Effectiveness of Acupotomy Combined with Epidural Steroid Injection for Lumbosacral Radiculopathy: A Randomized Controlled Pragmatic Pilot Study.

Background and Objectives: This pilot study aimed to evaluate the clinical effectiveness, cost-effectiveness, and safety of acupotomy combined with epidural steroid injection (ESI) in lumbosacral radiculopathy and examine its feasibility for the main study. Materials and Methods: This randomized, controlled, two-arm, parallel, assessor-blinded, pragmatic study included 50 patients with severe lumbosacral radiculopathy who had insufficient improvement after an ESI. Patients were randomized (1:1 ratio) into a combined treatment (acupotomy + ESI, experimental) and an ESI single treatment (control) group. Both groups underwent a total of two ESIs once every 2 weeks; the experimental group received eight additional acupotomy treatments twice a week for 4 weeks. Types of ESI included interlaminar, transforaminal, and caudal approaches. Drugs used in ESI comprised a 5-10 mL mixture of dexamethasone sodium phosphate (2.5 mg), mepivacaine (0.3%), and hyaluronidase (1500 IU). The primary outcome was the difference in changes from baseline in the Oswestry Disability Index (ODI) scores between the groups at weeks 4 and 8. The incremental cost-utility ratio (ICUR) was calculated to evaluate the cost-effectiveness between the groups. Adverse events (AEs) were assessed at all visits. Results: Mean ODI scores for the experimental and control groups were -9.44 (95% confidence interval [CI]: -12.71, -6.17) and -2.16 (95% CI: -5.01, 0.69) at week 4, and -9.04 (95% CI: -12.09, -5.99) and -4.76 (95% CI: -7.68, -1.84) at week 8, respectively. The difference in ODI score changes was significant between the groups at week 4 (p = 0.0021). The ICUR of the experimental group versus the control group was as economical as 18,267,754 won/quality-adjusted life years. No serious AEs were observed. Conclusions: These results demonstrate the potential clinical effectiveness and cost-effectiveness of acupotomy combined with ESI for lumbosacral radiculopathy and its feasibility for a full-scale study. Larger, long-term follow-up clinical trials are needed to confirm these findings.

Comparative Efficacy of Venetoclax-Based Combination Therapies and Other Therapies in Treatment-Naive Patients With Acute Myeloid Leukemia Ineligible for Intensive Chemotherapy: A Network Meta-Analysis.

OBJECTIVES: This network meta-analysis (NMA) assessed the efficacy of venetoclax (VEN) + azacitidine (AZA) and VEN + low-dose cytarabine (LDAC) compared with AZA, LDAC, and decitabine monotherapies and best supportive care (BSC) in adults with untreated acute myeloid leukemia ineligible for intensive chemotherapy. METHODS: A systematic literature review and feasibility assessment was conducted to select phase III randomized controlled trials for inclusion in the NMA. Complete remission + complete remission with incomplete blood count recovery and overall survival (OS) were compared using a Bayesian fixed-effects NMA. Treatments were ranked using surface under the cumulative ranking curves (SUCRAs) with higher values indicating a higher likelihood of being effective. RESULTS: A total of 1140 patients across 5 trials were included. VEN + LDAC (SUCRA 91.4%) and VEN + AZA (87.5%) were the highest ranked treatments for complete remission + complete remission with incomplete blood count recovery. VEN + LDAC was associated significantly higher response rates versus AZA (odds ratio 5.64), LDAC (6.39), and BSC (23.28). VEN + AZA was also associated significantly higher response rates than AZA (5.06), LDAC (5.74), and BSC (20.68). In terms of OS, VEN + AZA (SUCRA: 95.2%) and VEN + LDAC (75.9%) were the highest ranked treatments. VEN + AZA was associated with significant improvements in OS compared with AZA (hazard ratio 0.66), LDAC (0.57), and BSC (0.37), and VEN + LDAC was associated with significant improvements in OS compared with LDAC (0.70) and BSC (0.46). CONCLUSIONS: VEN + AZA and VEN + LDAC demonstrated improved efficacy compared with alternative therapies among treatment-naive patients with acute myeloid leukemia ineligible for intensive chemotherapy.

Expenditure on complementary and alternative medicine and productivity losses in patients with primary dysmenorrhea: A survey of women in Korea.

In women with primary dysmenorrhea (PD), the use of complementary and alternative medicine (CAM) and productivity losses at both workplaces and schools have not been comprehensively assessed. In this study, researchers evaluated the disease burden in women with PD in patients' perspective in two categories: direct cost (the use of CAM and associated costs) and indirect cost (productivity losses). Women with PD aged 16-49 years were asked to fill an online survey in 2017. The survey consisted of 49 questions. CAM included traditional Korean medicines, over-the-counter products, dietary supplements, and traditional remedies. All costs were expressed in US dollars in this study. The survey data from 86 patients with PD were analyzed. The total mean annual cost per patient with PD was $4053, comprising direct costs ($1245) and indirect costs ($2807). PD causes considerable expenditure on CAM and impairs work productivity (especially in presenteeism).

Traditional medicine for the treatment of common cold in Korean adults: A nationwide population-based study.

BACKGROUND: Traditional medicines (TMs) have been used to treat common cold in Asia, but no studies have been conducted to examine the trend of use for several years. The objective of this study was to analyze the prescription patterns of TMs for common cold using national claims data accrued over 7 years in Korea. This will contribute to the scientific evidence enhancing the understanding of TM use for the treatment of common cold. METHODS: This study analyzed national claims data from the Health Insurance Review and Assessment Service database. We extracted data for diagnosis of common cold (Korean Standard Classification of Diseases: J00, Acute nasopharyngitis) and prescriptions of TMs for adults who visited all types of oriental medical institutions during 2010-2016. We estimated the prescription patterns of TMs by sex, age group, and year. RESULTS: We extracted 3,014,428 prescriptions. The total number of prescriptions increased by 125.1% in 2016 compared to that in 2010. For all ages and periods, the number of prescriptions in women was higher than that in men. The age range with the most prescriptions was 70-79 years. The seven most prescribed TMs for common cold were Socheongnyongtang, Samso-eum, Yeongyopaedoksan, Insampaedoksan, Gumigohwaltang, Galgeuntang, and Hyeonggae-yeongyotang. CONCLUSION: This was the first study to analyze the prescription patterns of TMs for common cold using National Health Insurance data in Korea. This study provides scientific evidences on the disease burden and the utilization pattern of TMs for common cold to support decision making on initiatives such as allocation and management of health resources.

Efficacy and safety of herbal medicine (Dangguijagyag-san) for primary dysmenorrhea: study protocol for a randomized, double-blind, placebo-controlled, parallel-group, multi-center trial.

BACKGROUND: Dangguijagyag-san, also known as Dangguishaoyao-san in Chinese and Toki-shakuyakui-san in Japanese, has been frequently used to treat symptoms associated with dysmenorrhea. The purpose of this trial is to evaluate the efficacy and safety of the herbal medicine, Dangguijagyag-san, relative to those of active control, Gamisoyo-san, and a placebo control for primary dysmenorrhea. METHODS: This protocol details a randomized, double-blind, parallel-group, multi-center, investigator-initiated, controlled trial evaluating treatment of primary dysmenorrhea. Two hundred and forty participants will be randomly divided into one of three groups: 1) the Dangguijagyag-san experimental group (EG) (n = 105), 2) the Gamisoyo-san active control group (ACG) (n = 30), and 3) the placebo control group (PCG) (n = 105). The interventions will be administered for two menstrual cycles, and the follow-up will be carried out for the following six menstrual cycles. The primary outcomes are difference in response rates between the EG and the ACG (non-inferiority comparison) and difference in changes from baseline in average pain intensity measured by the visual analogue scale between the EG and PCG (superiority comparison). The secondary outcomes are pain scores derived from pain assessment tools (verbal multidimensional scoring system, retrospective symptom scale, and short form McGill pain questionnaire), dosage of analgesics, pattern diagnosis questionnaires, and short form 36 health survey. Adverse events and vital signs will be checked at every visit, and laboratory tests will be performed for safety evaluation. DISCUSSION: The results of this clinical trial will offer evidence for the efficacy and safety of Dangguijagyag-san for primary dysmenorrhea. TRIAL REGISTRATION: Clinical Research Information Service of Korea: KCT0003005.

Incremental economic burden associated with exudative age-related macular degeneration: a population-based study.

BACKGROUND: The exudative age-related macular degeneration (AMD) causes considerable healthcare costs for patients and healthcare system, which are expected to grow as the population ages. The objective of this study was to assess the incremental economic burden of exudative AMD by comparing total healthcare costs between the exudative AMD group and non-AMD group to understand economic burden related to exudative AMD. METHODS: This retrospective cohort study used the National Health Insurance Service database including the entire Korean population. Exudative AMD group included individuals with at least one claim for ranibizumab and one claim using the registration code for exudative AMD (V201). Non-AMD group was defined as individuals without any claims regarding the diagnostic code of H35.3 or ranibizumab. The exudative AMD group and non-AMD group were matched using a propensity-score model. Incremental healthcare resource utilization and healthcare costs were measured during a one-year follow-up by employing econometric models: ordinary least squares (OLS) with log transformation and heteroscedastic retransformation; and generalized linear model (GLM) with a log link function and gamma distribution. RESULTS: A total of 7119 exudative AMD patients were matched to 7119 non-AMD patients. The number of outpatient visits was higher in the exudative AMD group (P-value < 0.0001), while the length of hospitalization was shorter in exudative AMD group (P-value < 0.0001). Exudative AMD patients had total costs 2.13 times (95%CI, 2.08-2.17) greater than non-AMD group using OLS, and total costs 4.06 times (95%CI, 3.82-4.31) greater than non-AMD group using GLM. Annual incremental total costs were estimated as $5519 (OLS) and $3699 (GLM). CONCLUSIONS: Exudative AMD was associated with significantly increased healthcare costs compared to the non-AMD group. Attention is needed to manage the socioeconomic burden of exudative AMD.

Effectiveness, safety, and economic evaluation of adjuvant moxibustion therapy for aromatase inhibitor-induced arthralgia of postmenopausal breast cancer stage I to III patients: Study protocol for a prospective, randomized, assessor-blind, usual-care controlled, parallel-group, pilot clinical trial.

INTRODUCTION: This study is a prospective, assessor-blinded, parallel-group, randomized controlled pilot trial to explore the effectiveness of 12-week adjuvant moxibustion therapy for arthralgia in menopausal females at stage I to III breast cancer on aromatase inhibitor (AI) administration, compared with those receiving usual care. METHODS/DESIGN: Forty-six menopausal female patients with breast cancer who completed cancer therapy will be randomly allocated to either adjuvant moxibustion or usual care groups with a 1:1 allocation ratio. The intervention group will undergo 24 sessions of adjuvant moxibustion therapy with usual care for 12 weeks, whereas the control group will receive only usual care during the same period. The usual care consists of acetaminophen administration on demand and self-directed exercise education to manage AI-related joint pain. The primary outcome is the mean change of the worst pain level according to the Brief Pain Inventory-Short Form between the initial visit and the endpoint. The mean changes in depression, fatigue, and quality of life will also be compared between groups. Safety and pharmacoeconomic evaluations will also be included. DISCUSSION: Continuous variables will be compared by an independent t test or Wilcoxon rank-sum test between the adjuvant moxibustion and usual care groups. Adverse events will be analyzed using the chi-square or Fisher exact test. The statistical analysis will be performed by a 2-tailed test at a significance level of .05.

Prevalence and incidence of Parkinson's disease and drug-induced parkinsonism in Korea.

BACKGROUND: Parkinson's disease (PD) and drug-induced parkinsonism (DIP) are the major diseases of parkinsonism. To better understand parkinsonism, we aimed to assess the prevalence and incidence of PD and DIP in Korea from 2012 to 2015. METHODS: We used the Health Insurance Review and Assessment Service database, which covers the entire population in Korea. We used claims during 2011-2015 to assess epidemiology of PD and DIP during 2012-2015. Retrospective cross-sectional study design was employed to assess prevalence, whereas retrospective cohort study design was used to determine incidence. Patients with at least one claim with ICD-10 G20 and who received antiparkinsonian drugs for at least 60 days were classified as having PD. We excluded patients with antiparkinsonian drugs that can be used for indications other than PD. Patients with at least one claim with ICD-10 G211 or G251 during the prescription period of drugs that are frequently related with DIP were classified as having DIP. Incident cases had a disease-free period of 1 year before diagnosis. To evaluate the significance of changes in the prevalence or incidence over time, Poisson regression was used to determine p for trend. RESULTS: The prevalence of PD increased from 156.9 per 100,000 persons in 2012 to 181.3 per 100,000 persons in 2015 (p for trend< 0.0001). The incidence of PD decreased steadily from 35.4 per 100,000 person-years in 2012 to 33.3 per 100,000 person-years in 2015 (p for trend< 0.0001). The prevalence of DIP increased from 7.3 per 100,000 persons in 2012 to 15.4 per 100,000 persons in 2015 (p for trend< 0.0001) and the incidence of DIP increased from 7.1 per 100,000 person-years in 2012 to 13.9 per 100,000 person-years in 2015 (p for trend< 0.0001). CONCLUSIONS: Our study suggests that the incidence of PD has gradually decreased whereas, the incidence of DIP increased from 2012 to 2015. Further studies are warranted to examine possible causes of increased DIP incidence in order to develop management strategy for parkinsonism.

Complementary medicine use and costs in patients with breast cancer who experienced treatment-related side effects: A cross-sectional survey in Korea.

OBJECTIVES: Population-based information on the costs of complementary medicine for treatment-related side effects in patients with breast cancer is scarce. We aimed to investigate the prevalence and expenditure on complementary medicine in patients with breast cancer who experienced treatment-related side effects. DESIGN AND SETTING: Two datasets were analyzed: 1) a 2017 survey on direct and indirect costs for treatment-related side effects, which was completed by 100 patients with stage 0-IV breast cancer, and 2) a Korean representative cross-sectional survey (Patient Survey 2014) that examined the prevalence of integrative medicine in 41 patients with breast cancer. MAIN OUTCOME MEASURES: The direct and indirect costs for treatment-related side effects. RESULTS: In the first dataset, the mean total direct medical cost for complementary medicine was US$1,584 and the mean indirect cost was US$6,988 per patient per year. Some patients (6%) visited non-medical institutions to utilize complementary medicine and additionally spent US$460 per patient per year. Approximately one-third of participants reported a substantial-to-heavy financial burden for using complementary medicine. However, only 17% of patients got information about complementary medicine through their physician. In the second dataset, 49% of patients with breast cancer who were discharged from Korean Medicine hospitals in Patient Survey 2014 data indicated that integrative medicine had been used. CONCLUSIONS: Despite some complementary medicine could be reimbursed by National Health Insurance in Korea, a considerable number of patients reported an economic burden associated with their use of complementary medicine. Strategies for guiding patients to receive evidence-based and cost-effective complementary medicine are needed.

Effectiveness, safety, and economic evaluation of topical application of a herbal ointment, Jaungo, for radiation dermatitis after breast conserving surgery in patients with breast cancer (GREEN study): Study protocol for a randomized controlled trial.

INTRODUCTION: This is a prospective, open-label, parallel-group, randomized controlled trial that evaluates the effectiveness and safety of adjuvant application of Jaungo (JUG) for radiation-induced dermatitis (RD) in breast cancer patients undergoing radiation therapy, in comparison with general supportive care (GSC). METHODS/DESIGN: Eighty female patients, who have been diagnosed with unilateral breast cancer, will be allocated to either the JUG or GSC group with an allocation ratio of 1:1 after breast conservation surgery, in the Kyung Hee University Korean Medicine Hospital, Seoul, Republic of Korea. Both the groups will be subjected to GSC, but only the JUG group participants will apply adjuvant JUG ointment on the irradiated skin for 6 weeks, twice a day. The primary outcome of this study is the assessment of incidence rate of RD using the Radiation Therapy Oncology Group (RTOG) for toxicity gradation of 2 or more. Maximum pain level, quality of life, adverse reactions, and pharmacoeconomic evaluations will also be included. DISCUSSION: The primary outcome will be statistically compared using the logrank test after estimating the survival curve using the Kaplan-Meier method. Continuous variables will be tested using independent t test or Mann-Whitney U test. The adverse events will be evaluated with Chi-square or Fisher exact test. All the data will be analyzed at a significance level of 0.05 (two-sided) with R software (The R Foundation). TRIAL REGISTRATION: CRIS (Clinical Research Information Service), KCT0003506, 14 February 2019.

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.

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.