SARS and hospital priority setting: a qualitative case study and evaluation

BACKGROUND: Priority setting is one of the most difficult issues facing hospitals because of funding restrictions and changing patient need. A deadly communicable disease outbreak, such as the Severe Acute Respiratory Syndrome (SARS) in Toronto in 2003, amplifies the difficulties of hospital priority setting. The purpose of this study is to describe and evaluate priority setting in a hospital in response to SARS using the ethical framework 'accountability for reasonableness'. METHODS: This study was conducted at a large tertiary hospital in Toronto, Canada. There were two data sources: 1) over 200 key documents (e.g. emails, bulletins), and 2) 35 interviews with key informants. Analysis used a modified thematic technique in three phases: open coding, axial coding, and evaluation. RESULTS: Participants described the types of priority setting decisions, the decision making process and the reasoning used. Although the hospital leadership made an effort to meet the conditions of 'accountability for reasonableness', they acknowledged that the decision making was not ideal. We described good practices and opportunities for improvement. CONCLUSIONS: 'Accountability for reasonableness' is a framework that can be used to guide fair priority setting in health care organizations, such as hospitals. In the midst of a crisis such as SARS where guidance is incomplete, consequences uncertain, and information constantly changing, where hour-by-hour decisions involve life and death, fairness is more important rather than less

Advances in structure elucidation of small molecules using mass spectrometry

The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules

Meta-analysis of epigenome-wide association studies of carotid intima-media thickness.

Funder: Nederlandse Organisatie voor Wetenschappelijk Onderzoek; doi: http://dx.doi.org/10.13039/501100003246Funder: ZonMw; doi: http://dx.doi.org/10.13039/501100001826Funder: Research Institute for Diseases in the ElderlyFunder: Ministerie van Onderwijs, Cultuur en Wetenschap; doi: http://dx.doi.org/10.13039/501100003245Funder: Health Promotion Administration, Ministry of Health and Welfare; doi: http://dx.doi.org/10.13039/100013227Funder: Municipality of RotterdamCommon carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta = -0.0264, p value = 3.5 × 10-8) in the discovery panel and was replicated in replication panel (beta = -0.07, p value = 0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value = 1.4 × 10-13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p

SARS and hospital priority setting: a qualitative case study and evaluation-0

<p><b>Copyright information:</b></p><p>Taken from "SARS and hospital priority setting: a qualitative case study and evaluation"</p><p>BMC Health Services Research 2004;4():36-36.</p><p>Published online 19 Dec 2004</p><p>PMCID:PMC544195.</p><p>Copyright © 2004 Bell et al; licensee BioMed Central Ltd.</p

Blood transfer devices for malaria rapid diagnostic tests: evaluation of accuracy, safety and ease of use

<p>Abstract</p> <p>Background</p> <p>Malaria rapid diagnostic tests (RDTs) are increasingly used by remote health personnel with minimal training in laboratory techniques. RDTs must, therefore, be as simple, safe and reliable as possible. Transfer of blood from the patient to the RDT is critical to safety and accuracy, and poses a significant challenge to many users. Blood transfer devices were evaluated for accuracy and precision of volume transferred, safety and ease of use, to identify the most appropriate devices for use with RDTs in routine clinical care.</p> <p>Methods</p> <p>Five devices, a loop, straw-pipette, calibrated pipette, glass capillary tube, and a new inverted cup device, were evaluated in Nigeria, the Philippines and Uganda. The 227 participating health workers used each device to transfer blood from a simulated finger-prick site to filter paper. For each transfer, the number of attempts required to collect and deposit blood and any spilling of blood during transfer were recorded. Perceptions of ease of use and safety of each device were recorded for each participant. Blood volume transferred was calculated from the area of blood spots deposited on filter paper.</p> <p>Results</p> <p>The overall mean volumes transferred by devices differed significantly from the target volume of 5 microliters (p < 0.001). The inverted cup (4.6 microliters) most closely approximated the target volume. The glass capillary was excluded from volume analysis as the estimation method used is not compatible with this device. The calibrated pipette accounted for the largest proportion of blood exposures (23/225, 10%); exposures ranged from 2% to 6% for the other four devices. The inverted cup was considered easiest to use in blood collection (206/226, 91%); the straw-pipette and calibrated pipette were rated lowest (143/225 [64%] and 135/225 [60%] respectively). Overall, the inverted cup was the most preferred device (72%, 163/227), followed by the loop (61%, 138/227).</p> <p>Conclusions</p> <p>The performance of blood transfer devices varied in this evaluation of accuracy, blood safety, ease of use, and user preference. The inverted cup design achieved the highest overall performance, while the loop also performed well. These findings have relevance for any point-of-care diagnostics that require blood sampling.</p

The marsupial MHC: The Tammar wallaby, Macropus eugenii, contains an expressed DNA-like gene on chromosome 1

In the placental mammal major histocompatibility complex (MHC) three main families of class II genes, DR, DQ, and DP, have been recognized. Each family contains genes that code for one or more A- and B-chains. Recent evidence has indicated that a fourth family can be described, the DN/DO family. These four families arose sometime early in mammalian evolution. Our purpose was to deduce the MHC of an early mammalian ancestor of marsupials and eutherians. Using primers designed to conserved regions in exon 2 and exon 3 of the DQA gene we amplified an 830-bp band from the total genomic DNA of the marsupial, Macropus eugenii (tammar wallaby). However, sequence analysis of cloned genomic products showed that the primers had amplified three genes, two of which appeared to be alleles at one locus, while the other gene belonged to a closely related locus. Phylogenetic analysis showed that both these loci were most closely related to the human (HLA-DNA) and mouse (H-20a) DNA genes, with a bootstrap support of 78%. Expression of only one locus could be detected by RT-PCR from spleen RNA. In situ hybridization to tammar wallaby chromosomes mapped these genes to one region on the long arm of chromosome 1, indicating the position of the MHC in marsupials. Related A-chain genes were detected in monotremes, and human by southern blotting, and very faint bands were observed in the chicken. Hybridization with a tammar DNA-like gene on several marsupial species showed evidence of at least three DNA-like loci in the tammar wallaby, at least one in the koala, but none in the kowari. This indicates that the organization of the class II MHC may be more dynamic in marsupial than in placental mammals, but, in contrast to a previous study on the MHC of a marsupial, we cannot conclude that the class II gene families of placental and marsupial mammals evolved from different ancestral genes