Breast cancer surgery in patients with schizophrenia: short-term outcomes from a nationwide cohort.

BACKGROUND: Although patients with schizophrenia have a higher risk of developing breast cancer than the general population, studies that have investigated postoperative complications after breast cancer surgery in patients with schizophrenia are scarce. This study examined associations between schizophrenia and short-term outcomes following breast cancer surgery. METHODS: Patients who underwent surgery for stage 0-III breast cancer between July 2010 and March 2017 were identified from a Japanese nationwide inpatient database. Multivariable analyses were conducted to compare postoperative complications and hospitalization costs between patients with schizophrenia and those without any psychiatric disorder. Three sensitivity analyses were performed: a 1 : 4 matched-pair cohort analysis with matching for age, institution, and fiscal year at admission; analyses excluding patients with schizophrenia who were not taking antipsychotic medication; and analyses excluding patients with schizophrenia who were admitted to hospital involuntarily. RESULTS: The study included 3660 patients with schizophrenia and 350 860 without any psychiatric disorder. Patients with schizophrenia had a higher in-hospital morbidity (odds ratio (OR) 1.37, 95 per cent c.i. 1.21 to 1.55), with more postoperative bleeding (OR 1.34, 1.05 to 1.71) surgical-site infections (OR 1.22, 1.04 to 1.43), and sepsis (OR 1.20, 1.03 to 1.41). The total cost of hospitalization (coefficient €743, 95 per cent c.i. 680 to 806) was higher than that for patients without any psychiatric disorder. All sensitivity analyses showed similar results to the main analyses. CONCLUSION: Although causal inferences remain premature, multivariable regression analyses showed that schizophrenia was associated with greater in-hospital morbidity and higher total cost of hospitalization after breast cancer surgery than in the general population.

Secretory IgA accumulated in the airspaces of idiopathic pulmonary fibrosis and promoted VEGF, TGF-ß and IL-8 production by A549 cells.

Secretory IgA (SIgA) is a well-known mucosal-surface molecule in first-line defense against extrinsic pathogens and antigens. Its immunomodulatory and pathological roles have also been emphasized, but it is unclear whether it plays a pathological role in lung diseases. In the present study, we aimed to determine the distribution of IgA in idiopathic pulmonary fibrosis (IPF) lungs and whether IgA affects the functions of airway epithelial cells. We performed immunohistochemical analysis of lung sections from patients with IPF and found that mucus accumulated in the airspaces adjacent to the hyperplastic epithelia contained abundant SIgA. This was not true in the lungs of non-IPF subjects. An in-vitro assay revealed that SIgA bound to the surface of A549 cells and significantly promoted production of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-ß and interleukin (IL)-8, important cytokines in the pathogenesis of IPF. Among the known receptors for IgA, A549 cells expressed high levels of transferrin receptor (TfR)/CD71. Transfection experiments with siRNA targeted against TfR/CD71 followed by stimulation with SIgA suggested that TfR/CD71 may be at least partially involved in the SIgA-induced cytokine production by A549 cells. These phenomena were specific for SIgA, distinct from IgG. SIgA may modulate the progression of IPF by enhancing synthesis of VEGF, TGF-ß and IL-8.

Stent as a bridge to surgery or immediate colectomy for malignant right colonic obstruction: propensity-scored, national database study.

BACKGROUND: The aim of this study was to compare perioperative outcomes of urgent colectomy and placement of a self-expanding metallic stent followed by colectomy for patients with malignant right colonic obstruction. Right-sided malignant obstruction is less common than left-sided. Stenting for malignant left colonic obstruction has been reported to reduce postoperative complications. However, the impact of stenting for malignant right colonic obstruction remains undefined. METHODS: The study included patients with right-sided malignant obstruction or stenosis undergoing colectomy between April 2012 and March 2017 identified from a nationwide database. Propensity score matching analysis was used to compare mortality and morbidity rates, proportion receiving a stoma and postoperative stay between urgent colectomy and stent groups. RESULTS: From 9572 patients, 1500 pairs were generated by propensity score matching. There was no significant difference in in-hospital mortality between the urgent colostomy and stent groups (1·6 versus 0·9 per cent respectively; P = 0·069). Complications were more common after urgent colectomy than stenting (22·1 versus 19·1 per cent; P = 0·042). Surgical-site infection was more likely with urgent colectomy (7·1 versus 4·4 per cent; P = 0·001). There was no significant difference between the two groups in anastomotic leakage (3·8 versus 2·6 per cent; P = 0·062). The proportion of patients needing a stoma was higher with urgent colectomy than primary treatment with stents (5·1 versus 1·7 per cent; P < 0·001). Postoperative stay was longer after urgent colectomy (15 versus 13 days; P < 0·001). CONCLUSION: Stenting followed by colectomy in patients with malignant right colonic obstruction may provide more favourable perioperative outcomes than urgent colectomy.

ANTECEDENTES: El objetivo de este estudio fue comparar los resultados perioperatorios entre la colectomía urgente y la colocación de una endoprótesis (stent) metálica autoexpandible seguida de colectomía en pacientes con obstrucción maligna del colon derecho. La obstrucción maligna del colon derecho es menos frecuente que la del colon izquierdo. Se ha demostrado que la colocación de una endoprótesis en la obstrucción maligna del colon izquierdo reduce las complicaciones postoperatorias. Sin embargo, el impacto de la colocación de una endoprótesis en la obstrucción maligna del colon derecho no está definido. MÉTODOS: Los pacientes con obstrucción o estenosis maligna del colon derecho sometidos a colectomía desde abril de 2012 hasta marzo de 2017 se analizaron a partir de una base de datos nacional. Se realizó un análisis mediante emparejamiento por puntaje de propensión para comparar la mortalidad, la morbilidad, el porcentaje de pacientes en los que se realizó un estoma y la estancia postoperatoria entre los grupos de colectomía urgente y endoprótesis. RESULTADOS: A partir de 9.572 pacientes, se generaron 1.500 parejas mediante emparejamiento por puntaje de propensión. No hubo diferencias significativas en la mortalidad hospitalaria entre los dos grupos (1,6% versus 0,9%, P = 0,07). Las complicaciones fueron más frecuentes después de la colectomía urgente en comparación con las endoprótesis (22,1% versus 19,1%, P = 0,04). La infección del sitio quirúrgico ocurrió con mayor frecuencia en el grupo de la colectomía urgente en comparación con el grupo de endoprótesis (7,1% versus 4,4%, P = 0,001). No se observaron diferencias significativas en la fuga anastomótica entre los dos grupos (3,8% versus 2,6%, P = 0,06). La proporción de pacientes que precisaron estomas fue mayor con la colectomía urgente en comparación con aquellos tratados inicialmente con endoprótesis (5,1% versus 1,7%, P < 0,001). La estancia postoperatoria fue más larga después de la colectomía urgente que tras la colocación de una endoprótesis (15 días versus 13 días, P < 0,001) CONCLUSIÓN: En pacientes con obstrucción maligna del colon derecho, la colocación de una endoprótesis seguida de colectomía puede proporcionar resultados perioperatorios más favorables en comparación con la colectomía urgente.

Evaluation of an amplicon-based custom gene panel for the diagnosis of hereditary tumors.

Genetic testing based on next-generation sequencing (NGS) analysis has recently been used to diagnose hereditary diseases. In this study, we explored the usefulness of our custom amplicon panel that targeted 23 genes related to hereditary tumors given in the American College of Medical Genetics and Genomics recommendations. We applied our custom NGS panel to samples from 12 patients previously diagnosed by Sanger sequencing as having the diseases or diagnosed clinically by meeting the diagnostic criteria in this study. Our gene panel not only successfully identified all variants detected by Sanger sequencing but also identified previously unrecognized variants that resulted in confirmation of the disease, or even in the revision of the diagnosis. For instance, a patient identified with an SDHD gene mutation actually had von Hippel-Lindau (VHL) syndrome, as determined by the presence of a pathogenic VHL gene variant. We also identified false-positive results that were generated by amplification of genome regions that are not intended to be investigated. In conclusion, NGS-based amplicon sequencing is a highly effective method to detect germline variants, as long as they are also carefully reviewed by manual inspection.

Secretory immunoglobulin A induces human lung fibroblasts to produce inflammatory cytokines and undergo activation.

Immunoglobulin (Ig)A is the most abundant immunoglobulin in humans, and in the airway mucosa secretory IgA (sIgA) plays a pivotal role in first-line defense against invading pathogens and antigens. IgA has been reported to also have pathogenic effects, including possible worsening of the prognosis of idiopathic pulmonary fibrosis (IPF). However, the precise effects of IgA on lung fibroblasts remain unclear, and we aimed to elucidate how IgA activates human lung fibroblasts. We found that sIgA, but not monomeric IgA (mIgA), induced interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1 and granulocyte-macrophage colony-stimulating factor (GM-CSF) production by normal human lung fibroblasts (NHLFs) at both the protein and mRNA levels. sIgA also promoted proliferation of NHLFs and collagen gel contraction comparable to with transforming growth factor (TGF)-ß, which is involved in fibrogenesis in IPF. Also, Western blot analysis and real-time quantitative polymerase chain reaction (PCR) revealed that sIgA enhanced production of α-smooth muscle actin (α-SMA) and collagen type I (Col I) by NHLFs. Flow cytometry showed that NHLFs bound sIgA, and among the known IgA receptors, NHLFs significantly expressed CD71 (transferrin receptor). Transfection of siRNA targeting CD71 partially but significantly suppressed cytokine production by NHLFs co-cultured with sIgA. Our findings suggest that sIgA may promote human lung inflammation and fibrosis by enhancing production of inflammatory or fibrogenic cytokines as well as extracellular matrix, inducing fibroblast differentiation into myofibroblasts and promoting human lung fibroblast proliferation. sIgA's enhancement of cytokine production may be due partially to its binding to CD71 or the secretory component.

Nationwide observational study of mortality from complicated intra-abdominal infections and the role of bacterial cultures.

BACKGROUND: The benefit of taking intra-abdominal cultures during source control procedures in patients with complicated intra-abdominal infection (CIAI) is unknown. The aim of this study was to evaluate whether intra-abdominal cultures reduce the mortality rate of CIAI. METHODS: The Japanese Diagnosis Procedure Combination database was used to identify adult patients with CIAI who had undergone source control procedures on the first day of admission to hospital between April 2014 and March 2016. In-hospital mortality was compared between patients who did and those who did not have intra-abdominal cultures taken. A generalized linear mixed-effect logistic regression model and a random intercept per hospital were used to adjust for baseline confounders and institutional differences. Subgroup analyses were also performed according to disease cause, site of onset and severity of CIAI. RESULTS: Intra-abdominal cultures were taken from 16 303 of 41 495 included patients. Multivariable logistic regression analysis showed that patients with intra-abdominal cultures had a significantly lower mortality than those without (odds ratio 0·85, 95 per cent c.i. 0·77 to 0·95). Subgroup analyses revealed statistically significant differences in mortality between patients with and without cultures among those with lower intestinal perforation, biliary tract infection/perforation, healthcare-associated CIAI and high-risk community-acquired CIAI. CONCLUSIONS: Intra-abdominal cultures obtained during source control procedures may reduce in-hospital mortality, especially in patients with lower intestinal perforation, biliary tract infection/perforation, or healthcare-associated or high-risk community-acquired CIAI.

Preoperative oral care and effect on postoperative complications after major cancer surgery.

BACKGROUND: Improving patients' oral hygiene is an option for preventing postoperative pneumonia that may be caused by aspiration of oral and pharyngeal secretions. Whether preoperative oral care by a dentist can decrease postoperative complications remains controversial. A retrospective cohort study was undertaken to assess the association between preoperative oral care and postoperative complications among patients who underwent major cancer surgery. METHODS: The nationwide administrative claims database in Japan was analysed. Patients were identified who underwent resection of head and neck, oesophageal, gastric, colorectal, lung or liver cancer between May 2012 and December 2015. The primary outcomes were postoperative pneumonia and all-cause mortality within 30 days of surgery. Patient background was adjusted for with inverse probability of treatment weighting using propensity scoring. RESULTS: Of 509 179 patients studied, 81 632 (16·0 per cent) received preoperative oral care from a dentist. A total of 15 724 patients (3·09 per cent) had postoperative pneumonia and 1734 (0·34 per cent) died within 30 days of surgery. After adjustment for potential confounding factors, preoperative oral care by a dentist was significantly associated with a decrease in postoperative pneumonia (3·28 versus 3·76 per cent; risk difference - 0·48 (95 per cent c.i. -0·64 to-0·32) per cent) and all-cause mortality within 30 days of surgery (0·30 versus 0·42 per cent; risk difference - 0·12 (-0·17 to -0·07) per cent). CONCLUSION: Preoperative oral care by a dentist significantly reduced postoperative complications in patients who underwent cancer surgery.

Association between mode of anaesthesia and severe maternal morbidity during admission for scheduled Caesarean delivery: a nationwide population-based study in Japan, 2010-2013.

BACKGROUND: Although the incidence of maternal mortality during Caesarean delivery remains very low, the rate of severe maternal morbidity is increasing. Improvements in obstetric anaesthetic practice have resulted in a dramatic reduction in the risk of maternal death from general anaesthesia. Less clear is whether the risk of severe maternal morbidity differs according to mode of anaesthesia for women undergoing Caesarean delivery. We analysed the association between the mode of anaesthesia and severe maternal morbidity during Caesarean delivery using a nationally representative inpatient database. METHODS: We identified 89 225 women undergoing scheduled Caesarean delivery from the Diagnosis Procedure Combination database in Japan, 2010-2013. We defined severe maternal morbidity as the presence of any life-threatening complications and identified women with severe maternal morbidity from the database. Propensity score-matched analysis was carried out to compare the odds of severe maternal morbidity between women who underwent general vs neuraxial anaesthesia. RESULTS: Of 89 225 women, 10 058 received general anaesthesia and 79 167 received neuraxial anaesthesia. In the propensity score-matched analysis with 10 046 pairs, a higher incidence of severe maternal morbidity was observed among patients receiving general (2.00%) rather than neuraxial anaesthesia (0.76%). The odds ratio of severe maternal morbidity was 2.68 (95% CI, 1.97-3.64) among women receiving general compared with neuraxial anaesthesia. CONCLUSIONS: For scheduled Caesarean delivery, general anaesthesia compared with neuraxial anaesthesia is associated with greater odds for severe maternal morbidity. However, we should be cautious with interpretation of these findings because they may be explained by confounding indications.

Effectiveness of early administration of tranexamic acid in patients with severe trauma.

BACKGROUND: A reduction in mortality with the early use of tranexamic acid has been demonstrated in severely injured patients who are bleeding. However, the modest treatment effect with no reduction in blood transfusion has raised concerns. The aim of the present study was to estimate the effectiveness of regular use of tranexamic acid in severely injured patients. METHODS: This multicentre observational study used retrospectively collected data from consecutive injured patients (Injury Severity Score at least 16) treated in 15 Japanese academic institutions in 2012. A propensity score-matched analysis compared patients who did or did not receive tranexamic acid administration within 3 h of injury. Study outcomes included 28-day all-cause and cause-specific mortality, and need for blood transfusion. RESULTS: Of 796 eligible subjects, 281 were treated with tranexamic acid. Propensity score matching selected a total of 500 matched subjects (250 in each group). Tranexamic acid administration was associated with lower 28-day mortality (10·0 versus 18·4 per cent; difference -8·4 (95 per cent c.i. -14·5 to -2·3) per cent) and lower 28-day mortality from primary brain injury (6·0 versus 13·2 per cent; difference -7·2 (-12·3 to -2·1) per cent). However, there was no significant difference between groups in the need for blood transfusion (33·2 versus 34·8 per cent; difference -1·6 (-9·9 to 6·7) per cent). CONCLUSION: Early tranexamic acid use was associated with reduced mortality in severely injured patients, in particular those with a primary brain injury.

Prolonged propofol infusion for mechanically ventilated children.

We retrospectively analysed 30-day mortality and duration of intubation for 8016 children ventilated for three or more days, sedated with midazolam (n = 7716) or propofol (n = 300). We matched the propensity scores of 263 pairs of children. The propensity-matched 30-day mortality (95% CI) was similar: 17/263 (6.5%) with midazolam vs. 24/263 (9.1%) with propofol, p = 0.26. Weaning from mechanical ventilation of children sedated with midazolam was slower than weaning of children sedated with propofol, subhazard ratio (95% CI) 1.43 (1.18-1.73), p < 0.001.

Emergence of resistant variants detected by ultra-deep sequencing after asunaprevir and daclatasvir combination therapy in patients infected with hepatitis C virus genotype 1.

Daclatasvir (DCV) and asunaprevir (ASV) are NS5A and NS3 protease-targeted antivirals respectively, currently under development for the treatment of chronic hepatitis C virus (HCV) infection. We analysed the relationship between pre-existing drug-resistant variants and clinical outcome of the combination treatment with DCV and ASV. Ten patients with HCV genotype 1b were orally treated with a combination of ASV and DCV for 24 weeks. The frequencies of amino acid (aa) variants at NS3 aa positions 155, 156 and 168 and at NS5A aa31 and 93 before and after treatment were analysed by ultra-deep sequencing. We established a minimum variant frequency threshold of 0.3% based on plasmid sequencing. Sustained virological response (SVR) was achieved in 8 out of 10 patients (80%), and relapse of HCV RNA after cessation of the treatment and viral breakthrough occurred in the other two patients. Pre-existing DCV-resistant variants (L31V/M and/or Y93H; 0.9-99.4%) were detected in three out of eight patients who achieved SVR. Pre-existing DCV-resistant variants were detected in a relapsed patient (L31M, Y93H) and in a patient with viral breakthrough (Y93H); however, no ASV-resistant variants were detected. In these patients, HCV RNA rebounded with ASV- and DCV- double resistant variants (NS3 D168A/V plus NS5A L31M and Y93H). While pre-existing DCV-resistant variants might contribute to viral breakthrough in DCV and ASV combination therapy, the effectiveness of prediction of the outcome of therapy based on ultra-deep sequence analysis of pre-existing resistant variants appears limited.

Factors that predict in-hospital mortality in eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic small-vessel vasculitis associated with asthma, eosinophilia, and necrotizing vasculitis. EGPA is potentially life-threatening and often involves peripheral neuropathies, peptic ulcers, cerebral vessel disease, and cardiovascular disease. However, there is limited understanding of the prognostics factors for patients with EGPA. We investigated the clinical features and factors affecting patients' in-hospital mortality, using a national inpatient database in Japan. METHODS: We retrospectively collected data of EGPA patients who required hospitalization between July 2010 and March 2013, using the Diagnosis Procedure Combination database. We evaluated EGPA patients' characteristics and performed multivariate logistic regression analyses to assess the factors associated with in-hospital mortality. RESULTS: A total of 2195 EGPA patients were identified. The mean age was 61.9 years, 42.1% (924/2195) were male, and 41.6% (914/2195) had emergent admission. In-hospital deaths occurred in 97/2195 patients (4.4%). Higher in-hospital mortality was associated with age older than 65 years, disturbance of consciousness on admission, unscheduled admission, respiratory disease, cardio-cerebrovascular disease, renal disease, sepsis, and malignant disease on admission. Lower mortality was associated with female gender and peripheral neuropathies. CONCLUSIONS: Our study revealed the clinical features of EGPA patients who required hospitalization and the factors associated with their mortality. These results may be useful for physicians when assessing disease severity or treatments for hospitalized EGPA patients.

Prognostic nomogram for nonresectable pancreatic cancer treated with gemcitabine-based chemotherapy.

BACKGROUND: A nomogram is progressively being used as a useful predictive tool for cancer prognosis. A nomogram to predict survival in nonresectable pancreatic cancer treated with chemotherapy has not been reported. METHODS: Using prospectively collected data on patients with nonresectable pancreatic cancer receiving gemcitabine-based chemotherapy at five Japanese hospitals, we derived a predictive nomogram and internally validated it using a concordance index and calibration plots. RESULTS: In total, 531 patients were included between June 2001 and February 2013. The American Joint Committee on Cancer (AJCC) TNM stages were III and IV in 204 and 327 patients, respectively. The median survival time of the total cohort was 11.3 months. A nomogram was generated to predict survival probabilities at 6, 12, and 18 months and median survival time, based on the following six variables: age; sex; performance status; tumour size; regional lymph node metastasis; and distant metastasis. The concordance index of the present nomogram was higher than that of the AJCC TNM staging system at 12 months (0.686 vs 0.612). The calibration plots demonstrated good fitness of the nomogram for survival prediction. CONCLUSIONS: The present nomogram can provide valuable information for tailored decision-making early after the diagnosis of nonresectable pancreatic cancer.

Cardiac function in 10-year-old twins following different fetal therapies for twin-twin transfusion syndrome.

OBJECTIVES: To compare cardiac function at 10 years of age in four groups of monochorionic diamniotic (MCDA) twin pairs: uncomplicated MCDA twins (n = 6) (Group 1); twins that had had twin-twin transfusion syndrome (TTTS) managed by amnioreduction (TTTS-amnio, n = 9) (Group 2) or laser photocoagulation (TTTS-laser, n = 10) (Group 3); and dichorionic diamniotic controls (DCDA, n = 6) (Group 4). METHODS: Echocardiograms optimizing apical four-chamber and short-axis left ventricular views were stored for offline speckle-tracking analysis, blinded to twin type. Myocardial long-axis shortening and lengthening velocities were measured using pulsed Doppler ultrasound at the cardiac base. M-mode measurements of fractional shortening (short axis) and maximal excursion of the atrioventricular annulus (four-chamber) were recorded. Syngo Vector Velocity Imaging software tracked left ventricular myocardial motion offline to produce free wall strain, strain rate and rotation. Intertwin pair and group differences were investigated using ANOVA. RESULTS: Cardiac measurements were within the normal ranges for 10-year-olds. No significant within-twin-pair and intergroup differences were found in current size, heart rates, strain or strain rate. Compared to DCDA controls, TTTS twins showed less cardiac rotation (TTTS-laser, P < 0.001 and TTTS-amnio, P = 0.054) with significant intertwin reduction in the ex-recipient (TTTS-amnio, P = 0.006) and larger MCDA twins (P = 0.027) compared with their cotwins. A similar pattern was seen in left ventricular early diastolic mitral valve tissue velocity (MVE') in all monochorionic groups, but only achieving significance in TTTS-amnio twins (P = 0.037). Intrapair differences in rotation and MVE' were significantly different following treatment at Quintero stages III or IV. CONCLUSIONS: Within-twin-pair patterns of left ventricular rotation and diastolic function differ at 10 years of age in ex-recipients of TTTS twins treated with amnioreduction compared with those treated by laser photocoagulation and controls. .

Ovarian and hormonal responses to follicular phase administration of investigational metastin/kisspeptin analog, TAK-683, in goats.

This study evaluated the effects of follicular phase administration of TAK-683, an investigational metastin/kisspeptin analog, on follicular growth, ovulation, luteal function and reproductive hormones in goats. After confirmation of ovulation by transrectal ultrasonography (Day 0), PGF2α (2 mg/head of dinoprost) was administered intramuscularly on Day 10 to induce luteal regression. At 12 h after PGF2α administration, intravenous administration of vehicle or 35 nmol (50 µg)/head of TAK-683 was performed in control (n = 4) and treatment (n = 4) groups, respectively. Blood samples were collected at 6-h intervals for 96 h and then daily until the detection of subsequent ovulation (second ovulation). After the second ovulation, ultrasound examinations and blood sampling were performed every other day or daily until the subsequent ovulation (third ovulation). Mean concentrations of LH and FSH in the treatment group were significantly higher 6 h after TAK-683 treatment than those in the control group (12.0 ± 10.7 vs 1.0 ± 0.7 ng/ml for LH, 47.5 ± 28.2 vs 15.1 ± 3.4 ng/ml for FSH, p < 0.05), whereas mean concentrations of oestradiol in the treatment group decreased immediately after treatment (p < 0.05) as compared with the control group. Ovulation tended to be delayed (n = 2) or occurred early (n = 1) in the treatment group as compared with the control group. For the second ovulation, ovulatory follicles in the treatment group were significantly smaller in maximal diameter than in the control group (3.8 ± 0.5 vs 5.4 ± 0.2 mm, p < 0.05, n = 3). Administration of TAK-683 in the follicular phase stimulates gonadotropin secretion and may have resulted in ovulation of premature follicles in goats.

Financial incentives for infection prevention and antimicrobial stewardship to reduce antibiotic use: Japan's nationwide observational study.

BACKGROUND: The Japanese government introduced financial incentives to reduce nationwide antibiotic use in hospital settings. AIM: This study aimed to determine whether the nationwide financial incentives for creating infection prevention and control (IPC) teams introduced in 2012 and antimicrobial stewardship (ASP) teams introduced in 2018 were associated with changes in antibiotic use and health resource utilization at a national level. METHODS: We conducted time-series analyses and a difference-in-differences study consisting of 3,057,517 inpatients with infectious diseases from 472 medical facilities during fiscal years 2011-2018 using a nationally representative inpatient database in Japan. The primary outcome was the days of therapy (DOT) of antibiotic use per 100 patient-days (PDs). The secondary outcomes consisted of types of antibiotic used, health resource utilization, and mortality. RESULTS: A total of 5,201,304 financial incentives were observed during 2012-2018, which resulted in a total of 12.1 billion JPY (≈110 million USD). Time-series analyses found decreasing trends in total antibiotic use (79.3-72.5 DOTs/100 PDs (8.6% reduction)) and carbapenem use (9.0-7.0 DOTs/100 PDs (7.8% reduction)) from 2011 to 2018 without adversely affecting other healthcare outcomes (e.g., mortality). In the difference-in-differences analyses, we did not observe meaningful changes in total antibiotic use between the incentivized and unincentivized hospitals for ASP teams, except for the northern part of Japan. No dose-response relationships were observed between the amount of financial incentives and reductions in antibiotic use during 2011-2019. CONCLUSIONS: Further research and efforts are needed to accelerate antimicrobial stewardship in hospital settings in Japan.

Safety, pharmacokinetics and resistant variants of telaprevir alone for 12 weeks in hepatitis C virus genotype 1b infection.

BACKGROUND: Telaprevir in combination with peginterferon and ribavirin is a promising advancement in chronic hepatitis C treatment. However, the safety, tolerability, pharmacokinetics and antiviral profiles of telaprevir alone beyond 2 weeks have not been studied. METHODS: In a phase 1b study in Japan, 10 treatment-naïve patients infected with hepatitis C virus genotype 1b with high viral load (>5 log(10) IU/mL) received telaprevir 750 mg every 8 h (q8h) for 12 weeks. We examined the safety, tolerability, pharmacokinetics, hepatitis C virus (HCV) RNA levels and resistant variants of telaprevir. RESULTS: Neither serious adverse events nor discontinuations of study drug owing to an adverse event occurred. The most common adverse drug reactions were rash (80%) and anaemia (70%). Telaprevir concentration reached its steady state within 2 days after the first administration without abnormal accumulation. Telaprevir alone provided potent antiviral activity: a median log(10) decrease of 2.325 at 16 h and 5.175 on Day 14. During the treatment, HCV RNA levels at the nadir were below the limit of the quantification in seven patients and undetectable in three of 10 patients. Viral breakthrough associated with mainly Ala(156) -substituted variants occurred in eight patients, and only one patient showed end-of-treatment response. The selected variants reverted to the wild-type during the 24-week follow-up period. CONCLUSION: Telaprevir alone was well tolerated at 750 mg q8h for up to 12 weeks. The safety profile and emergence of resistant variants of genotype 1b under telaprevir monotherapy for 12 weeks will become increasingly important in evaluating an oral combination of telaprevir with other direct-acting antiviral agents.

Comparison of ex-vivo high-resolution episcopic microscopy with in-vivo four-dimensional high-resolution transvaginal sonography of the first-trimester fetal heart.

OBJECTIVE: To compare the capability of three-dimensional (3D) reconstructed images produced by high-resolution episcopic microscopy (HREM) with that of in-vivo four-dimensional high-resolution transvaginal sonography (4D-HRTVS) to discern morphological features of the first-trimester human fetal heart. METHODS: This was a prospective study of fetal hearts between 9 and 14 weeks' gestation. For ex-vivo 3D analysis, 30 human fetal hearts (at 9 + 0 to 14 + 6 weeks) were retrieved from surgical terminations of pregnancy. The specimens were embedded in resin and episcopic ('block-face') imaging was used to obtain a digital volume dataset (HREM) using 3-micron slicing. 4D-HRTVS was performed in 28 separate pregnancies at 10 + 2 to 14 + 0 weeks using a Voluson E8 ultrasound machine with volumetric transvaginal RIC 6-12-MHz transducers. Heart volumes obtained by both methods were compared to assess their ability to demonstrate first-trimester cardiac morphology. Comparisons were made in the transverse and sagittal planes, and using volume rendering. RESULTS: All hearts were structurally normal, although abdominal situs was not examined in the isolated hearts that underwent HREM. 4D-HRTVS demonstrated each of the complete five transverse cardiac views in 32-86% of cases. HREM showed four features unique to the first-trimester human heart: prominent atrial appendages, spiral ventricular arrangement, prominent coronary arteries and thickened arterial walls. 4D-HRTVS could demonstrate the first two, but ultrasound resolution was too poor to quantify wall thickness and demonstrate coronary arteries in the 3-5-mm diameter heart. CONCLUSIONS: 4D-HRTVS showed limited morphological features of the first-trimester fetal heart compared with HREM. HREM provides a gold standard of ex-vivo imaging against which developments in ultrasound resolution could be compared.

Comparison of postoperative infection after emergency inguinal hernia surgery with enterectomy between mesh repair and non-mesh repair: a national database analysis.

PURPOSE: Synthetic non-absorbable mesh is used for elective inguinal hernia repair but is not commonly used for incarcerated or strangulated inguinal hernia requiring enterectomy to reduce the risk of surgical-site infection. This study aimed to evaluate the safety of synthetic non-absorbable mesh repair in patients with incarcerated or strangulated inguinal hernia requiring enterectomy versus non-mesh repair. METHODS: We analyzed patients with incarcerated or strangulated inguinal hernia with enterectomy from April 2012 to March 2017 using a nationwide inpatient database in Japan. We conducted overlap propensity score-weighted analyses to compare surgical-site infection (SSI), duration of anesthesia, antibiotic use at > 3 days after surgery, postoperative hospital stay, and 30 day readmission. Two sensitivity analyses were performed. First, we compared the proportions of patients requiring wound culture at ≥ 3 days after surgery. Second, we performed overlap propensity score-weighted logistic regression analyses for surgical-site infection. RESULTS: We identified 668 eligible patients, comprising 223 patients with mesh repair and 445 with non-mesh repair. Overlap propensity score-weighted analyses showed no significant differences between the mesh repair and non-mesh repair groups for SSI (2.5 vs. 2.8%, P = 0.79). Secondary outcomes did not differ significantly between the groups. Proportion of wound culture at ≥ 3 days after surgery was similar in the two groups (11.1 vs. 14.6%, P = 0.18). Logistic regression analysis showed no significant association between mesh repair and SSI (odds ratio, 0.93; 95% confidence interval, 0.34-2.57). CONCLUSION: Synthetic non-absorbable mesh use may be safe for incarcerated or strangulated inguinal hernia requiring enterectomy.

Optical dynamics of energy-transfer from a CdZnO quantum well to a proximal Ag nanostructure.

We studied photoluminescence (PL) and energy-transfer dynamics in a hybrid structure comprising a Cd(0.08)Zn(0.92)O quantum well (QW) and an Ag nanostructure. The observed PL quenching was dependent on the electronic states in the QW. Quenching occurred at low temperature where excited carriers recombined radiatively because of excitonic localization, which disappeared with increasing temperature due to delocalization of excitons. Furthermore, nanostructured Ag surfaces produced local surface plasmon (LSP) absorption that was resonant with the PL peak energy of the QW emission. These results indicate that the recombination energy of excitons transfers nonradiatively to induce LSP excitation, which was revealed using time-resolved PL measurements.