Assessing the economics of biologic and small molecule therapies for the treatment of moderate to severe ulcerative colitis in Japan: a cost per responder analysis of upadacitinib.

AIM: Patients with moderately to severely active ulcerative colitis have an increasing number of advanced therapy options including several biologics and Janus kinase inhibitors. Though data on efficacy and safety of these advanced therapies are available, less is known about the potential economic implications of their utilization in Japan. We evaluated the relative value of these advanced therapies in Japan using a locally developed cost per responder model. METHODS: A model was developed using relevant clinical endpoints and treatment costs to calculate cost per responder of all advanced therapies used for moderately to severely active ulcerative colitis treatment in Japan. Cost per responder was assessed in biologic-naïve and biologic-exposed populations, respectively. The model incorporated induction and maintenance therapy pathways as patients progressed through based on efficacy rates (clinical response, clinical remission and endoscopic improvement). Total costs for induction and maintenance included: drug acquisition, drug administration and serious adverse event management (as necessary) for responders, with additional rescue treatment cost only for non-responders. RESULTS: Upadacitinib showed lower cost per clinical response and cost per clinical remission across both biologic-naïve and biologic-exposed populations with only one exemption in cost per clinical remission in biologic-naïve population. In addition, upadacitinib demonstrated lower cost per endoscopic improvement in both populations. Janus kinase inhibitors outperformed with lower cost per responder than other mediations across all outcomes and patient populations with the exception of tofacitinib for clinical remission in biologic-exposed UC population. LIMITATIONS: Comparative data used in this analysis have been derived from network meta-analysis, not from direct comparison. CONCLUSIONS: The results of this cost per responder analysis suggest upadacitinib is a cost-effective option for the first- and second-line treatment of moderately to severely active ulcerative colitis in Japan.

Healthcare resource utilisation and economic burden of patients with adequate and inadequate responses to biological and targeted synthetic disease-modifying antirheumatic drugs for rheumatoid arthritis in Japan.

OBJECTIVE: To compare healthcare resource utilisation (HCRU) and direct costs between responders vs non-responders to advanced therapies for rheumatoid arthritis (RA). METHODS: Patients initiating ≥1 advanced therapy (Oct 2018-Sept 2019) with ≥1 RA claim (6-month pre-index period), ≥2 RA claims (any period), and ≥12 months follow-up were identified from the Medical Data Vision claims database. HCRU and all-cause and RA-related costs (direct medical, emergency department [ED], laboratory, and pharmacy) were compared between responders vs non-responders. Adjusted incidence rate ratios (IRRs) for HCRU or cost were calculated via multivariable analyses. RESULTS: Among 2,446 patients (non-responders [n=1,817]; responders [n=629]), non-responders had significantly longer hospitalisation days (IRR: 1.8 [95% CI: 1.2-2.6]), and significantly more ED visits (2.5 [1.5-4.2]) and prescriptions (1.1 [1.1-1.2]). Mean all-cause hospital/outpatient medical costs were significantly higher for non-responders (1.4 [1.3-1.6], ¥530,895 vs ¥357,009 [$;3,992 vs $;2,684] for responders; ¥173,886 [$;1,307] difference); RA-related medical costs showed a similar trend (¥351,306 vs ¥253,030 [$;2,641 vs $1,902]; ¥98,276 [$;739] difference). No differences between responders and non-responders were observed in mean all-cause and RA-related pharmacy costs. CONCLUSIONS: Non-responders to advanced therapies had greater HCRU and all-cause/RA-related direct costs as compared with responders, suggesting a need for more effective RA therapies to reduce the economic burden associated with non-response.

Number needed to treat and cost per responder of Janus kinase inhibitors approved for the treatment of moderate-to-severe rheumatoid arthritis in Japan.

OBJECTIVE: This study evaluated the effectiveness and cost-effectiveness of baricitinib, tofacitinib, and upadacitinib regimens, compared to conventional synthetic disease-modifying antirheumatic drug (csDMARD) alone, among Japanese patients with moderate-to-severe rheumatoid arthritis (RA) inadequately responsive to csDMARD, measured in terms of number needed to treat (NNT) and cost per responder (CPR). METHODS: Efficacy data were derived from two recent network meta-analyses among global and Japanese population. The cost perspective was that of the Japanese Health Service. Both NNT and CPR were based on disease activity score for 28 joints with C-reactive protein (DAS28-CRP) remission and American College of Rheumatology (ACR) 20/50/70 at 12 and 24 weeks. RESULTS: Over 12 weeks, the median NNT and the median CPR to achieve DAS28-CRP remission were 4.3 and JPY 1,799,696 [USD 16,361], respectively, for upadacitinib 15 mg + csDMARD. The equivalent results were 6.0 and JPY 2,691,684 [USD 24,470] for baricitinib 4 mg + csDMARD and 5.6 and JPY 2,507,152 [USD 22,792] for tofacitinib 5 mg + csDMARD. Similar rankings were observed at 24 weeks and for other outcomes. CONCLUSIONS: Upadacitinib 15 mg was associated with the lowest NNT and CPR among the three Janus kinase inhibitors used in treatment regimens for Japanese patients with moderate-to-severe RA inadequately responsive to csDMARD.

An economic evaluation of risankizumab versus other biologic treatments of moderate to severe plaque psoriasis in Japan.

OBJECTIVE: To evaluate the cost-effectiveness of risankizumab versus other biologic treatments (adalimumab, infliximab, ustekinumab, secukinumab, brodalumab, ixekizumab, and guselkumab) of moderate-to-severe psoriasis in Japan. METHODS: A Markov cohort-level model was constructed to estimate quality-adjusted life years (QALYs) and costs for each treatment over a lifetime horizon. The model simulated patients' transition through one line of active biologic therapy followed by best supportive care and death. Transition probabilities were informed by network meta-analyses of Psoriasis Activity and Severity Index responses and adverse event-related discontinuation in clinical trials, as well as published real-world evidence and national mortality rates. Costs were evaluated from the health system, societal, and patient out-of-pocket perspectives. RESULTS: Risankizumab was expected to provide 0.30-0.89 additional QALYs versus comparator biologics. Under the health system perspective, incremental cost-effectiveness ratios (ICERs) of risankizumab ranged from ¥2,545,812/QALY versus ustekinumab to ¥6,077,134/QALY versus adalimumab. Societal ICERs were lower, ranging from ¥921,770/QALY to ¥4,350,879/QALY. From the patient perspective, risankizumab was estimated to be cost-saving versus four comparators and was associated with ICERs of <¥500,000/QALY versus the remaining comparators. CONCLUSION: Risankizumab was associated with higher QALYs and, based on typical willingness-to-pay benchmarks (¥5-6.7 million/QALY), considered cost-effective versus other biologics for the treatment of psoriasis in Japan.

Cost-Effectiveness Analysis of Etanercept 25 mg Maintenance Therapy After Treatment With Etanercept 50 mg for Moderate Rheumatoid Arthritis in the PRESERVE Trial in Japan.

OBJECTIVES: To use Markov modeling to estimate the cost-effectiveness of treatment with etanercept 25 mg once weekly plus methotrexate (MTX) in Japanese patients with rheumatoid arthritis who had achieved remission or low disease activity with etanercept 50 mg once weekly plus MTX. METHODS: Effectiveness data were estimated based on results from a clinical trial (PRESERVE) in patients with rheumatoid arthritis who had achieved remission or low disease activity and who were then randomized to receive etanercept 25 mg plus MTX or placebo plus MTX. A Markov model was established and included flare rates of 21% and 62% in the etanercept 25 mg and placebo groups, respectively. EQ-5D was calculated using an ordinary least-squares model that included the health assessment questionnaire disability index and pain visual analog scale. Worsening of the health assessment questionnaire score over 1 year was estimated to be 0.047 for patients with flare, and when associated with radiographic progression it was estimated to increase by 0.006 and 0.025 in the etanercept 25 mg and placebo groups, respectively. A cycle length of 1 year was applied to calculate the cumulative cost and effectiveness for a 10-year time span. RESULTS: Compared with the placebo group, the quality-adjusted life-years for the etanercept 25 mg group was increased by 0.841. The incremental cost-effectiveness ratio was ¥6 173 772. CONCLUSION: These results suggest that maintenance treatment with etanercept 25 mg is cost-effective.

Evaluating the burden of pruritus due to atopic dermatitis in Japan by patient-reported outcomes.

AIMS: Although pruritus is a hallmark feature of atopic dermatitis, no study has investigated the associated impact of pruritus, due to atopic dermatitis in Japan. The study aimed to evaluate the real-life burden of atopic dermatitis by pruritus severity in adult Japanese patients. The primary objective was to assess the correlation between pruritus severity and work productivity and activity impairment. A secondary objective was to characterize the impact of pruritus on quality of life and to evaluate the burden of symptoms severity and frequency. MATERIALS AND METHODS: A cross-sectional internet-based survey was conducted. Eligible patients were currently employed and working adults with atopic dermatitis for at least 6 months. Stratification on pruritus severity assessed by the Worst Pruritus Numerical Rating Scale at the screening was performed to ensure that different severity groups are represented. Correlations were assessed using Spearman's rank-order correlation coefficient. Multivariate regression analyses were performed to assess the impact of pruritus severity on work productivity and quality of life. RESULTS: The study analyzed 370 patients. Pruritus severity significantly correlated with work impairment (Rho = 0.622, P value (H0: Rho > 0.5) <.001). A greater pruritus severity was associated with greater work productivity and activity impairment and a greater impact on quality of life, sleep, emotional state, and everyday activities. Patients with a greater pruritus severity carried a higher economic burden of treatment and were more often not satisfied with the received therapy. LIMITATIONS: All data were self-reported by patients via an online survey, which is associated with the risk of misclassification for diagnosis, recall bias, and limited participation of patients. CONCLUSIONS: The study provides evidence that pruritus is associated with the overall disease burden and impacts many important life aspects of patients with atopic dermatitis in Japan.

A Cost-Effectiveness Analysis of Glecaprevir/Pibrentasvir Versus Existing Direct-Acting Antivirals to Treat Chronic Hepatitis C in Japan.

INTRODUCTION: The objective of the study was to evaluate the cost-effectiveness of glecaprevir/pibrentasvir versus other direct-acting antivirals (DAAs) for treating chronic hepatitis C virus (HCV) infections in Japan. METHODS: We developed a health state transition model to capture the natural history of HCV. A cost-effectiveness analysis of DAAs from the perspective of a public healthcare payer in Japan with a lifetime horizon over annual cycles was performed. Treatment attributes, baseline demographics, transition probabilities, health-state utilities, and costs data were extracted from publications. Costs and outcomes were discounted at 2% per annum. In the base case we focused on genotype 1 (GT1) treatment-naïve patients without cirrhosis. The scenario analysis examined a pan-genotype treatment in GT1-3 (i.e., portfolio), treatment-naïve, and treatment-experienced patients. The portfolio cost-effectiveness of DAAs was derived by calculating a weighted average of patient segments defined by treatment history, cirrhosis status, and genotype. RESULTS: The base case results indicated that glecaprevir/pibrentasvir was dominant (i.e., generating higher quality-adjusted life years [QALYs] and lower lifetime costs) compared to all other DAAs. The predicted lifetime risk of hepatocellular carcinoma was 3.66% for glecaprevir/pibrentasvir and sofosbuvir/ledipasvir, 4.99% for elbasvir/grazoprevir, and 5.27% for daclatasvir/asunaprevir/beclabuvir. In scenario analysis the glecaprevir/pibrentasvir (GLE/PIB) portfolio dominated the sofosbuvir (SOF)-based portfolio (namely sofosbuvir/ledipasvir in GT1-2 and sofosbuvir + ribavirin in GT3). The base case probabilistic sensitivity analysis (PSA) showed that glecaprevir/pibrentasvir was cost-effective in 93.4% of the simulations for a willingness-to-pay/QALY range of Japanese yen (JPY) 1.6-20 million. The PSA for the portfolio scenario indicated that the GLE/PIB portfolio was cost-effective in 100% of simulations until the willingness-to-pay/QALY reached JPY 5.2 million; this proportion decreased to 69.4% at a willingness-to-pay/QALY of JPY 20 million. Results were also robust in deterministic sensitivity analyses. CONCLUSION: In GT1 treatment-naïve non-cirrhotic patients GLE/PIB was a cost-effective strategy compared to other DAAs. When a pan-genotypic framework was used, the GLE/PIB portfolio dominated the SOF-based portfolio.

Patient preference for biologic treatments of psoriasis in Japan.

Psoriasis is a chronic autoimmune disease affecting skin which may also manifest in nails and joints. Several biologic treatments have been approved in Japan for psoriasis. Each biologic has a different profile for efficacy and safety, including different dosing regimens and co-payment considerations which may complicate treatment decisions made by patients and physicians during short consultations. Elucidating patient preference is expected to contribute to shared decision-making between patients and physicians to optimize treatment satisfaction and outcomes. However, the number of studies investigating this in Japan is very limited. The study used a discrete choice experiment methodology to elicit patient preferences for hypothetical options in an experimental framework. Participants were asked to choose their preferred treatment option from two hypothetical choices, defined by different levels of six attributes (i.e. early onset of efficacy, long-term efficacy, sustained efficacy after drug withdrawal, dosing convenience, co-payment and risk of serious infection). The survey included 16 treatment choice scenarios and was completed by 395 participants. Across all participants, the attribute regarded as most important was sustained efficacy after drug withdrawal, followed by dosing convenience, co-payment, long-term efficacy, early onset of efficacy and risk of serious infection. The study found that patients prefer treatments which have durable efficacy and lower treatment burden characterized as fewer injection frequency and lower co-payment. These results may be helpful to understand patient preference for biologic treatments used for psoriasis in Japan and contribute to shared decision-making between patients and physicians to improve patient satisfaction and treatment outcomes.

Effects of chronic γ-irradiation on growth and sexual maturation of the Tohoku hynobiid salamander, Hynobius lichenatus.

There are still considerable gaps in knowledge regarding the biological effects of chronic ionising radiation exposure in amphibians. To fill these gaps, Tohoku hynobiid salamanders, Hynobius lichenatus (Amphibia, Caudata), were chronically irradiated with 137Cs γ-rays from embryonic to adult stages over 1954 days, and the effects on their growth and sexual maturation were examined under laboratory conditions. Irradiation at a dose rate of 33 µGy h-1 had some stimulatory effects on growth (body weight increase) of H. lichenatus, while growth was temporarily or permanently suppressed at 150 or 510 µGy h-1, respectively. On day 1802, secondary sexual characteristics (a tubercle at the anterior angle of the cloacal vent for males and ovisac development for females) were observed in 91% of the salamanders irradiated at 33 µGy h-1, and in a similar percentage of non-irradiated controls. At 150 and 510 µGy h-1, secondary sexual characteristics were not observed in any individuals. These results suggest that the derived consideration reference level (DCRL) of the International Commission on Radiological Protection (ICRP) for Reference Frog, i.e. 40-400 µGy h-1, is applicable for the protection of H. lichenatus, and that growth and sexual maturation of this salamander may not have been adversely affected even in the most severely contaminated area in Fukushima, where the highest dose rate to salamanders was estimated to be 50 µGy h-1. However, observations in the contaminated area are required to confirm this conclusion, considering the possible confounding factors which may make this salamander more sensitive to radiation in the natural environment than under laboratory conditions.

Corrigendum: Tofacitinib induction and maintenance therapy in East Asian patients with active ulcerative colitis: subgroup analyses from three phase 3 multinational studies.

[This corrects the article on p. 233 in vol. 16, PMID: 29743836.].

Tofacitinib induction and maintenance therapy in East Asian patients with active ulcerative colitis: subgroup analyses from three phase 3 multinational studies.

BACKGROUND/AIMS: Tofacitinib is an oral, small-molecule Janus kinase inhibitor being investigated for ulcerative colitis (UC). In OCTAVE Induction 1 and 2, patients with moderately to severely active UC received placebo or tofacitinib 10 mg twice daily (BID) for 8 weeks. Clinical responders in OCTAVE Induction were re-randomized to 52 weeks' therapy with placebo, tofacitinib 5 mg BID, or tofacitinib 10 mg BID. METHODS: We conducted post-hoc efficacy and safety analyses of East Asian patients in OCTAVE Induction 1 and 2 and OCTAVE Sustain. RESULTS: A total of 121 East Asian (Japan, Korea, and Taiwan) patients were randomized in OCTAVE Induction 1 and 2 (placebo, n=26; tofacitinib 10 mg BID, n=95), and 63 in OCTAVE Sustain (placebo, n=20; tofacitinib 5 mg BID, n=22; tofacitinib 10 mg BID, n=21). At week 8 of OCTAVE Induction 1 and 2, 18.9% of patients (18/95) achieved remission with tofacitinib 10 mg BID versus 3.8% (1/26) with placebo. In OCTAVE Sustain, the week 52 remission rates were 45.5% (10/22), 47.6% (10/21), and 15.0% (3/20) with 5 mg BID, 10 mg BID, and placebo, respectively. Adverse event rates were similar between groups in OCTAVE Induction and numerically higher with tofacitinib in OCTAVE Sustain. Serious adverse event rates were similar across groups in all studies. Infections were numerically more frequent with tofacitinib than placebo. Increases in serum lipid levels were observed with tofacitinib. CONCLUSIONS: In East Asian patients with UC, tofacitinib demonstrated numerically greater efficacy versus placebo as induction and maintenance therapy, with a safety profile consistent with the global study population. ClinicalTrials.gov: NCT01465763; NCT01458951; NCT01458574.

Assessment of Instructions on Protection Against Food Contaminated with Radiocesium in Japan in 2011.

The Japan Ministry of Health, Labour and Welfare (MHLW) has published instructions for radiological protection against food after the Fukushima Daiichi nuclear power plant accident in 2011. Following the instructions, the export and consumption of food items identified as being contaminated were restricted for a certain period. We assessed the validity of the imposed restriction periods for two representative vegetables (spinach and cabbage) grown in Fukushima Prefecture from two perspectives: effectiveness for reducing dietary dose and economic efficiency. To assess effectiveness, we estimated the restriction period required to maintain consumers' dose below the guidance dose levels. To assess economic efficiency, we estimated the restriction period that maximizes the net benefit to taxpayers. All estimated restriction periods were shorter than the actual restriction periods imposed on spinach and cabbage from Fukushima in 2011, which indicates that the food restriction effectively maintained consumers' dietary dose below the guidance dose level, but in an economically inefficient manner. We also evaluated the response of the restriction period to the sample size for each weekly food safety test and the instructions for when to remove the restriction. Stringent MHLW instructions seemed to sufficiently reduce consumers' health risk even when the sample size for the weekly food safety test was small, but tended to increase the economic cost to taxpayers.

Tofacitinib for the treatment of moderate to severe chronic plaque psoriasis in Japanese patients: Subgroup analyses from a randomized, placebo-controlled phase 3 trial.

Tofacitinib is an oral Janus kinase inhibitor. These post-hoc analyses assessed tofacitinib efficacy and safety in Japanese patients with psoriasis enrolled in a 52-week global phase 3 study. Patients received tofacitinib 5 mg, tofacitinib 10 mg or placebo twice daily (b.i.d.); placebo-treated patients advanced to tofacitinib at week 16. Primary efficacy end-points were the proportions of patients with 75% or more reduction from baseline Psoriasis Area and Severity Index (PASI-75) and Physician's Global Assessment (PGA) of "clear" or "almost clear" (PGA response) at week 16. Other end-points included: Itch Severity Item (ISI), Dermatology Life Quality Index (DLQI) score and Nail Psoriasis Severity Index (NAPSI). Adverse events (AEs) were recorded throughout the study. Overall, 58 Japanese patients were included in this analysis (tofacitinib 5 mg b.i.d., n = 22; 10 mg b.i.d., n = 24; placebo, n = 12); 29 completed the study. At week 16, significantly more patients receiving tofacitinib 5 and 10 mg b.i.d. versus placebo achieved PASI-75 (50% and 75% vs 0%, P < 0.01) and PGA response (59% and 75% vs 0%, P < 0.001). Substantial improvements in ISI, DLQI and NAPSI score were observed with both tofacitinib doses. Over 52 weeks, similar rates of AEs were reported across treatment groups; one serious AE occurred with tofacitinib 10 mg b.i.d. Herpes zoster occurred in three patients receiving tofacitinib 10 mg b.i.d. No deaths, serious infections, malignancies or gastrointestinal perforations were reported. Results were generally consistent with global analysis, suggesting sustained efficacy and a manageable safety profile, with increased herpes zoster incidence, of tofacitinib in Japanese patients with psoriasis.

Chromosomal Aberrations in Large Japanese Field Mice (Apodemus speciosus) Captured near Fukushima Dai-ichi Nuclear Power Plant.

Since the Fukushima Dai-ichi Nuclear Power Plant accident, radiation effects on nonhuman biota in the contaminated areas have been a major concern. Here, we analyzed the frequencies of chromosomal aberrations (translocations and dicentrics) in the splenic lymphocytes of large Japanese field mice (Apodemus speciosus) inhabiting Fukushima Prefecture. A. speciosus chromosomes 1, 2, and 5 were flow-sorted in order to develop A. speciosus chromosome-specific painting probes, and FISH (fluorescence in situ hybridization) was performed using these painting probes to detect the translocations and dicentrics. The average frequency of the translocations and dicentrics per cell in the heavily contaminated area was significantly higher than the frequencies in the case of the noncontaminated control area and the slightly and moderately contaminated areas, and this aberration frequency in individual mice tended to roughly increase with the estimated dose rates and accumulated doses. In all four sampling areas, the proportion of aberrations occurring in chromosome 2 was approximately >3 times higher than that in chromosomes 1 and 5, which suggests that A. speciosus chromosome 2 harbors a fragile site that is highly sensitive to chromosome breaks induced by cellular stress such as DNA replication. The elevated frequency of chromosomal aberrations in A. speciosus potentially resulting from the presence of a fragile site in chromosome 2 might make it challenging to observe the mild effect of chronic low-dose-rate irradiation on the induction of chromosomal aberrations in A. speciosus inhabiting the contaminated areas of Fukushima.

Radiocaesium contamination and dose rate estimation of terrestrial and freshwater wildlife in the exclusion zone of the Fukushima Dai-ichi Nuclear Power Plant accident.

To characterise the radioactive contamination of terrestrial and freshwater wildlife caused by the Fukushima Dai-ichi Nuclear Power Plant accident, biological samples, namely, fungi, mosses, plants, amphibians, reptiles, insects, molluscs, and earthworms, were collected mainly from the forests of the exclusion zone in the Fukushima Prefecture from 2011 to 2012. Caesium-134 and 137Cs were detected by gamma spectrometry in almost all the samples. Fungi, ferns, and mosses accumulated high amounts of radiocaesium, as they did in Chernobyl, with 134Cs + 137Cs activity concentrations of 104-106 Bq kg-1 fresh mass (FM). Earthworms, amphibians, and the soft tissue of the garden snail Acusta despecta sieboldiana, also had levels as high as 104-105 Bq kg-1 FM of 134Cs + 137Cs. Most of the estimated total (internal + external) dose rates to herbaceous plants, amphibians, insects, and earthworms were below the corresponding derived consideration reference levels (DCRLs) recommended by the ICRP. This suggests that, in most cases, there was little chance of deleterious effects of ionising radiation on these organisms in the exclusion zone for the first year after the accident, though the dose rates were underestimated mainly due to the lack of consideration of short-lived radionuclides.

Biological measures to minimize the risk of radiotherapy-associated second cancer: A research perspective.

Purpose Second cancers are among the most serious sequelae for cancer survivors who receive radiotherapy. This article aims to review current knowledge regarding how the risk of radiotherapy-associated second cancer can be minimized by biological measures and to discuss relevant research needs. Results The risk of second cancer can be reduced not only by physical measures to decrease the radiation dose to normal tissues but also by biological means that interfere with the critical determinants of radiation-induced carcinogenesis. Requirements for such biological means include the targeting of tumor types relevant to radiotherapy-associated risk, concrete safety and efficacy evidence and feasibility and minimal invasiveness. Mechanistic insights into the process of radiation carcinogenesis provide rational approaches to minimize the risk. Five mechanism-based strategies are proposed herein based on the current state of knowledge. Epidemiological studies on the joint effects of radiation and lifestyle or other factors can provide evidence for factors that modify radiation-associated risks if deliberately controlled. Conclusions Mechanistic and epidemiological evidence indicates that it is possible to develop interventional measures to minimize the second cancer risk associated with radiotherapy. Research is needed regarding the critical determinants of radiation-induced carcinogenesis available for intervention and joint effects of radiation and controllable factors.

The association between osteoporosis and patient outcomes in Japan.

Objective To quantify the burden of osteoporosis and examine the interplay between osteoporosis and various comorbidities as it relates to patient outcomes. Methods Data from the 2011 Japan National Health and Wellness Survey (NHWS; n = 30 000), an internet health survey fielded to a nationally representative sample of the Japanese population were used. Only women between the ages of 50-90 years were included in the analyses (n = 6950). Results Compared with matched controls (n = 404), patients with osteoporosis (n = 404) had lower MCS scores (48.94 vs 51.63), PCS scores (45.57 vs 49.12) (all p < 0.05). The presence of osteoporosis was associated with worse patient outcomes among those with hypertension, high cholesterol, and insomnia, among other conditions. Conclusions The results suggest a significant quality-of-life and economic burden for patients with osteoporosis in Japan. Moreover, in a complex co-morbid environment, the presence of osteoporosis contributes more to patient outcomes than other chronic conditions.

Morphological defects in native Japanese fir trees around the Fukushima Daiichi Nuclear Power Plant.

After the accident at the Fukushima Daiichi Nuclear Power Plant (F1NPP) in March 2011, much attention has been paid to the biological consequences of the released radionuclides into the surrounding area. We investigated the morphological changes in Japanese fir, a Japanese endemic native conifer, at locations near the F1NPP. Japanese fir populations near the F1NPP showed a significantly increased number of morphological defects, involving deletions of leader shoots of the main axis, compared to a control population far from the F1NPP. The frequency of the defects corresponded to the radioactive contamination levels of the observation sites. A significant increase in deletions of the leader shoots became apparent in those that elongated after the spring of 2012, a year after the accident. These results suggest possibility that the contamination by radionuclides contributed to the morphological defects in Japanese fir trees in the area near the F1NPP.

Chromosomal Aberrations in Wild Mice Captured in Areas Differentially Contaminated by the Fukushima Dai-Ichi Nuclear Power Plant Accident.

Following the Fukushima Dai-ichi Nuclear Power Plant accident, radiation effects on nonhuman biota in the contaminated areas have been a great concern. The induction of chromosomal aberrations in splenic lymphocytes of small Japanese field mice (Apodemus argenteus) and house mice (Mus musculus) inhabiting Fukushima Prefecture was investigated. In mice inhabiting the slightly contaminated area, the average frequency of dicentric chromosomes was similar to that seen in mice inhabiting a noncontaminated control area. In contrast, mice inhabiting the moderately and heavily contaminated areas showed a significant increase in the average frequencies of dicentric chromosomes. Total absorbed dose rate was estimated to be approximately 1 mGy d(-1) and 3 mGy d(-1) in the moderately and heavily contaminated areas, respectively. Chromosomal aberrations tended to roughly increase with dose rate. Although theoretically, the frequency of chromosomal aberrations was considered proportional to the absorbed dose, chromosomal aberrations in old mice (estimated median age 300 days) did not increase with radiation dose at the same rate as that observed in young mice (estimated median age 105 days).