Stepwise dose increase of febuxostat is comparable with colchicine prophylaxis for the prevention of gout flares during the initial phase of urate-lowering therapy: results from FORTUNE-1, a prospective, multicentre randomised study.

OBJECTIVES: To determine whether febuxostat with stepwise dose increase is as useful as colchicine prophylaxis in reducing gout flares during the initial introduction of urate-lowering therapy in patients with gout in comparison with febuxostat with no dose titration. METHODS: In this prospective, multicentre, randomised open-label comparative study, patients were randomised to group A (stepwise dose increase of febuxostat from 10 to 40 mg/day), group B (fixed-dose febuxostat 40 mg/day plus colchicine 0.5 mg/day) or group C (fixed-dose febuxostat 40 mg/day) and observed for 12 weeks. Gout flare was defined as non-steroidal anti-inflammatory drug use for gout symptoms. RESULTS: A total of 255 patients were randomised, and 241 patients were treated. Among the treated patients, gout flares were experienced by 20/96 (20.8%) in group A, 18/95 (18.9%) in group B and 18/50 (36.0%) in group C. The incidence of flare was significantly lower in groups A and B than that in group C (P=0.047 and P=0.024, respectively), although the differences were not significant after correction for multiple comparisons. No significant difference was noted between the incidence of gout flare in groups A and B. CONCLUSIONS: Our data suggested that stepwise dose increase of febuxostat and low-dose colchicine prophylaxis effectively reduced gout flares in comparison with fixed-dose febuxostat alone. Stepwise dose increase of febuxostat may be an effective alternative to low-dose colchicine prophylaxis during the introduction of urate-lowering therapy. TRIAL REGISTRATION NUMBER: UMIN 000008414.

GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes.

OBJECTIVE: A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. METHODS: Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zealand Polynesian samples was done to further validate the loci identified in this study. RESULTS: In addition to the five loci we reported previously, further susceptibility loci were identified at a genome-wide significance level (p<5.0×10-8): urate transporter genes (SLC22A12 and SLC17A1) and HIST1H2BF-HIST1H4E for all gout cases, and NIPAL1 and FAM35A for the renal underexcretion gout subtype. While NIPAL1 encodes a magnesium transporter, functional analysis did not detect urate transport via NIPAL1, suggesting an indirect association with urate handling. Localisation analysis in the human kidney revealed expression of NIPAL1 and FAM35A mainly in the distal tubules, which suggests the involvement of the distal nephron in urate handling in humans. Clinically ascertained male patients with gout and controls of Caucasian and Polynesian ancestries were also genotyped, and FAM35A was associated with gout in all cases. A meta-analysis of the three populations revealed FAM35A to be associated with gout at a genome-wide level of significance (p meta =3.58×10-8). CONCLUSIONS: Our findings including novel gout risk loci provide further understanding of the molecular pathogenesis of gout and lead to a novel concept for the therapeutic target of gout/hyperuricaemia.

Effects of febuxostat on serum urate level in Japanese hyperuricemia patients.

OBJECTIVE: We assessed the efficacy and adverse effects of febuxostat in male hyperuricemia patients. SUBJECTS AND METHODS: This was a 12-week, multicenter, open-label, uncontrolled study. The enrolled subjects were 89 hyperuricemic male patients (12 overexcretors, 56 normal excretors, and 21 underexcretors). The endpoint was percent change in serum urate level. RESULTS: The concentration of urate in serum before and 12 weeks after beginning administration of febuxostat in the overexcretors was 9.34 ± 1.48 and 5.59 ± 1.17 mg/dl, respectively, while those were 8.59 ± 1.24 and 5.41 ± 1.35 mg/dl, respectively, in the normal excretors, and 8.29 ± 1.01and 5.11 ± 1.71 mg/dl, respectively, in the underexcretors. After 12 weeks, the rate of change in serum urate after beginning administration of febuxostat was - 0.384 ± 0.186 in the overexcretors, - 0.368 ± 0.128 in the normal excretors, and - 0.365 ± 0.217 in the underexcretors, with no significant differences among them. A common adverse event related to febuxostat was gout flare. CONCLUSION: Febuxostat effectively reduced the concentration of urate in serum in hyperuricemic patients regardless of the level of uric acid excreted in urine without severe adverse effects.

Effects of topiroxostat on the serum urate levels and urinary albumin excretion in hyperuricemic stage 3 chronic kidney disease patients with or without gout.

BACKGROUND: Topiroxostat, a selective xanthine oxidase inhibitor, shows effective reduction in the serum urate level in hyperuricemic patients with or without gout. The objective of this study was to evaluate the efficacy and safety of topiroxostat in hyperuricemic stage 3 chronic kidney disease patients with or without gout. METHODS: The study design was a 22-week, randomized, multicenter, double-blind study. The enrolled patients were randomly assigned to treatment with topiroxostat 160 mg/day (n = 62) or to the placebo (n = 61). The endpoints were the percent change in the serum urate level, change in the estimated glomerular filtration rate, the urinary albumin-to-creatinine ratio, the proportion of patients with serum urate levels of 356.88 µmol/L or less, blood pressure, and serum adiponectin. RESULTS: After 22 weeks, although the changes in the estimated glomerular filtration rate and blood pressure were not significant, the percent change in the serum urate level (-45.38 vs. -0.08 %, P < 0.0001) and the percent change in urinary albumin-to-creatinine ratio (-33.0 vs. -6.0 %, P = 0.0092) were found to have decreased in the topiroxostat as compared with the placebo. Although the incidence of 'alanine aminotransferase increased' was higher in the topiroxostat, serious adverse event rates were similar in the two groups. CONCLUSION: Topiroxostat 160 mg effectively reduced the serum urate level in the hyperuricemic stage 3 chronic kidney disease patients with or without gout.

An allopurinol-controlled, randomized, double-dummy, double-blind, parallel between-group, comparative study of febuxostat (TMX-67), a non-purine-selective inhibitor of xanthine oxidase, in patients with hyperuricemia including those with gout in Japan: phase 3 clinical study.

BACKGROUND: Allopurinol has been widely used for treatment of hyperuricemia, however, it may be associated with various adverse effects. Febuxostat is potentially a safe and efficacious alternative. OBJECTIVES: Febuxostat or allopurinol was administered to patients with hyperuricemia including gout for 8 weeks to compare the efficacy and safety of these drugs. METHODS: Doses of febuxostat and allopurinol were 10 and 100 mg/d, respectively, during a 12-day introduction period and were increased to 40 and 200 mg/d for the subsequent treatment period of 44 days. RESULTS: : The percent changes in serum uric acid levels after 8 weeks were -40.75% for the febuxostat group and -34.41% for the allopurinol group (P < 0.001, analysis of variance, closing testing procedure). The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less after 8 weeks was 82.0% for the febuxostat group and 70.0% for the allopurinol group (P = 0.019, logistic regression analysis). Regarding safety, 213 adverse events were observed in the febuxostat group and 220 events in the allopurinol group. For 10 patients (8.2%) in the febuxostat group and 14 patients (11.6%) in the allopurinol group, association with the study drugs could not be ruled out. There were no severe adverse drug reactions in the febuxostat group other than a high frequency of gout attacks induced by the sudden reduction in blood uric acid levels during the early treatment period. CONCLUSIONS: Febuxostat at 40 mg/d demonstrated more potent hypouricemic effects than allopurinol at 200 mg/d, was efficacious regardless of medical history of gout, and is considered safe for treatment of hyperuricemia.

Multicenter, open-label study of long-term administration of febuxostat (TMX-67) in Japanese patients with hyperuricemia including gout.

BACKGROUND: In previous clinical studies of hyperuricemia including gout, although serum uric acid (sUA) levels reduced to 6.0 mg/dL or less in about 80% of patients treated with 40 mg/d febuxostat, a nonpurine selective xanthine oxidase inhibitor, a few patients did not show this result. OBJECTIVE: The objective of the study was to evaluate the efficacy and safety of long-term febuxostat administration at up to 60 mg/d in patients with hyperuricemia and gout. METHODS: In a 52-week, multicenter, open-label trial, febuxostat was initially administered at 10 mg/d; then, the dosage was increased in a stepwise fashion to 40 mg/d. For sUA levels greater than 6.0 mg/dL at week 10, the dosage was increased to 60 mg/d from week 14 onward (60-mg group), but it was maintained at 40 mg/d until the end of the study for patients with sUA levels 6.0 mg/dL or less at week 10 (40-mg group). RESULTS: The sUA levels in both groups decreased dose dependently. At 52 weeks, 84.5% and 85.0% of the 40- and 60-mg groups, respectively, achieved mean sUA levels 6.0 mg/dL or less. There was no marked difference between the 2 dosage groups in terms of the incidence of adverse events. Furthermore, there were no noteworthy adverse events or adverse drug reactions in the patients with renal dysfunction, and no differences in drug efficacy up to 60 mg/d were noted between the patients with moderate or mild renal dysfunction and those with normal renal function. CONCLUSIONS: Febuxostat seems to be a promising therapeutic drug for gout or hyperuricemia, even in patients with renal dysfunction.

Placebo-controlled, double-blind study of the non-purine-selective xanthine oxidase inhibitor Febuxostat (TMX-67) in patients with hyperuricemia including those with gout in Japan: phase 3 clinical study.

BACKGROUND: : Allopurinol has been widely used for treatment of hyperuricemia, however, it may be associated with various adverse effects. Febuxostat has been identified as a potentially safe and efficacious alternative. OBJECTIVES: : A multicenter study with randomized, placebo-controlled, double-blind, parallel-group comparison was carried out to evaluate the efficacy and safety of febuxostat in 103 patients with hyperuricemia (including patients with gout) in Japan. METHODS: : Subjects were treated with febuxostat (20 or 40 mg/d) or a placebo for 8 weeks. The variables evaluated were the percentage of patients achieving serum uric acid levels 6.0 mg/dL or less and the percent change in serum uric acid levels after 8 weeks. RESULTS: : The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less after 8 weeks was 91.2% in the febuxostat 40-mg/d group, 45.7% in the 20-mg/d group, and 0.0% in the placebo group. The percent changes in serum uric acid levels after 8 weeks were -44.9% in the febuxostat 40-mg/d group, -28.9% in the 20-mg/d group, and -0.6% to -0.5% in the placebo group. No severe or medically significant adverse reaction attributable to febuxostat was noted, and there was no event that could pose a clinical problem. The efficacy did not differ depending on the presence/absence of gout history. CONCLUSIONS: : These results suggest that febuxostat (20 or 40 mg/d) is useful as a new means of treating hyperuricemia and is capable of reducing serum uric acid levels to 6.0 mg/dL or less (goal of treatment) with high safety regardless of the presence/absence of gout history.

Placebo-controlled double-blind dose-response study of the non-purine-selective xanthine oxidase inhibitor febuxostat (TMX-67) in patients with hyperuricemia (including gout patients) in japan: late phase 2 clinical study.

BACKGROUND: Allopurinol has been widely used for the treatment of hyperuricemia, however, it may be associated with various adverse effects. Febuxostat has been identified as a potentially safe and efficacious alternative. OBJECTIVES: A multicenter study with randomized, placebo-controlled, double-blind, parallel, intergroup comparison was carried out to evaluate the dose-response relationship, efficacy, and safety of febuxostat in 202 patients with hyperuricemia (including patients with gout) in Japan. METHODS: The subjects were treated with febuxostat at fixed maintenance doses (20-80 mg/d) or a placebo for 16 weeks. The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less and the percent change in serum uric acid levels after 16 weeks of treatment were evaluated. RESULTS: The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less at 16 weeks was 87.8% in the 80-mg/d dose group, 83.3% in the 60-mg/d group, 82.9% in the 40-mg/d group, 46.5% in the 20-mg/d group, and 2.6% in the placebo group (P < 0.001, Mantel-Haenszel test). A statistically significant dose-response relationship was found. The percent change in serum uric acid levels after 16 weeks of treatment differed significantly between each febuxostat dose group and the placebo group and increased in a dose-dependent manner above 40 mg/d. No deaths, events posing a clinical problem, or serious adverse reactions attributable to febuxostat were noted. Similar results were obtained regardless of gout history. CONCLUSIONS: Febuxostat can safely reduce serum uric acid levels to 6.0 mg/dL or less in 80% or more of patients with hyperuricemia (including gout) at doses of 40 mg/d or higher.

An allopurinol-controlled, multicenter, randomized, open-label, parallel between-group, comparative study of febuxostat (TMX-67), a non-purine-selective inhibitor of xanthine oxidase, in patients with hyperuricemia including those with gout in Japan: phase 2 exploratory clinical study.

BACKGROUND: Allopurinol has been widely used for the treatment of hyperuricemia, however, it may be associated with various adverse effects. Febuxostat has been identified as a potentially safe and efficacious alternative. OBJECTIVES: Febuxostat was administered to patients with hyperuricemia including gout in Japan to compare its efficacy and safety with those of allopurinol. METHODS: The starting dose of febuxostat and allopurinol was 10 and 100 mg/d, respectively, and was increased to the fixed maintenance dose of 40 or 60 mg/d for febuxostat and 300 mg/d for allopurinol for 16 weeks. RESULTS: : The percent change in the serum uric acid level at 16 weeks compared with the baseline serum uric acid level was -42.96% ± 13.33% and -52.47% ± 9.79% for the febuxostat 40- and 60-mg/d groups, respectively, and -36.55% ± 18.59% for the allopurinol group, indicating that the hypouricemic effects of febuxostat increased in a dose-dependent manner and equaled to or surpassed those of allopurinol (P = 0.0239, 2-sample t test). The percentage of patients with serum uric acid levels of 6.0 mg/dL or less at 16 weeks was 88.9% and 100% for the febuxostat 40- and 60-mg/d groups, respectively, and 68.8% for the allopurinol group, showing higher achievements for the febuxostat groups compared with the allopurinol group. All adverse drug reactions were mild to moderate in severity, and there were no severe symptoms or reactions leading to drug discontinuation. CONCLUSIONS: These results suggest that febuxostat is safe at doses of 40 and 60 mg/d and has equal or greater efficacy than 300 mg/d allopurinol.

Associations between diabetes duration and self-stigma development in Japanese people with type 2 diabetes: a secondary analysis of cross-sectional data.

OBJECTIVES: To examine the associations between self-stigma and diabetes duration in a sample of Japanese people with type 2 diabetes. DESIGN: A secondary analysis of a cross-sectional study. SETTING: Two university hospitals, one general hospital and one clinic in Tokyo, Japan. PARTICIPANTS: Outpatients with type 2 diabetes aged 20-74 years and receiving treatment from diabetes specialist physicians (n=209) completed a self-administered questionnaire. PRIMARY AND SECONDARY OUTCOME MEASURES: Self-stigma was measured as the primary outcome. Patient Activation Measure, body mass index and haemoglobin A1c were measured as secondary outcomes. RESULTS: One-way analysis of covariance showed significant differences in self-stigma levels between the five groups of diabetes duration (≤5 years, 6-10 years, 11-15 years, 16-21 years and 22 years or more) after controlling for age, gender, education, marital status, diabetes treatment (insulin use) and diabetes-related complications, F(4,198)=2.83, p=0.026. Multiple comparisons using Bonferroni correction showed statistically significant differences in self-stigma levels between the groups with ≤5 years (95% CI 59.63 to 69.73) and 11-15 years with diabetes (95% CI 71.12 to 80.82; p=0.020). The highest mean level of self-stigma was observed in the group having diabetes for 11-15 years. CONCLUSIONS: Self-stigma was associated with diabetes duration and was lowest after diagnosis and gradually increased, with its highest levels being observed in those having diabetes for 11-15 years. Self-stigma takes time to develop and gradually increases in individuals as it is learnt through direct experiences of diabetes-related stigma after self-administering treatment in everyday social situations.

Determination of total purine and purine base content of 80 food products to aid nutritional therapy for gout and hyperuricemia.

The aim of this work is to facilitate the nutritional therapy of gout and hyperuricemia. In Japan, patients with gout or hyperuricemia are recommended to consume less than 400 mg of dietary purines per day. When receiving nutritional therapy for gout or hyperuricemia, purine-rich foods (>200 mg/100 g) should be eaten in even lower quantities. The purine content of foods reported in this study are as follows: noodles, 0.6-12.1 mg/100 g; bread, 4.4 mg/100 g; peas or seeds, 19.6-67.1 mg/100 g; dairy, 0.0-1.4 mg/100 g; Japanese vegetables, 0.9-47.1 mg/100 g; seasonings, 0.7-847.1 mg/100 g; meat or fish, 19.0-385.4 mg/100 g; fish milt, 375.4-559.8 mg/100 g; and supplements, 81.9-516.0 mg/100 g. Foods containing very large amounts of purine (>300 mg/100 g) included anchovy, cutlassfish (hairtail), cod milt, globefish milt, dried Chinese soup stock, dried yeast, a Euglena supplement, and a Lactobacillus supplement. When eating these high-purine food or supplements, the quantity taken at one meal should be limited, especially milt because they typically consumed amount of 20-30 g is equivalent to 75-168 mg total purines. This is 20%-40% of the recommended daily amount (400 mg/day) for patients with gout or hyperuricemia. Thus, these patients should restrict the amount of purine-rich foods they consume. Good dietary habits with a good balance of nutrients are recommended.

Soft x-ray irradiation induced metallization of layered TiNCl.

We have performed soft x-ray spectroscopy in order to study the photoirradiation time dependence of the valence band structure and chemical states of layered transition metal nitride chloride TiNCl. Under the soft x-ray irradiation, the intensities of the states near the Fermi level (EF) and the Ti3+component increased, while the Cl 2pintensity decreased. Ti 2p-3dresonance photoemission spectroscopy confirmed a distinctive Fermi edge with Ti 3dcharacter. These results indicate the photo-induced metallization originates from deintercalation due to Cl desorption, and thus provide a new carrier doping method that controls the conducting properties of TiNCl.

How self-stigma affects patient activation in persons with type 2 diabetes: a cross-sectional study.

OBJECTIVES: Self-stigma is associated with lower patient activation levels for self-care in persons with type 2 diabetes mellitus (T2DM). However, the causal pathway linking self-stigma with patient activation for self-care has not been shown. In order to determine how self-stigma affects patient activation for self-care, we tested a two-path hypothetical model both directly and as mediated by self-esteem and self-efficacy. DESIGN: A cross-sectional study. SETTING: Two university hospitals, one general hospital and one clinic in Japan. PARTICIPANTS: T2DM outpatients receiving treatment (n=209) completed a self-administered questionnaire comprising the Self-Stigma Scale, Patient Activation Measure, Rosenberg Self-Esteem Scale, General Self-Efficacy Scale, Patient Health Questionnaire, haemoglobin A1c test, age, sex and body mass index. PRIMARY AND SECONDARY OUTCOME MEASURES: Self-stigma levels were measured by using the Self-Stigma Scale. Patient activation levels were measured by the Patient Activation Measure. RESULTS: Path analysis showed a strong relationship between self-stigma and patient activation (χ2=27.55, p=0.120; goodness-of-fit index=0.97; adjusted goodness-of-fit index=0.94; comparative fit index=0.98; root mean square error of approximation=0.04). Self-stigma had a direct effect on patient activation (ß=-0.20; p=0.002). Indirectly, self-stigma affected patient activation along two paths (ß=0.31; p<0.001) by reducing self-esteem (ß=-0.22; p<0.001) and self-efficacy (ß=-0.36; p<0.001). CONCLUSIONS: Due to the cross-sectional design of the study, longitudinal changes between all the variables cannot be established. However, the findings indicate that self-stigma affected patient activation for self-care, both directly and as mediated by self-esteem and self-efficacy. Interventions that increase self-esteem and self-efficacy may decrease self-stigma in patients with T2DM, thus increasing patient activation for self-care.

Understanding the experiences of long-term maintenance of self-worth in persons with type 2 diabetes in Japan: a qualitative study.

OBJECTIVE: Persons with type 2 diabetes are often stigmatised for having what is considered a lifestyle-related disease. Accordingly, some blame themselves for their condition, resulting in feelings of low self-worth that ultimately impact their self-management behaviours. However, there are no studies examining why some do not blame themselves for their condition and manage to maintain their self-worth in relation to their illness. This study aimed to explore an understanding of how such persons experience the maintenance of self-worth in relation to their illness over the lifelong course of treatment. DESIGN: A cross-sectional qualitative study. Face-to-face semistructured interviews were conducted with a purposive sampling strategy. The data was analysed using a qualitative descriptive method that involved concurrent data collection and constant comparative analysis. SETTING: Two tertiary-level hospitals in Japan. PARTICIPANTS: Thirty-three outpatients with type 2 diabetes who currently had good glycaemic control but had previously had poor glycaemic control. RESULTS: Three themes explaining the maintenance of self-worth were identified: (1) Participants gained 'control' over their illness by living a 'normal life.' They found a way to eat preferred foods, dine out with family and friends, travel and work as usual; (2) Participants discovered the positive aspects of type 2 diabetes, as they felt 'healthier' from the treatment and felt a sense of security and gratitude for the care they received from healthcare professionals; (3) Participants discovered a new sense of self-worth by moving towards goals for type 2 diabetes treatment and experienced inner growth through positive lifestyle choices. CONCLUSIONS: The process of restoring and maintaining self-worth should be brought to the attention of healthcare professionals in diabetes care. These professionals could help patients discover positive self-representations through diabetes treatment (eg, a realisation that one does not lack self-control) and could aid in increasing patient engagement in diabetes self-management.

Patient health literacy and patient-physician information exchange during a visit.

BACKGROUND: Health literacy (HL), the capacity of individuals to access, understand and use health information to make informed and appropriate health-related decisions, is recognized as an important concept in patient education and disease management. OBJECTIVE: To examine the relation of three levels of HL (i.e. functional, communicative and critical HL) to patient-physician information exchange during a visit. METHODS: Participants were 134 outpatients with type 2 diabetes who were under continuous care by four attending physicians at a university-affiliated hospital. The visit communication was recorded and analysed using the Roter Interaction Analysis System. Patient HL was measured through a self-reported questionnaire using newly developed self-rated scales of functional, communicative and critical HL. Sociodemographic and clinical characteristics and patient's perception of the information exchange were assessed for each patient through self-reported questionnaires and review of electronic medical records. RESULTS: Patient HL levels were related to the information exchange process during the visit. Among the three HL scales, communicative HL (the capacity to extract information, derive meaning from different forms of communication and apply new information to changing circumstances) was related to patient's perceptions of the information exchange. Further, patient communicative HL had a modifying effect on the relationship between physician's information giving and patient's perception of it, suggesting that physician's communication may be perceived differently depending on the patient's HL. CONCLUSION: The exploration of patient HL may provide a better understanding of potential barriers to patient-physician communication and patient's self-management of disease.

Determination of purine contents of alcoholic beverages using high performance liquid chromatography.

The purine contents of alcoholic beverages were determined in order to utilize them in the dietary care of gout and hyperuricemia. In the management of these diseases, restriction of both alcohol and purine intake are important. The method employed in this study is a quantitative determination of purine contents by HPLC. Alcoholic beverages were hydrolyzed to corresponding purine bases, which were then separated by HPLC, and base peaks were identified using an enzymatic peak-shift technique. This method is sufficiently accurate and reproducible to examine the purine contents of various alcoholic beverages that patients consume. Purine contents were as follows: spirits, 0.7-26.4 micromol/L; regular beer, 225.0-580.2 micromol/L; low-malt beer, 193.4-267.9 micromol/L; low-malt and low-purine beer, 13.3 micromol/L; other liquors, 13.1-818.3 micromol/L. Some local and low-alcohol beers were found to contain about 2.5 times more purines than regular beer. As some alcoholic beverages contain considerable amounts of purines, we recommend that excess consumption of these beverages be avoided. These data should be useful in the management of hyperuricemia and gout, not only for patients but also for physicians.

[Establishment of therapeutic goal and plan of gout and asymptomatic hyperuricemia].

Gout is a crystal deposition disease. European and Japanese guidelines of management for gout recommend that serum urate concentration should be maintained below 6.0 mg/dL to promote crystal dissolution leading to prevention of recurrent gouty attack. Although allopurinol is recommended to be an adequate drug for urate lowering therapy in all gouty patients by European guideline, it is desirable that allopurinol is indicated in patients with overproduction type and benzbromarone in patients with underexcretion type, recommended by Japanese guideline. Asymptomatic hyperuricemia dose not equate to gout. As there is no evidence to support treatment of isolated hyperuricemia with urate lowering therapy currently, it is difficult to establish lowering goal of serum urate level in patients with asymptomatic hyperuricemia. Advice regarding lifestyle and treatment of associated comorbidity should be preferred to urate lowering therapy. However, urate lowering therapy may be indicated in high risk patients with hyperuricemia who are suffered from hypertension, diabetes mellitus, ischemic heart disease and renal insufficiency.

Psychological and behavioural patterns of stigma among patients with type 2 diabetes: a cross-sectional study.

OBJECTIVES: The aim of this study was to test the psychological and behavioural patterns of stigma (self-esteem and social participation) and their relationship to self-stigma, patient activation for engaging in self-care and glycaemic control among patients with type 2 diabetes mellitus (T2DM). DESIGN: A cross-sectional study. SETTING: 2 tertiary-level hospitals and 2 secondary-level hospitals in Japan. PARTICIPANTS: A consecutive sample of 209 outpatients with T2DM. Inclusion criteria were as follows: presence of T2DM, age 20-74 years, no diagnosis of dementia and/or psychosis, and no need for urgent medical procedures. OUTCOME MEASURES: Study measures included a self-administered questionnaire to assess the Rosenberg Self-Esteem Scale (SES), the 3 subscales of 36-question Short Form Health Survey (SF-36; Social Function, Role Physical, Role Emotional), Self-Stigma Scale and Patient Activation Measure (PAM-13). Glycated haemoglobin was obtained from same day blood work. In our previous qualitative study, we found that psychological and behavioural patterns of stigma varied according to patients' levels of illness-related self-esteem as well as attitudes towards social participation. For quantitative consistency, we used the SES scale to measure self-esteem and the SF-36 subscales to measure social participation. We then divided participants into 4 groups by exhibited psychological and behavioural patterns: group A (high SES/high SF-36), group B (high SES/low SF-36), group C (low SES/high SF-36) and group D (low SES/low SF-36). RESULTS: Using analysis of covariance after controlling for age and sex, there was a significant difference in self-stigma levels between the four groups (F[3203]=15.70, p<0.001). We observed the highest mean self-stigma levels in group D. Group D also had significantly lower PAM-13 scores than those of groups A (p<0.001) and B (p=0.02). CONCLUSIONS: The psychological and behavioural pattern of group D was found to be associated with higher levels of self-stigma and poorer patient activation for self-care.

Band structures of 4f and 5f materials studied by angle-resolved photoelectron spectroscopy.

Recent remarkable progress in angle-resolved photoelectron spectroscopy (ARPES) has enabled the direct observation of the band structures of 4f and 5f materials. In particular, ARPES with various light sources such as lasers (hν ~ 7 eV) or high-energy synchrotron radiations (hν >/~ 400 eV) has shed light on the bulk band structures of strongly correlated materials with energy scales of a few millielectronvolts to several electronvolts. The purpose of this paper is to summarize the behaviors of 4f and 5f band structures of various rare-earth and actinide materials observed by modern ARPES techniques, and understand how they can be described using various theoretical frameworks. For 4f-electron materials, ARPES studies of CeMIn5(M = Rh, Ir, and Co) and YbRh2Si2 with various incident photon energies are summarized. We demonstrate that their 4f electronic structures are essentially described within the framework of the periodic Anderson model, and that the band-structure calculation based on the local density approximation cannot explain their low-energy electronic structures. Meanwhile, electronic structures of 5f materials exhibit wide varieties ranging from itinerant to localized states. For itinerant U5f compounds such as UFeGa5, their electronic structures can be well-described by the band-structure calculation assuming that all U5f electrons are itinerant. In contrast, the band structures of localized U5f compounds such as UPd3 and UO2 are essentially explained by the localized model that treats U5f electrons as localized core states. In regards to heavy fermion U-based compounds such as the hidden-order compound URu2Si2, their electronic structures exhibit complex behaviors. Their overall band structures are generally well-explained by the band-structure calculation, whereas the states in the vicinity of EF show some deviations due to electron correlation effects. Furthermore, the electronic structures of URu2Si2 in the paramagnetic and hidden-order phases are summarized based on various ARPES studies. The present status of the field as well as possible future directions are also discussed.

A qualitative study on the impact of internalized stigma on type 2 diabetes self-management.

OBJECTIVE: To explore how patients with type 2 diabetes (T2DM) psychologically and behaviorally respond to internalized stigma through social stigma. METHODS: A qualitative study with semi-structured interviews was recorded on audiotapes, transcribed verbatim, and analyzed using a grounded theory approach. Participants were adults aged 30-64 years and diagnosed with T2DM. A total of 26 patients participated. RESULTS: The qualitative data revealed that participants' responses to social stigma, although varied, could be organized into a four-step process: Encountering Negative Experiences, Reevaluating the Self with Type 2 Diabetes, Reconstructing a Sense of Identity, and Maintaining Balance between Patient and Social Roles. When participants form a negative image of and relationship to their illness, they tend to internalize stigma, which can affect their sense of self-worth, attitude toward social participation, and compliance. CONCLUSION: Participants who internalize stigma tend to have a lower sense of self-worth and their social participation falls somewhere between severely limited (Social Avoidance) and highly active (Role Conflict). This can hinder devotion to their treatment regimen and affect their degree of compliance with physicians. PRACTICE IMPLICATIONS: Internalized stigma can be assessed by observing a patient's illness-related negative self-image.