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Summary: We developed a Markov microsimulation model among hypothetical cohorts of community-dwelling US white women without prior major osteoporotic fractures over a lifetime horizon. At ages 75 and 80, adding 1 year of exercise to 5 years of oral bisphosphonate therapy is cost-effective at a conventionally accepted threshold compared with bisphosphonates alone. Introduction: The purpose of this study was to examine the cost-effectiveness of the combined strategy of oral bisphosphonate therapy for 5 years and falls prevention exercise for 1 year compared with either strategy in isolation. Methods: We calculated incremental cost-effectiveness ratios [ICERs] (2014 US dollars per quality-adjusted life year [QALY]), using a Markov microsimulation model among hypothetical cohorts of community-dwelling US white women with different starting ages (65, 70, 75, and 80) without prior history of hip, vertebral, or wrist fractures over a lifetime horizon from the societal perspective. Results: At ages 65, 70, 75, and 80, the combined strategy had ICERs of $202,020, $118,460, $46,870, and $17,640 per QALY, respectively, compared with oral bisphosphonate therapy alone. The combined strategy provided better health at lower cost than falls prevention exercise alone at ages 70, 75, and 80. In deterministic sensitivity analyses, results were particularly sensitive to the change in the opportunity cost of participants' time spent exercising. In probabilistic sensitivity analyses, the probabilities of the combined strategy being cost-effective compared with the next best alternative increased with age, ranging from 35 % at age 65 to 48 % at age 80 at a willingness-to-pay of $100,000 per QALY. Conclusions: Among community-dwelling US white women ages 75 and 80, adding 1 year of exercise to 5 years of oral bisphosphonate therapy is cost-effective at a willingness-to-pay of $100,000 per QALY, compared with oral bisphosphonate therapy only. This analysis will help clinicians and policymakers make better decisions about treatment options to reduce fracture risk. [ABSTRACT FROM AUTHOR]

Summary: Our objective was to examine associations of physical activity in different life domains with peak femoral neck strength relative to load in adult women. Greater physical activity in each of the domains of sport, active living, home, and work was associated with higher peak femoral neck strength relative to load. Introduction: Our objective was to examine the associations of physical activity in different life domains with peak femoral neck strength relative to load in adult women. Composite indices of femoral neck strength integrate body size with femoral neck size and bone mineral density to gauge bone strength relative to load during a fall, and are inversely associated with incident fracture risk. Methods: Participants were 1,919 pre- and early perimenopausal women from the Study of Women's Health Across the Nation. Composite indices of femoral neck strength relative to load in three failure modes (compression, bending, and impact) were created from hip dual-energy X-ray absorption scans and body size. Usual physical activity within the past year was assessed with the Kaiser Physical Activity Survey in four domains: sport, home, active living, and work. We used multiple linear regression to examine the associations. Results: Greater physical activity in each of the four domains was independently associated with higher composite indices, adjusted for age, menopausal transition stage, race/ethnicity, Study of Women's Health Across the Nation study site, smoking status, smoking pack-years, alcohol consumption level, current use of supplementary calcium, current use of supplementary vitamin D, current use of bone-adverse medications, prior use of any sex steroid hormone pills or patch, prior use of depo-provera injections, history of hyperthyroidism, history of previous adult fracture, and employment status: standardized effect sizes ranged from 0.04 ( p < 0.05) to 0.20 ( p < 0.0001). Conclusions: Physical activity in each domain examined was associated with higher peak femoral neck strength relative to load in pre- and early perimenopausal women. [ABSTRACT FROM AUTHOR]

Purpose: Recently, direct communication with children about cancer seems to have shifted, but little is known about communication regarding discussions of future infertility risk due to cancer therapy. This study conducted cross-cultural comparisons between Japan and the United States to clarify communication patterns about cancer notification and develop appropriate information about fertility issues. Methods: An online survey was distributed to members of the Japanese Society of Pediatric Hematology/Oncology in July 2019 and the American Society of Pediatric Hematology/Oncology in July 2020. Based on the results from the survey, we developed three types of educational videos: a prepubertal version A, B, and a pubertal version. Next, we conducted a survey to assess whether these were appropriate for clinical practice. Results: We analyzed 325 physicians in Japan and 46 in the United States. In Japan, 80.5%, 91.7%, and 92.1% of the physicians notified patients aged 7-9, 10-14, and 15-17 years of their cancer diagnosis directly, respectively, compared within the United States, where the rate was 100%, regardless of age. Further, 9% and 45% of physicians in Japan and the United States, respectively, discuss fertility issues directly with patients aged 7-9 years. In the survey to assess the educational videos, 85% of the physicians preferred to use the educational videos in clinical practice. Conclusion: This is the first step in bringing concordance to communication patters for emerging cancer care around the globe and that this study and its intervention arm provide guidance in ways that ensure global equity in care.

Direct oral anticoagulants (DOACs) are used in anticoagulant therapy. The purpose of this study was to evaluate the association of DOAC-induced gastrointestinal (GI) and nervous system hemorrhage using the FDA's Adverse Event Reporting System (FAERS) database and the Japanese Adverse Drug Event Report (JADER) database. We identified and analyzed the reports of hemorrhagic reactions between 2004 and 2016 from the FAERS and JADER databases, and calculated the adjusted reported odds ratio (ROR) using the multiple logistic regression method. Additionally, we used the time-to-onset analysis. In the FAERS database, the adjusted ROR of apixaban, rivaroxaban, and dabigatran for GI hemorrhage was 6.79 (5.84-7.91), 19.58 (18.85-20.34), and 14.51 (13.58-15.51), respectively. In the JADER database, the adjusted ROR of apixaban, rivaroxaban, edoxaban, and dabigatran for GI hemorrhage was 11.80 (9.50-14.64), 11.03 (9.18-13.26), 10.17 (6.95-14.88), and 9.85 (7.23-13.42), respectively. We found that the association of GI hemorrhage with DOACs was affected by sex (female). Additionally, 30% of GI hemorrhage was observed after 30 days. Hemorrhagic reactions of both GI and nervous systems were observed in both the spontaneous reporting system databases. We recommend that female patients who experience symptoms related to GI hemorrhage should be closely monitored and advised to adhere to an appropriate care plan. Additionally, our results show that patients should be closely monitored for hemorrhage even after a month., Competing Interests: Competing Interests: JA is an employee of Medical Database Co., Ltd. The other authors have no conflict of interest., (© The author(s).)

Our objective was to examine the associations of lifetime parity and accumulated length of lactation with bone strength in women prior to the menopause transition and fracture risk during and after the transition. Participants were 2239 pre- or early peri-menopausal women from the Study of Women's Health Across the Nation (SWAN), ages 42-53 years at baseline, who had no childbirths after age 42. Bone mineral density (BMD) was measured in the femoral neck and the lumbar spine at the baseline SWAN visit using dual-energy x-ray absorptiometry, and the composite indices of femoral neck strength relative to load (in three failure modes: compression, bending, and impact) were calculated from femoral neck BMD, femoral neck size, and body size. Data on fractures after age 42 were collected for a median follow-up of 15.7 years (interquartile range, 11.4-18.5 years). In multiple linear regressions adjusted for covariates, lifetime parity was associated positively with femoral neck strength relative to load (0.024 standard deviation (SD) increment in impact strength index per childbirth, p=0.049), but accumulated length of lactation was associated negatively with lumbar spine BMD (0.018 SD decrement per every additional 6 months of lactation, p=0.040). In Cox proportional hazards regressions adjusted for covariates, neither parity nor lactation was associated with fracture hazard after age 42. In conclusion, parity and lactation have little impact on peak bone strength prior to menopause, and do not affect fracture risk after age 42 over 16-year follow-up., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Ocular graft-versus-host disease (GVHD) is a common complication after hematopoietic stem cell transplantation (HSCT). Here we compared the diagnostic rates of ocular GVHD, including its severity, prognosis and the agreement, obtained using three grading scales: the National Institutes of Health (NIH) eye score, Japanese dry eye score, and dry eye workshop score, by retrospectively reviewing the records of 82 patients who underwent HSCT. Tear dynamics and ocular surface assessments made 6-9 months after HSCT were used to determine ocular GVHD severity with the three scales. By the three scales, ocular GVHD was diagnosed in 56 patients (68.3%), 51 patients (62.2%), and 52 patients (63.4%), respectively. The Kappa coefficient was calculated to determine the agreement between scales for diagnosing ocular GVHD. The severity progression within two years after onset was also assessed by tear dynamics and ocular surface examination. The patients were categorized as no change, improved, or progressive. The three grading scales showed good agreement (Kappa = 0.87 to 0.97) in diagnosing patients with ocular GVHD, and the scores by all three were significantly associated with the patients' prognosis (p < 0.01). We recommend that multi-center research is needed for further validation and investigation.

To validate the National Institutes of Health (NIH) consensus criteria for chronic GVHD, we retrospectively reviewed 143 patients who developed GVHD later than 100 days after allogeneic hematopoietic stem cell transplantation. Their GVHD was reclassified and the severity was graded according to the criteria. Only four patients (2.8 %) could not be reclassified into any type of GVHD. In the remaining 139 patients, reclassified subtypes were late acute GVHD in 52 patients (37.4 %), classic chronic GVHD in 33 (23.7 %), and overlap syndrome in 54 (38.8 %). Of 87 patients with classic chronic GVHD or overlap syndrome, the severity was graded as mild in 21 patients (24 %), moderate in 53 (61 %), and severe in 13 (15 %). The proportions of moderate (70 %) and severe (20 %) disease were significantly higher in patients with overlap syndrome than those with classic chronic GVHD (46 and 6 %, respectively; P < 0.001). Univariate and multivariate analyses of subtypes and severity did not identify any significant prognostic values in any of the transplant outcomes, such as transplant-related mortality, overall survival, GVHD-specific survival, or discontinuation of systemic immunosuppressants. These findings suggest that the NIH consensus criteria are useful for classification of chronic GVHD, but have limited significance in predicting clinical outcomes. The validity of these criteria remains inconclusive, and future prospective studies will be required to refine them.

The Standards of Tuberculosis Treatment of Japan issued by the government and some related announcements by the Japanese Society of Tuberculosis are compared with the Recommendations of American Thoracic Society, CDC, and Infectious Diseases Society of America, and the Treatment Guidelines of WHO. International Standards of Tuberculosis Care by Tuberculosis Coalition for Technical Assistance is also referenced as appropriate. Although they are different in many ways in minor points, they share the basic principle of using the regimen of the initial phase with four drugs followed by the maintenance with two or three drugs including rifampicin and isoniazid for new cases. They also stress the importance of support of patients for treatment completion, but the ways to realize it are delicately different among them.

Despite the decline in the overall incidence of tuberculosis (TB) in many developed countries, it remains an important problem among the older population. The control of TB in the elderly remains a major challenge because of the limitations of the existing tools for the diagnosis and treatment of latent TB infection and clinically active disease. This article examines the current and possible future status of TB in the elderly, focusing on epidemiology, risk factors, preventive treatment strategies, and clinical disease., (Copyright 2010 Elsevier Inc. All rights reserved.)

Beef lean, fat, and connective tissues were inoculated with Escherichia coli O157:H7 before and after a prewashing procedure to compare the efficacy of prewashing and no prewashing on bacterial adherence and, consequently, on the removal of bacteria from the inoculated surfaces. Prewashing consisted of spraying tissues with tap water before inoculation. Final washing with disinfectant solutions compared the efficacy of several chemicals for the removal or destruction of E. coli O157:H7. The results showed that prewashing was very effective in reducing the numbers of bacterial cells on beef tissues, mainly lean tissue, in the control samples which received final washing with water. An opposite effect of prewashing was observed when disinfectant solutions were used for final washing; this may be due to dilution by water carried on the tissues after prewashing. The efficacy of chemicals was dependent on the type of exposed tissue. Hydrogen peroxide (3%) was more efficient in the removal of E. coli O157:H7 from connective tissues, with reductions greater than 4 log CFU/cm2, compared to a normally washed control (P < 0.01). Chlorhexidine (0.1%) was very efficient on fat and lean tissues, causing reductions over 5 log CFU/cm2 on not prewashed fat and lean tissues, compared to the control (P < 0.01). Acetic acid (5%) was the least effective, decreasing the number of CFU by under 1 log/cm2 as compared to the control; and no statistically significant difference was found among tissues, even though the removal of bacteria seemed less in lean tissue compared to fat or connective tissues.

Familial male precocious puberty (FMPP) is a gonadotropin-independent disorder that is inherited in an autosomal dominant, male-limited pattern. A heterozygous mutation encoding substitution of Asp578 with Gly in transmembrane helix 6 of the G protein-coupled receptor for luteinizing hormone (LHR) has been found in affected males from nine American FMPP families. Cells expressing the mutant LHR exhibit markedly increased cyclic adenosine monophosphate (cAMP) production in the absence of agonist, suggesting that autonomous Leydig cell activity in FMPP is caused by a constitutively activated LHR. We have now analyzed genomic DNA from affected males from six additional FMPP families. PCR was used to amplify a fragment of the LHR gene encoding amino acid residues 441-594. None of the six new samples contained the Asp578-->Gly mutation, as indicated by absence of digestion with MspI. PCR products were then screened for heterozygous mutations using temperature-gradient gel electrophoresis. DNA fragments from two of the patients migrated abnormally. Direct sequencing of PCR product from one affected German male revealed a heterozygous mutation (ATG-->ATA) encoding Met571-->Ile at the cytoplasmic end of helix 6, the same mutation that has been reported in another European FMPP kindred. Affected males in the second family had a novel Thr577-->Ile mutation (ACC-->ATC). Mutations in different portions of the LHR or in a different gene may be responsible for disease in the other FMPP kindreds. Agonist binding and functional coupling of the mutant receptors to the cAMP and inositol phosphate pathways were studied by transiently expressing them in COS-7 cells. Agonist affinity was unaffected by the mutations.(ABSTRACT TRUNCATED AT 250 WORDS)

We searched for germ-line mutations of the APC gene in 79 unrelated patients with familial adenomatous polyposis using a ribonuclease protection analysis coupled with polymerase chain reaction amplifications of genomic DNA. Mutations were found in 53 patients (67%); 28 of the mutations were small deletions and 2 were 1- to 2-base-pair insertions; 19 were point mutations resulting in stop codons and only 4 were missense point mutations. Thus, 92% of the mutations were predicted to result in truncations of the APC protein. More than two-thirds (68%) of the mutations were clustered in the 5' half of the last exon, and nearly two-fifths of the total mutations occurred at one of five positions. This information has significant implications for understanding the role of APC mutation in inherited forms of colorectal neoplasia and for designing effective methods for genetic counseling and presymptomatic diagnosis.

A group of Japanese were investigated for evidence of an association between Graves' disease and HL-A. Forty-four patients with the disease and 83 normal, unrelated random Japanese and Japanese-American controls were selected for study. The frequency of the W5 antigen among patients (57%) was significantly (P less than .0001) greater than among controls (20%). Of the 34 patients with abnormally elevated serum levels of anti-(thyroid) microsomal (anti-M) auto-antibodies, 56% had the W5 antigen. In contrast, of 48 control individuals tested for anti-M, only seven were seropositive and none (0%) of the seven had the W5 antigen. As expected the HL-A8 antigen was absent from this non-Caucasian population. These data demonstrate that the W5 antigen in Japanese, analogous to the HL-A8 antigen in Caucasians, is associated with Graves' disease but not with anti-M seropositivity in controls. The occurrence of different HL-A antigens in association with the same disease in different ethnic groups requires that the use of a major histocompatibility system antigen as a disease susceptibility marker must be confirmed for each ethnic group under study.