Value-Based Pricing and Budget Impact Analysis for Multi-Indication Drugs: A Case Study of Immunotherapies.

We aimed to calculate the value-based price of each indication and compare the drug price and budget impact among value-based pricing (VBP) scenarios, using immunotherapy as a case. Atezolizumab, nivolumab, and pembrolizumab prices were estimated for VBP scenarios, namely indication value-based pricing (IBP), IBP with refund, and weighted-average pricing (WAP). To estimate the value-based price of each indication, cost-effectiveness analyses were conducted by setting the incremental cost-effectiveness ratio of the first reimbursed indication to the threshold. The budget impact for each scenario was compared with that of the pricing system in Korea (which has a 4.75% price reduction). The value-based prices of non-reimbursed indications were lower for atezolizumab and higher for nivolumab than those for the reimbursed indication. The drug price fluctuations were the largest in IBP, varying between 28.56-328.81% of the current list price. The net price of the non-reimbursed indications decreased from 0% to 71.44% in IBP with refund, and the budget impact was the lowest among VBPs. Although the fluctuation in the budget impact in WAP was smaller than IBP, higher drug prices were identified for low-value indications. In conclusion, IBP with refund is a viable method for multi-indication drugs, because it has minimal drug price and budget impact changes.

Reflux esophagitis in patients with chronic obstructive pulmonary disease.

ABSTRACT: The relationship between chronic obstructive pulmonary disease (COPD) and reflux esophagitis (RE) was controversial. We investigated the factors influencing RE development in patients with COPD and evaluated the association between RE and AECOPD.Patients with COPD who underwent esophagogastroduodenoscopy from January 2003 to December 2013 in St. Paul's Hospital, the Catholic University of Korea (Seoul, Korea) were enrolled retrospectively. The grade of RE was based on the Los Angeles classification and minimal change esophagitis. Body mass index, smoking history, medical history, AECOPD, pulmonary function test data, endoscopic findings, and comorbidities were reviewed.Of a total of 218 patients with COPD, 111 (50.9%) were diagnosed with RE. None of age, sex, smoking history, or the severity of airflow limitation was associated with RE. AECOPD was not related to either the presence or severity of RE. There was no significant correlation between RE grade by Los Angeles classification and severity of airflow limitation (P = .625). Those who had RE used theophylline (P = .003) and long-acting muscarinic antagonists (P = .026) significantly more often than did controls. The use of theophylline (OR 2.05; 95% CI, 1.16-3.65, P = .014) was associated with an increased incidence of RE.The use of theophylline might increase the risk of RE in COPD patients. RE may not be associated with airflow limitation or AECOPD.

Comparative Cost-Effectiveness of Tofacitinib With Continuing Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs for Active Rheumatoid Arthritis in South Korea.

INTRODUCTION: The objective of this study was to evaluate the cost-effectiveness of initiating treatment with tofacitinib and subsequently incorporating it into a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) treatment sequence and to compare the cost-effectiveness of this sequence with that of continuing csDMARDs alone in patients with active rheumatoid arthritis (RA). METHODS: A cohort-based Markov model was used to evaluate the cost-effectiveness of two tofacitinib treatment sequences compared with that of continuing the csDMARD treatment sequence over a lifetime. Of the two tofacitinib sequences, the first consisted of initial tofacitinib treatment followed by biologic DMARDs (bDMARDs) and the second consisted of csDMARD treatments followed by tofacitinib. A third treatment sequence, continuing the csDMARD treatment sequence before starting bDMARDs, was used as a comparator. Efficacy was assessed using the American College of Rheumatology (ACR) response rates (ACR 20, ACR 50, and ACR 70) after 6 months, which were converted to changes in the health assessment questionnaire-disability index (HAQ-DI) score. Utility was estimated by mapping from the HAQ-DI score, costs were analyzed from a Korean societal perspective, and outcomes were considered in terms of quality-adjusted life-years (QALYs). One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model. RESULTS: The incremental cost-effectiveness ratios over a lifetime for starting with tofacitinib and incorporating tofacitinib into the csDMARD treatment sequence versus continuing csDMARDs only were US$14,537 per QALY and US$7,086 per QALY, respectively. One-way sensitivity analysis and probabilistic sensitivity analysis confirmed the robustness of these results. CONCLUSION: Starting with tofacitinib and incorporating it into a csDMARDs treatment sequence is cost-effective compared to continuing csDMARDs alone in patients with RA.

The effect of automatic external defibrillator with a real-time feedback on quality of bystander cardiopulmonary resuscitation: A before-and-after simulation study.

High-quality bystander cardiopulmonary resuscitation (CPR) and early defibrillation in the community are important for survival in out-of hospital-cardiac-arrest, but maintaining the quality of CPR in bystanders is difficult. We aimed to determine the effect of an automated external defibrillator (AED) with real-time feedback on the quality of bystander CPR in a community setting. A before-and-after simulation study was designed. Trainees of basic life support education were recruited for the simulation experiment. Each team consisted of two bystanders with different roles (initial witness and CPR supporter). 82 teams performed simulation scenarios with the real-time feedback function of AED disabled initially, and then repeated it with feedback function enabled. Quality measures of chest compression depth and no-flow fraction were compared between each of the two simulation scenarios. CPR quality data from 82 teams were analysed. The mean percentage of chest compressions with adequate depth was significantly higher in simulations with real-time feedback (78.1% vs. 89.3%, p < 0.01). Similarly, no-flow fractions were lower in simulation scenarios with real-time feedback (32.0% vs. 30.3% p = 0.05). In a subgroup with the lowest percentage of adequate depth performance in the initial simulation without real-time feedback, a mean increase of 47.7% (95% CI 31.3-64.0) in the fraction of chest compressions with adequate depth was seen with real-time feedback. Use of an AED with real-time feedback improves the quality of bystander CPR in a simulated community setting. The positive effect of real-time feedback is greatest among people with a low level of CPR skill.

Differences in the risk of mood disorders in patients with asthma-COPD overlap and in patients with COPD alone: a nationwide population-based retrospective cohort study in Korea.

BACKGROUND: Although feelings of anxiety and depression are common in patients with chronic obstructive pulmonary disease (COPD), little is known about the estimates of their incidence in patients with asthma-COPD overlap (ACO), which has been described and acknowledged as a distinct clinical entity. We aimed to estimate the risk of depression and anxiety among patients with ACO and compare it with the risk among those with COPD alone in the general population. METHODS: We conducted a nationwide population-based retrospective cohort study using the Korean National Sample Cohort database between 1 January, 2002, and 31 December, 2013. Patients who were diagnosed with COPD (International Classification of Diseases, 10th revision [ICD-10] codes J42-J44) at least twice and prescribed COPD medications at least once between 2003 and 2011 were classified into two categories: patients who were diagnosed with asthma (ICD-10 codes J45-J46) more than twice and at least once prescribed asthma medications comprised the ACO group, and the remaining COPD patients comprised the COPD alone group. Patients who had been diagnosed with depression or anxiety within a year before the index date were excluded. We defined the outcome as time to first diagnosis with depression and anxiety. Matched Cox regression models were used to compare the risk of depression and anxiety among patients with ACO and patients with COPD alone after propensity score matching with a 1:1 ratio. RESULTS: After propensity score estimation and matching in a 1:1 ratio, the cohort used in the analysis included 15,644 patients. The risk of depression during the entire study period was higher for patients with ACO than for patients with COPD alone (adjusted hazard ratio, 1.10; 95% confidence interval, 1.03-1.18; P value = 0.0039), with an elevated risk in patients aged 40-64 years (1.21; 1.10-1.34; 0.0001) and in women (1.18; 1.07-1.29; 0.0005). The risk of anxiety was higher for patients with ACO than for patients with COPD alone (1.06; 1.01-1.12; 0.0272), with a higher risk in patients aged 40-64 years (1.08; 1.00-1.17; 0.0392); however, the risk was not significant when stratified by sex. CONCLUSIONS: This population-based study revealed a higher incidence of depression and anxiety in patients with ACO than in patients with COPD alone.

Estimation of Health Utilities Based on the Response to Treatment in Atopic Dermatitis: a Population-based Study.

PURPOSE: This study estimated utility weights based on the response to treatment for atopic dermatitis in the general population. METHODS: The Korean general population aged 20-60 years was stratified by using a random sampling method based on age and sex. Two hypothetical health states of atopic dermatitis were developed: response to treatment and no response to treatment. Health utility values were estimated by using time trade-off (TTO) based on a period of 10 years, TTO based on life expectancy, and EuroQol 5-Dimension (EQ-5D) including a visual analog scale (VAS). The mean utility value and 95% CI were derived, and comparisons of subgroups using the t test and ANOVA were performed. We conducted a multilevel analysis after controlling the sociodemographic variables to consider repeated measures. FINDINGS: A total of 155 participants were included in the survey. Their mean age was 39.7 years; 58.7% of participants were women. The mean health utility values for response and no response using TTO based on 10 years were 0.847 and 0.380, respectively. The estimated health utility values of response and no response were 0.865 and 0.476 using TTO based on life expectancy, and 0.814 and 0.279 using EQ-5D. For VAS, the response and no response were 0.744 and 0.322. After controlling the covariates, the important factors that affected utility values were response and no response to treatment (P < 0.001). IMPLICATIONS: This study showed that the utility weights of people with no response to atopic dermatitis treatment were lower compared with response from the general population. Health care providers should therefore consider symptom control as an important factor affecting the quality of life of those with atopic dermatitis.

Actinomyces meyeri Empyema: A Case Report and Review of the Literature.

Actinomyces meyeri is an uncommon cause of human actinomycosis. Here, we report a rare case of empyema caused by A. meyeri. A 49-year-old male presented with a history of 10 days of dyspnea and chest pain. A large amount of loculated pleural effusion was present on the right side and multiple lung nodules were documented on radiological studies. A chest tube was inserted and purulent pleural fluid was drained. A. meyeri was isolated in anaerobic cultures of the pleural fluid. The infection was alleviated in response to treatment with intravenous penicillin G (20 million IU daily) and oral amoxicillin (500 mg every 8 hours) for 4 months, demonstrating that short-term antibiotic treatment was effective.

Tenofovir disoproxil fumarate monotherapy for nucleos(t)ide analogue-naïve and nucleos(t)ide analogue-experienced chronic hepatitis B patients.

BACKGROUND/AIMS: This study investigated the antiviral effects of tenofovir disoproxil fumarate (TDF) monotherapy in nucleos(t)ide analogue (NA)-naive and NA-experienced chronic hepatitis B (CHB) patients. METHODS: CHB patients treated with TDF monotherapy (300 mg/day) for ≥12 weeks between December 2012 and July 2014 at a single center were retrospectively enrolled. Clinical, biochemical, and virological parameters were assessed every 12 weeks. RESULTS: In total, 136 patients (median age 49 years, 96 males, 94 HBeAg positive, and 51 with liver cirrhosis) were included. Sixty-two patients were nucleos(t)ide (NA)-naïve, and 74 patients had prior NA therapy (NA-exp group), and 31 patients in the NA-exp group had lamivudine (LAM)-resistance (LAM-R group). The baseline serum hepatitis B virus (HBV) DNA level was 4.9±2.3 log IU/mL (mean±SD), and was higher in the NA-naïve group than in the NA-exp and LAM-R groups (5.9±2.0 log IU/mL vs 3.9±2.0 log IU/mL vs 4.2±1.7 log IU/mL, P<0.01). The complete virological response (CVR) rate at week 48 in the NA-naïve group (71.4%) did not differ significantly from those in the NA-exp (71.3%) and LAM-R (66.1%) groups. In multivariate analysis, baseline serum HBV DNA was the only predictive factor for a CVR at week 48 (hazard ratio, 0.809; 95% confidence interval, 0.729-0.898), while the CVR rate did not differ with the NA experience. CONCLUSIONS: TDF monotherapy was effective for CHB treatment irrespective of prior NA treatment or LAM resistance. Baseline serum HBV DNA was the independent predictive factor for a CVR.

Experience of advance directives in a hospice center.

To protect patient autonomy when confronting death, the importance of advance directives (ADs) has recently became an issue and gradually accepted in Korea. However, in real practice, ADs were not completed by patients but their families in most cases. To analyze the current situation of performing ADs, we reviewed medical charts of 214 terminal cancer patients admitted to the hospice center from October 2012 to September 2013. Seventy-six (35.5%) patients completed ADs. All ADs were completed by patients themselves. The most common reason for not completing ADs was poor physical and/or mental condition. As a proxy, the majority of patients preferred their spouses (55.3%). Few patients wanted life sustaining treatment (1.3%), however palliative sedation was accepted in 89.5%. The median timing of ADs after admission was three (0-90) days, and duration of survival since ADs was 22 (1-340) days. In conclusion, approximately one third of terminal cancer patients completed ADs by themselves. Considering that patient's poor condition is the main reason for not completing ADs, earlier discussion regarding ADs is necessary to enhance patients' participation.

Dispatcher-assisted bystander cardiopulmonary resuscitation in a metropolitan city: a before-after population-based study.

BACKGROUND: The goal of this study was to determine the effects of dispatcher-assisted bystander cardiopulmonary resuscitation (DA-CPR) on outcomes of out-of-hospital cardiac arrest (OHCA). METHODS: All EMS in a metropolitan city with a population of 10 million are dispatched by a single, centralized, and physician-supervised center. Data on patients with adult OHCA with cardiac etiology were collected from the dispatch center registry and from EMS run sheets and hospital medical record review from 2009 to 2011. A standardized DA-CPR protocol (aligned with the 2010 AHA guidelines) we implemented as an intervention in January 2011. The end points were survival to discharge, good neurological outcome, and bystander CPR rate. Multivariate logistic analysis was used to compare between intervention group (2011) and historical control group (2009-2010). RESULTS: Of 8.144 eligible patients, bystander CPR was performed for the patients in 5.7% (148/2600) of cases in 2009, 6.7% (190/2857) in 2010, and 12.4% (334/2686) in 2011 (p<0.001). The survival to discharge rates was 7.1% (2009), 7.1% (2010), and 9.4% (2011) (p=0.001). Good neurological outcomes occurred in 2.1% (2009), 2.0% (2010), and 3.6% (2011) of cases (p<0.001). The adjusted ORs (95% CIs) for survival to discharge compared with 2009 were 1.33 (1.07-1.66) in 2011 and 1.12 (0.89-1.41) in 2010. The adjusted ORs (95% CIs) for good neurological outcomes were 1.67 (1.13-2.45) in 2011 and 1.13 (0.74-1.72) in 2010. CONCLUSIONS: An EMS intervention using the DA-CPR protocol was associated with a significant increase in bystander CPR and an improved survival and neurologic outcome after OHCA.

The prevalence and clinical characteristics of cancer among anemia patients treated at an outpatient clinic.

BACKGROUND: Anemia is the most common hematologic condition encountered in outpatient clinics. It is often overlooked because it is common among patients; however, anemia is one of the leading indicators of cancer. This study examined the prevalence and characteristics of cancer among anemia patients who visited an outpatient clinic. METHODS: The data were collected by reviewing the records of an outpatient clinic from January 2007 to December 2011. RESULTS: In total, 502 patients (52 males, 450 females) were diagnosed with anemia. Cancer prevalence among anemia patients was 5.57% (25.0%, men; 3.3%, women); further, the most frequently diagnosed cancer was colorectal cancer (22.5%), followed by advanced gastric cancer (16.1%), breast cancer (9.6%), myelodysplastic syndrome (9.6%), cervical cancer (6.4%), renal-cell carcinoma (6.4%), and thyroid cancer (6.4%). The prevalence of cancer was 4.1% in those aged 40-49 years, 4.2% in the subjects in their fifties, 8.0% in those in their sixties, 21.6% in those in their seventies, and 55.6% in those aged over 80 years. The cancer prevalence among iron deficiency anemia (IDA) patients was 6.18% (28.8%, men; 3.5%, women). The cancer prevalence in postmenopausal and premenopausal female IDA patients was 16.0% and 1.6%, respectively. CONCLUSION: Among anemia patients, male patients aged over 40 years and female patients aged over 60 years, along with postmenopausal female patients, were more likely to be diagnosed with cancer. Consequently, male IDA patients, and female patients aged over 60 years must be carefully evaluated for the possibility of malignancy.

Long-term treadmill exercise-induced neuroplasticity and associated memory recovery of streptozotocin-induced diabetic rats: an experimenter blind, randomized controlled study.

We investigated a long-term exercise-induced neuroplasticity and spatial memory recovery in 15 rats in a treadmill as follows: normal control rats (NC), streptozotocin (STZ)-induced diabetic control rats (DC), and STZ-induced diabetic rats exercising in a treadmill (DE). As per the DE group, the running exercise in a treadmill was administered for 30 minutes a day for 6 weeks. Neuronal immediate-early gene (IEG) expression (c-Fos) in the hippocampus and radial arm maze (RAM) tests were measured and revealed that the c-Fos levels in DE were significantly higher than those in NC and DC (p < 0.05). Behavioral data analysis indicated that spatial memory performance scores, obtained from the RAM test, were significantly different among the three groups (p < 0.05). The memory scores of NC and DE were higher than those of DC (p < 0.05). These findings suggest that exercising in the treadmill increased neuronal immediate-early gene expression associated with neuroplasticity, thereby improving spatial memory. This is the first experimental evidence in literature that supports the efficacy of exercise-induced neuroplasticity and spatial motor memory in diabetes care.