10 research outputs found
Genome-wide association study in Japanese females identifies fifteen novel skin-related trait associations
No full text博士(医学) 乙第3020号(主論文の要旨、要約、審査結果の要旨、本文)，著者名:Chihiro ENDO・Todd A. JOHNSON・Ryoko MORINO・Kazuyuki NAKAZONO・Shigeo KAMITSUJI・Masanori AKITA・Maiko KAWAJIRI・Tatsuya YAMASAKI・Azusa KAMI・Yuria HOSHI・Asami TADA・Kenichi ISHIKAWA・Maaya HINE・Miki KOBAYASHI・Nami KURUME・Yuichiro TSUNEMI・Naoyuki KAMATANI・Makoto KAWASHIMA, タイトル:Genome-wide association study in Japanese females identifies fifteen novel skin-related trait associations，掲載誌:Scientific reports.(2045-2322)，巻・頁・年:8巻 1号 p.8974(2018)，著作権関連情報:© The Author(s) 2018，DOI:10.1038/s41598-018-27145-2
Influence of gastrointestinal activity on the absorption of nilotinib
No full textNilotinib has bioavailability (BA) of only about 25% or less. The purpose of this study was to evaluate the influence of gastrointestinal activity on the absorption of nilotinib. In order to change gastrointestinal activity, mosapride was used for enhancement and butylscopolamine was used for suppression. Experiments on oral administration of nilotinib using rats whose gastrointestinal activity was altered by mosapride or butylscopolamine were carried out. The results of oral administration of acetaminophen to rats with peristalsis movement changed showed that the effects of peristalsis and gastric emptying rate (GER) on drug absorption could be evaluated in this experimental system. Similarly, even with nilotinib, no change in T-max was observed, but C-max increased and decreased significantly. Due to the change in gastrointestinal activity, C-max of nilotinib changed greatly. This showed that gastrointestinal activity affected the emulsifying action of bile and that the absorbability changed. As a result of examining the contribution to the emulsifying action, it was found that when the bile does not exist in the gastrointestinal tract, absorption of nilotinib did not change even when gastrointestinal motility was enhanced. Therefore, the results suggested that gastrointestinal activity influenced the emulsifying action of bile and the absorption of nilotinib was changed. (C) 2019 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved
Genome-wide association study in Japanese females identifies fifteen novel skin-related trait associations
No full text東京女子医科大学博士(医学)博士(医学) 乙第3020号(主論文の要旨、要約、審査結果の要旨、本文)，著者名:Chihiro ENDO・Todd A. JOHNSON・Ryoko MORINO・Kazuyuki NAKAZONO・Shigeo KAMITSUJI・Masanori AKITA・Maiko KAWAJIRI・Tatsuya YAMASAKI・Azusa KAMI・Yuria HOSHI・Asami TADA・Kenichi ISHIKAWA・Maaya HINE・Miki KOBAYASHI・Nami KURUME・Yuichiro TSUNEMI・Naoyuki KAMATANI・Makoto KAWASHIMA, タイトル:Genome-wide association study in Japanese females identifies fifteen novel skin-related trait associations，掲載誌:Scientific reports.(2045-2322)，巻・頁・年:8巻 1号 p.8974(2018)，著作権関連情報:© The Author(s) 2018，DOI:10.1038/s41598-018-27145-2.doctoral thesi
High flow nasal oxygen therapy in preventing post Extubation Hy-Poxaemia and postoperative pulmonary complications: a systematic review and meta-analysis
No full textBackgroundHigh flow nasal oxygen therapy (HFNOT) has gained popularity in recent years in the treatment of respiratory failure in post-extubation of non-surgical and surgical patients. This systematic review and meta-analysis investigated the role of HFNOT in reducing the incidence of postoperative pulmonary complications (PPC) and post-extubation hypoxaemia.MethodsA comprehensive search of PubMed, Scopus, EBSCOHost, ProQuest, Ovid MEDLINE and Web of Science was performed. Randomised controlled trials (RCTs) that com-pared HFNOT to conventional oxygen therapy (COT) during the postoperative period were identified. Data were pooled and estimates of effect were reported using odds ratio for dichotomous outcomes and mean difference for continuous outcomes, with 95% confidence intervals.ResultsSeventeen RCTs (n = 1761 patients) were included. Compared to COT, HFNOT re-duced the incidence of PPC (OR 0.66, 95% CI 0.47 – 0.91, p = 0.01), hospital length of stay (MD = -0.31, 95% CI -0.53 – -0.1, p = 0.004) and mortality rates (OR 0.3, 95% CI 0.11 – 0.82, p = 0.02). HFNOT also resulted in significantly higher PF ratio (MD 18.17, 95% CI 9.76 – 26.57, p < 0.0001). In the subgroup analysis, the incidence of PPC was significantly lower in patients who had HFNOT applied for more than 24 hours (OR 0.5, 0.28 – 0.88 95% CI) and in non-cardiothoracic surgeries (OR 0.57, 0.38 – 0.85 95% CI). PF ratio was also significantly higher in non-cardiothoracic surgeries (MD 32.36,19.88 – 44.84 95% CI). However, PF ratio was found to be better in the HFNOT group when applied for 24 hours or less (MD 33.96, 19.25 – 48.67 95% CI).ConclusionThis meta-analysis suggests that HFNOT reduces the incidence of PPC and improves PF ratio, resulting in less post-extubation hypoxaemia. It was associated with lower mortality rates and shorter length of stay in the hospital. Larger trials should be con-ducted to validate these findings
Factors Associated with Food Form in Long-Term Care Insurance Facilities
No full textWe examined factors related to dietary intake status (food form) of long-term care facility (LTCF) residents to identify factors related to proper food form choice for older individuals requiring nursing care. We surveyed 888 residents from 37 LTCFs in Japan. We evaluated basic information (age, sex, body mass index [BMI]), food form (swallowing-adjusted diet class), Barthel Index (BI), Clinical Dementia Rating (CDR), simply evaluated eating and swallowing functions, the number of present/functional teeth, oral diadochokinesis, repetitive saliva swallowing test (RSST), and modified water swallowing test. To clarify factors associated with food form, participants who had good nutrition by oral intake were categorized into the dysphagic diet (DD) and normal diet (ND) groups. Multi-level analyses were used to detect oral functions associated with food form status. Among objective assessments, BMI (odds ratio [OR] 0.979, 95% confidence interval [CI] - 0.022- to 0.006, p = 0.001), BI (OR 0.993, 95% CI - 0.007 to - 0.004, p < 0.001), CDR 3.0 (OR 1.002, 95% CI 0.002-0.236, p = 0.046), present teeth (OR 0.993, 95% CI - 0.007 to - 0.001, p = 0.011), functional teeth (OR 0.989, 95% CI - 0.011 to - 0.005, p < 0.001), and RSST (OR 0.960, 95% CI - 0.041 to - 0.007, p = 0.006) were significantly associated with DD vs ND discrimination. Simple evaluations of coughing (OR 1.056, 0.054-0.198, p = 0.001) and rinsing (OR 1.010, 0.010-0.174, p = 0.029) could also discriminate food form status. These simple evaluations provide insight into the discrepancies between food form status and eating abilities of LTCF residents. Periodic evaluations by the nursing caregiver may help to prevent aspiration by older individuals with dysphagia
External Validation of Risk Prediction Score for Candidemia in Critically Ill Patients: A Retrospective Observational Study
No full textCandidemia is associated with high mortality in critically ill patients. Early diagnosis of candidemia is imperative for starting treatment. Therefore, this study was designed to externally validate the candidemia risk prediction scores. This single-center, retrospective observational study included all critically ill patients admitted to the intensive care unit at a tertiary referral center from January 2018 to December 2023. The risks and patient outcomes were analyzed using bivariate and multivariate regression analysis. A total of 500 patients were analyzed with 2 dropouts due to incomplete data. Candidemia incidence was 8.86%, with parenteral nutrition and candida colonization identified as independent risk factors. Compared to an established risk prediction score, this study demonstrated a sensitivity of 75.0% [59.7–86.8], a specificity of 65.4% [60.8–69.8], a negative predictive value of 96.4% [94.2–97.8], and a positive predictive value of 17.3% [14.5–20.5]. The candidemia group had a significantly higher mean SOFA score, longer time in ICU, longer hospital length of stay, and higher rates of both ICU and in-hospital mortality. This study shows that the risk prediction score is more effective as a tool for excluding rather than predicting candidemia. We recommend against using it as the sole diagnostic guide
異なる骨吸収抑制薬に起因する顎骨壊死様病変の早期段階における免疫病理的相違
No full textThere is limited information about denosumab-related osteonecrosis of the jaw (DRONJ), unlike bisphosphonate-related ONJ (BRONJ). The mode of action is clearly different between denosumab and bisphosphonates. DRONJ occurs mainly following tooth extraction in cancer patients treated with the combination of denosumab and other drugs including chemotherapy. However, DRONJ animal models similar to these clinical situations have not been developed. The aims of this study were to 1) create a new model of high-prevalence chemotherapy/anti-RANKL antibody-related ONJ-like lesions to mimic patients receiving a denosumab/chemotherapy combination; and 2) compare the histopathological and immunopathological findings in the early stages of BRONJ-like and anti-RANKL antibody-related ONJ-like lesions. Cyclophosphamide (CY) and anti-mouse RANKL monoclonal antibody (mAb) or zoledronate combination therapy (CY/mAb and CY/ZA, respectively) was performed to create ONJ-like lesions in female C57BL/6J mice. Both maxillary first molars were extracted at 3 weeks after drug administration. The animals were euthanized at either 2 or 4 weeks after tooth extraction. Increased necrotic bone and empty lacunae with decreased living bone and osteocyte numbers were common histopathological findings in CY/mAb- and CY/ZA-induced impaired wound healing at 4 weeks after tooth extraction, and they were diagnosed as ONJ-like lesions based on validation of BRONJ and DRONJ in humans. In areas of impaired healing at 2 weeks post-extraction, decreases in angiogenesis and F4/80+LYVE-1− macrophages were noted as common immunopathological findings, although anti-angiogenesis was worse with CY/mAb than with CY/ZA. Interestingly, CY/mAb did not reduce F4/80+LYVE-1+ cells and normal lymphangiogenesis remained, whereas CY/ZA profoundly suppressed the larger size of F4/80+LYVE-1+ cells, similar to vessels with a concomitant decrease in lymphangiogenesis. Therefore, the distribution of the larger size of F4/80+LYVE-1+ cells differed in the early stages between different antiresorptive-induced ONJ-like lesions in conjunction with lymphangiogenesis, although the histopathological findings were similar. These findings suggest that the pathogenesis of BRONJ and DRONJ may differ due to the distributions of F4/80+LYVE-1+ tube-like-structured cells.長崎大学学位論文 学位記番号:博(医歯薬)甲第1259号 学位授与年月日:令和2年6月3日Author: Hiroki Hayano, Shinichiro Kuroshima, Muneteru Sasaki, Saki Tamaki, Maaya Inoue, Akira Ishisaki, Takashi SawaseCitation: Bone, 135, 115308; 202
Ultrasonography Assessment of Neck Anatomy for Prediction of Difficult Mask Ventilation in Obese Patients: A Prospective Observational Study
No full textBackground: Effective mask ventilation is a very important aspect of ensuring adequate oxygenation and ventilation. However, predicting difficult mask ventilation (DMV) using bedside clinical tests remains challenging due to poor sensitivity. Our objective was to determine the correlation between the preoperative ultrasonography of anterior neck anatomy and difficult mask ventilation in different obesity classes. Methods: A prospective, observational study enrolled 90 adult obese patients undergoing general anesthesia from December 2020 to November 2021 (30 patients for each class of obesity). Ultrasonography measurements were recorded for the distance of skin (DS) to hyoid bone (DSHB), epiglottis (DSEM), the anterior commissure of the vocal cords (DSAC), thyroid isthmus (DSTI), and trachea at jugular notch (DSTJ). The difficulty of bag mask ventilation was graded using the Han scale. The Kendall Tau correlation coefficient was used to correlate the different ultrasonography parameters to DMV. Receiver-operating characteristic (ROC) curves were used to determine the sensitivity and specificity of the measured ultrasonography distances, and the Youden index was used to calculate the optimal cut-off values. Results: Results revealed twenty patients (22.2%) were categorized as having difficult mask ventilation. There was a statistically significant increase (p = 0.011) in the number of patients with Mallampati II in class III obesity compared to class I obesity. DSHB showed a statistically significant and strong correlation with difficult mask ventilation in patients with class II (p = 0.002, r = 0.464) and class III obesity (p = 0.002, r = 0.475). A DSHB cut-off value of 1.35 cm has a sensitivity of 83.3% and specificity of 78.8% for class III obesity. Similarly, a DSTJ cut-off value of 1.13 cm has a sensitivity of 83.3% and specificity of 66.7% for class III obesity. Conclusions: Notably, DSHB was the most specific parameter and equally as sensitive as DSTJ in predicting difficult mask ventilation in morbidly obese patients
SOFA Score Trends in Predicting Mortality in Critically Ill COVID-19 Patients
No full textThe COVID-19 pandemic increased demand for intensive care unit (ICU) beds, requiring reliable disease severity scoring tools to optimise patient management and resource allocation. This retrospective study investigated the accuracy of the Sequential Organ Failure Assessment (SOFA) score in predicting mortality among critically ill COVID-19 patients. Data from 357 patients aged 18 years and above admitted to the ICU with COVID-19 category 5a and above, requiring ventilatory support throughout 2021, were analysed. The SOFA scores were calculated on days 1, 3 and 5 of ICU admission. The highest score and trends were noted; whether scores increased, were maintained or decreased was also determined. Patient outcomes were classified as survivors and non-survivors. There were significant differences in SOFA score trends between survivors and non-survivors. The high sensitivity (83.95%) and positive predictive value (PPV) (86.08%) in those with increased SOFA score trends showed that a SOFA score of ≥9 strongly predicted mortality, albeit with moderate specificity (65.63%). High sensitivity (81.85%) with low PPV (49.45%) was seen in those with decreased SOFA score trends. A high negative predictive value (87.50%) was observed for survivors. The SOFA score trend is effective in prognosticating survival in critically ill patients with COVID-19 infection, making it useful for critical care resource management
Global, regional, national, and selected subnational levels of stillbirths, neonatal, infant, and under‐5 mortality during 1980‐2015 : a systematic analysis for the Global Burden of Disease Study 2015
No full textBackground
Established in 2000, Millennium Development Goal 4 (MDG4) catalysed extraordinary political, financial, and social commitments to reduce under-5 mortality by two-thirds between 1990 and 2015. At the country level, the pace of progress in improving child survival has varied markedly, highlighting a crucial need to further examine potential drivers of accelerated or slowed decreases in child mortality. The Global Burden of Disease 2015 Study (GBD 2015) provides an analytical framework to comprehensively assess these trends for under-5 mortality, age-specific and cause-specific mortality among children under 5 years, and stillbirths by geography over time.
Methods
Drawing from analytical approaches developed and refined in previous iterations of the GBD study, we generated updated estimates of child mortality by age group (neonatal, post-neonatal, ages 1–4 years, and under 5) for 195 countries and territories and selected subnational geographies, from 1980–2015. We also estimated numbers and rates of stillbirths for these geographies and years. Gaussian process regression with data source adjustments for sampling and non-sampling bias was applied to synthesise input data for under-5 mortality for each geography. Age-specific mortality estimates were generated through a two-stage age–sex splitting process, and stillbirth estimates were produced with a mixed-effects model, which accounted for variable stillbirth definitions and data source-specific biases. For GBD 2015, we did a series of novel analyses to systematically quantify the drivers of trends in child mortality across geographies. First, we assessed observed and expected levels and annualised rates of decrease for under-5 mortality and stillbirths as they related to the Soci-demographic Index (SDI). Second, we examined the ratio of recorded and expected levels of child mortality, on the basis of SDI, across geographies, as well as differences in recorded and expected annualised rates of change for under-5 mortality. Third, we analysed levels and cause compositions of under-5 mortality, across time and geographies, as they related to rising SDI. Finally, we decomposed the changes in under-5 mortality to changes in SDI at the global level, as well as changes in leading causes of under-5 deaths for countries and territories. We documented each step of the GBD 2015 child mortality estimation process, as well as data sources, in accordance with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).
Findings
Globally, 5·8 million (95% uncertainty interval [UI] 5·7–6·0) children younger than 5 years died in 2015, representing a 52·0% (95% UI 50·7–53·3) decrease in the number of under-5 deaths since 1990. Neonatal deaths and stillbirths fell at a slower pace since 1990, decreasing by 42·4% (41·3–43·6) to 2·6 million (2·6–2·7) neonatal deaths and 47·0% (35·1–57·0) to 2·1 million (1·8-2·5) stillbirths in 2015. Between 1990 and 2015, global under-5 mortality decreased at an annualised rate of decrease of 3·0% (2·6–3·3), falling short of the 4·4% annualised rate of decrease required to achieve MDG4. During this time, 58 countries met or exceeded the pace of progress required to meet MDG4. Between 2000, the year MDG4 was formally enacted, and 2015, 28 additional countries that did not achieve the 4·4% rate of decrease from 1990 met the MDG4 pace of decrease. However, absolute levels of under-5 mortality remained high in many countries, with 11 countries still recording rates exceeding 100 per 1000 livebirths in 2015. Marked decreases in under-5 deaths due to a number of communicable diseases, including lower respiratory infections, diarrhoeal diseases, measles, and malaria, accounted for much of the progress in lowering overall under-5 mortality in low-income countries. Compared with gains achieved for infectious diseases and nutritional deficiencies, the persisting toll of neonatal conditions and congenital anomalies on child survival became evident, especially in low-income and low-middle-income countries. We found sizeable heterogeneities in comparing observed and expected rates of under-5 mortality, as well as differences in observed and expected rates of change for under-5 mortality. At the global level, we recorded a divergence in observed and expected levels of under-5 mortality starting in 2000, with the observed trend falling much faster than what was expected based on SDI through 2015. Between 2000 and 2015, the world recorded 10·3 million fewer under-5 deaths than expected on the basis of improving SDI alone
