A Pediatric Case of B Cell Precursor ALL With Blinatumomab-associated Encephalopathy.

Blinatumomab is a CD3/CD19-directed bispecific T-cell engager used to treat relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Although blinatumomab has shown efficacy, it can cause serious adverse events, including cytokine release syndrome and neurological events. Among the neurological events, encephalopathy is rare, and knowledge is lacking. Herein, we present a pediatric case of blinatumomab-associated encephalopathy that initially presented with refractory convulsions and later developed into a cerebral infarction. The patient experienced prolonged paralysis and increased brain damage.

Assessing the Impact of COVID-19 on Incident Reporting and Elucidating the Characteristics of Incident Reports for COVID-19 Patients at the Critical Care Center of a Tertiary-Care Teaching Hospital in Japan.

The global coronavirus disease 2019 (COVID-19) pandemic has necessitated the establishment of new medical care systems worldwide. Medical staff treating COVID-19 patients perform their care duties in highly challenging and psychologically demanding situations, raising concerns about their impact on patient safety. Therefore, this study aimed to investigate and characterize incident reports related to COVID-19 patients to clarify the impact of COVID-19 on patient safety. The study included data from 557 patients admitted to the Critical Care Center of a tertiary-care teaching hospital in Osaka, Japan, from April 2020 to March 2021. The patients were divided into two groups: COVID-19 (n = 106) and non-COVID-19 (n = 451) and compared based on various characteristics, incident reporting rates, and the content of incident reports. The findings indicated a significantly higher rate of patients with incident reports in the COVID-19 group compared to the non-COVID-19 group (49.1% vs. 24.4%, P < 0.001). In addition, quantitative text analysis revealed that the topic ratio, consisting of "respiration," "circuit," "settings," "connection," "nursing," "ventilator," "control," "tape," "Oxylog®," and "artificial nose" was significantly higher in the incident reports of the COVID-19 group (P = 0.003). In conclusion, COVID-19 patients are more susceptible to adverse incidents and may face a higher risk of patient safety issues. The characteristic topics in incident reports involving COVID-19 patients primarily revolved around ventilator-related issues. In the future, the methodology used in the current study may be utilized to identify incident characteristics and implement appropriate countermeasures in the event of unknown patient safety issues.

Age-specific incidence of joint disease in paediatric patients with haemophilia: A single-centre real-world outcome based on consecutive US examination.

INTRODUCTION: Joint health is one of the most important factors contributing to a healthy life in patients with haemophilia. Recent study revealed that starting early prophylaxis was not enough to prevent joint disease in most paediatric patients with haemophilia. AIM: In this study, we aimed to determine the age-specific incidence of acute joint disease during childhood at single haemophilia treatment centre (HTC). METHOD: The joint health in 48 patients was evaluated based on consecutive US testing for 5 years at annual multidisciplinary comprehensive care. RESULTS: During the study period, 23 patients (47.9%) had no joint disease since the initial examination, whereas 13 patients (27.0%) showed development from negative to positive findings. The incidence of joint disease increased with age: 0% in preschool, 5.3% in elementary school, 14.3% in junior high school and 35% beyond high school age. Among the 13 patients who developed joint disease, two experienced acquired synovitis that resolved during the follow-up period. Statistical analysis revealed that the patients who routinely underwent follow-up by the HTC exhibited a significantly lower incidence of joint disease than did those followed up at other institutions (p < .001). CONCLUSION: These results indicated that close check-up, including routine joint examination using US as well as frequent assessment of pharmacokinetic profile at the HTC, might play an important role in avoiding joint disease among paediatric patients with haemophilia.

Hematopoietic Cell Transplantation for Inborn Errors of Immunity Other than Severe Combined Immunodeficiency in Japan: Retrospective Analysis for 1985-2016.

PURPOSE: Hematopoietic cell transplantation (HCT) is a curative therapy for most patients with inborn errors of immunity (IEI). We conducted a nationwide study on HCT for patients with IEI other than severe combined immunodeficiency (non-SCID) in Japan. METHODS: Data from the Japanese national database (Transplant Registry Unified Management Program, TRUMP) for 566 patients with non-SCID IEI, who underwent their first HCT between 1985 and 2016, were retrospectively analyzed. RESULTS: The 10-year overall survival (OS) and event-free survival (EFS) were 74% and 64%, respectively. The 10-year OS for HCT from unrelated bone marrow (URBM), accounting for 39% of HCTs, was comparable to that for HCT from matched sibling donor (MSD), 79% and 81%, respectively. HCT from unrelated cord blood (URCB), accounting for 28% of HCTs, was also common, with a 10-year OS of 69% but less robust engraftment. The intensity of conditioning was not associated with OS or neutrophil recovery; however, myeloablative conditioning was more frequently associated with infection-related death. Patients who received myeloablative irradiation showed poor OS. Multivariate analyses revealed that HCT in 1985-1995 (hazard ratio [HR], 2.0; P = 0.03), URCB (HR, 2.0; P = 0.01), and related donor other than MSD (ORD) (HR, 2.9; P < 0.001) were associated with poor OS, and URCB (HR, 3.6; P < 0.001) and ORD (HR, 2.7; P = 0.02) showed a higher incidence of retransplantation. CONCLUSIONS: We present the 1985-2016 status of HCT for non-SCID IEI in Japan with sufficient statistical power, highlighting the potential of URBM as an alternative donor and the feasibility of reduced intensity conditioning.

Altered brain metabolite concentration and delayed neurodevelopment in preterm neonates.

BACKGROUND: A very-low-birth-weight (VLBW) preterm infants is associated with an increased risk of impaired neurodevelopmental outcomes. In this study, we investigated how neonatal brain metabolite concentrations changed with postmenstrual age and examined the relationship between changes in concentration (slopes) and neurodevelopmental level at 3-4 years. METHODS: We retrospectively examined 108 VLBW preterm infants who had brain single-voxel magnetic resonance spectroscopy at 34-42 weeks' postmenstrual age. Neurodevelopment was assessed using a developmental test, and subjects were classified into four groups: developmental quotient <70, 70-84, 85-100, and >100. One-way analyses of covariance and multiple-comparison post hoc tests were used to compare slopes. RESULTS: We observed correlations between postmenstrual age and the concentrations of N-acetylaspartate and N-acetylaspartylglutamate (tNAA) (p < 0.001); creatine and phosphocreatine (p < 0.001); glutamate and glutamine (p < 0.001); and myo-inositol (p = 0.049) in the deep gray matter; and tNAA (p < 0.001) in the centrum semiovale. A significant interaction was noted among the tNAA slopes of the four groups in the deep gray matter (p = 0.022), and we found a significant difference between the <70 and 85-100 groups (post hoc, p = 0.024). CONCLUSIONS: In VLBW preterm infants, the slopes of tNAA concentrations (adjusted for postmenstrual age) were associated with lower developmental quotients at 3-4 years. IMPACT: In very-low-birth-weight preterm-born infants, a slower increase in tNAA brain concentration at term-equivalent age was associated with poorer developmental outcomes at 3-4 years. The increase in tNAA concentration in very-low-birth-weight infants was slower in poorer developmental outcomes, and changes in tNAA concentration appeared to be more critical than changes in tCho for predicting developmental delays. While tNAA/tCho ratios were previously used to examine the correlation with neurodevelopment at 1-2 years, we used brain metabolite concentrations.

Trends in osteoporosis prevalence over a 10-year period in Japan: the ROAD study 2005-2015.

INTRODUCTION: This study aimed to clarify the trends in the prevalence of osteoporosis among general inhabitants using population-based cohort data of the baseline and the survey 10 years later. MATERIALS AND METHODS: The baseline survey of the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study was conducted in 2005-2007; 1690 participants (596 men, 1094 women, mean age 65.2 years) completed all examinations of osteoporosis, including a questionnaire of medical information in the present/past and bone mineral density measurement using dual-energy absorptiometry. The fourth survey was performed in 2015-2016; 1906 individuals (637 men, 1269 women, 65.0 years) completed assessments identical to those at the baseline survey. Osteoporosis was defined using the World Health Organization criteria. RESULTS: The prevalence of lumbar spine (L2-L4) osteoporosis at the baseline survey was 13.6% (men, 3.4%; women, 19.2%) and that at the fourth survey was 9.7% (men, 1.4%; women, 13.9%), which decreased significantly (p < 0.01), while that of the femoral neck was not significantly different between the baseline and fourth surveys. Regarding the prevalence of osteoporosis of L2-L4 or the femoral neck, the prevalence of osteoporosis in women aged ≥ 70 was 38.8% at the fourth survey and 48.9% at the baseline study; thus, the prevalence at the fourth survey was significantly lower than that at the baseline survey (p < 0.01). CONCLUSIONS: In the population-based survey with a 10-year interval, the prevalence of osteoporosis at lumbar spine tended to decrease significantly. This preferable change in osteoporosis could contribute to the decrease in the occurrence of osteoporotic fracture in the future.

Epidemiology of locomotive syndrome using updated clinical decision limits: 6-year follow-ups of the ROAD study.

INTRODUCTION: Locomotive syndrome (LOCOMO) is defined by the Japanese Orthopaedic Association (JOA) as a condition requiring nursing care due to a decline in mobility resulting from musculoskeletal disorders. In 2020, the JOA announced the new definition of LOCOMO stage 3 and revision of clinical decision limits in stages of LOCOMO. However, there are few reports on the epidemiological indices of LOCOMO. This prospective cohort study aimed to investigate the prevalence, incidence, and association of poor prognosis with LOCOMO stages. MATERIALS AND METHODS: The third survey of the Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study was conducted during 2012-2013, examining a population-based cohort of 1575 participants (513 men and 1062 women, mean age 65.6 years). Three LOCOMO risk tests were performed, and patients were classified into LOCOMO stages 0, 1, 2, and 3. They were followed up for 6 years, and identical examination of LOCOMO was performed in 3- and 6-year follow-ups. Data on patients' prognoses, including disability and death, were collected. RESULTS: The prevalence of LOCOMO stages 1, 2, and 3 was 41.3, 14.9, and 11.6%, respectively. The incidence of LOCOMO stages 1, 2, and 3 were 83.7, 23.0, and 18.6 per 1000 person-years, respectively. Compared with LOCOMO stage 0, logistic regression analysis showed that LOCOMO stage 3 significantly increased the risk of disability and mortality. In addition, each value of LOCOMO risk tests for LOCOMO stage 3 increased the risk of poor prognosis. CONCLUSION: LOCOMO stage 3 is a sensitive indicator of future disability and mortality.

Body Mass Index of Elderly Patients with Normal Renal Function as a Determining Factor for Initial Vancomycin Regimen Designing.

INTRODUCTION: Currently, the use of actual body weight is recommended for dosing in vancomycin regimen designs, and it is important to perform therapeutic drug monitoring for efficacy and safety. However, the method to determine the appropriate vancomycin regimen for underweight or obese patients remains controversial. The aim of this study was to evaluate the impact of body mass index (BMI) on the relationship among vancomycin doses, trough concentration, and area under the curve (AUC). In addition, we identified the group of patients who were potentially more affected by BMI and evaluated the optimal dosing regimen to achieve the target AUC. METHODS: We retrospectively collected data from 462 patients who received vancomycin at the Osaka City University Hospital between January 2013 and September 2019. Patients were classified by their BMI group (underweight <18.5, normal weight 18.5-24.9, and obese ≥25.0 kg/m2). We assessed the association between vancomycin dose versus trough concentration or AUC as well as dose-adjusted trough concentration and AUC in each BMI subgroup to determine the doses for achieving the target AUC. RESULTS: The dose-adjusted trough concentration and AUC in elderly patients with normal renal function appeared to increase significantly with an increase in BMI (p < 0.05). Vancomycin doses that enabled the achievement of AUC400 in elderly patients with normal renal function decreased with increasing BMI: 17.7, 15.8, and 12.9 mg/kg per time in the underweight, normal weight, and obesity groups, respectively (p < 0.05). CONCLUSION: Elderly patients with normal renal function were the most affected by BMI on vancomycin trough concentration and AUC. The vancomycin regimen design in these patients should be adjusted carefully, not only based on the patient's renal function but also based on BMI.

Cervical muscle stiffness and parasympathetic nervous system improvements for treatment-resistant depression.

BACKGROUND: Although treatment-resistant depression (TRD) is a major public health problem that increases mortality due to suicides, a considerable percentage of patients do not respond adequately to variable treatments. Patients with TRD sometimes have comorbid cervical stiffness. This observational study aims to examine the association of local modulation of cervical muscles with TRD and to learn the involvement of the parasympathetic nervous system in the underlying mechanism. METHODS: A total of 1103 hospitalized patients with TRD who were resistant to outpatient care were enrolled between May 2006 and October 2021. All patients underwent local modulation of the cervical muscles by physical therapy during hospitalization. The presence or absence of TRD and whole-body disorders, such as headache, dazzling, cervical stiffness, and cardiovascular and gastrointestinal disorders, was determined by the patient's subjectivity using the self-rated medical interview sheet at admission and discharge. Pupil light reflex parameters were also measured at admission and discharge using a binocular infrared pupilometer. RESULTS: The improvement rate of TRD during hospitalization was 72.1%, and did not differ significantly by sex, age, and hospitalization period. The improvement of TRD showed a strong association with those of cervical stiffness and dazzling, a pupil light reflex disorder (p < 0.001: odds ratios = 12.76 and 6.39, respectively), but not with those of headache or cardiovascular and gastrointestinal disorders (p > 0.05). In the TRD-improved patients, the pupil light reflex parameters representative of the parasympathetic nervous system function ameliorated: pupil diameter decreased, while constriction rate and velocity increased during hospitalization. In contrast, little amelioration of the parameters was seen in the TRD-unimproved patients. CONCLUSIONS: Cervical muscle stiffness may be associated with TRD, possibly through dysfunction of the parasympathetic nervous system. TRIAL REGISTRATION: ID: UMIN000040590. First registration date: 30/05/2020.

Targeting brain regions of interest in functional near-infrared spectroscopy-Scalp-cortex correlation using subject-specific light propagation models.

Targeting specific brain regions of interest by the accurate positioning of optodes (emission and detection probes) on the scalp remains a challenge for functional near-infrared spectroscopy (fNIRS). Since fNIRS data does not provide any anatomical information on the brain cortex, establishing the scalp-cortex correlation (SCC) between emission-detection probe pairs on the scalp and the underlying brain regions in fNIRS measurements is extremely important. A conventional SCC is obtained by a geometrical point-to-point manner and ignores the effect of light scattering in the head tissue that occurs in actual fNIRS measurements. Here, we developed a sensitivity-based matching (SBM) method that incorporated the broad spatial sensitivity of the probe pair due to light scattering into the SCC for fNIRS. The SCC was analyzed between head surface fiducial points determined by the international 10-10 system and automated anatomical labeling brain regions for 45 subject-specific head models. The performance of the SBM method was compared with that of three conventional geometrical matching (GM) methods. We reveal that the light scattering and individual anatomical differences in the head affect the SCC, which indicates that the SBM method is compulsory to obtain the precise SCC. The SBM method enables us to evaluate the activity of cortical regions that are overlooked in the SCC obtained by conventional GM methods. Together, the SBM method could be a promising approach to guide fNIRS users in designing their probe arrangements and in explaining their measurement data.

Risk factors for acute kidney injury in vancomycin and piperacillin/tazobactam combination therapy: A retrospective study.

INTRODUCTION: Combined use of vancomycin (VCM) and piperacillin/tazobactam (PIPC/TAZ) has been reported to increase the incidence of acute kidney injury (AKI). However, the risk factors associated with AKI after VCM and PIPC/TAZ (VPT) administration have not yet been identified. Therefore, we retrospectively assessed patients treated with VPT to investigate the risk factors for AKI development. METHODS: The study involved patients who were treated with VPT from January 1, 2016 to March 31, 2020. The patients were divided into the AKI or non-AKI group. The clinical characteristics of patients and antimicrobial therapy were compared between the groups. Their association with AKI risk was evaluated using multivariate logistic regression analysis. RESULTS: In total, 182 patients were included, with 118 in the non-AKI group and 64 in the AKI group. Therefore, the incidence of AKI was 35.2 %. The initiation of VPT combination therapy on the same day and concomitant use of vasopressors were associated with an increased risk of AKI (odds ratio [OR] 2.55, 95 % confidential interval [CI] 1.20-5.44 and OR 3.22, 95 % CI 1.31-7.89, respectively). CONCLUSION: Our findings suggest that the concomitant use of vasopressors and initiating VPT combination therapy on the same day are likely risk factors for AKI development.

Association between types of Modic changes in the lumbar region and low back pain in a large cohort: the Wakayama spine study.

PURPOSE: The clinical significance of Modic changes in low back pain (LBP) is yet to be clarified. Thus, this study aimed to examine the association between Modic changes and LBP after adjustment for confounding factors. METHODS: We evaluated participants in the second Wakayama Spine Study. The degree of endplate changes as measured using magnetic resonance imaging was classified based on the Modic classification system. The prevalence of the types of Modic change in the lumbar region and at each level was assessed. Multivariate logistic regression analysis was conducted to determine the association between the types of Modic changes and LBP with adjustment for age, sex, body mass index, disc degeneration score, and disc displacement score. The LBP intensity was also compared according to the Visual Analogue Scale (VAS) score among the three types of Modic change. RESULTS: Overall, 814 subjects were evaluated. Type II Modic changes were the most prevalent (41.9%). Only type I Modic changes were significantly associated with LBP (odds ratio): 1.84, 95% confidence interval [CI]: 1.1-2.9). The LBP VAS score was significantly higher in subjects with type I Modic change than that in those with no Modic change (23.9 ± 26.3 vs. 9.9 ± 19.4, p < 0.05). CONCLUSION: Type I Modic changes in the lumbar region are significantly associated with LBP. Profiling Modic changes may be helpful to improve targeted treatment of LBP.

Possible involvement of the autonomic nervous system in cervical muscles of patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS).

BACKGROUND: Patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) sometimes present with stiffness of the cervical muscles. To investigate the pathophysiology of ME/CFS, this observational study compared patients with versus without recovery from ME/CFS through local modulation of the cervical muscles. METHODS: Over a period of 11 years, a total of 1226 inpatients with ME/CFS who did not respond to outpatient care were enrolled in this study. All patients received daily cervical muscle physical therapy during hospitalization. Self-rated records documenting the presence or absence of ME/CFS, as well as the representative eight symptoms that frequently accompany it at admission and discharge, were compared. Pupil diameter was also measured to examine autonomic nervous system function involvement. RESULTS: The recovery rate of ME/CFS after local therapy was 55.5%, and did not differ significantly by sex, age strata, and hospitalization period. The recovery rates of the eight symptoms were variable (36.6-86.9%); however, those of ME/CFS in the symptom subpopulations were similar (52.3-55.8%). The recovery rates of all symptoms showed strong associations with that of ME/CFS (p < 0.001). The pupil diameter was more constricted in the ME/CFS-recovered patients than in the ME/CFS-unrecovered patients in the total population and the subpopulations stratified by sex, age, and hospitalization period. CONCLUSIONS: There was a strong association between the recovery of ME/CFS and other related whole-body symptoms. The recovery of ME/CFS may be partly linked to amelioration of the autonomic nervous system in the cervical muscles. TRIAL REGISTRATION: UMIN000036634 . Registered 1 May 2019 - Retrospectively registered.

Cervical muscle diseases are associated with indefinite and various symptoms in the whole body.

PURPOSE: Patients with various and indefinite symptoms in the whole body occasionally have coincident with stiffness or tenderness of the cervical muscles. This prospective case series examined the effect of local modulation of the cervical muscles in patients with cervical disorders reporting indefinite whole-body symptoms. METHODS: A total of 1863 hospitalized patients with cervical disorders accompanying three or more indefinite whole-body symptoms, who were resistant to outpatient care, were enrolled in this study for 12 years. All patients underwent daily physical therapies to the cervical muscles during hospitalization. Self-rated records on the medical interview sheets documenting 30 representative symptoms including cervical/shoulder pain or stiffness and 28 representative indefinite whole-body symptoms at admission and discharge were compared across the population. RESULTS: The number of symptoms decreased significantly with the local modulation of the cervical muscles during hospitalization. All of the 28 indefinite whole-body symptoms at admission showed recovery rates greater than 50% at discharge. The mean number of symptoms decreased significantly from 17.8 at admission to 7.4 at discharge (p < 0.0001). The percentages of patients reporting 10 or more symptoms were 91.1% and 29.3% at admission and discharge, respectively. Moreover, 8.2% of patients reported no residual symptoms at discharge. CONCLUSION: Cervical muscle lesions may contribute to indefinite whole-body symptoms, possibly through dysfunction of the parasympathetic nervous system in the muscles. Local modulation of cervical muscles could lead to a breakthrough in the management of patients with indefinite whole-body symptoms. TRIAL REGISTRATION ID: UMIN000035445. These slides can be retrieved under Electronic Supplementary Material.

Spatiotemporal dynamics of red blood cells in capillaries in layer I of the cerebral cortex and changes in arterial diameter during cortical spreading depression and response to hypercapnia in anesthetized mice.

OBJECTIVE: Control of red blood cell velocity in capillaries is essential to meet local neuronal metabolic requirements, although changes of capillary diameter are limited. To further understand the microcirculatory response during cortical spreading depression, we analyzed the spatiotemporal changes of red blood cell velocity in intraparenchymal capillaries. METHODS: In urethane-anesthetized Tie2-green fluorescent protein transgenic mice, the velocity of fluorescence-labeled red blood cells flowing in capillaries in layer I of the cerebral cortex was automatically measured with our Matlab domain software (KEIO-IS2) in sequential images obtained with a high-speed camera laser-scanning confocal fluorescence microscope system. RESULTS: Cortical spreading depression repeatedly increased the red blood cell velocity prior to arterial constriction/dilation. During the first cortical spreading depression, red blood cell velocity significantly decreased, and sluggishly moving or retrograde-moving red blood cells were observed, concomitantly with marked arterial constriction. The velocity subsequently returned to around the basal level, while oligemia after cortical spreading depression with slight vasoconstriction remained. After several passages of cortical spreading depression, hypercapnia-induced increase of red blood cell velocity, regional cerebral blood flow and arterial diameter were all significantly reduced, and the correlations among them became extremely weak. CONCLUSIONS: Taken together with our previous findings, these simultaneous measurements of red blood cell velocity in multiple capillaries, arterial diameter and regional cerebral blood flow support the idea that red blood cell flow might be altered independently, at least in part, from arterial regulation, that neuro-capillary coupling plays a role in rapidly meeting local neural demand.

Prevalence and co-existence of locomotive syndrome, sarcopenia, and frailty: the third survey of Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study.

This study aimed to estimate the prevalence of locomotive syndrome, sarcopenia, and frailty and clarify their co-existence in a population-based cohort. The third survey of Research on Osteoarthritis/Osteoporosis Against Disability (ROAD) study was conducted between 2012 and 2013, examining 963 subjects (aged ≥ 60 years; 321 men, 642 women). Locomotive syndrome, sarcopenia, and frailty were defined using three tests proposed by Japanese Orthopaedic Association, Asian Working Group for Sarcopenia criteria, and Fried's definition, respectively. Prevalence of locomotive syndrome stages 1 and 2 were 81.0% (men, 80.4%; women, 81.3%) and 34.1% (men, 30.5%; women, 35.8%), respectively, and those of sarcopenia and frailty were 8.7% (men, 9.7%; women, 8.3%) and 4.5% (men, 2.8%; women, 5.3%), respectively. Locomotive syndrome stage 1, sarcopenia, and frailty co-existed in 2.1%; 6.5% had locomotive syndrome stage 1 and sarcopenia, 2.4% had locomotive syndrome stage 1 and frailty, while none had sarcopenia and frailty. Locomotive syndrome stage 1 presented alone in 70.0%, sarcopenia in 0.1%, and no frailty. The remaining 18.9% had none of these conditions. Co-existence of locomotive syndrome stage 2, sarcopenia, and frailty was observed in 2.0%; 5.0% had locomotive syndrome stage 2 and sarcopenia, 2.2% had locomotive syndrome stage 2 and frailty, and 0.1% had sarcopenia and frailty. Locomotive syndrome stage 2, sarcopenia, and frailty alone, presented in 24.9%, 1.7%, and 0.2%, respectively. The remaining 64.0% had none of these conditions. Most subjects with sarcopenia and/or frailty also had locomotive syndrome. Preventing locomotive syndrome may help prevent frailty and sarcopenia and subsequent disability.

Differences in prevalence and associated factors between mild and severe vertebral fractures in Japanese men and women: the third survey of the ROAD study.

Vertebral fracture (VF) is a common osteoporotic fracture, while its epidemiology varies according to regions and ethnicities, little is known about it in Japan. Using whole-spine radiographs from a population-based cohort study, the Research on Osteoarthritis/Osteoporosis Against Disability study 3rd survey performed in 2012-2013, we estimated the sex- and age-specific prevalence of VF in the Japanese. Genant's semiquantitative method (SQ) was used to define VF; SQ ≥ 1 as VF, SQ = 1 as mild VF, SQ≥ 2 as severe VF. We also revealed accurate site-specific prevalence, and associated factors with mild and severe VF. The participants were 506 men [mean age 66.3 years, standard deviation (SD):13.0] and 1038 women (mean age 65.3 years, SD: 12.6). The prevalence of VF in participants aged under 40, in their 40s, 50s, 60s, 70s, and ≥ 80 years was 17.4, 7.9, 18.5, 25.6, 26.3, and 41.5%, respectively, in men, and 2.9%, 2.4%, 7,3, 10.3, 27.1, and 53.0%, respectively, in women. Men had a significantly higher prevalence of mild VF (21.2%) than women (10.0%, p < 0.001); whereas, severe VF was significantly more prevalent in women (9.1%) than in men (4.7%, p = 0.003). VF was distributed with 2 peaks regarding site; one large peak at the thoracolumbar region, and another at the middle thoracic lesion. Low back pain and decreased walking ability were independently associated with severe VF, but not with mild VF, after adjustment for participant characteristics. Decreased walking ability was associated with multiple VFs in women, but not in men.

The effects of antifungal stewardship programs at a tertiary-care teaching hospital in Japan.

Patients with invasive fungal diseases (IFDs) generally have a high mortality rate, and resistance to antifungal drugs and the high costs associated with it have led to recent problems, necessitating the appropriate use of antifungals. To this end, we launched Antifungal Stewardship Programs (AFSPs) in our hospital. Patients who were systemically administered antifungals from January 2011 to December 2016 were enrolled this study and divided into pre-intervention and intervention groups. No significant difference was observed in defined daily doses per 1000 patient-days (23.3 ± 8.0 vs 20.4 ± 10.8, p = 0.251) between the groups. The monthly average for the days of therapy per 1000 patient-days was significantly lower in the intervention group (15.1 ± 3.1 vs 12.7 ± 4.3, p = 0.009). The cost of the antifungals reduced over the 3-year period by $260,520 (13.5%). Furthermore, a decreasing trend was observed in both the 30-day mortality (40.9% vs 30.0%, p = 0.414) and in-hospital mortality (63.6% vs 36.7%, p = 0.054) in patients with candidemia. Our results indicate that AFSPs are efficacious and cost-effective approaches.

The intervention by an antimicrobial stewardship team can improve clinical and microbiological outcomes of resistant gram-negative bacteria.

Antibiotic stewardship (AS) improves patient outcomes and rates of antibiotic susceptibilities. However, the long-term effect of AS programs (ASPs) on mortality is unclear. This study aimed to assess the impact of bedside interventions by an AS team (AST) on clinical and microbiological outcomes. This retrospective study enrolled patients with bloodstream infections (BSI) and long-term use of broad-spectrum antibiotics (more than 7 days). The main outcomes were 30-day and in-hospital mortality of patients with BSI. The secondary outcomes were the day of therapy (DOT) and susceptibility of antipseudomonal agents. Cases were classified into two groups: the pre-ASP group comprised cases between 2011 and 2013 and the post-ASP group, between 2014 and 2016. The outcomes were then compared between the two groups. Among the patients with all BSI (n = 1187), no significant differences in 30-day mortality were observed between those in the pre-ASP and post-ASP groups. However, in-hospital mortality was significantly lower in the post-ASP group than that in the pre-ASP group (24.8% vs. 18.0%; P = 0.004). Furthermore, the 30-day and in-hospital mortality of resistant gram-negative bacteraemia was significantly lower (20.4% vs.10.5%; P = 0.04 and 28.0% vs.16.1%; P = 0.03). The DOT of broad-spectrum antibiotics decreased except that of tazobactam/piperacillin. The susceptibilities of tazobactam/piperacillin, ceftazidime, cefepime, sulbactam/cefoperazone, gentamicin, ciprofloxacin levofloxacin, imipenem and meropenem were significantly better. Interventions by the AST can improve the clinical and microbiological outcomes, especially resistant gram-negative bacteria. Furthermore, this effect of our ASP can continue for a long term.

Impact of Transferrin Saturation on All-Cause Mortality in Patients on Maintenance Hemodialysis.

BACKGROUND: Transferrin saturation (TSAT) is an index that represents the iron-binding capacity of transferrin, which is the main transport protein for iron, and is widely used to evaluate iron status. OBJECTIVE: To evaluate the prognostic importance of TSAT in Japanese patients on maintenance hemodialysis (MHD). METHODS: A total of 398 patients on MHD were recruited and divided into 3 groups on the basis of their baseline TSAT levels (<20, 20-40, and >40%). RESULTS: There was no difference in the proportion of patients on erythropoiesis-stimulating agents or iron supplements between the 3 groups. During a mean follow-up period of 52.2 ± 1 6.3 months, 130 patients died of cardiovascular causes (n = 63, 15.8%) or infection (n = 47, 11.8%). Compared with the reference group (TSAT 20-40%), patients with a TSAT <20% had a significantly higher all-cause mortality rate (6.44 vs. 9.55 events per 100 patient-years, p = 0.0452). Kaplan-Meier analysis showed that all-cause mortality rate was significantly higher in patients with TSAT <20% than in the other 2 groups (p = 0.0353). CONCLUSIONS: Low TSAT was a significant independent risk factor for all-cause mortality in a cohort of Japanese patients on MHD. The findings of this study suggest that the adverse clinical outcomes in patients with low TSAT can be partly attributed to infection-related iron deficiency.