Efficacy and Safety of Monthly Minodronate Therapy in Postmenopausal Breast Cancer Patients Receiving Aromatase Inhibitors.

BACKGROUND/AIM: Post-menopausal breast cancer (BC) patients who receive adjuvant aromatase inhibitor (AI) therapy may be at increased risk of bone loss, osteoporosis, and bone fracture. We aimed to evaluate the efficacy and safety of oral bisphosphonate minodronate in preventing bone loss complications. PATIENTS AND METHODS: Patients receiving AI and 80% of those with suboptimal bone mineral density (BMD) were prescribed monthly oral minodronate 50 mg every 4 weeks for 72 weeks. BMD, bone metabolism markers, incidence of bone fractures, medication compliance, and other adverse events (AE) were examined every 24 weeks following administration. RESULTS: Fifty postmenopausal BC patients with a median age of 64.0 years were enrolled. The mean value of lumbar spine BMD was higher than that of the value before the minodronate administration at each observation point. Before and after the treatment, the median serum values of Tartrate-resistant Acid Phosphatase 5b (TRACP-5b) (mU/dl) and serum type I collagen cross-linked N-telopeptide (NTX) (nmolBCE/l) were decreased from 535.7 and 18.5 to 230.1 and 11.9, respectively. No adverse grade 2 or higher event was observed throughout this study. CONCLUSION: The combined administration of minodronate and AIs was safe and effective in preventing bone loss complications in postmenopausal BC patients.

Association between having a hot spring water supply in the home and prevention of long-term care.

BACKGROUND AND OBJECTIVE: According to basic studies, hot spring use has positive effects on the mind and body. However, the association between habitual hot spring use and prevention of long-term care is unknown. Using long-term care insurance data for the residents of Atami City, Japan, who can choose to install hot spring water supply in their homes, this study aimed to determine the association between the installation of a hot spring water supply in the home and prevention of long-term care. METHODS: 1. STUDY DESIGN: case-control study 2. SUBJECTS: 2719 residents (754 men, 1965 women) of Atami City, Shizuoka Prefecture, Japan, who received long-term care insurance and were certified as "Needing Support" or "Needing Long-Term Care" as of March 2017. 3. Survey methods: Information on long-term care insurance certification was linked to subjects' care level dating back to their initial certification. Also, the installation (or lack thereof) of hot spring water supply in each subject's home was linked to information on Atami household water use as of March 2017. 4. Analysis methods: The age distribution of the subjects was determined. Initial care status and care status as of March 2017 were then compared for the 2194 subjects who received long-term care certification at least twice. These subjects were classified into two groups: those whose care level had not changed or had improved (no change/improvement group) and those whose care level had worsened (worsening group). Subjects were then compared by sex and initial care level in terms of hot spring installation and percentages of no change/improvement or worsening of care level; odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the chi-square test. Lastly, the same analysis was performed for all subjects grouped together, and ORs and 95% CIs were calculated using the Mantel-Haenszel test. RESULTS: Hot springs were installed in the homes of 2359 subjects overall (86.8%). The no change/improvement group and the worsening group comprised 1192 and 1002 subjects, respectively. Overall, improvement or no change in care level was observed in 1050 subjects (55.2%) in the hot spring group and 142 subjects in the no hot spring group (48.5%). Sex-adjusted OR (95% CI) was 1.311 (1.025-1.677, p = 0.036), which represented a significant association. Having a hot spring water supply in the home may be associated with preventing worsening of care level. CONCLUSION: Having a hot spring water supply in the home may be associated with preventing worsening of care level.

Determining the general utilization and characteristics of orthopedic complementary and alternative medicine using a self-administered online questionnaire in Japan.

BACKGROUND: Acupuncture and moxibustion, massage, bone-setting, manual therapy, and chiropractic treatments are representative components of orthopedic complementary and alternative medicine (OCAM) in Japan. However, the state of their utilization and characteristics are unclear, and have yet to be thoroughly surveyed. The objective of this study was to survey the utilization and characteristics of OCAM in the general public. MATERIALS AND METHODS: In January 2011, we conducted a self-administered online questionnaire survey with 10,400 members of the general public, who were registered as consumer reviewers at the internet survey company. Survey topics were the use of OCAM within one month prior to the survey, the objective of using OCAM, and the presence or absence of consultation with and recommendation or referral by a physician. The subjects were divided into those who used and did not use OCAM as user and non-user groups, respectively, and the age, sex, and prevalence of past treatment for orthopedic diseases at medical institutions were compared between the groups. Data of 3,211 subjects (1,611 males and 1,600 females, mean age: 44.7 years old) were analyzed. RESULTS: Four hundred and thirty-eight subjects (13.6%) used OCAM within one month prior to the survey. The subjects in their forties used OCAM most frequently, followed by those in their twenties. The most frequent objective of OCAM usage was treatment, accounting for 63% (275 subjects) of the subjects. Fifty-three subjects (12.1%) consulted a physician, and 48 (11%) were recommended or referred by a physician. Upon logistic regression analysis, significant differences were detected in age, sex, and prevalence of treatment at a medical institution in the user group. A decreasing trend in the odds ratio correlated with subjects having received previous treatment at a medical institution, female subjects, and subjects of a younger age (p = 0.01; odds ratio = 4.33, 1.43, and 1.01, respectively), and these factors were independent. CONCLUSION: It was determined that 13.6% of the subjects had used OCAM, and many relatively young females (especially those in their forties or twenties) with a past medical history used it based on their own judgment.

Virological escape in HCV genotype-1-infected patients receiving daclatasvir plus ribavirin and peginterferon alfa-2a or alfa-2b.

BACKGROUND: Daclatasvir (DCV; BMS-790052) is a picomolar inhibitor of HCV non-structural protein 5A (NS5A) and has demonstrated efficacy in patients chronically infected with HCV. METHODS: In the double-blind, randomized studies AI444021 and AI444022, 71 Japanese patients chronically infected with HCV genotype 1 (predominantly genotype 1b) received DCV (10 mg or 60 mg) plus peginterferon alfa-2b or alfa-2a and ribavirin. Virological failure occurred in 14% (5/36) of treatment-naive patients and 54% (19/35) of prior alfa/ribavirin non-responders. Resistance testing was performed on baseline samples and samples with HCV RNA≥1,000 IU/ml at week 1 through post-treatment week 24. RESULTS: Baseline NS5A resistance-associated polymorphisms had less impact on virological response rates than IL28B genotype. All patients with virological failure had NS5A DCV-resistant variants at the time of failure. The predominant NS5A variants were L31V/M/I plus Y93H; this combination was detected in 100% (5/5) of treatment-naive patients and 74% (14/19) of non-responders with failure. Emergent resistance variants in prior non-responders (four viral breakthroughs, one relapse) were more varied with novel combinations such as L31F-ΔP32 and L28M-R30Q-A92K detected. Significant loss in DCV antiviral activity was generally only seen with ≥ two resistance-associated NS5A substitutions. All DCV-resistant variants were still detected at end of study. CONCLUSIONS: Virological failure in HCV genotype 1b treatment-naive Japanese patients receiving DCV plus alfa-2a/ribavirin or alfa-2b/ribavirin was associated with enrichment of NS5A resistance variants L31V/M-Y93H. In prior non-responders, emergent variants associated with failure also included NS5A-A92K or NS5A-ΔP32. As with L31-Y93 variants, these variants persisted.

MDMA-evoked changes in cerebral blood flow in living porcine brain: correlation with hyperthermia.

3,4-Methylenedioxymethamphetamine (MDMA) acutely releases intraneuronal dopamine and serotonin and evokes hyperthermia which is linked to toxicity for serotonin fibers. The acute effects of MDMA on cerebral blood flow (CBF) in living brain have not been described in an animal model of MDMA intoxication. We predicted that MDMA-induced hyperthermia should correlate with increased CBF in the hypothalamus, a serotonin-rich brain region subserving thermoregulation. To test this prediction, we used positron emission tomography with statistical parametric mapping for exploratory analysis of the focal changes in the magnitude of CBF in the anesthetized female Landrace pig (n = 9) at 30 and 150 min after acute challenge with MDMA-HCl (1 mg/kg, i.v.). The MDMA treatment was followed by increased CBF in the occipital cortex and in the medial mesencephalon overlapping the dorsal raphé nucleus, and reduced CBF in the cerebellar vermis and in a cluster in the medulla encompassing the left locus coeruleus. The individual increase of body temperature correlated positively with increased CBF in the vicinity of the raphé nucleus, in the hypothalamus (regions linked to thermoregulation), and also in the medial frontal cortex, which together comprise the regions receiving the most dense serotonin innervations in pig brain. Thus, individual differences in the susceptibility to MDMA-induced hyperthermia in this population correlated with the magnitude of focal increases in CBF within specific brain regions endowed with a dense serotonin innervation, including regions linked to thermoregulation.