A Retrospective Database Study of Gastrointestinal Events and Medical Costs Associated with Nonsteroidal Anti-Inflammatory Drugs in Japanese Patients of Working Age with Osteoarthritis and Chronic Low Back Pain.

CONTEXT: The real-world burden of gastrointestinal (GI) events associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in Japanese patients with osteoarthritis (OA) and/or chronic low back pain (CLBP) remains unreported. OBJECTIVE: To assess the incidence and economic burden of NSAID-induced GI events by using data from large-scale real-world databases. METHODS: We used the Japanese Medical Data Center database to retrospectively evaluate anonymized claims data of medical insurance beneficiaries employed by middle- to large-size Japanese companies who were prescribed NSAIDs for OA and/or CLBP between 2009 and 2018. RESULTS: Overall, 180,371 patients were included in the analysis, of whom 32.9% had OA, 53.8% had CLBP, and 13.4% had both OA and CLBP. NSAIDs were administered as first-line analgesics to 161,152 (89.3%) of the patients in the sample, in oral form to 90.3% and as topical patches to 80.4%. A total of 65.1% used combined oral/topical patches. Of the 21.0% of patients consistently using NSAIDs (percentage of days supplied ≥70%), 54.5% received patches. A total of 51.5% patients used NSAIDs for >1 to ≤6 months. The incidence of GI events was 9.97 per 10,000 person-years (95% confidence interval: 8.92-11.03). The risk of developing GI events was high in elderly patients and patients with comorbidities and remained similar for patients receiving oral vs. topical NSAIDs. Longer treatment duration and consistent NSAID use increased the risk of GI events. The cost (median [interquartile range]) of medications (n = 327) was US$ 80.70 ($14.10, $201.40), that of hospitalization (n = 33) was US$ 2,035.50 ($1,517.80, $2,431.90), and that of endoscopic surgery (n = 52) was US$ 418.20 ($418.20, $418.20). CONCLUSION: NSAID-associated GI toxicity imposes a significant health and economic burden on patients with OA and/or CLBP, irrespective of whether oral or topical NSAIDs are used.

Molecular and biochemical characteristics of inulosucrase InuBK from Alkalihalobacillus krulwichiae JCM 11691.

Information about the inulosucrase of nonlactic acid bacteria is scarce. We found a gene encoding inulosucrase (inuBK) in the genome of the Gram-positive bacterium Alkalihalobacillus krulwichiae JCM 11691. The inuBK open reading frame encoded a protein comprising 456 amino acids. We expressed His-tagged InuBK in culture medium using a Brevibacillus system. The optimal pH and temperature of purified InuBK were 7.0-9.0 and 50-55 °C, respectively. The findings of high-performance anion-exchange chromatography, nuclear magnetic resonance spectroscopy, and high-performance size-exclusion chromatography with multiangle laser light scattering showed that the polysaccharide produced by InuBK was an inulin with a molecular weight of 3806, a polydispersity index (PI) of 1.047, and fructosyl chain lengths with 3-27 degrees of polymerization. The size of InuBK was smaller than commercial inulins, and the PI of the inulin that it produced was lower.

UPA-seq: prediction of functional lncRNAs using differential sensitivity to UV crosslinking.

While a large number of long noncoding RNAs (lncRNAs) are transcribed from the genome of higher eukaryotes, systematic prediction of their functionality has been challenging due to the lack of conserved sequence motifs or structures. Assuming that some lncRNAs function as large ribonucleoprotein complexes and thus are easily crosslinked to proteins upon UV irradiation, we performed RNA-seq analyses of RNAs recovered from the aqueous phase after UV irradiation and phenol-chloroform extraction (UPA-seq). As expected, the numbers of UPA-seq reads mapped to known functional lncRNAs were remarkably reduced upon UV irradiation. Comparison with ENCODE eCLIP data revealed that lncRNAs that exhibited greater decreases upon UV irradiation preferentially associated with proteins containing prion-like domains (PrLDs). Fluorescent in situ hybridization (FISH) analyses revealed the nuclear localization of novel functional lncRNA candidates, including one that accumulated at the site of transcription. We propose that UPA-seq provides a useful tool for the selection of lncRNA candidates to be analyzed in depth in subsequent functional studies.

The societal burden of chronic pain in Japan: an internet survey.

OBJECTIVES: Chronic pain affects between 10-20 % of the population of Japan and several specific types of chronic pain have been found to be associated with worse health outcomes. The aim of the current study was to investigate the economic burden of chronic pain as well as the health status among Japanese patients. METHODS: Data from the Japan National Health and Wellness Survey (NHWS), a cross-sectional health survey of adults, were used (N = 30,000). Respondents with chronic pain (N = 785) were compared with respondents without chronic pain (N = 29,215) with respect to health status (using the SF-12v2), work productivity and activity impairment (WPAI questionnaire), and healthcare resource use using regression modeling, controlling for demographic and health history covariates. Indirect costs were calculated using wage rates and the human capital method. RESULTS: Back pain (72.10 %) and shoulder pain/stiffness (54.90 %) were the most prevalent pain types. Adjusting for demographic and health history differences, respondents with chronic pain reported lower health status [mental component summary (MCS): 44.26 vs. 51.14; physical component summary (PCS): 44.23 vs. 47.48; both p < 0.05], greater absenteeism (4.74 vs. 2.74 %), presenteeism (30.19 vs. 15.19 %), overall work impairment (31.70 vs. 16.82 %), indirect costs (¥ 1488,385 vs. ¥ 804,634), activity impairment (33.45 vs. 17.25 %), physician visits (9.31 vs. 4.08), emergency room (ER) visits (0.19 vs. 0.08), and hospitalizations (0.71 vs. 0.34) (all p < 0.05). Nearly 60 % of respondents with chronic pain were untreated. The mean level of pain severity in the last week was 5.26 (using a 0-11 scale); being female, being elderly, having low income, and having multiple pain types were significantly associated with greater pain severity (all p < 0.05). Regular exercise was associated with lower pain severity (p < 0.05). CONCLUSIONS: The results suggest that chronic pain has a significant association in an individual's health status, work productivity, daily activity impairment, healthcare resource use, and economic burden in Japan. Along with low treatment rates, a multidisciplinary approach may lead to an improved quality of life and reduce the economic burden among patients with chronic pain in Japan.

Medial ridge elevation wedge trochleoplasty for medial patellar luxation: a clinical study in 5 dogs.

OBJECTIVE: To develop a surgical technique to elevate the medial trochlear ridge for surgical correction of medial patellar luxation, and to evaluate clinical outcome. STUDY DESIGN: Case series. ANIMALS: Dogs (n = 5) with Grade 3 medial patellar luxation. METHODS: An asymmetrical wedge was removed from the trochlear groove, rotated 180°, and placed in the recess to create an elevated medial trochlear ridge. Postoperative radiography, CT scan, and subjective evaluation of clinical outcomes were performed. RESULTS: Surgical procedure and postoperative recovery were uncomplicated. There was no recurrence of spontaneous luxation and subjectively, gait improved in all dogs. Postoperative radiographs and CT images confirmed the elevated medial trochlear ridge, a significantly increased groove depth/patellar thickness ratio (P < .01), and seating of the patella in the trochlear groove. CONCLUSION: Elevating the medial trochlear ridge, instead of deepening the groove, can be considered a viable surgical technique to stabilize luxating patellae.

Safety and effectiveness responses to etanercept for rheumatoid arthritis in Japan: a sub-analysis of a post-marketing surveillance study focusing on the duration of rheumatoid arthritis.

The aim is to investigate the relationship of duration of rheumatoid arthritis (RA) with safety and effectiveness of etanercept (ETN) in Japan. Post-marketing surveillance data for 7,099 patients treated with ETN were analyzed. Baseline characteristics, treatment effectiveness, incidence of adverse events (AEs), and serious AEs (SAEs) in relation to duration of RA were studied. At baseline, patients with RA for longer duration were older, weighed less, had more comorbidities, allergies, and corticosteroid use, but smoked less and had less morning stiffness. By 2-5 years with RA, more than half of the patients had advanced to Steinbrocker radiographic stage III or IV. Methotrexate (MTX) was the most commonly used pre-treatment disease-modifying antirheumatic drug; however, concomitant MTX use and its dose were lower among patients with longer duration of RA. Remission rates (26.6%) were greatest among patients having RA for <2 years. Less AEs and SAEs were observed among patients with shorter duration of RA. These results suggest that RA treatment in Japan in the era pre-biologics may not have been adequate to control disease activity and prevent joint destruction. Patients with shorter duration of RA may have better physical status which allows the opportunity to treat more intensively putting a higher percentage of patients in remission and possibly decreasing exposure to SAEs.

Safety and effectiveness of switching from infliximab to etanercept in patients with rheumatoid arthritis: results from a large Japanese postmarketing surveillance study.

Finding an effective treatment strategy for rheumatoid arthritis (RA) patients who have not benefited from previous tumor necrosis factor-α antagonist treatment is important for minimizing RA disease activity and improving patient outcomes. The aim of this study was to compare the safety and effectiveness of etanercept in patients with and without infliximab (IFX) treatment experience. Patients (n = 7,099) from a large postmarketing observational study of etanercept use in Japan were divided into 2 cohorts based on previous IFX use (pre-IFX and non-IFX). Baseline characteristics were assessed in each cohort. Adverse events (AEs) and European League Against Rheumatism (EULAR) responses were monitored every 4 weeks for 24 weeks. At baseline, pre-IFX patients were younger and had fewer comorbidities and a shorter RA duration than non-IFX patients. During the study, pre-IFX patients received concomitant methotrexate more often than non-IFX patients. The incidence of AEs and serious AEs were significantly lower in pre-IFX patients, as was the percentage of patients who discontinued treatment. Both cohorts had significant improvement (P < 0.001) in EULAR responses at the end of the treatment period. This study demonstrated that etanercept was effective and well tolerated in active RA patients with and without prior IFX treatment.

Cost-Effectiveness Analysis of the Treatment Strategies with or without Opioid Medications in Surgery-Eligible Patients with Osteoarthritis in Japan.

AIM: The aim of this study was to evaluate the cost effectiveness of treatment strategies without opioid medications (non-opioid treatment strategy) versus strategies with opioid medications (opioid treatment strategy) among surgery-eligible patients with osteoarthritis (OA) of the knee or hip in Japan. MATERIALS AND METHODS: We built a Markov cohort model to evaluate outcomes for the treatment strategies in surgery-eligible patients aged ≥ 65 years with OA of the knee or hip in Japan. The opioid treatment strategy as an intervention includes a health state with opioid medication in the treatment pathway. On the other hand, for the non-opioid treatment strategy, there is no health state with opioid medication. A targeted literature review and database analysis were conducted to identify and define the values of the variables included in the model. The time horizon was set to 30 years, and a 2% discount was applied for cost and quality-adjusted life-years (QALYs). Sensitivity analysis and scenario analysis were performed in the model. The outcomes were QALYs and the incremental cost-effectiveness ratio (ICER). RESULTS: In the base-case analysis, the non-opioid treatment strategy was dominant over the opioid treatment strategy and associated with an incremental cost and QALYs of - 53,878 JPY (- 499 USD) and 0.03 QALYs, respectively, in patients with knee OA, and - 54,129 JPY (- 502 USD) and 0.02 QALYs, respectively, in patients with hip OA. One-way sensitivity analysis showed the ICER was most sensitive to the QALY for opioid monotherapy. Probabilistic sensitivity analyses showed a high degree of uncertainty associated with the results. LIMITATIONS: Study limitations included assumptions related to transition probabilities of the health states, and a lack of Japanese-specific data for transition probabilities, incidence of adverse events and utility values. CONCLUSIONS: This study suggests that the non-opioid treatment strategy is cost effective compared with the opioid treatment strategy in the management of surgery-eligible patients with OA of the knee or hip. However, this final conclusion may not be accurate as the methodology is heavily reliant on assumptions.

Efficacy, General Safety, and Joint Safety of Tanezumab in Japanese Patients with Osteoarthritis: Subgroup Analyses from Two Randomized, Phase 3 Studies.

INTRODUCTION: Tanezumab is a monoclonal antibody against nerve growth factor that is under investigation for the treatment of osteoarthritis (OA) pain. We conducted subgroup analyses of two randomized phase 3 studies to summarize efficacy, general safety, and adjudicated joint safety of tanezumab in Japanese patients with moderate-to-severe OA. METHODS: In Study 1 (NCT02528188), patients received subcutaneous tanezumab 2.5 mg or 5 mg every 8 weeks or daily oral nonsteroidal anti-inflammatory drugs (NSAID) for 56 weeks. The co-primary efficacy endpoints were change from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain subscale score and WOMAC Physical Function subscale score at Week 16 (overall study and Japan-specific endpoints) as well as Patient Global Assessment (PGA)-OA score at Week 16 (overall study endpoint only). In Study 2 (NCT02709486), patients received subcutaneous tanezumab 2.5 mg, 5 mg, or placebo every 8 weeks for 24 weeks. Safety monitoring included adjudicated composite joint safety endpoint (CJSE) including rapidly progressive osteoarthritis type 1 (RPOA1), RPOA2, primary osteonecrosis, pathological fracture, or subchondral insufficiency fracture. RESULTS: For Study 1, Japanese patients (n = 200) treated with tanezumab 2.5 mg and 5 mg showed numerically greater improvements in WOMAC Pain, WOMAC Physical Function, and PGA-OA scores versus NSAID at Week 16. Incidences of treatment-emergent adverse events were generally similar between tanezumab 2.5 mg, 5 mg, and NSAID groups. In the integrated safety analysis (Studies 1 + 2; n = 306), ten patients were adjudicated to have a component of CJSE: RPOA1 [tanezumab 2.5 mg (n = 2), tanezumab 5 mg (n = 5)], RPOA2 [tanezumab 2.5 mg (n = 1), tanezumab 5 mg (n = 1)], or primary osteonecrosis [tanezumab 2.5 mg (n = 1)]. Time-adjusted adjudicated rates of RPOA1 and RPOA2 were higher with tanezumab than NSAID or placebo and increased with dose of tanezumab. CONCLUSION: Observations from the Japanese subgroup were generally consistent with the overall study populations.

Postmarketing surveillance of safety and effectiveness of etanercept in Japanese patients with rheumatoid arthritis.

Our aim was to evaluate real-world safety and effectiveness in a 6-month postmarketing surveillance study covering all Japanese patients with rheumatoid arthritis (RA) who received etanercept during a 2-year period. Data for 13,894 patients (1334 sites) enrolled between March 2005 and April 2007 were collected. Adverse events (AEs) and serious adverse events (SAEs) were reported in 4336 (31.2%) and 857 (6.2%) patients, respectively. The most frequent AEs were injection site reactions (n = 610, 4.4%) and rash (n = 339, 2.4%), whereas pneumonia (n = 116, 0.8%) and interstitial lung disease (n = 77, 0.6%) were the most frequent SAEs. Significant improvement in the proportion of patients with a good European League Against Rheumatism (EULAR) response was observed from week 4 (17.6%) to week 24 (31.6%) (p < 0.001); 84.3% of patients had good or moderate EULAR responses at week 24. The percentage of patients achieving remission increased significantly from week 4 (9.3%) to week 24 (18.9%) (p < 0.001). Patients with early moderate RA were less likely to experience SAEs and were more likely to achieve remission compared with patients with more severe disease. The safety and effectiveness of etanercept was demonstrated in Japanese patients in one of the largest observational trials conducted thus far in RA patients treated with biologics.

Burden of Renal Events Associated with Nonsteroidal Anti-inflammatory Drugs in Patients with Osteoarthritis and Chronic Low Back Pain: A Retrospective Database Study.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) have long-term benefits but are limited by side effects. We assessed the health and economic burden of renal events associated with NSAID use in patients with osteoarthritis (OA) and/or chronic low back pain (CLBP). METHODS: This retrospective, large-scale, medical claims database study of Japanese patients receiving NSAIDs for OA and/or CLBP between 2009 and 2018 assessed the incidence of renal events and effect of treatment duration, mode of administration, and usage consistency of NSAIDs. RESULTS: Of 180,371 patients, NSAIDs were prescribed as first-line analgesics in 89.3%. Incidence per 10,000 person-years (95% confidence interval [CI]) for renal events was 23.46 (21.84-25.08) and for progression of chronic kidney disease (CKD) was 267.12 (189.93-344.32). Longer treatment duration (> 1 to ≤ 3 years, risk ratio [RR] 1.32, 95% CI 1.12-1.54; P = 0.0007; > 3 to ≤ 5 years, RR: 1.38, 95% CI 1.04-1.84; P = 0.0254 vs. < 1 year) and consistent use (RR: 1.24, 95% CI 0.99-1.55; P = 0.0595) increased the risk of renal events but the latter did not reach statistical significance. The risk was similar in patients using patch/oral NSAIDs and high in elderly patients and in those with diabetes, hypertension, and other cardiovascular disease. Following a renal event, median 1-year cost of drug treatment was $27.90; hospitalization, $1779.40; and dialysis, $33,018.40. CONCLUSIONS: Risk of renal events significantly increased with prolonged and consistent NSAID use (irrespective of mode of administration), with age, and in patients with certain comorbidities. Careful NSAID use is recommended in patients with CKD and those at high risk for CKD.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in patients with osteoarthritis (OA) and/or chronic low back pain (CLBP) for pain relief but their use is limited by side effects. These side effects may include abdominal, heart, and kidney problems. This article presents the results from a large claims database study in Japan that assessed the incidence of renal events and the associated healthcare cost. Impact of NSAIDs treatment duration, mode of administration, and usage consistency on the risk of developing renal events was evaluated. Results showed high incidence of renal events and progression of chronic kidney disease. Longer treatment duration and consistent use increased the risk of developing renal events. The risk was similar in patients using patch/oral NSAIDs and high in elderly patients and those with diabetes, hypertension, and other heart diseases. The estimated cost of drug treatment, hospitalization, and dialysis was also high. The author of the study would recommend NSAIDs to be used carefully in patients at risk for (or with) chronic kidney disease.

Database Analysis on the Relationships Between Nonsteroidal Anti-inflammatory Drug Treatment Variables and Incidence of Acute Myocardial Infarction in Japanese Patients with Osteoarthritis and Chronic Low Back Pain.

INTRODUCTION: We aimed to analyze the relationships between nonsteroidal anti-inflammatory drug (NSAID) treatment variables and the incidence of acute myocardial infarction (AMI) in Japanese patients with osteoarthritis (OA) and chronic low back pain (CLBP) using the data from a large-scale, real-world database. METHODS: We retrospectively analyzed anonymized claims data from the Japanese Medical Data Center of medical insurance beneficiaries who were prescribed NSAIDs for OA and/or CLBP from 2009 to 2018. RESULTS: Of 180,371 patients, 89.3% received NSAIDs as first-line analgesics (oral, 90.3%; patch, 80.4%; other transdermal drugs, 24.0%). Incidence of AMI was 10.27 per 10,000 person-years (95% confidence interval 9.20-11.34) in the entire study population. There was a trend towards increased risk in patients using NSAIDs for more than 5 years (P = 0.0784) than in those using NSAIDs for less than 1 year. Risk of AMI significantly increased with age and comorbidities of diabetes and cardiovascular disease (CVD). The risk for AMI was similar for patients who consistently used NSAIDs compared to those using them intermittently and patients who used patch compared to oral NSAIDs. Elderly patients used NSAIDs more consistently and used NSAID patches more frequently. CONCLUSION: In Japanese patients with OA and CLBP, we saw a trend of increased risk for AMI in patients using NSAIDs for more than 5 years. Elderly patients had a higher prevalence of diabetes, hypertension, and other CVD which increased the risk of AMI. Although NSAID patches were preferred to oral NSAIDs in elderly patients, risk for AMI was similar between the two modalities. Therefore, we suggest using NSAIDs carefully, especially in elderly patients and those at risk of developing CVD.

Direct and Indirect Pathways for Health-Related Quality of Life Change from Pain Improvement in Neuropathic Pain Patients with Spine Diseases: Path Analysis with Structural Equation Modeling Using Non-Interventional Study Results of Pregabalin.

BACKGROUND: Chronic low back pain or chronic cervical pain often has a neuropathic pain (NeP) component and patients with these conditions complain of sleep deprivation, loss of physical function, and reduced productivity due to pain. The objective of this study was to clarify the pathway by which pain, sleep disturbance due to pain, and physical function status influence QOL measures in chronic low back pain patients with NeP associated with lumbar spine diseases (CLBP-NeP) and in chronic cervical pain patients with NeP associated with cervical spine diseases (CCP-NeP). METHODS: A model assuming pain numeric rating scale (NRS), pain-related sleep interference scale (PRSIS), and functional indices (Roland Morris Disability Questionnaire [RMDQ], Neck Disability index [NDI]) as factors that can affect outcomes such as QOL (calculated using EuroQoL 5 Dimensions (EQ-5D)), the Patient Global Impression of Change (PGIC), and the Clinical Global Impression of Change (CGIC) was developed using structural equation modeling. RESULTS: Overall trends were frequently observed in both patients with CLBP-NeP and CCP-NeP. Pain NRS had the largest comprehensive direct impact on QOL based on EQ-5D and an overall impression of changing symptoms. The effects of pain NRS on each outcome were largely due to direct pain-related effects; however, for EQ-5D, an indirect effect via functional improvement was the primary factor. CONCLUSION: Although the results of this study suggest that the indirect functional improvement of pain relief may not be recognized as a significant component of therapeutic effects by both physicians and patients, the pain-relieving intervention contributes directly to improvement of patients' overall QOL and also indirectly via functional improvement in Japanese primary care settings. Accordingly, to achieve the therapeutic goal for patients with NeP and minimize the impact of pain burden, our findings indicate that pain relief interventions are also crucial from the perspective of the patient's HRQOL.

Light transmittance characteristics and refractive indices of light-activated pit and fissure sealants.

We examined the light transmittance characteristics and refractive indices of light-activated pit and fissure sealants. Five commercial pit and fissure sealants and human enamel were studied, along with the CIE L*a*b* color values of the materials and enamel. The light transmittance spectra of the pit and fissure sealants showed a similar trend to the enamel, especially at wavelengths below 530 nm. The average light transmittance values from 400 to 500 nm of the materials at 0.5-mm-thick ranged from 10.0% to 40.4%. The refractive indices at 589.3 nm ranged from 1.504 to 1.546, and were approximately 4-8% lower than that of enamel. The measurements for the surface hardness of materials indicate that the light-attenuating effect of enamel and the material itself reduced the polymerization efficiency of the material. For all materials, chromatic a* showed negative and b* showed positive values, as did enamel. Significant differences in light transmittance characteristics and refractive indices between the materials and enamel may affect color matching between them.

Treatment and Healthcare Cost Among Patients with Hip or Knee Osteoarthritis: A Cross-sectional Study Using a Real-world Claims Database in Japan Between 2013 and 2019.

BACKGROUND AND OBJECTIVES: The guidelines for osteoarthritis (OA) treatment recommend different therapies including pharmacotherapy, and several analgesic options are available for pain management. In Japan, research on hip and knee OA treatment trends is scarce and OA-related healthcare costs are unknown. Therefore, this study aimed to examine the treatment and healthcare cost trends among Japanese patients with hip or knee OA. METHODS: This was a cross-sectional study held between 2013 and 2019, using a medical claims database. The demographic and treatment characteristics of hip or knee OA patients for each year were descriptively analyzed and the medians for healthcare utilization and all-cause healthcare costs were calculated. RESULTS: The yearly mean age of 59,218 hip OA and 270,722 knee OA patients ranged from 66.3 to 68.6 years and 71.1 to 73.1 years, respectively. The prevalence of comorbidities was higher in knee OA than hip OA. In both groups, > 70% of patients were female, and the most common treatment was pain-related medication. In hip OA, topical and systemic nonsteroidal anti-inflammatory drugs (NSAIDs) were mostly used throughout the study period (34.1-41.4% and 32.0-40.3%, respectively). Similarly, in knee OA, topical and systemic NSAIDs were used in 58.3-63.3% and 36.5-46.0% patients, respectively. Increase in the use of acetaminophens (10.9% in hip OA and 10.2% in the knee OA) and weak opioids (3.7%, and 3.4%, respectively) from 2013 to 2019 were observed. Most patients were treated as outpatients in both groups. The median all-cause healthcare costs were approximately 35,000 JPY for hip OA and 74,000 JPY for knee OA. CONCLUSIONS: Although a considerable change in total healthcare cost was not observed in our study, the contents of medical treatment and cost breakdown were greatly altered due to the treatment and cost for OA itself, and the treatment and cost for comorbidities. Similar studies to investigate such a trend may help predict necessary resources and social needs. Thus, further investigation utilizing other databases is needed.

Mechanical properties and cytotoxicity of experimental soft lining materials based on urethane acrylate oligomers.

The purpose of this investigation was to determine whether experimental light-curing soft lining materials (ESLMs) based on commercially available urethane acrylate oligomers (UA-160TM, UV-3200B, UV-3500BA, and UV-3700B) are suitable for clinical use by measuring their viscosity, compressive modulus, Shore A hardness, tensile strength, adhesive strength, and cytotoxicity. The viscosities of the four ESLMs at 25 degrees C were 10.5 Pa.s, UV-3500BA; 144.0 Pa.s, UA-160TM; 328.8 Pa.s, UV-3700B; and 1079.7 Pa.s, UV-3200B. Polymerized UV-3700B was very soft, whereas the softness of the other ESLMs was similar to that of conventional soft lining materials. No significant difference in adhesive strength was observed between UV-3500BA and UV-3700B at 1 day and those at 12 months. Cytotoxicity was measured by a MTT-based assay using HeLa S3 and Ca9-22 cells. UV-3200B and UV-3700B oligomers and all four polymerized ESLMs showed cell viability over 95.2% (p < 0.05).

The efficacy of pregabalin for the treatment of neuropathic pain in Japanese subjects with moderate or severe baseline pain.

PURPOSE: Although analyses of pooled clinical trial data have reported how international populations respond to pregabalin by baseline neuropathic pain (NeP) severity, no studies have evaluated this specifically in patients from Japan. Thus, this post hoc pooled analysis evaluated the efficacy of pregabalin in Japanese subjects for treating moderate or severe baseline NeP. PATIENTS AND METHODS: Data were pooled from three placebo-controlled trials enrolling Japanese subjects with postherpetic neuralgia (PHN), diabetic peripheral neuropathy (DPN), and spinal cord injury (SCI). The efficacy of pregabalin was evaluated by baseline pain severity (moderate or severe NeP). The trials on PHN and DPN included a 1-week titration of pregabalin from 150 mg/day to 300 or 600 mg/day; the SCI trial included a 4-week dose optimization phase (150 mg/day, titrated up to 600 mg/day). Treatment durations were 13-16 weeks (excluding 1-week taper periods), and pregabalin was administered in two divided doses per day. RESULTS: Mean baseline pain scores and demographic characteristics were comparable between treatment cohorts. Pregabalin treatment significantly reduced pain scores from baseline to endpoint compared with placebo in subjects with both moderate (P<0.001) and severe (P<0.05) baseline pain. Significant improvements in mean sleep scores from baseline to endpoint were associated with pregabalin compared with placebo in subjects with both moderate and severe baseline pain (both P<0.0001). A greater proportion of subjects in both pain cohorts achieved a ≥30% reduction in pain from baseline with pregabalin vs placebo (P<0.05). Higher proportions of pregabalin-treated vs placebo-treated subjects shifted to a less severe pain category at endpoint. Consistent with the known safety profile of pregabalin, common adverse events included dizziness, somnolence, weight gain, and peripheral edema. CONCLUSION: Pregabalin demonstrated efficacy for pain relief and sleep improvement with a consistent safety profile in Japanese subjects with either moderate or severe baseline pain severity. CLINICALTRIALSGOV IDENTIFIERS: NCT0039490130, NCT0055347522, NCT0040774524.

Effectiveness of pregabalin for treatment of chronic cervical radiculopathy with upper limb radiating pain: an 8-week, multicenter prospective observational study in Japanese primary care settings.

Background: Despite high prevalence of chronic neck pain in Japan and the negative impact pain has on patient's quality of life (QoL), the therapeutic value of pregabalin for chronic neck pain with a neuropathic pain (NeP) component has not been assessed in a typical Japanese health care setting. Methods: An 8-week, non-interventional, multicenter, observational study of Japanese adults (≥20 years) with chronic refractory cervical pain including a NeP element (for ≥12 weeks) and sleep disturbance on the Pain-Related Sleep-Interference Scale (PRSIS) ≥1 (from 0 "does not interfere with sleep" to 10 "completely interferes"). Patients received either usual care with conventional analgesics or pregabalin (150-600 mg/day) for 8 weeks. "Usual care" with analgesics or other treatment(s) was determined based on physician's best clinical judgment. Primary endpoint was change from baseline to week 8 in PRSIS. Secondary endpoints included: change from baseline to week 4 in PRSIS, and to week 4 and 8 in pain Numerical Rating Scale (NRS; from 0 "no pain" to 10 "worst possible pain"), and on the Neck Disability Index (NDI). Other assessments of QoL were undertaken. Safety was monitored. Results: Overall, 369 patients received pregabalin (n=145) or usual care (n=224). The median (range) dose of pregabalin was 49.6 (25.0-251.5) mg/day. Least-squares mean change in PRSIS from baseline to week 8 favored pregabalin (-1.167 vs -0.269; treatment difference -0.898 [95% CI -1.262, -0.535], P<0.001). Similar observations were seen at week 4 in favor of pregabalin versus usual care (P<0.001). Pregabalin significantly improved pain NRS and NDI scores at weeks 4 and 8 (all P<0.001). Improvements in QoL versus usual care were also observed. Pregabalin was generally well tolerated. Conclusion: In this open-label study, pregabalin improved PRSIS and resulted in clinically meaningful reductions in pain in Japanese patients with NeP associated with chronic cervical pain. ClinicalTrials.gov identifier: NCT02868359.

A Cost-Effectiveness Analysis Of Pregabalin For The Treatment Of Patients With Chronic Cervical Pain With A Neuropathic Component In Japan.

PURPOSE: To evaluate the cost-effectiveness of pregabalin versus other analgesics among patients with chronic cervical pain with neuropathic components during routine clinical practice in Japan. PATIENTS AND METHODS: The analysis considered patients with chronic cervical pain with a neuropathic pain component (radiating pain to the upper limb) and who were treated with pregabalin with or without other analgesics (pregabalin-containing treatments) or other analgesics alone (usual care) for 8 weeks. Other analgesics included non-steroidal anti-inflammatory drugs (NSAIDs), weak opioids, antidepressants, and antiepileptic drugs. A Markov cohort simulation model was constructed to estimate costs and effectiveness (in terms of quality-adjusted life-years, QALYs) of each treatment over a 12-month time horizon. In the model, patients transitioned among three states of pain severity (no/mild, moderate, and severe). Data were derived from a previous observational study (pregabalin-containing treatments, n = 138; usual care, n = 211). Cost inputs included medical costs and productivity losses. QALYs were calculated using the EuroQol five-dimensional, five-level questionnaire. The cost-effectiveness was evaluated using incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were conducted to assess the robustness of results. RESULTS: From the payer's perspective, pregabalin-containing treatments were more costly (JPY 61,779 versus JPY 26,428) but also more effective (0.763 QALYs versus 0.727 QALYs) than the usual care, with an ICER of JPY 970,314 per QALY gained. From the societal perspective, which also included productivity losses, the ICER reduced to JPY 458,307 per QALY gained. One-way sensitivity analyses demonstrated the robustness of the results. Given a hypothetical threshold value of one additional QALY of JPY 5,000,000, the probability of pregabalin-containing treatments being cost-effective was 100%. CONCLUSION: Compared with using other analgesics alone, the use of pregabalin, alone or in addition to other analgesics, was cost-effective for the treatment of chronic cervical pain with a neuropathic pain component in Japan.

Patterns of drug treatment in patients with osteoarthritis and chronic low back pain in Japan: a retrospective database study.

Purpose: Musculoskeletal diseases, including osteoarthritis (OA) and low back pain (LBP), are the leading causes of years lived with disability, and are associated with lowered quality-of-life, lost productivity, and increased healthcare costs. However, information publicly available regarding the Japanese real-world usage of prescription medications is limited. This study aimed to describe the clinical characteristics of patients with OA and chronic LBP (CLBP), and to investigate the patterns of medications and opioid use in Japanese real-world settings. Materials and methods: A retrospective study was conducted using a Japanese administrative claims database between 2013 and 2017. The outcomes were patient characteristics and prescription medications, and they were evaluated separately for OA and CLBP. Results: The mean age of 118,996 patients with OA and 256,402 patients with CLBP was 68.8±13.1 years and 64.8±16.4 years, respectively. Approximately 90% of patients with OA and CLBP were prescribed non-steroidal anti-inflammatory drugs (NSAIDs). Other prescriptions included hyaluronate injection (35.6%), acetaminophen (21.4%), and steroid injection (20.0%) in patients with OA, and pregabalin (39.0%) and acetaminophen (22.4%) in patients with CLBP. Weak opioids were prescribed to 10.7% and 20.6% of patients with OA and CLBP, respectively. The prescription of COX-2 inhibitors (OA: +6.5%; CLBP: +6.7%) and acetaminophen (OA: +16.4%; CLBP: +14.4%) increased between 2013 and 2017. The first commonly prescribed medication among patients with OA and CLBP were NSAIDs; hyaluronate injection (patients with OA) and pregabalin (patients with CLBP) were also common first-line medications. Acetaminophen, steroid injection (patients with OA), and weak opioids were prescribed more in the later phases of treatment. Conclusion: Most patients were prescribed limited classes of pain drugs, with NSAIDs being the most common pain medication in Japan for patients with OA and CLBP. Opioid prescription was uncommon, and were weak opioids when prescribed.