What is the evidence for the management of patients along the pathway from the emergency department to acute admission to reduce unplanned attendance and admission? An evidence synthesis

Background Globally, the rate of emergency hospital admissions is increasing. However, little evidence exists to inform the development of interventions to reduce unplanned Emergency Department (ED) attendances and hospital admissions. The objective of this evidence synthesis was to review the evidence for interventions, conducted during the patient’s journey through the ED or acute care setting, to manage people with an exacerbation of a medical condition to reduce unplanned emergency hospital attendance and admissions. Methods A rapid evidence synthesis, using a systematic literature search, was undertaken in the electronic data bases of MEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of Science, for the years 2000–2014. Evidence included in this review was restricted to Randomised Controlled Trials (RCTs) and observational studies (with a control arm) reported in peer-reviewed journals. Studies evaluating interventions for patients with an acute exacerbation of a medical condition in the ED or acute care setting which reported at least one outcome related to ED attendance or unplanned admission were included. Results Thirty papers met our inclusion criteria: 19 intervention studies (14 RCTs) and 11 controlled observational studies. Sixteen studies were set in the ED and 14 were conducted in an acute setting. Two studies (one RCT), set in the ED were effective in reducing ED attendance and hospital admission. Both of these interventions were initiated in the ED and included a post-discharge community component. Paradoxically 3 ED initiated interventions showed an increase in ED re-attendance. Six studies (1 RCT) set in acute care settings were effective in reducing: hospital admission, ED re-attendance or re-admission (two in an observation ward, one in an ED assessment unit and three in which the intervention was conducted within 72 h of admission). Conclusions There is no clear evidence that specific interventions along the patient journey from ED arrival to 72 h after admission benefit ED re-attendance or readmission. Interventions targeted at high-risk patients, particularly the elderly, may reduce ED utilization and warrant future research. Some interventions showing effectiveness in reducing unplanned ED attendances and admissions are delivered by appropriately trained personnel in an environment that allows sufficient time to assess and manage patients

Vitamin status and cognitive function in a long-term care population

BACKGROUND: Ageing can be associated with poor dietary intake, reduced nutrient absorption, and less efficient utilization of nutrients. Loss of memory and related cognitive function are also common among older persons. This study aimed to measure the prevalence of inadequate vitamin status among long-term care patients and determine if an association exists between vitamin status and each of three variables; cognitive function, vitamin supplementation, and medications which alter gastric acid levels. METHODS: Seventy-five patients in a long-term care hospital in Guelph, Ontario were recruited to a cross-sectional study. 47 were female and the mean age was 80.7 (+/-11.5) years, ranging from 48 to 100 years. Blood was used to measure levels of vitamins B12 (cobalamin), B6 (pyridoxal-5'-phosphate/PLP), erythrocyte folate, vitamin B3 (niacin) and homocysteine (Hcy). The Standardized Mini-Mental State Examination (SMMSE) was administered to measure cognitive function. A list of medications and vitamin supplementation for each patient was provided by the pharmacy. RESULTS: The prevalence of low vitamin (B12, B6, erythrocyte folate, niacin) or high metabolite (homocysteine) levels among 75 patients were as follows: B12 <148 pmol/L in 5/75 (6.7%); B12 between 148 and 221 pmol/L in 26/75 (34.7%); B6 ≤30 nmol/L in 4/75 (5.3%); erythrocyte folate <370 nmol/L in 1/75 (1.3%); niacin ratio ≤1 in 20/75 (26.7%); homocysteine >13.3 μmol/L in 31/75 (41.3%). There was no significant difference among residents grouped into marked (n = 44), mild (n = 14), or normal (n = 9) cognitive function when evaluating the effect of vitamin status. There were no significant differences in mean B12 and homocysteine levels between users and non-users of drug therapy (Losec, Zantac, or Axid). Compared to vitamin supplement non-users, supplemented residents had significantly higher mean B12 (p < 0.0001) and erythrocyte folate (p < 0.05) concentrations and significantly lower mean homocysteine (p < 0.01) levels; 229.1 versus 423.6 pmol/L for B12, 882.9 versus 1043.6 nmol/L for erythrocyte folate and 14.4 versus 12.0 μmol/L for homocysteine. CONCLUSION: Given the prevalence data on vitamin status in this sample population, the possible benefits of vitamin supplementation should be considered in clinical intervention studies using these populations of elderly

Genomic Structure of and Genome-Wide Recombination in the Saccharomyces cerevisiae S288C Progenitor Isolate EM93

The diploid isolate EM93 is the main ancestor to the widely used Saccharomyces cerevisiae haploid laboratory strain, S288C. In this study, we generate a high-resolution overview of the genetic differences between EM93 and S288C. We show that EM93 is heterozygous for >45,000 polymorphisms, including large sequence polymorphisms, such as deletions and a Saccharomyces paradoxus introgression. We also find that many large sequence polymorphisms (LSPs) are associated with Ty-elements and sub-telomeric regions. We identified 2,965 genetic markers, which we then used to genotype 120 EM93 tetrads. In addition to deducing the structures of all EM93 chromosomes, we estimate that the average EM93 meiosis produces 144 detectable recombination events, consisting of 87 crossover and 31 non-crossover gene conversion events. Of the 50 polymorphisms showing the highest levels of non-crossover gene conversions, only three deviated from parity, all of which were near heterozygous LSPs. We find that non-telomeric heterozygous LSPs significantly reduce meiotic recombination in adjacent intervals, while sub-telomeric LSPs have no discernable effect on recombination. We identified 203 recombination hotspots, relatively few of which are hot for both non-crossover gene conversions and crossovers. Strikingly, we find that recombination hotspots show limited conservation. Some novel hotspots are found adjacent to heterozygous LSPs that eliminate other hotspots, suggesting that hotspots may appear and disappear relatively rapidly

Transcriptional Profiling of Human Brain Endothelial Cells Reveals Key Properties Crucial for Predictive In Vitro Blood-Brain Barrier Models

Brain microvascular endothelial cells (BEC) constitute the blood-brain barrier (BBB) which forms a dynamic interface between the blood and the central nervous system (CNS). This highly specialized interface restricts paracellular diffusion of fluids and solutes including chemicals, toxins and drugs from entering the brain. In this study we compared the transcriptome profiles of the human immortalized brain endothelial cell line hCMEC/D3 and human primary BEC. We identified transcriptional differences in immune response genes which are directly related to the immortalization procedure of the hCMEC/D3 cells. Interestingly, astrocytic co-culturing reduced cell adhesion and migration molecules in both BECs, which possibly could be related to regulation of immune surveillance of the CNS controlled by astrocytic cells within the neurovascular unit. By matching the transcriptome data from these two cell lines with published transcriptional data from freshly isolated mouse BECs, we discovered striking differences that could explain some of the limitations of using cultured BECs to study BBB properties. Key protein classes such as tight junction proteins, transporters and cell surface receptors show differing expression profiles. For example, the claudin-5, occludin and JAM2 expression is dramatically reduced in the two human BEC lines, which likely explains their low transcellular electric resistance and paracellular leakiness. In addition, the human BEC lines express low levels of unique brain endothelial transporters such as Glut1 and Pgp. Cell surface receptors such as LRP1, RAGE and the insulin receptor that are involved in receptor-mediated transport are also expressed at very low levels. Taken together, these data illustrate that BECs lose their unique protein expression pattern outside of their native environment and display a more generic endothelial cell phenotype. A collection of key genes that seems to be highly regulated by the local surroundings of BEC within the neurovascular unit are presented and discussed

Comparative Phylogeography of a Coevolved Community: Concerted Population Expansions in Joshua Trees and Four Yucca Moths

Comparative phylogeographic studies have had mixed success in identifying common phylogeographic patterns among co-distributed organisms. Whereas some have found broadly similar patterns across a diverse array of taxa, others have found that the histories of different species are more idiosyncratic than congruent. The variation in the results of comparative phylogeographic studies could indicate that the extent to which sympatrically-distributed organisms share common biogeographic histories varies depending on the strength and specificity of ecological interactions between them. To test this hypothesis, we examined demographic and phylogeographic patterns in a highly specialized, coevolved community – Joshua trees (Yucca brevifolia) and their associated yucca moths. This tightly-integrated, mutually interdependent community is known to have experienced significant range changes at the end of the last glacial period, so there is a strong a priori expectation that these organisms will show common signatures of demographic and distributional changes over time. Using a database of >5000 GPS records for Joshua trees, and multi-locus DNA sequence data from the Joshua tree and four species of yucca moth, we combined paleaodistribution modeling with coalescent-based analyses of demographic and phylgeographic history. We extensively evaluated the power of our methods to infer past population size and distributional changes by evaluating the effect of different inference procedures on our results, comparing our palaeodistribution models to Pleistocene-aged packrat midden records, and simulating DNA sequence data under a variety of alternative demographic histories. Together the results indicate that these organisms have shared a common history of population expansion, and that these expansions were broadly coincident in time. However, contrary to our expectations, none of our analyses indicated significant range or population size reductions at the end of the last glacial period, and the inferred demographic changes substantially predate Holocene climate changes

Predictors for prolonged hospital stay solely to complete intravenous antifungal treatment in patients with candidemia: Results from the ECMM candida III multinational European observational cohort study

Background To date, azoles represent the only viable option for oral treatment of invasive Candida infections, while rates of azole resistance among non-albicans Candida spp. continue to increase. The objective of this sub-analysis of the European multicenter observational cohort study Candida III was to describe demographical and clinical characteristics of the cohort requiring prolonged hospitalization solely to complete intravenous (iv) antifungal treatment (AF Tx). Methods Each participating hospital (number of eligible hospitals per country determined by population size) included the first ~ 10 blood culture proven adult candidemia cases occurring consecutively after July 1st, 2018, and treating physicians answered the question on whether hospital stay was prolonged only for completion of intravenous antifungal therapy. Descriptive analyses as well as binary logistic regression was used to assess for predictors of prolonged hospitalization solely to complete iv AF Tx. Findings Hospital stay was prolonged solely for the completion of iv AF Tx in 16% (100/621) of candidemia cases by a median of 16 days (IQR 8 – 28). In the multivariable model, initial echinocandin treatment was a positive predictor for prolonged hospitalization to complete iv AF Tx (aOR 2.87, 95% CI 1.55 – 5.32, p < 0.001), while (i) neutropenia, (ii) intensive care unit admission, (iii) catheter related candidemia, (iv) total parenteral nutrition, and (v) C. parapsilosis as causative pathogen were found to be negative predictors (aOR 0.22 – 0.45; p < 0.03). Interpretation Hospital stays were prolonged due to need of iv AF Tx in 16% of patients with candidemia. Those patients were more likely to receive echinocandins as initial treatment and were less severely ill and less likely infected with C. parapsilosis