Development of a respiratory severity score for hospitalized adults in a high HIV-prevalence setting—South Africa, 2010-2011

BACKGROUND : Acute lower respiratory tract infections (LRTI) are a frequent cause of hospitalization and mortality in South Africa; however, existing respiratory severity scores may underestimate mortality risk in HIV-infected adults in resource limited settings. A simple predictive clinical score for low-resource settings could aid healthcare providers in the management of patients hospitalized with LRTI. METHODS : We analyzed 1,356 LRTI hospitalizations in adults aged ≥18 years enrolled in Severe Acute Respiratory Illness (SARI) surveillance in three South African hospitals from January 2010 to December 2011. Using demographic and clinical data at admission, we evaluated potential risk factors for in-hospital mortality. We evaluated three existing respiratory severity scores, CURB-65, CRB-65, and Classification Tree Analysis (CTA) Score assessing for discrimination and calibration. We then developed a new respiratory severity score using a multivariable logistic regression model for in-hospital mortality and assigned points to risk factors based on the coefficients in the multivariable model. Finally we evaluated the model statistically using bootstrap resampling techniques. RESULTS : Of the 1,356 patients hospitalized with LRTI, 101 (7.4%) died while hospitalized. The CURB-65, CRB-65, and CTA scores had poor calibration and demonstrated low discrimination with c-statistics of 0.594, 0.548, and 0.569 respectively. Significant risk factors for in-hospital mortality included age ≥ 45 years (A), confusion on admission (C), HIV-infection (H), and serum blood urea nitrogen >7 mmol/L (U), which were used to create the seven-point ACHU clinical predictor score. In-hospital mortality, stratified by ACHU score was: score ≤1, 2.4%, score 2, 6.4%, score 3, 11. 9%, and score ≥ 4, 29.3%. Final models showed good discrimination (c-statistic 0.789) and calibration (chi-square 1.6, Hosmer-Lemeshow goodness-of-fit p-value = 0.904) and discriminated well in the bootstrap sample (average optimism of 0.003). CONCLUSIONS : Existing clinical predictive scores underestimated mortality in a low resource setting with a high HIV burden. The ACHU score incorporates a simple set a risk factors that can accurately stratify patients ≥18 years of age with LRTI by in-hospital mortality risk. This score can quantify in-hospital mortality risk in an HIV-endemic, resource-limited setting with limited clinical information and if used to facilitate timely treatment may improve clinical outcomes.Additional file 1: BMC Pulmonary_Severity Score Data.xlsx. Severity Score Dataset. Dataset generated and used for analysis and creation of the ACHU score. Two tabs are included 1) includes the data used for the analysis 2) includes important notes related to the analytical methods and definitions for several composite variables.Additional file 2: Table S1. CURB-65, CRB-65, Classification Tree Analysis (CTA) severity scores. Table S2. Predicted and observed risk of mortality based on CURB-65, CRB-65, Classification Tree Analysis (CTA), and CURB-45 severity scores among hospitalized adults with lower respiratory tract infections, South Africa, 2010–2011. Table S3. Predicted and observed risk of mortality based by ACHU (Age, confusion, HIV, urea) respiratory severity score among hospitalized adults with lower respiratory tract infections, South Africa, 2010–2011.The Centers for Disease Control and Preventionhttp://www.biomedcentral.com/bmccom/plementalternmedam2017Medical Virolog

Opportunities for mesoscopics in thermometry and refrigeration: Physics and applications

This review presents an overview of the thermal properties of mesoscopic structures. The discussion is based on the concept of electron energy distribution, and, in particular, on controlling and probing it. The temperature of an electron gas is determined by this distribution: refrigeration is equivalent to narrowing it, and thermometry is probing its convolution with a function characterizing the measuring device. Temperature exists, strictly speaking, only in quasiequilibrium in which the distribution follows the Fermi-Dirac form. Interesting nonequilibrium deviations can occur due to slow relaxation rates of the electrons, e.g., among themselves or with lattice phonons. Observation and applications of nonequilibrium phenomena are also discussed. The focus in this paper is at low temperatures, primarily below 4 K, where physical phenomena on mesoscopic scales and hybrid combinations of various types of materials, e.g., superconductors, normal metals, insulators, and doped semiconductors, open up a rich variety of device concepts. This review starts with an introduction to theoretical concepts and experimental results on thermal properties of mesoscopic structures. Then thermometry and refrigeration are examined with an emphasis on experiments. An immediate application of solid-state refrigeration and thermometry is in ultrasensitive radiation detection, which is discussed in depth. This review concludes with a summary of pertinent fabrication methods of presented devices.Comment: Close to the version published in RMP; 59 pages, 35 figure

Failure of adaptive self-organized criticality during epileptic seizure attacks

Critical dynamics are assumed to be an attractive mode for normal brain functioning as information processing and computational capabilities are found to be optimized there. Recent experimental observations of neuronal activity patterns following power-law distributions, a hallmark of systems at a critical state, have led to the hypothesis that human brain dynamics could be poised at a phase transition between ordered and disordered activity. A so far unresolved question concerns the medical significance of critical brain activity and how it relates to pathological conditions. Using data from invasive electroencephalogram recordings from humans we show that during epileptic seizure attacks neuronal activity patterns deviate from the normally observed power-law distribution characterizing critical dynamics. The comparison of these observations to results from a computational model exhibiting self-organized criticality (SOC) based on adaptive networks allows further insights into the underlying dynamics. Together these results suggest that brain dynamics deviates from criticality during seizures caused by the failure of adaptive SOC.Comment: 7 pages, 5 figure

Trends of the Major Porin Gene (ompF) Evolution: Insight from the Genus Yersinia

OmpF is one of the major general porins of Enterobacteriaceae that belongs to the first line of bacterial defense and interactions with the biotic as well as abiotic environments. Porins are surface exposed and their structures strongly reflect the history of multiple interactions with the environmental challenges. Unfortunately, little is known on diversity of porin genes of Enterobacteriaceae and the genus Yersinia especially. We analyzed the sequences of the ompF gene from 73 Yersinia strains covering 14 known species. The phylogenetic analysis placed most of the Yersinia strains in the same line assigned by 16S rDNA-gyrB tree. Very high congruence in the tree topologies was observed for Y. enterocolitica, Y. kristensenii, Y. ruckeri, indicating that intragenic recombination in these species had no effect on the ompF gene. A significant level of intra- and interspecies recombination was found for Y. aleksiciae, Y. intermedia and Y. mollaretii. Our analysis shows that the ompF gene of Yersinia has evolved with nonrandom mutational rate under purifying selection. However, several surface loops in the OmpF porin contain positively selected sites, which very likely reflect adaptive diversification Yersinia to their ecological niches. To our knowledge, this is a first investigation of diversity of the porin gene covering the whole genus of the family Enterobacteriaceae. This study demonstrates that recombination and positive selection both contribute to evolution of ompF, but the relative contribution of these evolutionary forces are different among Yersinia species

New Approaches in the Differentiation of Human Embryonic Stem Cells and Induced Pluripotent Stem Cells toward Hepatocytes

Orthotropic liver transplantation is the only established treatment for end-stage liver diseases. Utilization of hepatocyte transplantation and bio-artificial liver devices as alternative therapeutic approaches requires an unlimited source of hepatocytes. Stem cells, especially embryonic stem cells, possessing the ability to produce functional hepatocytes for clinical applications and drug development, may provide the answer to this problem. New discoveries in the mechanisms of liver development and the emergence of induced pluripotent stem cells in 2006 have provided novel insights into hepatocyte differentiation and the use of stem cells for therapeutic applications. This review is aimed towards providing scientists and physicians with the latest advancements in this rapidly progressing field

Impact of GeneXpert MTB/RIF Assay on Triage of Respiratory Isolation Rooms for Inpatients With Presumed Tuberculosis: A Hypothetical Trial

BackgroundPlacing inpatients with presumed active pulmonary tuberculosis in respiratory isolation pending results of serial sputum acid-fast bacilli (AFB) smear microscopy is standard practice in high-income countries. However, this diagnostic strategy is slow and yields few tuberculosis diagnoses. We sought to determine if replacing microscopy with the GeneXpert MTB/RIF (Xpert) nucleic acid amplification assay could reduce testing time and usage of isolation rooms.MethodsWe prospectively followed inpatients at San Francisco General Hospital undergoing tuberculosis evaluation. We performed smear microscopy and Xpert testing on concentrated sputum, and calculated diagnostic accuracy for both strategies in reference to serial sputum mycobacterial culture. We measured turnaround time for microscopy and estimated hypothetical turnaround times for Xpert on concentrated and unconcentrated sputum. We compared median and total isolation times for microscopy to those estimated for the 2 Xpert strategies.ResultsAmong 139 patients with 142 admissions, median age was 54 years (interquartile range [IQR], 43-60 years); 32 (23%) patients were female, and 42 (30%) were HIV seropositive. Serial sputum smear microscopy and a single concentrated sputum Xpert had identical sensitivity (89%; 95% confidence interval [CI], 52%-100%) and similar specificity (99% [95% CI, 96%-100%] vs 100% [95% CI, 97%-100%]). A single concentrated sputum Xpert could have saved a median of 35 hours (IQR, 24-36 hours) in unnecessary isolation compared with microscopy, and a single unconcentrated sputum Xpert, 45 hours (IQR, 35-46 hours).ConclusionsReplacing serial sputum smear microscopy with a single sputum Xpert could eliminate most unnecessary isolation for inpatients with presumed tuberculosis, greatly benefiting patients and hospitals

Review of the status and challenges associated with increasing influenza vaccination coverage among pregnant women in China

Influenza vaccination coverage in pregnant women in China remains low. In this review, we first provide an overview of the evidence for the use of influenza vaccination during pregnancy. Second, we discuss influenza vaccination policy and barriers to increased seasonal influenza vaccination coverage in pregnant women in China. Third, we provide case studies of successes and challenges of programs for increasing seasonal influenza vaccination in pregnant women from other parts of Asia with lessons learned for China. Finally, we assess opportunities and challenges for increasing influenza vaccination coverage among pregnant women in China

Impact of GeneXpert MTB/RIF Assay on Triage of Respiratory Isolation Rooms for Inpatients With Presumed Tuberculosis: A Hypothetical Trial

Background. Placing inpatients with presumed active pulmonary tuberculosis in respiratory isolation pending results of serial sputum acid-fast bacilli (AFB) smear microscopy is standard practice in high-income countries. However, this diagnostic strategy is slow and yields few tuberculosis diagnoses. We sought to determine if replacing microscopy with the GeneXpert MTB/RIF (Xpert) nucleic acid amplification assay could reduce testing time and usage of isolation rooms. Methods. We prospectively followed inpatients at San Francisco General Hospital undergoing tuberculosis evaluation. We performed smear microscopy and Xpert testing on concentrated sputum, and calculated diagnostic accuracy for both strategies in reference to serial sputum mycobacterial culture. We measured turnaround time for microscopy and estimated hypothetical turnaround times for Xpert on concentrated and unconcentrated sputum. We compared median and total isolation times for microscopy to those estimated for the 2 Xpert strategies. Results. Among 139 patients with 142 admissions, median age was 54 years (interquartile range [IQR], 43–60 years); 32 (23%) patients were female, and 42 (30%) were HIV seropositive. Serial sputum smear microscopy and a single concentrated sputum Xpert had identical sensitivity (89%; 95% confidence interval [CI], 52%–100%) and similar specificity (99% [95% CI, 96%–100%] vs 100% [95% CI, 97%–100%]). A single concentrated sputum Xpert could have saved a median of 35 hours (IQR, 24–36 hours) in unnecessary isolation compared with microscopy, and a single unconcentrated sputum Xpert, 45 hours (IQR, 35–46 hours). Conclusions. Replacing serial sputum smear microscopy with a single sputum Xpert could eliminate most unnecessary isolation for inpatients with presumed tuberculosis, greatly benefiting patients and hospitals