The prevalence, burden of disease, and healthcare utilization of patients with eosinophilic granulomatosis with polyangiitis in Japan: a retrospective, descriptive cohort claims database study.

OBJECTIVES: To estimate eosinophilic granulomatosis with polyangiitis (EGPA) prevalence and disease burden in patients with newly diagnosed EGPA in Japan. METHODS: This retrospective descriptive cohort study (GSK ID: 209751, HO-18-19652) used administrative claim data from patients (aged ≤74 years) with EGPA (study period: January 1, 2005-December 31, 2017), identified from their first ICD-10 code for EGPA (index). Data were examined during the 12 months before (baseline) and 12 months following the index date (follow-up). EGPA prevalence, respiratory comorbidities, all-cause healthcare utilization, and oral corticosteroid (OCS) use were assessed. RESULTS: EGPA prevalence (95%CI) increased from 4.2 (0,23.7)/million people (2005) to 38.0 (31.8,45.1)/million people (2017), was generally more common in females versus males, and increased with age. Of the 45 patients with newly diagnosed EGPA, 57.8% had acute bronchitis and 42.2% had upper respiratory tract infections during baseline. During follow-up, 60.0% of patients were hospitalized at least once and 77.8% used OCS (OCS dependent [≥80% of days]: 73.1%). CONCLUSIONS: In Japan, EGPA prevalence increased over time, was generally more common in females, and increased with patient age. EGPA burden was high; respiratory comorbidities were common, and most patients required hospitalization and OCS use. Our data suggest additional EGPA treatment options are needed.

Clinical characteristics, treatment patterns, disease burden, and persistence/adherence in patients with asthma initiating inhaled triple therapy: real-world evidence from Japan.

Objectives: To help optimize triple therapy use, treatment patterns and disease burden were investigated in patients in Japan with persistent asthma who initiated multi-inhaler triple therapy (inhaled corticosteroid/long-acting ß2-agonist/long-acting muscarinic antagonist; ICS/LABA/LAMA).Methods: This retrospective, observational cohort study using health insurance claims data included adults with persistent asthma who initiated triple therapy in 2016. Patients who were prescribed ICS/LABA in 2016 were included as an ICS/LABA-matched cohort. Patients were stratified into those with asthma only and those with asthma and chronic obstructive pulmonary disease (COPD) codes (asthma-COPD overlap [ACO]). Patient data from 1-year prior to 1 year post index date were analyzed.Results: For patients with asthma only in the triple therapy and ICS/LABA cohorts, baseline demographics were similar. A higher proportion of the triple-therapy cohort than the ICS/LABA cohort was receiving high-dose ICS at index (68.2% and 27.6%, respectively), and had experienced an exacerbation in the last year (64.0% and 29.4%, respectively). The proportion of patients with asthma only who developed any exacerbation was lower in the year following initiation of triple therapy compared with the year prior to initiation of triple therapy (45.8% vs 64.0%, respectively). For asthma only patients receiving triple therapy, the mean (standard deviation) proportion of days covered and medication possession ratio was 0.51 (0.36) and 0.86 (0.16), respectively. Similar trends were seen in patients with ACO in the triple-therapy and ICS/LABA cohorts.Conclusion: Evidence from this study may serve as a reference for the use of inhaled triple therapy for asthma.

Unpleasantness of Amplified Environmental Sound Used in Tinnitus Sound Therapy: A Preliminary Study of Clinical Assessment.

OBJECTIVES: In this study, our aim was to use environmental sounds amplified in the frequency region corresponding to the tinnitus frequency of individual patients and apply them as sound therapy in tinnitus retraining therapy (TRT). In this pilot study, we 1) investigated the unpleasantness of processed environmental sounds using the amplification, attenuation, and removal in different frequency regions; 2) compared the unpleasantness of processed sounds for older and younger groups of participants; and 3) determined the amplification level appropriate for a clinical test. MATERIALS AND METHODS: We processed the sound of a river with three types of modification (amplified, attenuated, and notched) at a one-octave width of seven central frequencies, in the range 250-8000 Hz. Amplified and attenuated sounds were processed with five positive gains (+6, +12, +15.6, +18, and +20 dB) and two negative gains (-6 and -12 dB). Twenty-three older participants and 23 younger participants rated the unpleasantness of sounds using a visual analog scale. RESULTS: We found that, in the older group, there was no difference in unpleasantness among the three modifications. Older participants rated the level of unpleasantness as lower than younger participants for processed sounds in the high-frequency region. There were no marked differences among the amplification levels in the group of older participants. CONCLUSION: Based on the results, we decided that our clinical study would target older patients who had a tinnitus frequency over 4000 Hz and would compare the effect of an amplified sound with a 20 dB gain at the frequency corresponding to individual tinnitus with notched sound.

The prevalence and disease burden of severe eosinophilic asthma in Japan.

Background: There are limited data on the prevalence and burden of severe eosinophilic asthma (SEA) both in Japan and globally. This study aimed to assess the prevalence and burden of SEA in Japan. Methods: This study was a retrospective, observational cohort analysis using health records or health insurance claims from patients with severe asthma treated at Kyoto University Hospital. The primary outcome was the prevalence of SEA, defined as a baseline blood eosinophil count ≥300 cells/µL. Secondary outcomes included frequency and risk factors of asthma exacerbations, and asthma-related healthcare resource utilization and costs. Results: Overall, 217 patients with severe asthma were included; 160 (74%) had eosinophil assessments. Of these, 97cases (61%), 54cases (34%), and 33cases (21%) had a blood eosinophil count ≥150, ≥300, and ≥500 cells/µL, respectively. Proportion of SEA was 34%. Blood eosinophil count was not associated with a significantly increased frequency of exacerbations. In the eosinophilic group, lower % forced expiratory volume in 1 second and higher fractional exhaled nitric oxide were predictive risk factors, while the existence of exacerbation history was a predictive risk factor for asthma exacerbations in the non-eosinophilic group. Severe asthma management cost was estimated as ¥357,958/patient-year, and asthma exacerbations as ¥26,124/patient-year. Conclusions: Approximately, one-third of patients with severe asthma in Japan have SEA. While risk factors for exacerbations differed between SEA and severe non-eosinophilic asthma, both subgroups were associated with substantial disease and economic burden. From subgroup analysis, blood eosinophil counts could be an important consideration in severe asthma management.

Impact of rotavirus vaccination on the burden of acute gastroenteritis in Nagoya city, Japan.

BACKGROUND: In Nagoya city, Japan, rotavirus (RV) vaccination has been available since 2011 with estimated coverage reaching 92% by 2015 after the introduction of a public subsidy in 2012. This study assessed the impact of vaccination on the RV gastroenteritis (RVGE) burden in children aged <5 years old (y) by comparing RVGE hospitalizations and outpatient visits during pre-vaccination (2007-2011), transition (2011-2012) and subsidization (2012-2016) periods. METHODS: All hospitalizations and outpatient visits in children aged <5 y from 2 administrative districts of Nagoya city were identified from the hospital-based electronic databases of 4 hospitals. RVGE cases were identified by diagnostic code and/or positive results of diagnostic kits. RESULTS: Compared to the pre-vaccination period, there was a decrease in RVGE hospitalizations for children <5 y from 5.59 per 1000 person-year (kPY) to 3.65/kPY in the subsidization period (i.e. 34.69%). In children <1 y, the incidence of RVGE hospitalizations decreased continuously from 6.62/kPY in the pre-vaccination period to 1.84/kPY in the subsidization period (i.e. 72.19%). The highest decrease was observed in the subsidization season i.e. when high coverage was reached: 69% and 75.57% in the 2013/2014 season for 2-3 y and 3-4 y, and 74.03% in the 2014/2015 season for 4-5 y, respectively. Proportion of RVGE outpatient visits decreased by 87.44% for children <1 y and 57.05% for <5 y from the pre-vaccination to the subsidization period. This decrease started the first year of subsidization for children <1 y, 1-2 y and 2-3 y (78.89%, 18.86% and 5.80%) and the second year (2013/2014 season) for children 3-4 y and 4-5 y (87.73% and 51.78%). CONCLUSIONS: Although yearly fluctuations have been observed, the introduction of vaccination significantly decreased pediatric RVGE hospitalizations and outpatient visits, especially in the age group eligible for vaccination. During the second and third year of subsidization, we observed a herd protection effect on other age groups <5 y who were not eligible for vaccination. Clinicaltrial.gov.registered#:NCT01733862.

Economic Burden of Herpes Zoster and Post-Herpetic Neuralgia in Adults 60 Years of Age or Older: Results from a Prospective, Physician Practice-Based Cohort Study in Kushiro, Japan.

BACKGROUND AND OBJECTIVE: Herpes zoster has a high incidence rate among people aged ≥ 60 years and can lead to serious complications such as post-herpetic neuralgia. There are currently no data on the economic burden of herpes zoster and post-herpetic neuralgia in Japan, and the objective of this study was to address this gap. METHODS: A total of 412 patients aged ≥ 60 years diagnosed with herpes zoster were recruited. Demographic, clinical, and healthcare resource utilization data on patients with herpes zoster or post-herpetic neuralgia collected via case report forms were used to estimate direct medical cost. Data obtained from a questionnaire survey among patients with herpes zoster/post-herpetic neuralgia were used to estimate transportation cost and productivity loss. RESULTS: The mean number of outpatient visits was 5.7. Prescription medications were the main cost driver accounting for 60% of the direct medical cost. The mean direct medical and total herpes zoster-related costs per patient were ¥43,925 and ¥57,112, respectively, and were higher in patients with post-herpetic neuralgia than in those with herpes zoster without complications. Direct medical cost represented 77%, productivity loss 19%, and transportation cost 4% of the total. CONCLUSIONS: This is the first study of the economic burden of herpes zoster and post-herpetic neuralgia in Japan and it demonstrated substantial direct medical cost as a result of the multiple outpatient visits and prescription medications required. These findings provide baseline data for possible future economic evaluations of new herpes zoster/post-herpetic neuralgia interventions. TRIAL REGISTRATION: This cost analysis is part of a prospective, physician practice-based cohort study conducted between June 2013 and February 2015 in Kushiro, Japan (Clinicaltrials.gov identifier NCT01873365, registered on 6 June, 2013).

Non-invasive assessment of liver fibrosis in patients after the Fontan operation.

BACKGROUND: This study analyzed the change in liver fibrosis markers after the Fontan operation and investigated their clinical usefulness as an index of congestive liver fibrosis. METHODS: The study enrolled 24 patients who underwent the Fontan operation between January 1994 and December 2008. We subdivided the postoperative period into four intervals and then compared the hepatological markers during each. Eighteen patients underwent postoperative cardiac catheterization and the correlation between hepatological markers and the inferior vena cava (IVC) pressure was analyzed. RESULTS: The mean age of the patients was 138.6 months and the mean interval between the Fontan operation and the examination was 97.8 months. Type IV collagen was extremely high in every interval (I, 286 ± 93; II, 265 ± 93; III, 305 ± 143; IV, 206 ± 70), while none of the laboratory variables changed significantly in each interval. A significant positive correlation was observed between type IV collagen and the IVC pressure, but no significant correlation with any other hepatological marker was detected. CONCLUSIONS: No specific parameter that reflects the progress in liver fibrosis was identified in this study. The possibility exists that type IV collagen reflects the degree of hepatic congestion.

Associations between hours worked, symptoms and health resource utilization among full-time male Japanese workers.

OBJECTIVES: To investigate the association between hours worked, symptoms experienced, and health resource utilization. METHODS: Data were collected from a nationally representative sample of households in Japan. We studied full-time male workers aged 18-65 yr who worked 100 h or more per month. First, we examined the association between hours worked and symptoms experienced. Second, we examined the association between hours worked and the type of health resource utilized, such as physician visits, over-the-counter (OTC) medication use, dietary supplement use, and complementary and alternative medicine (CAM) provider visits. We used a multivariable negative binominal model in each analysis. RESULTS: Of the 762 male workers, 598 reported experiencing symptoms at least once a month. We categorized participants based on the number of hours worked per month (h/mo): 100-200 h/mo, 201-250 h/mo, and over 250 h/mo. Compared with those working 201-250 h/mo, those working 100-200 h/mo had more frequent physician visits (rate ratio:1.67, 95% CI: 1.17 to 2.38) and those working over 250 h/mo had significantly lower rates of CAM provider visits and tended to use dietary supplements for symptoms. Participants who worked 201-250 h/mo used OTC medication most frequently. No significant association was observed between the number of hours worked and number of symptoms experienced. CONCLUSIONS: The more hours worked by full-time male workers, the more likely they were to use health resources that had a lower time requirement. Greater attention should be paid to patterns of health resource utilization among workers and their consequent influence on long-term health status.

[Cost effectiveness of hypertension treatment based on the measurement of ambulatory blood pressure].

In recent years soaring medical costs have become a major social problem in developed countries. Ambulatory blood pressure (ABP) measurements have a stronger predictive power for cardiovascular events than clinic blood pressure (CBP) measurements. Therefore the introduction of ABP measurement for the diagnosis and treatment of hypertension should lead to a decrease in medical expenditure. This study presents calculations of the cost saving and life years associated with changing from CBP to ABP measurement as diagnostic tool. We constructed a Markov model using data from the Ohasama study and a Japanese national database. Study population was 7.042 million individuals aged 40 years and above living in Japan. The introduction of ABP for hypertension would result in a reduction of about 9.48 trillion yen per 10 years. We conducted a sensitivity analysis and found that the introduction of ABP was associated with at least a cost reduction of 47500 billion yen. But it did not provide significant extension of average life years. However the introduction of ABP for hypertension treatment would be a very effective method in perspective of public health because it reduced about 59600 individuals of stroke and about 18900 individuals of death. Given its cost-effectiveness, extensive application of ABP measurement in clinical practice is expected.

Practical aspects of designing and conducting pharmacoeconomic studies in Japan.

The advent of simultaneous global clinical trials and drug registration strategies has increased the demand for global pharmacoeconomic strategies. Outcomes researchers in pharmaceutical companies are faced with the challenge of assessing at a strategic level what pharmacoeconomic data are most useful in Japan and when, and then deciding at a tactical level what type of study designs are feasible. This paper is written mainly for the benefit of researchers working outside of Japan in the pharmaceutical/medical device industry or academia who are interested in conducting research in Japan. We reviewed the existing pharmacoeconomic literature in Japan, and found that the number of studies per year has been steadily increasing. The majority of studies have been cost-effectiveness and cost-consequence analyses. Typical data sources available in Japan are somewhat limited compared with other Western countries. However, charge data can be easily accessed through the national uniform reimbursement fee system and these data are particularly relevant for pharmaceutical pricing negotiations with the Ministry of Health, Labor and Welfare (MHLW). The present use of pharmacoeconomic data by pharmaceutical companies is mainly for pricing negotiations but recent reforms make certain types of data useful for marketing strategies too. The demand for pharmacoeconomic data may increase because of upcoming MHLW pharmaceutical pricing and/or recent health insurance system reforms. Economic evaluation of medical technologies in Japan, though lagging behind North America, Australia and Europe, has the potential to rapidly gather momentum as increasing cost-escalation worries contribute to a growing interest in pharmacoeconomic data.