Guideline adherence by physicians for management of glucocorticoid-induced osteoporosis in Japan: a nationwide health insurance claims database study.

Risk of fracture due to glucocorticoid-induced osteoporosis (GIO) can be reduced by anti-osteoporosis (OP) medications. The proportion of patients on long-term glucocorticoid therapy who received anti-OP medications according to the GIO management guidelines has increased in recent years, but is still suboptimal. INTRODUCTION: Adherence of physicians to guidelines for glucocorticoid (GC)-induced osteoporosis (GIO) management is currently unclear. This study aimed to clarify the state of guideline adherence by physicians in Japan and identify factors associated with guideline adherence using a nationwide health insurance claims database (NDBJ). METHODS: Patients aged ≥ 50 years who were prescribed GC for ≥ 90 days after 180 days without a GC prescription and who were followed up for osteoporosis (OP) management for the subsequent 360 days during the period spanning 2012-2018 were selected from the NDBJ. Guideline adherence was evaluated with the proportion of patients who received OP management as recommended by the Japanese guidelines. Information on previous vertebral and hip fractures, dementia, and polypharmacy was obtained. Factors associated with OP management were evaluated by logistic regression analysis. RESULTS: A total of 512,296 patients were considered to be at high risk of fracture according to the guidelines. Proportions of patients receiving OP management (BMD testing or anti-OP medications) have increased in recent years. In 2017, 33.7% of men and 55.3% of women received OP management in the initial 90 days of GC therapy. Female sex, previous anti-OP medications, polypharmacy, and higher GC dose were significantly associated with receiving OP management, while dementia showed an inverse association. A prior history of hip fracture, a strong risk factor for future fracture, was not significantly associated with receiving OP management. CONCLUSIONS: Although guideline adherence by physicians has increased in recent years, it remains suboptimal. Further efforts to improve guideline adherence are necessary. TRIAL REGISTRATION NUMBER: The present study is not registered.

Impact of smoking on bone mineral density and bone metabolism in elderly men: the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study.

UNLABELLED: Our cross-sectional analysis of 1,576 men aged ≥65 years examined smoking effects on bone status. Number of smoking years was associated with decreased bone mineral density (BMD), after adjusting for age, height, weight, and number of cigarettes smoked daily. Smoking did not affect biochemical marker serum values for bone turnover. INTRODUCTION: The impact of smoking on bone status in men has not been conclusively established. We examined how smoking and its cessation influence bone status and metabolism in men. METHODS: We analyzed 1,576 men among a baseline survey of Japanese men aged ≥65 years, the Fujiwara-kyo Osteoporosis Risk in Men study, conducted during 2007-2008. RESULTS: Lumbar spine (LS) BMD values among never, former, and current smokers were 1.045 ± 0.194, 1.030 ± 0.189, and 1.001 ± 0.182 g/cm(2) (P = 0.005), respectively, while total hip (TH) BMD values were 0.888 ± 0.120, 0.885 ± 0.127, and 0.870 ± 0.124 (P = 0.078), respectively. The significant trend for LS BMD remained after adjusting for the covariates; age, height, weight, physical activity, milk consumption, and drinking habit (P = 0.036). Among never and ever (current and former) smokers, LS and TH BMD decreased with the number of pack years or the number of smoking years, respectively, adjusted for those covariates. Among ever smokers, LS and TH BMD decreased with the number of smoking years after adjusting for age, height, weight, and number of cigarettes smoked daily. Smoking did not reveal significant effect for serum osteocalcin or tartrate resistant acid phosphatase isoenzyme 5b. CONCLUSION: The impact of smoking on bone status is mainly associated with the number of smoking years in elderly men.

Low bone mass is associated with carotid atherosclerosis in postmenopausal women: the Japanese Population-based Osteoporosis (JPOS) Cohort Study.

UNLABELLED: We analyzed 609 women belonging to the JPOS study in a 10-year follow-up survey, to examine the association of osteoporosis with atherosclerosis. Osteoporosis or prevalent vertebral fracture at baseline was associated with increased intima-media thickness of the carotid bifurcation in postmenopausal women, adjusted for age, BMI, and other variables at baseline. INTRODUCTION: Whether low bone mass predicts increased carotid atherosclerosis has not been fully investigated. METHODS: In 2006, we conducted a 10-year follow-up survey of 1,040 women (follow-up rate: 68.6%). We analyzed 609 women > or =50 years old in 2006 without a history of cardiovascular or connective tissue diseases at baseline. BMD and evaluation of vertebral fracture at baseline were used. The intima-media thickness of carotid bifurcation (BIF-IMT) was measured by B-mode ultrasonography in 2006. RESULTS: Adjusted BIF-IMT values of subjects with spine T-score > or =-1, between-2.5 and -1, and <-2.5 or prevalent vertebral fracture were 1.19 mm, 1.34 mm, 1.57 mm, respectively, in women with less than 10 years since menopause (YSM) (n = 159), 1.30 mm, 1.32 mm, 1.53 mm, in women with YSM > or =10 without a history of hypertension at baseline (n = 144) (both with p < 0.05 for linear trend). Those values among no versus prevalent vertebral fracture in women with YSM > or =10 were 1.40 mm, 1.66 mm with p < 0.05 (n = 202). Those associations were independent of age, BMI, total cholesterol, smoking and drinking habits, history of diabetes mellitus, and hypertension (for women with YSM < 10) at baseline. CONCLUSION: Osteoporosis including prevalent vertebral fracture may be associated with carotid atherosclerosis in the first 10 years of postmenopausal women.

Biochemical markers of bone turnover predict bone loss in perimenopausal women but not in postmenopausal women-the Japanese Population-based Osteoporosis (JPOS) Cohort Study.

INTRODUCTION: The predictive value of biochemical markers of bone turnover for subsequent change in bone density in a population sample of healthy women with a wide range of ages has not been fully established. METHODS: We followed 1,283 women aged 15-79 years at baseline selected randomly from the inhabitants of three areas in Japan for 6 years, and examined 1,130 subjects with no disease or administration of drugs affecting bone metabolism. The annual change in bone density at the spine, total hip, and distal one third of the radius was determined during the follow-up period by dual x-ray absorptiometry and was compared among the groups using different levels of biochemical markers at baseline, including serum osteocalcin (OC) and bone-specific alkaline phosphatase (bone ALP), free and total (tDPD) forms of immunoreactive deoxypyridinoline, and type I collagen crosslinked C-terminal telopeptide (CTX) in urine. RESULTS: Premenopausal women aged 45 years or older with elevated levels of OC, bone ALP, CTX, or tDPD showed significantly greater bone loss at most skeletal sites during the follow-up period than those with lower levels, after adjustment for the effects of age, height, weight, dietary calcium intake, regular exercise, and current smoking. The greatest coefficient of determination of the model was observed in the association between CTX and bone loss at the hip during the first 3 years of follow-up (42.8%). These subjects were pooled with perimenopausal women at baseline, and those who still menstruated at follow-up in this pooled group showed significant but more modest associations, whereas those who entered menopause during the follow-up period showed clear associations. However, early postmenopausal women with less than 5 or 10 years since menopause showed an association that was limited mostly to the distal radius, and other postmenopausal groups had virtually no association. CONCLUSION: Biochemical markers of bone turnover may predict bone loss in women undergoing menopausal transition but may not predict bone loss in postmenopausal women.

Cross-sectional study of allergic disorders in relation to familial factors in Japanese adolescents.

AIM: The roles of heredity and the household environment in the development of allergic disorders are not clearly established. This study examined the relationship between selected familial factors and the prevalence of symptoms of wheeze, atopic eczema and rhinoconjunctivitis in Japanese adolescents. METHODS: Study subjects were 5539 students aged 12-15 y in Suita City. A questionnaire ascertained gender, grade, number of older siblings, maternal age at childbirth, smoking in the household, domestic pets and parental history of allergy, as well as signs and symptoms of allergy in the previous 12 mo. The latter were based on diagnostic criteria from the International Study of Asthma and Allergies in Childhood. RESULTS: Male gender was independently associated with an increased prevalence of wheeze and a decreased prevalence of atopic eczema. The prevalence of rhinoconjunctivitis, but not wheeze or atopic dermatitis, significantly increased with advancing grade. A significant inverse dose-response relationship between the number of older siblings and the prevalence of rhinoconjunctivitis, but not wheeze or atopic dermatitis, was observed. Maternal age at childbirth, smoking in the household and domestic pets were not apparently related to any of the allergic disorders. A positive maternal allergic history was more evidently associated with an increased prevalence of wheeze and rhinoconjunctivitis, but not atopic eczema, than a positive paternal allergic history. CONCLUSION: The findings suggest that the factors associated with allergic disorders in Japan are largely the same as those already identified in Western populations.

Factors that influence functional prognosis in elderly patients with hip fracture.

The purpose of this study was to evaluate in aged patients with hip fracture, the degree of recovery at discharge and after discharge relative to the pre-fracture walking level, to clarify the factors involved in unsuccessful recovery. The patients were 189 patients aged 60 years and older who underwent surgery between 1988 and 1994. Patients who died within 1 year or lacked data on walking were excluded. Multiple logistic regression analysis was applied to data on the walking level before fracture, that at discharge, and the best walking level after discharge, to clarify factors involved in unsuccessful recovery. The rate of recovery to the pre-fracture level was 55.1% at discharge. Unsuccessful recovery at discharge was influenced by prior dementia, a history of cerebrovascular diseases, and an age of 85 or more years. Analysis showed an "after-discharge" recovery rate of 63.2%. Prior dementia and the residence outside one's own home influenced unsuccessful recovery rate.These findings suggested that it is important to provide patients with such factors a more effective postoperative rehabilitation program not merely the standard rehabilitation program. In addition, a walking rehabilitation program should be offered to those who were re-hospitalized or admitted to other health care facilities.

Cyclin E overexpression in transitional cell carcinoma of the bladder.

We attempted to clarify the relationship between cyclin E to p27(Kip1), Ki-67 and clinicopathologic features in transitional cell bladder carcinoma. Immunohistochemical staining of archival tissue specimens of transitional cell bladder carcinoma obtained from 94 patients was performed by the labeled streptavidin-biotin-peroxidase method. Overexpression of cyclin E protein was observed in 38 of the 94 (40.4%) specimens, and was positively correlated with histological grade, Ki-67 LI and p27(Kip1) labeling index (LI). These data suggest that cyclin E may be associated with aggressive tumor growth, and may have a relationship with p27(Kip1) for the regulation of cell cycle progression in transitional cell bladder carcinoma.

Cyclin-dependent kinase inhibitor p27(Kip1) expression in transitional cell carcinoma of renal pelvis and ureter.

We examined the expression and significance of p27(Kip1) protein in 79 patients with transitional cell carcinoma of the renal pelvis and ureter. Immunohistochemical staining of archival tissue specimens was done using a labeled streptavidin-biotin-peroxidase method. There was no significant association between p27(Kip1) labeling index and histologic grade or pathologic stage. Patients with p27(Kip1) labeling indices of 27 or greater had more favorable prognoses in comparison to those with p27(kip1) labeling indices less than 27 (P<0.01). Multivariate analysis indicated that p27(Kip1) had an independent predictive prognostic value (P<0.05). The p27(Kip1) may be a novel prognostic marker for transitional cell carcinoma of the renal pelvis and ureter.

Acute health problems among the people engaged in the cleanup of the Nakhodka oil spill.

To determine if the Nakhodka oil spill and subsequent cleanup efforts had any health effects on the residents along the oil-contaminated coast, we investigated the health status of Anto residents who resided nearest to the coast where the bow ran aground. Two hundred eighty-two men and women involved in the cleanup activities between January 7 and January 20 were interviewed and examined by public health nurses to determine whether they suffered physical symptoms after exposure to the oil spill. Urine examinations for hydrocarbon toxicological markers were performed on 97 residents. The average number of days worked on cleanup activities was 4.7 days for men and 4.3 for women. Seventeen percent of the subjects had worked on cleanup activities for more than 10 days. Protective equipment was used against direct exposure to oil during the cleanup jobs and consisted of gloves used by almost 100% of the subjects and masks used by 87.1% of women and by only 35.4% of men. Glasses were worn by less than 30% of the subjects. Many symptoms emerged after the beginning of cleanup activities. The principal symptoms included low back pain and leg pain, headache, and symptoms of eyes and throat. Among the subjects undergoing urine tests, only three people showed a higher level of hippuric acid, although they returned to normal in the second examination. Accordingly, the exposure to the oil and the subsequent cleanup efforts were suggested to inflict acute health problems on local residents.

The worst histologic elements predict prognosis in moderately-differentiated prostate cancer patients with androgen-withdrawal endocrine therapy.

OBJECTIVES: We evaluated the prognostic value of the worst histologic elements in 155 patients with moderately-differentiated prostate cancer (Gleason sum 5-7) treated with androgen-withdrawal endocrine therapy. METHODS: In individual cases, the proportion (%) of medullary/solid combined with columns-and-cords/trabecular (MED & C-C), regarded as the worst histologic elements, determined according to WHO-Mostofi's classification of histologic patterns, within the total adenocarcinoma area obtained from needle specimens was estimated. RESULTS: Patients with proportion of MED & C-C >5% had a significantly poorer prognosis than those with <5% (p < 0.05). A significant difference was also found in the survival curves of patients grouped by stage (p < 0.01). There was no significant difference among the patients with Gleason sum of 5, 6 and 7. Multivariate analysis showed that stage and MED & C-C had independent prognostic value. CONCLUSIONS: Proportion of MED & C-C may provide useful prognostic information about patients with moderately-differentiated, Gleason sum 5-7, prostate cancer treated with androgen-withdrawal endocrine therapy.

Expression and prognostic value of CD44 isoforms in transitional cell carcinoma of renal pelvis and ureter.

PURPOSE: We retrospectively evaluated the expression and prognostic value of CD44 isoforms in transitional cell carcinoma of the renal pelvis and ureter. MATERIALS AND METHODS: Using a labeled streptavidin-biotin-peroxidase method we performed immunohistochemical staining of archival tissue specimens from 62 men and 26 women with a mean age of 66.5 years who had transitional cell carcinoma of the renal pelvis and ureter. RESULTS: The expression of CD44 standard (CD44s) and splice variant 6 (CD44v6) proteins was significantly decreased in relation to histological grade and pathological stage, while expression of the CD44 splice variant 3 (CD44v3) protein was decreased in relation to histological grade. The prognosis was more favorable in patients with greater versus less than 25% CD44s positive cells. CD44v3 and CD44v6 proteins had no prognostic value. Multivariate analysis indicated that only pathological stage has an independent prognostic value. CONCLUSIONS: The expression of CD44 isoforms is closely associated with tumor differentiation and progression. However, it is not an independent marker and has no statistical significance greater than that of stage.

Association between tumor angiogenesis and Borrmann type 4 carcinomas of the stomach.

A total of 202 gastric carcinomas, including 33 type 4 carcinomas, were studied. Intratumoral vessels were stained with an anti-CD34 monoclonal antibody before being quantitated by light microscopy (x200). The mean vessel counts for type 4 carcinomas were significantly higher than those for any other type of carcinoma, with the exception of type 1 carcinomas. Multivariate logistic regression showed that the vessel count was one of independent variables associated with type 4 carcinomas. In addition, survival analysis demonstrated that patients with type 4 carcinoma had significantly less favorable survival rates than those with other types of carcinomas.

Cyclin D1 protein overexpression is related to tumor differentiation, but not to tumor progression or proliferative activity, in transitional cell carcinoma of the bladder.

PURPOSE: We attempted to clarify the significance of cyclin D1 in the development and progression of transitional cell carcinoma of the bladder in humans. MATERIALS AND METHODS: Immunohistochemical staining of archival tissue specimens of transitional cell bladder carcinoma obtained from 163 patients was performed by the labeled streptavidin-biotin-peroxidase method. RESULTS: Cyclin D1 protein overexpression was observed in 51 of the 163 specimens (31.3%). Cyclin D1 protein overexpression was showed a highly significant inverse correlation with the histological grade of malignancy (p < 0.01). Grade 3 tumors showed a highly significant low incidence of cyclin D1 protein overexpression as compared with grade 2 tumors (p < 0.01). There was no significant correlation between the overexpression of cyclin D1 protein and tumor stage or the Ki-67 labeling index. CONCLUSION: Cyclin D1 in transitional cell bladder carcinoma was closely related to tumor differentiation but not to tumor progression. Transitional cell carcinoma of the bladder may utilize another pathway for proliferation that is independent of cyclin D1.

Prognostic significance of p53 protein overexpression in transitional cell carcinoma of the renal pelvis and ureter.

Fifty-three patients with invasive transitional cell carcinoma of the renal pelvis and ureter were studied for p53 protein overexpression by immunohistochemistry. Overexpression of p53 protein was observed in 19 patients (35.8%). There was a significant correlation between overexpression of p53 protein and histologic grade (p < 0.01). However, there was no correlation found between p53 immunoreactivity and pathologic stage. By univariate survival analysis, a significant difference in cumulative survival was observed between stage pT2 and stage pT3 or pT4 tumors (p < 0.05). The difference in survival between patients with p53-positive and negative tumors did not reach statistical significance (0.05 < p < 0.01). Multivariate analysis revealed that pathologic stage had an independent prognostic value (p < 0.05). The independent prognostic value of p53 protein overexpression did not quite reach statistical significance (p = 0.07). p53 protein nuclear overexpression appears to be a relatively weak prognostic indicator for patients with invasive transitional cell carcinoma of the renal pelvis and ureter.

Prognostic significance of Ki-67, p53, and Bcl-2 expression in prostate cancer patients with lymph node metastases: a retrospective immunohistochemical analysis.

The prognostic significance of Ki-67, p53, and Bcl-2 expression was evaluated in prostate cancer patients with lymph node metastases. Immunohistochemical staining of archived material obtained from 56 patients was performed by the streptavidin-biotin method. Univariate survival analysis showed that a Ki-67 labeling index (Ki-67 LI) of > or = 8.4 in the primary tumor identified a group of patients with a significantly poorer prognosis (P < 0.001). furthermore, a Ki-67 LI of > or = 8.7 in the nodal metastatic tumor was also associated with a poorer prognosis (P < 0.01). Multivariate analysis showed that the Ki-67 LI of primary tumors (P < 0.01) and lymph node metastases (P < 0.01) had independent prognostic value. p53 and Bcl-2 expression had no prognostic value in patients with prostate cancer and lymph node involvement. The Ki-67 LI has more prognostic value than p53 and Bcl-2 expression for patients with prostate cancer that has spread to the lymph nodes.

Smoking conditions and the relationships between smoking habits and such factors as exercise habits and morning diet among male students aged 16 to 20 years.

This article explores the smoking behavior of 307 sixteen- to twenty-year-old students, and examines the relationships between their smoking and such factors as weight, exercise or morning diets. Four-year follow-up data on their physical characteristics, exercise and morning diet, and a five-year retrospective questionnaire on smoking habits were analyzed. Our longitudinal analysis revealed that: the prevalence of smoking increased from 17.6% to 54.1%, while the semi-annual incidence of smoking decreased from 12.0% to 4.3%. The number of cigarettes smoked per day increased for 3 years after the initiation of smoking, from less than 10 cigarettes per day in the first year to more than 15 in the third year. Although there was no relationship between smoking and exercise habits, smoking habits related significantly to morning diet. In the eighteen- and nineteen-year-old age category, smoking habits affected the weight of the subjects.

Apoptosis in transitional cell carcinoma of the renal pelvis and ureter: association with proliferative activity, bcl-2 expression and prognosis.

PURPOSE: We attempted to clarify the significance of apoptosis in tumor development and progression in 64 cases of transitional cell carcinoma of the renal pelvis and ureter by investigating apoptosis, proliferative activity and bcl-2 expression. MATERIALS AND METHODS: We used in situ deoxyribonucleic acid nick end labeling for apoptotic cells and immunohistochemical staining for bcl-2 on archival tumor material. RESULTS: The apoptotic index correlated significantly with mitotic index, histological grade and pathological stage. There was no significant relationship between apoptotic index and bcl-2 expression. Patients with an apoptotic index greater than or equal to 0.22 had a poor prognosis. CONCLUSIONS: Apoptosis is closely related to proliferative activity, tumor differentiation and depth of invasion in transitional cell carcinoma of the renal pelvis and ureter.

Prognostic value of Ki-67 for recurrence and progression of superficial bladder cancer.

PURPOSE: We retrospectively reviewed 104 cases of superficial bladder cancer to ascertain whether the Ki-67 labeling index predicts recurrence and progression. MATERIALS AND METHODS: Archival specimens from superficial bladder cancer cases were immunostained with Ki-67. RESULTS: The recurrence rate was significantly higher in cases with a Ki-67 labeling index of 5.35 or greater than in those with a value less than 5.35 (p < 0.001). The recurrence rate at 2 years was 70% in cases with a Ki-67 labeling index of 5.35 or greater and 22% in those with an index less than 5.35 (p < 0.001). Using multivariate analysis the index predicted recurrence of bladder cancer (p < 0.005). Median Ki-67 labeling index in cases with progression was significantly higher than in those without progression (p < 0.01). CONCLUSIONS: The Ki-67 labeling index is an independent predictive factor for recurrence of superficial bladder cancer.

Predictive value of argyrophilic nucleolar-organizer-region-associated proteins in bladder cancer, using cell-imprint preparations.

The predictive value of quantifying argyrophilic nucleolar-organizer-region-associated proteins (Ag-NOR) in routinely processed paraffin-embedded tissue sections of bladder cancer remains controversial. The purpose of this study was to determine whether cell-imprint preparations facilitate a more accurate determination of the mean number of Ag-NOR per cell (Ag-NOR score). The utility of using the Ag-NOR scores of cell-imprint preparations as a prognostic indicator in patients with bladder cancer was explored. We evaluated 90 patients with newly diagnosed bladder cancer using cell-imprint preparations to determine Ag-NOR score. The score significantly correlated with known prognostic factors associated with this tumor, including histological grade (P < 0.001), pathological stage (P < 0.01), and papillary structure (P < 0.001). Furthermore, the Ag-NOR score appeared to be an independent predictor of intravesical tumor recurrence of superficial bladder cancer (P < 0.05). These results suggest that the Ag-NOR score determined in a cell imprint preparation may serve as a useful prognostic indicator in bladder cancer.

Prognostic significance of Ki-67 expression in transitional cell bladder carcinoma after radical cystectomy.

We evaluated the prognostic significance of the Ki-67 labeling index (Ki-67 LI) in 75 patients with transitional cell carcinoma of the bladder who underwent radical cystectomy. Immunohistochemical staining of archival material was performed by the streptavidin-biotin method. Univariate survival analysis showed that Ki-67 LI (p < 0.001), histologic grade (p < 0.05), tumor stage (p < 0.001) and the number of positive lymph nodes (p < 0.001) significantly correlated with prognosis. Multivariate survival analysis indicated that the Ki-67 LI (p < 0.05), histologic grade (p < 0.01), tumor stage (p < 0.01), presence of lymph node metastases (p < 0.05) and use of neo-adjuvant therapy (p < 0.05) had independent prognostic value. The Ki-67 LI is an independent prognostic factor for patients with transitional cell bladder cancer treated by radical cystectomy.