新機能性物質設計の基礎的研究 : 熱力学量と構造の関係について

博士（理学）神戸大

Decrease in All-Cause 30-Day Mortality after Bacteraemia over a 15-Year Period:A Population-Based Cohort Study in Denmark in 2000-2014

Introduction: Bacteraemia is a frequent infectious condition that strongly affects morbidity and mortality. The incidence is increasing worldwide. This study explores all-cause 30-day mortality after bacteraemia in two out of Denmark’s five healthcare regions with approximately 2.4 million inhabitants. Methods: Clinically significant bacteraemia episodes (n = 55,257) were identified from a geographically well-defined background population between 2000 and 2014, drawing on population-based data regarding bacterial species and vital status. All-cause 30-day mortality was assessed in relation to bacteraemia episodes, number of patients with analysed blood cultures and the background population. Results: We observed a decreasing trend of all-cause 30-day mortality between 2000 and 2014, both in relation to the number of bacteraemia episodes and the background population. Mortality decreased from 22.7% of the bacteraemia episodes in 2000 to 17.4% in 2014 (annual IRR [95% CI]: 0.983 [0.979–0.987]). In relation to the background population, there were 41 deaths per 100,000 inhabitants in 2000, decreasing to 39 in 2014 (annual IRR [95% CI]: 0.988 [0.982–0.993]). Numbers of inhabitants, bacteraemia episodes, and analysed persons having BCs increased during the period. Conclusions: All-cause 30-day mortality in patients with bacteraemia decreased significantly over a 15-year period

Social autopsy: INDEPTH Network experiences of utility, process, practices, and challenges in investigating causes and contributors to mortality

<p>Abstract</p> <p>Background</p> <p>Effective implementation of child survival interventions depends on improved understanding of cultural, social, and health system factors affecting utilization of health care. Never the less, no standardized instrument exists for collecting and interpreting information on how to avert death and improve the implementation of child survival interventions.</p> <p>Objective</p> <p>To describe the methodology, development, and first results of a standard social autopsy tool for the collection of information to understand common barriers to health care, risky behaviors, and missed opportunities for health intervention in deceased children under 5 years old.</p> <p>Methods</p> <p>Under the INDEPTH Network, a social autopsy working group was formed to reach consensus around a standard social autopsy tool for neonatal and child death. The details around 434 child deaths in Iganga/Mayuge Health and Demographic Surveillance Site (HDSS) in Uganda and 40 child deaths in Dodowa HDSS in Ghana were investigated over 12 to 18 months. Interviews with the caretakers of these children elicited information on what happened before death, including signs and symptoms, contact with health services, details on treatments, and details of doctors. These social autopsies were used to assess the contributions of delays in care seeking and case management to the childhood deaths.</p> <p>Results</p> <p>At least one severe symptom had been recognized prior to death in 96% of the children in Iganga/Mayuge HDSS and in 70% in Dodowa HDSS, yet 32% and 80% of children were first treated at home, respectively. Twenty percent of children in Iganga/Mayuge HDSS and 13% of children in Dodowa HDSS were never taken for care outside the home. In both countries most went to private providers. In Iganga/Mayuge HDSS the main delays were caused by inadequate case management by the health provider, while in Dodowa HDSS the main delays were in the home.</p> <p>Conclusion</p> <p>While delay at home was a main obstacle to prompt and appropriate treatment in Dodowa HDSS, there were severe challenges to prompt and adequate case management in the health system in both study sites in Ghana and Uganda. Meanwhile, caretaker awareness of danger signs needs to improve in both countries to promote early care seeking and to reduce the number of children needing referral. Social autopsy methods can improve this understanding, which can assist health planners to prioritize scarce resources appropriately.</p

Sequence analysis of the capsid gene during a genotype II.4 dominated norovirus season in one university hospital: identification of possible transmission routes.

Norovirus (NoV) is a leading cause of gastroenteritis and genotype II.4 (GII.4) is responsible for the majority of nosocomial NoV infections. Our objective was to examine whether sequencing of the capsid gene might be a useful tool for the hospital outbreak investigation to define possible transmission routes. All NoV positive samples submitted from one university hospital during the 2007/8 season were selected. Genotyping of selected samples by partial polymerase gene sequencing had shown that the majority belonged to the GII.4 variant Den Haag 2006b and had identical polymerase sequences. Sequences of the capsid gene (1412 nucleotides) were obtained from the first available sample from 55 patients. From six immunocompromised patients with persistent infections a second sample was also included. As a control for a point-source outbreak, five samples from a foodborne outbreak caused by the same GII.4 variant were analyzed. Forty-seven of the inpatients (85%) were infected with the GII.4 variant Den Haag 2006b. Phylogenetic analysis of the Den Haag 2006b sequences identified four distinct outbreaks in different departments and a fifth outbreak with possible inter-department spread. In addition, a more heterogeneous cluster with evidence of repeated introductions from the community, but also possible inter-department spread was observed. In all six patients with paired sequences, evidence for in vivo evolution of the virus was found. Capsid gene sequencing showed substantial sequence variation among NoV GII.4 variant Den Haag 2006b strains from one single institution during a nine months' period. This method proved useful to understand the local epidemiology and, when used promptly, has the potential to make infection control measures more targeted

Norovirus Genotypes in Hospital Settings - Differences between Nosocomial and Community-Acquired Infections.

Norovirus is a major cause of gastroenteritis and hospital outbreaks, leading to substantial morbidity and direct healthcare expenses as well as indirect societal costs. The aim of the study was to estimate the proportion of nosocomial norovirus infections among inpatients tested positive for norovirus in Denmark, 2002-2010, and to study the distribution of norovirus genotypes among inpatients with nosocomial and community-acquired norovirus infections, respectively

Local and temporal distribution of genotypes, variants and GII.4 2006b clusters.

<p>The first sample per inpatient is shown (n = 105). Units on vertical axes represent numbers of patients. NA (n = 49): no sequence information available (n = 29: sample not stored, n = 20: GII.4 specific PCR negative). The sequences from the first samples from six patients with persistent diarrhea are marked with diagonal shading.</p

Comparative phylogenetic analysis of polymerase (a.) and capsid (b.) gene sequences.

<p>Neighbor Joining trees based on polymerase sequences (a., 226–285 nt) and capsid sequences (b., 1412 nt) of 27 samples from which both sequences were available are shown. Color labels indicate clustering according to the phylogenetic analysis of all capsid sequences shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0115331#pone.0115331.g001" target="_blank">Fig. 1</a> (cluster 1: pink, cluster 2: yellow, cluster 3: brown, cluster 4: red, cluster 5: orange, foodborne cluster 7: empty black circle, singleton 2: black triangle, singleton 3: black square, singleton 4: black diamond.</p