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.

Clinical and economic burden of immune tolerance induction in entire patients with hemophilia A: Insights from a real-world Korean setting.

INTRODUCTION: The most notable challenge facing hemophilia A treatment is the development of inhibitors against factor VIII, resulting in increased clinical and socioeconomic burdens due to the need for expensive bypassing agents (BPAs). Although immune tolerance induction (ITI) is currently the primary approach for inhibiting and reducing the inhibitors, the lengthy duration of ITI necessitates the continued use of BPA to manage bleeding episodes. In this study, we aimed to obtain real-world evidence on the clinical and economic aspects and associated burdens experienced by patients with hemophilia A with inhibitors undergoing ITI in Korea. METHODS: Claims data from January 1, 2007, to December 31, 2020, were used in this study. The study cohort comprised patients with hemophilia A undergoing ITI, who were categorized into three groups: successful, failed, or continuation of ITI. We evaluated clinical and economic burdens, including monthly healthcare visits, medication costs, and total medical expenses. RESULTS: The study involved 33 cases of ITI across 32 patients. Excluding seven continuation cases where success could not be determined at the observation point, the estimated success rate of ITI was 80.8 %. The median duration of ITI for all patients was 25.7 months. While no significant disparities were noted in the ITI duration between successful and unsuccessful cases (24.51 vs. 25.66 months), substantial discrepancies were observed in the duration of BPA usage (11.10 vs. 25.66 months) and the number of prescribed BPAs (1.79 vs. 2.97). CONCLUSION: Successful ITI reduced both clinical and economic burdens, resulting in decreased monthly medication expenses and overall medical costs.

Clinical pharmacokinetic study of tacrolimus in continuous intravenous administration for lung transplantation.

Tacrolimus is a cornerstone of immunosuppression after lung transplantation. However, there are no clear guidelines on how to administer the drug and the duration to achieve the required therapeutic range in the early phase of lung transplantation. This is a single-center cohort study of adult patients who had lung transplantation. Tacrolimus was administered beginning with a low dose of 0.01 mg/kg/day immediately after transplantation. In addition, the designated clinical pharmacist conducted a daily intervention with trough concentrations to achieve the target of 10-15 ng/mL. Time in the therapeutic range (TTRin, %), time to the therapeutic range (TTRto, days), and coefficient of variation (CoV) of tacrolimus were evaluated for the 2-week post-transplant period. A total of 67 adult patients who had received first-time lung transplantation were included in the analysis. The median percentage of tacrolimus TTRin was 35.7% (21.4-42.9%) for the 2-week postoperative period. The median day of TTRto was 7 days (5-9 days), and the median tacrolimus trough concentration was 10.02 ng/mL (7.87-12.26 ng/mL) for the 2-week postoperative period. The median CoV of tacrolimus was 49.7% (40.8-61.6%). Acute kidney injury following tacrolimus infusion occurred in 23 (34.3%) patients, but there was no neurotoxicity or acute cellular rejection within 1 month of the postoperative period. In conclusion, continuous intravenous administration with the daily measure and dose titration of tacrolimus trough concentrations allowed the therapeutic range of tacrolimus to be reached within 1 week without significant adverse events, although the pharmacokinetic parameters were highly variable over time.

A comparison of methods for the measurement of adherence to antihypertensive multidrug therapy and the clinical consequences: a retrospective cohort study using the Korean nationwide claims database.

OBJECTIVES: In observational studies, the methods used to measure medication adherence may affect assessments of the clinical outcomes of drug therapy. This study estimated medication adherence to multidrug therapy in patients with hypertension using different measurement methods and compared their impacts on clinical outcomes. METHODS: This was a retrospective cohort study using the Korean National Health Insurance Service-National Sample Cohort database (2006-2015). Adults diagnosed with hypertension who initiated multidrug antihypertensive therapy in the index year 2007 were included. Adherence was defined as over 80% compliance. Adherence to multidrug antihypertensive therapy was measured in 3 ways using the proportion of days covered (PDC) with 2 approaches to the end-date of the study observations: PDC with at least one drug (PDCwith≥1), PDC with a duration weighted mean (PDCwm), and the daily polypharmacy possession ratio (DPPR). The primary clinical outcome was a composite of cardiovascular and cerebrovascular disease-specific hospitalizations or all-cause mortality. RESULTS: In total, 4,226 patients who initiated multidrug therapy for hypertension were identified. The mean adherence according to the predefined measurements varied from 72.7% to 79.8%. Non-adherence was associated with an increased risk of a primary outcome. The hazard ratios (95% confidence intervals, CIs) primary outcomes varied from 1.38 (95% CI, 1.19 to 1.59) to 1.44 (95% CI, 1.25 to 1.67). CONCLUSIONS: Non-adherence to multidrug antihypertensive therapy was significantly associated with an increased risk of a primary clinical outcome. Across the varying estimates based on different methods, medication adherence levels were similar. These findings may provide evidence to support decision-making when assessing medication adherence.

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.

Comparing the Sensitivities of Measures of Adherence to Antihypertensive Drugs Using Korean National Health Insurance Claims Data.

PURPOSE: Numerous studies have utilized various forms of adherence measures. However, methods for measuring adherence are inconsistent. Moreover, few studies are available that have compared sensitivities of the effects of several criteria on medication adherence. This study aims to compare measures of adherence using varied analytical decisions. MATERIALS AND METHODS: We included three measures for adherence: proportion of days covered with one or more medications (PDCwith≥1), duration weighted mean PDC (PDCwm), and daily polypharmacy possession ratio (DPPR). We compared the sensitivities of the measures by changing parameters in the Korean nationwide claims database. First, we used PDCwith≥1 as our base model. Then, we divided an adherence measure algorithm into three categories: (1) definition of data cleaning, (2) inclusion criteria and observation period, and (3) calculation methods of medication adherence. The categories included eight decision nodes that incorporated 25 alternative options. Finally, we assessed the medication adherence for the base-case with commonly used values and then varied to measure with each alternative option. RESULTS: The base-case included 14,288 beneficiaries with antihypertensives. Among eight decisions, both handling an end-date-of-study and overlaps had the strongest impacts on measuring PDCwith≥1, PDCwm, and DPPR, with small differences in sample size. Instead of the estimates of adherence from PDCwm, those of PDCwith≥1 and DPPR were similar. Furthermore, a tendency toward a higher medication adherence was observed with a smaller study population. CONCLUSION: The decisions regarding identifying an end-date-of-study and overlaps showed meaningful impacts of all three measures including PDCwith≥1, PDCwm, and DPPR on measuring medication adherence.

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.

Comprehensive Trends and Patterns of Antihypertensive Prescriptions Using a Nationwide Claims Database in Korea.

PURPOSE: The number of people receiving antihypertensive prescriptions in Korea has increased more than threefold from 2002 to 2016. However, previous studies regarding the current use of these medications have been fairly limited. We aimed to examine the current trends and changes in the patterns of antihypertensive prescriptions based on a nationwide claims database. PATIENTS AND METHODS: Patients receiving antihypertensive medications over 30 days, without any limited therapeutic indication, were identified using the Health Insurance Review and Assessment Service (HIRA) database between 2015 and 2017. For each patient, the use of antihypertensive medication was specified as the class of drug used for the longest duration in each year. RESULTS: A total of 8,625,821 patients in 2015, 8,997,829 patients in 2016, and 9,357,751 patients in 2017 taking antihypertensives were included in this study. Angiotensin II receptor blockers (ARB) (35.9% in 2015 and 38.9% in 2017) and calcium channel blockers (CCB) (37.1% in 2015 and 35.2% in 2017) for monotherapy, ARB+CCB combinations (49.3% in 2015 and 56.3% in 2017) for dual therapy, and ARB+CCB+diuretics combinations (48.8% in 2015 and 48.9% in 2017) for more than triple therapy were the most frequently prescribed. Subjects aged ≥70 showed the highest prescription rate of antihypertensives compared with those <70; however, a decreasing trend presented from 62.3% in 2015 to 54.2% in 2017. Additionally, in subjects aged >70 years, the rate in women was higher than that in men, but this was reversed in younger patients. While changes arose in the patterns of the use of antihypertensives, these were similar each year. CONCLUSION: The trends and changes in the patterns of the use of antihypertensive medications were affected by age, sex, and type of therapy. Our findings may contribute to a better understanding of the actual status regarding the use of antihypertensive medications in Korea.

Study of hospitalization and mortality in Korean diabetic patients using the diabetes complications severity index.

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) is expected to increase from 7.7% in 2017 to 8.4% in 2045 worldwide. Diabetes complications contribute to morbidity and mortality. To evaluate whether the diabetes complications severity index (DCSI) was associated with increased risks of mortality and hospitalization. METHODS: A retrospective cohort study was conducted using the National Health Insurance Database (NHID) sample cohort of 1,102,047 patients (2002-2015) in Korea. Diabetes complications were evaluated at 2 years after the initial diagnosis and during the subsequent follow-up period (mean duration 6.56 ± 2.81 years). The type and severity of complications were evaluated on the basis of the International Classification of Disease Ninth (ICD-9) codes used in DCSI with 7 categories and 55 subcategories of complications. The Cox proportional hazard and Poisson regression models were used to evaluate the mortality and hospitalization rates. The incidence and relative risk of diabetes complications as well as the risk of mortality and hospitalization were the main outcome measures. RESULTS: A total of 27,871 patients were finally included and grouped by the number of complications present at 2 years. Four hundred ninety patients (5.37%) died without complications, 659 (7.31%) died with one complication and 1153 (11.85%) died with two or more complications. As DCSI at index date increased, the risk of additional new diabetes complications increased by 26% [relative risk (RR) 1.26, 95% CI 1.25-1.27]. The risks of mortality and hospitalization were linearly related to DCSI [hazard ratio 1.13 (95% CI 1.11-1.16), relative risk 1.04 (95% CI 1.03-1.06)]. CONCLUSIONS: Patients with higher incidence and severity of diabetes complications have increased risks of mortality and hospitalization.