Association between renal function and fracture incidence during treatment with teriparatide or alendronate: an exploratory subgroup analysis of the Japanese Osteoporosis Intervention Trial-05.

The association of renal function with fracture incidence during teriparatide or alendronate treatment in elderly Japanese women was examined. Fracture incidence differed by fracture type, renal function, and treatment protocol. The results provide important information on pharmacotherapy in clinical practice for osteoporosis. PURPOSE: Incidence rate of morphometric vertebral fracture was lower under treatment with once-weekly teriparatide (TPTD) followed by alendronate (ALN) than under treatment with ALN throughout the study among elderly Japanese women at high fracture risk in JOINT-05. This is an exploratory subgroup analysis according to chronic kidney disease (CKD) status at baseline. METHODS: Participants received sequential therapy with TPTD for 72 weeks, followed by ALN for 48 weeks (TPTD-ALN group, N = 483) or ALN monotherapy for 120 weeks (ALN group, N = 496). Baseline CKD status was classified by the estimated glomerular filtration rate (eGFR) and categorized as: CKD 1/2 (eGFR ≥ 60 mL/min/1.73 m2), CKD 3a (eGFR 45-59 mL/min/1.73 m2), or CKD 3b/4 (eGFR < 45 mL/min/1.73 m2). Incidences of vertebral fractures including morphometric fractures, non-vertebral fractures, and all fractures were evaluated during follow-up. RESULTS: Baseline characteristics were not different between treatment groups. Higher stages of CKD were associated with age and number of prevalent vertebral fracture. In CKD 1/2 patients (N = 556 with 90 incidents of morphometric vertebral fracture), the incidence of vertebral fractures was lower in the TPTD-ALN group than in the ALN group (p = 0.01). In CKD 3b/4 patients (N = 112 with 10 incidents of non-vertebral fracture), the incidence of non-vertebral fractures was lower in the ALN group than in the TPTD-ALN group, although the number of fractures was small. In the ALN group, the incidences of vertebral fractures, non-vertebral fractures, and all fractures remained constant across CKD stages. CONCLUSION: This exploratory analysis showed that fracture incidence on ALN was constant regardless of renal function. It also suggested that the incidence of vertebral fractures on TPTD-ALN was lower than ALN monotherapy in CKD 1/2 patients. These results provide important information for drug selection in the clinical practice of osteoporosis.

Achieving osteoporosis treat-to-target goals with teriparatide or alendronate: sub-analysis of Japanese Osteoporosis Intervention Trial-05 (JOINT-05).

INTRODUCTION: The purpose of this study was to evaluate whether bone mineral density (BMD) ≥ -2.5 SD could be used as the treat-to-target (T2T) goal when treating osteoporosis with teriparatide (TPTD) and alendronate (ALN), and to investigate the relationship with incident vertebral fracture by re-analyzing data from a randomized, controlled trial (JOINT-05) involving postmenopausal Japanese women at high fracture risk. MATERIALS AND METHODS: Participants received sequential therapy with once-weekly TPTD for 72 weeks, followed by ALN for 48 weeks (TPTD-ALN group) or ALN monotherapy for 120 weeks (ALN group). BMDs were measured at the lumbar spine (L2-4), total hip, and femoral neck at 0, 24, 48, 72, and 120 weeks by dual-energy X-ray absorptiometry. The T2T goal was BMD ≥ -2.5 SD, and the endpoint was the proportion of participants with baseline BMD < -2.5 SD in three measurement sites achieving BMD ≥ -2.5 SD. RESULTS: A total of 559 participants were selected. BMD ≥ -2.5 SD at 120 weeks in the L2-4, total hip, and femoral neck sites was achieved in 20.5%, 23.1%, and 5.9%, respectively, in the TPTD-ALN group and 22.2%, 11.7%, and 7.3%, respectively, in the ALN group. Incident vertebral fractures occurred in areas of both lower and high BMD. CONCLUSION: During the 1.5-year treatment period, more than 20% of participants achieved BMD ≥ -2.5 SD as a T2T goal at L2-4. Since the achievement level differed depending on the BMD measurement site, the appropriate site should be selected according to the baseline BMD level.

Predictors of discontinuation of osteoporosis treatment: sub-analysis of the Japanese osteoporosis intervention trial-05 (JOINT-05).

INTRODUCTION: To identify predictors of discontinuing treatment with teriparatide (TPTD) and alendronate (ALN), data from a randomized, controlled trial (JOINT-05) involving postmenopausal Japanese women at high risk of fracture were re-analyzed. MATERIALS AND METHODS: Participants received sequential therapy with once-weekly TPTD for 72 weeks followed by ALN for 48 weeks (TPTD-ALN group) or monotherapy with ALN for 120 weeks (ALN group). Background data including comorbidities, fracture prevalence, cognitive function, quality of life, activities of daily living, bone metabolism parameters, and nutrient intake were collected. The endpoints were 3 types of discontinuations by the reason: a poor compliance, adverse events (AEs), or any reason including those unrelated to AEs or poor compliance. Odds ratios (ORs) of baseline predictors of discontinuation were evaluated by single or multiple regression analysis. RESULTS: A total of 234 (49.0%) patients in the TPTD-ALN group and 167 (34.2%) patients in the ALN group discontinued. In the TPTD-ALN group, a lower serum calcium level was a significant predictor of compliance-related discontinuation. Serum 25-hydroxyvitamin D levels were lower in patients with lower serum calcium levels than with higher serum calcium levels. In the ALN group, poor cognitive function was significantly associated with compliance-related discontinuation, and higher body mass index and alcohol intake were predictors of AE-related discontinuation. Predictors of discontinuation were drug-specific. Lower serum calcium levels and poor cognitive function were predictors of discontinuing once-weekly TPTD and ALN, respectively. CONCLUSION: When starting TPTD and ALN treatment, careful attention to patients with lower serum calcium levels and poor cognitive function, respectively, may be needed for better treatment continuity.

Sequential therapy with once-weekly teriparatide injection followed by alendronate versus monotherapy with alendronate alone in patients at high risk of osteoporotic fracture: final results of the Japanese Osteoporosis Intervention Trial-05.

In this randomized, controlled trial, sequential therapy with once-weekly subcutaneous injection of teriparatide for 72 weeks, followed by alendronate for 48 weeks resulted in a significantly lower incidence of morphometric vertebral fracture than monotherapy with alendronate for 120 weeks in women with osteoporosis at high risk of fracture. PURPOSE: To determine whether the anti-fracture efficacy of sequential therapy with teriparatide, followed by alendronate is superior to that of monotherapy with alendronate, a prospective, randomized, open-label, blinded-endpoint trial was performed. METHODS: Japanese women aged at least 75 years were eligible for the study, if they had primary osteoporosis and if they were at high risk of fracture. Patients were randomly assigned (1:1) to receive the sequential therapy (once-weekly subcutaneous injection of teriparatide 56.5 µg for 72 weeks, followed by alendronate for 48 weeks) or monotherapy with alendronate for 120 weeks. The primary endpoint in the final analysis was the incidence of morphometric vertebral fracture during the 120-week follow-up period. RESULTS: Between October 2014 and June 2020, 505 patients in the sequential therapy group and 506 in the monotherapy group were enrolled. Of these, 489 and 496, respectively, were included in the main analysis. The incidence of morphometric vertebral fracture during the 120-week follow-up period in the sequential therapy group (64 per 627.5 person-years, annual incidence rate 0.1020) was significantly lower than that in the monotherapy group (126 per 844.2 person-years, annual incidence rate 0.1492), with a rate ratio of 0.69 (95% confidence interval 0.54 to 0.88, P < 0.01). After 72 weeks, no patient had a severe adverse event that was considered related to the study drug. CONCLUSION: Once-weekly injection of teriparatide, followed by alendronate resulted in a significantly lower incidence of morphometric vertebral fracture than alendronate monotherapy in women with osteoporosis who were at high risk of fracture. TRIAL REGISTRATION NUMBER, DATE OF REGISTRATION: jRCTs031180235 and UMIN000015573, March 12, 2019.

Effect of Bone Resorption Inhibitors on Serum Cholesterol Level and Fracture Risk in Osteoporosis: Randomized Comparative Study Between Minodronic Acid and Raloxifene.

The positive link between osteoporosis and hypercholesterolemia has been documented, and bone resorption inhibitors, such as nitrogen-containing bisphosphonates (N-BP) and selective estrogen receptor modulators (SERMs), are known to reduce serum cholesterol levels. However, the relationship between the baseline cholesterol level and incident fracture rate under the treatment using the bone resorption inhibitors has not been documented. We investigated the relation between vertebral fracture incident and the baseline cholesterol levels and cholesterol-lowering effect of N-BP and SERM in osteoporosis through a prospective randomized open-label study design. Patients with osteoporosis (n = 3986) were allocated into two groups based on the drug used for treatment: minodronic acid (MIN) (n = 1624) as an N-BP and raloxifene (RLX) as an SERM (n = 1623). Serum levels of cholesterol and incidence of vertebral fracture were monitored for 2 years. The vertebral fracture rates between the two groups were compared using the pre-specified stratification factors. The patients receiving MIN with baseline low-density lipoprotein (LDL)-cholesterol level of ≥ 140 mg/dL, high-density lipoprotein cholesterol level < 40 mg/dL, age group of ≥ 75 years, and T score of BMD ≥ -3 SD had significantly lower vertebral fracture rates than those receiving RLX (incidence rate ratios (IRR) 0.45 [95% confidence interval (CI) 0.30 0.75, p = 0.001], 0.25 [95% CI 0.09 0.65, p = 0.005], 0.71 [95% CI 0.56 0.91, p = 0.006], 0.47 [95% CI 0.30 0.75, p = 0.0012], respectively). The cholesterol-lowering effect was stronger in the RLX group than in the MIN group, regardless of prior statin use. These results indicated that MIN treatment was more effective in reducing fracture risk in patients with higher LDL cholesterol levels, although its cholesterol-lowering ability was lesser than the RLX treatment.Trial registration University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR), No. UMIN000005433; date: April 13, 2011.

Reliability of early stage symptoms/clinical findings of osteonecrosis of the jaw: Japanese Osteoporosis Intervention Trial-05 (JOINT-05).

INTRODUCTION: To investigate the differences in the incidence rates of suspected stage 0/1 osteonecrosis of the jaw (ONJ) and incidence risk of relevant clinical findings of suspected stage 0 ONJ between patients treated with sequential therapy comprising weekly teriparatide for 72 weeks followed by alendronate for 48 weeks vs. those who received monotherapy with alendronate for 120 weeks. MATERIALS AND METHODS: Suspected stage 0/1 ONJ was defined by non-specific symptoms. Tooth mobility and periodontal symptoms (gingival bleeding, swelling, and/or pain) were selected as clinical findings of suspected stage 0 ONJ. Poisson regression models were applied to calculate the incidence rate ratios of suspected stage 0/1 between the teriparatide group (TG) and alendronate group (AG). Generalized linear models were used to calculate the risk ratios of clinical findings between groups. RESULTS: Two hundred and sixty-one participants in the TG and 344 in the AG answered a structured questionnaire on oral health and were included in this study. There were no significant differences between the groups in the incidence rate of suspected stage 0/1 ONJ at both 72 and 120 weeks. The risk ratio of the TG to AG for tooth mobility was 0.34 (95% confidence interval [CI] 0.13-0.88, p = 0.02) at 72 weeks and 0.90 (95% CI 0.40-2.03, p = 0.83) at 120 weeks. The incidence rate of tooth mobility related to periodontal symptoms decreased in the TG and increased in the AG during the study. CONCLUSION: Tooth mobility accompanied by clinical periodontal symptoms may be a useful early sign of stage 0 ONJ.

Risk factors for incident vertebral fractures in osteoporosis pharmacotherapy: a 2-year, prospective, observational study.

INTRODUCTION: To identify predictors for incident fractures in patients on pharmaceutical treatment for osteoporosis by a secondary analysis of the Japanese Osteoporosis Intervention Trial protocol number 4 (JOINT-04), which was a 2-year, randomized, parallel-group, controlled trial of minodronate and raloxifene in women with primary osteoporosis. MATERIALS AND METHODS: This was a prospective, observational study using JOINT-04 data, in which biomarkers, such as undercarboxylated osteocalcin (ucOC), N-telopeptide of type 1 collagen, tartrate-resistant acid phosphatase 5b (TRACP-5b), bone alkaline phosphatase, homocysteine, and pentosidine in blood, and physical functions, such as the timed up and go test and one-leg standing test with eyes open (OLST), and the fall risk index, were measured. The relationships of incident morphometric vertebral fractures during the treatment period, as well as prevalent vertebral fractures, and baseline data were analyzed. RESULTS: The full analysis set of the JOINT-04 included 3247 patients (1623 in the minodronate group and 1624 in the raloxifene group). The hazard ratio (95% confidence interval) for incident vertebral fractures over 2 years of pharmacotherapy, adjusted for confounders, was 0.93 (0.90-0.96) for ucOC, 1.15 (1.08-1.23) for TRACP-5b, 1.02 (1.01-1.03) for pentosidine, 0.91 (0.88-0.94) for the OLST, and 1.27 (1.01-1.60) for the fall risk index, which were all independent predictors. CONCLUSION: Evaluating fracture risk for patients with osteoporosis considering these potential risk factors for fracture in addition to the established risk factors may be useful when starting pharmaceutical treatment.

Design of a randomized trial of teriparatide followed by alendronate: Japanese Osteoporosis Intervention Trial-05 (JOINT-05).

INTRODUCTION: Despite advances in drug treatment, the optimal treatment strategy for severe osteoporosis remains uncertain. MATERIALS AND METHODS: This article reports the design and rationale for the Japanese Osteoporosis Intervention Trial-05 (JOINT-05), a randomized, controlled trial that compares the efficacy and safety of teriparatide followed by alendronate with alendronate monotherapy for severe osteoporosis. RESULTS: Postmenopausal women aged at least 75 years were eligible for the study if they were at high risk of fracture. Patients were recruited from 113 institutions in Japan between October 2014 and December 2017. They were randomly assigned in a 1:1 ratio to the sequential therapy arm (once-weekly subcutaneous injections of teriparatide 56.5 µg for 72 weeks followed by alendronate for 48 weeks) or monotherapy arm (alendronate for 120 weeks). The regimens for alendronate are 5 mg (orally administered once daily), 35 mg (orally administered once weekly), or 900 µg (intravenously administered once every 4 weeks). The primary endpoint is the incidence of morphometric vertebral fracture at 72 weeks. The secondary endpoints include the incidence of morphometric vertebral fracture at 120 weeks; incidence of morphometric vertebral or non-vertebral fractures at 72 and 120 weeks; incidence of clinical vertebral fracture at 72 and 120 weeks; changes in bone mineral density, quality of life scores (EuroQol 5 Dimensions and the Japanese Osteoporosis Quality of Life Questionnaire short form), and a visual analog scale for back pain; and adverse events. CONCLUSION: We reported the design and rationale for the JOINT-05. The trial is registered with the Japan Registry of Clinical Trials (jRCTs031180235) and the University Hospital Medical Information Network-Clinical Trials Registry (UMIN000015573).

Study design of multi-center, open-label randomized controlled, head-to-head trial comparing minodronic acid and raloxifene: Japanese Osteoporosis Intervention Trial (JOINT)-04.

We planned to conduct multi-center, open-labeled, blinded-endpoints, head-to-head randomized trial of minodronate and raloxifene to compare incidences of vertebral and non-vertebral fractures. The study is the Japanese Osteoporosis Intervention Trial protocol number 4 (JOINT-4). Here, we present the pre-fixed study design. The inclusion criteria are ambulatory older women with osteoporosis, aged > 60 years, and without pre-specified risk factors for secondary osteoporosis and dementia. The subjects who meet selection criteria will be randomly allocated to the raloxifene (60 mg/day) or minodronate (1 mg/day or 50 mg/4 weeks) groups using the central registry. The co-primary endpoints are osteoporotic (vertebral, humeral, femoral, and radial), vertebral, and major osteoporotic (clinical vertebral, humeral, femoral, and radial) fractures. Furthermore, we plan to use the Hochberg procedure to preserve an overall type 1 error rate. In addition, changes in bone mineral density (BMD), hip-structure analysis (HSA) variables, height, bone turnover markers, serum cholesterol and triglyceride concentrations, dental health questionnaire, fall frequency, fall risk index, nursing care level, physical function, quality of life (QOL), and safety profiles were assessed as secondary endpoints. To detect 24% reduction of major osteoporotic fractures with 80% power and a two-sided significance level of 5% with a 2-year observation period, 1734 patients/treatment arm would be required. Subgroup analysis stratified to the following factors age, body mass index, BMD, 25-hydroxyvitamin D concentration, estimated glomerular filtration rate (eGFR), prevalent vertebral fracture number, hypertension status, and diabetes mellitus is pre-specified. The protocol is registered in the trial registry system, and the trial identification number is UMIN000005433.

[A Case of Sentinel Lymph Node Biopsy for Breast Cancer in an Elderly Man].

A 75-year-old man noted an elastic hard tumor under his left areola.Mammography showed a microlobulated mass, so he was diagnosed with category Ⅳ breast cancer.Ultrasonography showed a circular hypo-echoic mass that was 21mm in diameter with a moderately indistinct border.Based on core needle biopsy, the tumor was diagnosed as invasive ductal carcinoma.We performed a whole-body check-up, and he was diagnosed with T1N0M0, StageⅠ breast cancer.The patient underwent mastectomy and sentinel lymph node biopsy.The pathological diagnosis based on the resected surgical specimen was invasive ductal carcinoma, positive for ER and negative for PgR and HER2/neu protein expression, and the Ki-67 positive cell index was 20%.The surgical margins were negative, and there was no metastasis in the sentinel lymph nodes.He was administered endocrine therapy as adjuvant therapy.Two years after the surgery, he remains well without metastases.

Treatment status and radiographic features of patients with atypical femoral fractures.

BACKGROUND: The Japanese Orthopaedic Association (JOA) has been surveying approximately 3000 orthopedic surgery hospitals and clinics with inpatient facilities nationwide to collect information on atypical femoral fractures (AFFs) and patient characteristics since 2010. The present study aims to examine radiographic images and clarify the relationship between radiographic and patient characteristics of patients with AFF and treatment status. METHODS: The study involved 1996 facilities certified as clinical training sites by the JOA and 912 clinics with inpatient facilities affiliated with the Japanese Clinical Orthopaedic Association (JCOA). Additional clinical data collection and radiographic image review were performed in patients aged 35 years or older who met the American Society for Bone and Mineral Research (ASBMR) case definition for AFF and received treatment at participating facilities registered with JOA in 2013. Radiographic images were evaluated in accordance with the ASBMR case definition. RESULTS: Radiographic images of 304 fractures in 304 patients were collected. Among them, 230 fractures were determined to be AFFs. The fracture site was the proximal third in 70 AFFs (30.4%), middle third in 157 AFFs (68.3%), and distal third in 3 AFFs (1.3%). Among patients with AFFs, 173 (75.2%) were treated with bisphosphonates (BPs) and 45 patients (19.6%) were not (unknown in 12 patients). Duration of use was three years or longer in 103 patients (59.5%) and between one and three years in 24 patients (13.9%). Radiographic beaking was observed in 149 fractures (86.1%) in patients treated with BPs and 17 fractures (37.8%) in patients who were not treated with BPs (odds ratio 11.3, 95% CI 5.7-22.3). CONCLUSIONS: Radiographic beaking was observed more frequently in patients treated with BPs than in patients not treated with BPs.

Influence of the marvelous™ three-way stopcock on the natural frequency and damping coefficient in blood pressure transducer kits.

Two types of Planecta™ ports are commonly used as sampling ports in blood pressure transducer kits: a flat-type port (FTP) and a port with a three-way stopcock (PTS). Recently, a new type of three-way stopcock (Marvelous™) has been released as a Planecta™ counterpart, but its effects on the frequency characteristics and reliability of blood pressure monitoring have not been investigated. We assessed the influence of the Marvelous™ stopcock on the frequency characteristics of the pressure transducer kit. The basic pressure transducer kit, DT4812J, was modified by replacing one or two of the original three-way stopcocks with Marvelous™ stopcocks. The frequency characteristics (i.e., natural frequency and damping coefficient) of each kit were determined using wave parameter analysis software, and subsequently evaluated on a Gardner chart. Replacement of the original blood pressure transducer kit stopcocks with Marvelous™ stopcocks decreased the natural frequency (48.3 Hz) to 46.3 Hz or 44.8 Hz, respectively; the damping coefficient was not significantly changed. Plotting the data on a Gardner chart revealed that the changes fell within the adequate dynamic response region, indicating they were within the allowable range. Insertion of Marvelous™ stopcocks slightly affects the natural frequency of the pressure transducer kit, similar to inserting a PTS. The results indicate that the Marvelous™ stopcock is useful for accurate monitoring of arterial blood pressure, and may be recommended when insertion of two or more closed-loop blood sampling systems is necessary.

[Asynchronous Bilateral Neuroendocrine Breast Carcinoma - A Case Report].

We report a case of asynchronous bilateral neuroendocrine breast carcinoma. The patient was a 49-year-old woman presenting with a bloody nipple discharge from the right breast. We suspected intraductal papilloma and performed a microdochectomy. A pathological analysis of the resected specimen confirmed the diagnosis as neuroendocrine carcinoma. The tumor was positive for estrogen receptor, progesterone receptor, chromogranin A, and synaptophysin, but negative for the HER2/neu marker. The Ki-67 labeling-index was 40%. As the tumor margin was positive, breast-conserving surgery plus level II axillary lymph node dissection was performed. After surgery, radiotherapy(total dose of 50 Gy)was administered for treating residual breast involvement. Adjuvant hormonal therapy was performed for 5 years. Ten years after surgery, ultrasonography revealed a 12mm irregular hypoechoic mass in the left breast. The mass was diagnosed as a solid tubular carcinoma based on core needle biopsy findings. Subsequently, we performed breast-conserving surgery. The pathological diagnosis was a neuroendocrine carcinoma, and the tumor was positive for estrogen receptor, progesterone receptor, chromogranin A, synaptophysin, and CD56, but negative for the HER2/neu marker. The Ki-67 labeling-index was 50%. We report our experiences with a rare case of asynchronous bilateral neuroendocrine breast carcinoma. In this case, ultrasonography was a useful modality for detecting both the lesions.

Comparison of concurrent treatment with vitamin K2 and risedronate compared with treatment with risedronate alone in patients with osteoporosis: Japanese Osteoporosis Intervention Trial-03.

The aim of this study was to investigate the efficacy of concurrent treatment with vitamin K2 and risedronate compared with treatment with risedronate alone in patients with osteoporosis and to explore subsets of patients for which concurrent treatment is particularly efficacious. Women with osteoporosis aged 65 years or older were recruited from 123 institutes in Japan and allocated to take either vitamin K2 (45 mg/day) and risedronate (2.5 mg/day or 17.5 mg/week) or risedronate (2.5 mg/day or 17.5 mg/week) alone. The primary end point was the incidence of any fracture (vertebral and nonvertebral). The secondary end points were bone mineral density, height, undercarboxylated osteocalcin concentration, quality of life, and safety. Over a 2-year follow-up, vertebral or nonvertebral fractures occurred in 117 or 22 sites respectively among 931 patients in the risedronate and vitamin K2 group and in 104 or 26 sites respectively among 943 patients in the risedronate alone group. The rates of any incident fracture were similar between the two groups (incidence rate ratio 1.074, 95 % confidence interval 0.811-1.422, p = 0.62), implying that the primary end point was not met. There were no differences in the degree of increase in bone mineral density between the two groups. Undercarboxylated osteocalcin concentration decreased from 5.81 ± 3.93 ng/mL to 2.59 ± 1.52 ng/mL at 6 months in the risedronate and vitamin K2 group, whereas the change in the risedronate alone group was minimal (from 5.96 ± 4.36 ng/mL to 4.05 ± 3.40 ng/mL at 6 months) (p < 0.01). The treatment discontinuation rate was higher in the risedronate and vitamin K2 group than in the risedronate alone group (10.0 % vs 6.7 %). No unknown adverse drug reactions were reported. In conclusion, concurrent treatment with vitamin K2 and risedronate was not efficacious compared with monotherapy with risedronate in terms of fracture prevention.

Survey of hip fractures in Japan: Recent trends in prevalence and treatment.

BACKGROUND: A nationwide survey of hip fractures by the Japanese Orthopaedic Association (JOA) from 1998 to 2008 found a drastic increase in incidence. The aims of this study were to elucidate the status of hip fractures from 2009 to 2014 and to survey the causes for delayed surgery. METHODS: A tally of all hip fractures that occurred in patients from 2009 to 2014 was conducted in hospitals authorized by the JOA or in clinics with inpatient facilities of the Japanese Clinical Orthopaedic Association (JCOA). A survey of the causes for delay in surgery was conducted at 849 sites and 526 sites participated. RESULTS: A total of 488,759 hip fractures were registered. Increases in incidence from 2009 to 2014 were prominent in the 90-94-year-old age group among women and the 85-89-year-old age group among men. More trochanteric fractures than neck fractures occurred; however, the neck/trochanter ratio increased over time. The mean duration of preoperative hospital stay was 4.8 and 4.5 days, and the mean duration of hospitalization was 40.5 and 36.8 days in 2009 and 2014, respectively. There were significant differences between patients who waited for surgery up to 3 days and those who waited longer than 3 days in date of hospitalization, fracture type, comorbidities, anticoagulant use, surgical procedure, type of physician who administered anesthesia, type of anesthesia, and operating room schedule. Physicians in charge of each patient who waited for surgery for more than 3 days most frequently cited difficulties in securing operating rooms as the cause for delayed surgery. CONCLUSION: A drastic increase occurred in the number of patients with hip fractures with time in Japan. One problem in the treatment of hip fractures is the long waiting time from hospitalization to surgery resulting from difficulties in securing operating rooms.

Frequency characteristics of pressure transducer kits with inserted pressure-resistant extension tubes.

The accurate monitoring of arterial blood pressure is important for cardiovascular management. However, the frequency characteristics of pressure transducer kits are influenced by the length of the pressure-resistant tube. To date, there have been few studies addressing the frequency characteristics of pressure transducer kits with inserted pressure-resistant extension tubes (pressure-resistant extension tube (ET) circuits). In this study, we examine ET circuits from the viewpoint of the frequency characteristics of pressure transducer kits. DT4812J transducer kits (length 150 cm; Argon Medical Devices, TX, USA) were used. Three original ET circuits were prepared, with the pressure-resistant tube of the DT4812J being extended with a 30-cm length of pressure-resistant tube (180ET circuit), a 60-cm length of pressure-resistant tube (210ET circuit), and a 90-cm length of pressure-resistant tube (240ET circuit). Each of these circuits was evaluated as part of this study. The natural frequency of the original DT4812J circuit was 45.90 Hz while the damping coefficient was 0.160. For the 180 ET circuit, the natural frequency and damping coefficient were 36.4 Hz and 0.162, respectively. For the ET210 circuit, the natural frequency and damping coefficient were 30.3 Hz and 0.175, respectively. For the ET210 circuit, the natural frequency and damping coefficient were 25.3 Hz and 0.180, respectively. As a result of extending the circuit, it was found that the natural frequency decreased drastically, while the damping coefficient increased slightly. When the extension of a pressure transducer kit is required, we should pay careful attention to the major decrease in the natural frequency, which may influence the pressure monitoring.

Individual differences in sensory responses influence decision making by Drosophila melanogaster larvae on exposure to contradictory cues.

Animals make decisions on behavioral choice by evaluating internal and external signals. Individuals often make decisions in different ways, but the underlying neural mechanisms are not well understood. Here, we describe a system for observing the behavior of individual Drosophila melanogaster larvae simultaneously presented with contradictory signals, in this case attractive (yeast paste) and aversive (NaCl) signals. Olfaction was used to detect the yeast paste, whereas the ENaC/Pickpocket channel was important for NaCl detection. We found that wild-type (Canton-S) larvae fall into two decision making groups: one group decided to approach the yeast paste by overcoming the aversive signal, whereas the other group decided to forgo the yeast paste because of the aversive signal. Our findings indicate that different endogenous sensitivities to NaCl contribute to make differences between two groups and that diverse decision making steps occur in individual animals.

Factors associated with diagnostic stage of hip osteoarthritis due to acetabular dysplasia among Japanese female patients: a cross-sectional study.

BACKGROUND: In Japan, the majority of hip osteoarthritis (OA) was caused by acetabular dysplasia, and about 90 % of patients were female. The present study focused on Japanese female patients with hip OA due to acetabular dysplasia, and examined the associated factors with OA staging at diagnosis, in special reference to body weight. METHODS: Study subjects were 336 Japanese women who were newly diagnosed with hip OA caused by acetabular dysplasia at 15 hospitals in 2008. The self-administered questionnaire elicited patients' body weight at age 20 and at OA diagnosis. Four ranked OA staging according to radiographic findings of the hip joint (pre-OA, initial stage, advanced stage or terminal stage) was regarded as the outcome index. Proportional odds models in logistic regression were used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs) for severer stage of OA. RESULTS: At diagnosis, 45 % of patients suffered from terminal stage of OA, whereas 13 % and 14 % were categorized into pre-OA and initial stage, respectively. After adjustment for potential confounders, weight gain since age 20 revealed the increased ORs for severer OA stage at diagnosis (OR 2.02; 95 % CI, 1.07-3.80). Other significant characteristics were age (67+ vs. 20-49 years, OR 12.4), lower education (junior high school vs. junior college or higher, OR 4.00), parity (OR 2.19), lower acetabular head index (<60.0 vs. 71.1+, OR 2.36), and longer duration since symptom onset (6.0+ vs. <1.0 year, OR 2.94). CONCLUSIONS: Weight gain since age 20 might be involved in mechanisms of OA development, which is independent of age or severity of acetabular dysplasia.

Effect of using a Planecta™ port with a three-way stopcock on the natural frequency of blood pressure transducer kits.

Blood pressure transducer kits are equipped with two types of Planecta™ ports-the flat-type Planecta™ port (FTP) and the Planecta™ port with a three-way stopcock (PTS). We reported that FTP application decreased the natural frequency of the kits. However, Planecta™ is an invaluable tool as it prevents infection, ensures technical simplicity, and excludes air. Hence, an ideal Planecta™ port that does not decrease the frequency characteristics is required. As a first step in this direction, we aimed to assess the influence of PTSs on the natural frequency of blood transducer kits. A DTXplus transducer kit (DT4812J; Argon Medical Devices, TX, USA) was used along with ≥1 PTSs (JMS, Hiroshima, Japan), and the frequency characteristics were assessed. The natural frequency and damping coefficient of each kit were obtained by using frequency characteristics analysis software, and these parameters were evaluated by plotting them on Gardner's chart. Regardless of whether one or two PTSs were inserted, the natural frequency of the kits only slightly decreased (from 42.5 to 41.1 Hz, when 2 PTSs were used). Thus, the frequency characteristics of the kits with PTSs were adequate for pressure monitoring. The insertion of ≥2 FTPs in pressure transducer kits should be avoided, as they markedly decrease the natural frequency and lead to underdamping. However, the effect of PTS insertion in pressure transducer kits on the frequency characteristics is minimal. Thus, we found that the use of PTS markedly improved the frequency characteristics as compared to the use of FTP.