by reductions in the overall volume of prescriptions, but by some shifts in use and shifting costs to patients, with consequent adverse effects on the equity of access to medicines. Other price and profit controls remain almost completely lacking in evaluative evidence. CONCLUSIONS: It may be that the undesirable consequences of policies influencing patients, particularly user charges, can outweigh the benefits. To influence demand for pharmaceuticals, it is more appropriate to influence prescribing doctors and although interventions to improve prescribing practice have been developed, they often achieve relatively modest benefits and sometimes at high cost. Good evaluative evidence related to industry regulation is scarce despite its policy importance.