Changes in weekend and weekday care quality of emergency medical admissions to 20 hospitals in England during implementation of the 7-day services national health policy.

BACKGROUND: In 2013, the English National Health Service launched the policy of 7-day services to improve care quality and outcomes for weekend emergency admissions. AIMS: To determine whether the quality of care of emergency medical admissions is worse at weekends, and whether this has changed during implementation of 7-day services. METHODS: Using data from 20 acute hospital Trusts in England, we performed randomly selected structured case record reviews of patients admitted to hospital as emergencies at weekends and on weekdays between financial years 2012-2013 and 2016-2017. Senior doctor ('specialist') involvement was determined from annual point prevalence surveys. The primary outcome was the rate of clinical errors. Secondary outcomes included error-related adverse event rates, global quality of care and four indicators of good practice. RESULTS: Seventy-nine clinical reviewers reviewed 4000 admissions, 800 in duplicate. Errors, adverse events and care quality were not significantly different between weekend and weekday admissions, but all improved significantly between epochs, particularly errors most likely influenced by doctors (clinical assessment, diagnosis, treatment, prescribing and communication): error rate OR 0.78; 95% CI 0.70 to 0.87; adverse event OR 0.48, 95% CI 0.33 to 0.69; care quality OR 0.78, 95% CI 0.70 to 0.87; all adjusted for age, sex and ethnicity. Postadmission in-hospital care processes improved between epochs and were better for weekend admissions (vital signs with National Early Warning Score and timely specialist review). Preadmission processes in the community were suboptimal at weekends and deteriorated between epochs (fewer family doctor referrals, more patients with chronic disease or palliative care designation). CONCLUSIONS AND IMPLICATIONS: Hospital care quality of emergency medical admissions is not worse at weekends and has improved during implementation of the 7-day services policy. Causal pathways for the weekend effect may extend into the prehospital setting.

Real-time audio and visual display of the Coronavirus genome.

BACKGROUND: This paper describes a web based tool that uses a combination of sonification and an animated display to inquire into the SARS-CoV-2 genome. The audio data is generated in real time from a variety of RNA motifs that are known to be important in the functioning of RNA. Additionally, metadata relating to RNA translation and transcription has been used to shape the auditory and visual displays. Together these tools provide a unique approach to further understand the metabolism of the viral RNA genome. This audio provides a further means to represent the function of the RNA in addition to traditional written and visual approaches. RESULTS: Sonification of the SARS-CoV-2 genomic RNA sequence results in a complex auditory stream composed of up to 12 individual audio tracks. Each auditory motive is derived from the actual RNA sequence or from metadata. This approach has been used to represent transcription or translation of the viral RNA genome. The display highlights the real-time interaction of functional RNA elements. The sonification of codons derived from all three reading frames of the viral RNA sequence in combination with sonified metadata provide the framework for this display. Functional RNA motifs such as transcription regulatory sequences and stem loop regions have also been sonified. Using the tool, audio can be generated in real-time from either genomic or sub-genomic representations of the RNA. Given the large size of the viral genome, a collection of interactive buttons has been provided to navigate to regions of interest, such as cleavage regions in the polyprotein, untranslated regions or each gene. These tools are available through an internet browser and the user can interact with the data display in real time. CONCLUSION: The auditory display in combination with real-time animation of the process of translation and transcription provide a unique insight into the large body of evidence describing the metabolism of the RNA genome. Furthermore, the tool has been used as an algorithmic based audio generator. These audio tracks can be listened to by the general community without reference to the visual display to encourage further inquiry into the science.

Resolving a clinical tuberculosis outbreak using palaeogenomic genome reconstruction methodologies.

This study describes the analysis of DNA from heat-killed (boilate) isolates of Mycobacterium tuberculosis from two UK outbreaks where DNA was of sub-optimal quality for the standard methodologies routinely used in microbial genomics. An Illumina library construction method developed for sequencing ancient DNA was successfully used to obtain whole genome sequences, allowing analysis of the outbreak by gene-by-gene MLST, SNP mapping and phylogenetic analysis. All cases were spoligotyped to the same Haarlem H1 sub-lineage. This is the first described application of ancient DNA library construction protocols to allow whole genome sequencing of a clinical tuberculosis outbreak. Using this method it is possible to obtain epidemiologically meaningful data even when DNA is of insufficient quality for standard methods.

How to manipulate friends and influence practice: Application of complexity science leads to quality improvement in laboratory sample submissions.

BACKGROUND: We sought to reduce healthcare-associated infections (HCAIs) through the application of complexity science. OBJECTIVE: To confirm incidental findings that altering the structure of microbiology reports with targeted education led to better utilisation of laboratory resources, while participating in efforts to reduce HCAI. METHODS: We adopted a different approach to laboratory result authorisation, using narrative to engage the clinicians and induce behavioural change. Subsequent educational opportunities emphasised key messages. FINDINGS/RESULTS: Positive urine means calculated by the analysis tool numbered 2179/month throughout the study period. Negative urines started at 5576/month, reduced to 5134/month in November 2014 and to 4602/month in April 2016, coinciding with our changes. Opportunity costs were saved. DISCUSSION: The changes in both policy and reporting were contemporaneous with a decline in negative samples. There were no significant changes in the number of positive specimens. The efficiency and effectiveness of the laboratory was improved and resources released: £145,000 ($182,000) for a resident population of 384,000. This suggests an annual release of about £25 million ($31 million) may be possible in the UK and £122 million ($155 million) in the USA.

The interactions of novel mononuclear platinum-based complexes with DNA.

BACKGROUND: Cisplatin has been widely used for the treatment of cancer and its antitumour activity is attributed to its capacity to form DNA adducts, predominantly at guanine residues, which impede cellular processes such as DNA replication and transcription. However, there are associated toxicity and drug resistance issues which plague its use. This has prompted the development and screening of a range of chemotherapeutic drug analogues towards improved efficacy. The biological properties of three novel platinum-based compounds consisting of varying cis-configured ligand groups, as well as a commercially supplied compound, were characterised in this study to determine their potential as anticancer agents. METHODS: The linear amplification reaction was employed, in conjunction with capillary electrophoresis, to quantify the sequence specificity of DNA adducts induced by these compounds using a DNA template containing telomeric repeat sequences. Additionally, the DNA interstrand cross-linking and unwinding efficiency of these compounds were assessed through the application of denaturing and native agarose gel electrophoresis techniques, respectively. Their cytotoxicity was determined in HeLa cells using a colorimetric cell viability assay. RESULTS: All three novel platinum-based compounds were found to induce DNA adduct formation at the tandem telomeric repeat sequences. The sequence specificity profile at these sites was characterised and these were distinct from that of cisplatin. Two of these compounds with the enantiomeric 1,2-diaminocyclopentane ligand (SS and RR-DACP) were found to induce a greater degree of DNA unwinding than cisplatin, but exhibited marginally lower DNA cross-linking efficiencies. Furthermore, the RR-isomer was more cytotoxic in HeLa cells than cisplatin. CONCLUSIONS: The biological characteristics of these compounds were assessed relative to cisplatin, and a variation in the sequence specificity and a greater capacity to induce DNA unwinding was observed. These compounds warrant further investigations towards developing more efficient chemotherapeutic drugs.

A website to identify shared genes in Saccharomyces cerevisiae homozygous deletion library screens.

BACKGROUND: The homozygous yeast deletion library includes approximately 4800 diploid strains each containing one deleted non-essential gene. Hundreds of publications have arisen through experimentation using this genome-wide biological resource. As part of this work over 677 genesets have been collated from these experiments representing the phenotypic responses of the library to a diverse set of chemical and physical challenges. DESCRIPTION: A website called the Saccharomyces cerevisiae Homozygous Deletion Library Tools (ScHo DeLiTo-96) has been developed with the primary goal of browsing and identifying genes shared between these responsive phenotypes (available at yeastdb.org ). Geneset comparisons have been performed for each phenotype against all others to identify common genes. Genesets and other curated information are stored in a relational database and a website interface allows users to query and browse the data in an intuitive way to reveal commonality between selected phenotypic responses. The most commonly occurring genes in all of the stored phenotypes are highly over-represented in the GO slim term "cellular ion homeostasis" indicating that genes shared between phenotypes may highlight a common cellular response. Additionally, user derived genesets can be uploaded and intersected against the stored data to reveal common responses which may otherwise have been obscure. CONCLUSION: These tools provide a simple method to perform niche enquiries between datasets derived from the yeast deletion library.

Implementing the future hospital.

For the last 4 years, this part of the Future Healthcare Journal has been the place to find regular overview updates on progress made by the Future Hospital Programme of the Royal College of Physicians, together with its partners, in realising the vision of the Future Hospital Commission. As outlined in this article, the Future Hospital Programme has now concluded. However, much of its work is being carried on by the RCP Quality Improvement Programme, which can be contacted on RCPQI@rcplondon.ac.uk. Follow the Quality Improvement Programme on Twitter: @RCP_QI.

An auditory display tool for DNA sequence analysis.

BACKGROUND: DNA Sonification refers to the use of an auditory display to convey the information content of DNA sequence data. Six sonification algorithms are presented that each produce an auditory display. These algorithms are logically designed from the simple through to the more complex. Three of these parse individual nucleotides, nucleotide pairs or codons into musical notes to give rise to 4, 16 or 64 notes, respectively. Codons may also be parsed degenerately into 20 notes with respect to the genetic code. Lastly nucleotide pairs can be parsed as two separate frames or codons can be parsed as three reading frames giving rise to multiple streams of audio. RESULTS: The most informative sonification algorithm reads the DNA sequence as codons in three reading frames to produce three concurrent streams of audio in an auditory display. This approach is advantageous since start and stop codons in either frame have a direct affect to start or stop the audio in that frame, leaving the other frames unaffected. Using these methods, DNA sequences such as open reading frames or repetitive DNA sequences can be distinguished from one another. These sonification tools are available through a webpage interface in which an input DNA sequence can be processed in real time to produce an auditory display playable directly within the browser. The potential of this approach as an analytical tool is discussed with reference to auditory displays derived from test sequences including simple nucleotide sequences, repetitive DNA sequences and coding or non-coding genes. CONCLUSION: This study presents a proof-of-concept that some properties of a DNA sequence can be identified through sonification alone and argues for their inclusion within the toolkit of DNA sequence browsers as an adjunct to existing visual and analytical tools.

Update on the Future Hospital Programme.

This part of the Future Hospital Journal is where you will find regular overview updates on -progress made by the Future Hospital Programme of the Royal -College of Physicians, together with its -partners, in realising the vision of the Future -Hospital -Commission. We very much welcome your feedback. If you have any comments, or would like to be involved in the work of the Programme, please contact futurehospital@rcplondon.ac.uk.

Update from the Future Hospital Programme.

This part of the Future Hospital Journal is where you will find regular overview updates on progress made by the Future Hospital Programme of the Royal College of Physicians, together with its partners, in realising the vision of the Future Hospital Commission. We very much welcome your feedback. If you have any comments, or would like to be involved in the work of the Programme, please contact futurehospital@rcplondon.ac.uk. Follow the Future Hospital Programme on Twitter: @RCPFutureHosp.

Update from the Future Hospital Programme.

This part of the Future Healthcare Journal is where you will find regular overview updates on progress made by the Future Hospital Programme of the Royal College of Physicians, together with its partners, in realising the vision of the Future Hospital Commission. We very much welcome your feedback. If you have any comments, or would like to be involved in the work of the Programme, please contact futurehospital@rcplondon.ac.uk. Follow the Future Hospital Programme on Twitter: @RCPFutureHosp.

Weekend specialist intensity and admission mortality in acute hospital trusts in England: a cross-sectional study.

BACKGROUND: Increased mortality rates associated with weekend hospital admission (the so-called weekend effect) have been attributed to suboptimum staffing levels of specialist consultants. However, evidence for a causal association is elusive, and the magnitude of the weekend specialist deficit remains unquantified. This uncertainty could hamper efforts by national health systems to introduce 7 day health services. We aimed to examine preliminary associations between specialist intensity and weekend admission mortality across the English National Health Service. METHODS: Eligible hospital trusts were those in England receiving unselected emergency admissions. On Sunday June 15 and Wednesday June 18, 2014, we undertook a point prevalence survey of hospital specialists (consultants) to obtain data relating to the care of patients admitted as emergencies. We defined specialist intensity at each trust as the self-reported estimated number of specialist hours per ten emergency admissions between 0800 h and 2000 h on Sunday and Wednesday. With use of data for all adult emergency admissions for financial year 2013-14, we compared weekend to weekday admission risk of mortality with the Sunday to Wednesday specialist intensity ratio within each trust. We stratified trusts by size quintile. FINDINGS: 127 of 141 eligible acute hospital trusts agreed to participate; 115 (91%) trusts contributed data to the point prevalence survey. Of 34,350 clinicians surveyed, 15,537 (45%) responded. Substantially fewer specialists were present providing care to emergency admissions on Sunday (1667 [11%]) than on Wednesday (6105 [42%]). Specialists present on Sunday spent 40% more time caring for emergency patients than did those present on Wednesday (mean 5·74 h [SD 3·39] vs 3·97 h [3·31]); however, the median specialist intensity on Sunday was only 48% (IQR 40-58) of that on Wednesday. The Sunday to Wednesday intensity ratio was less than 0·7 in 104 (90%) of the contributing trusts. Mortality risk among patients admitted at weekends was higher than among those admitted on weekdays (adjusted odds ratio 1·10, 95% CI 1·08-1·11; p<0·0001). There was no significant association between Sunday to Wednesday specialist intensity ratios and weekend to weekday mortality ratios (r -0·042; p=0·654). INTERPRETATION: This cross-sectional analysis did not detect a correlation between weekend staffing of hospital specialists and mortality risk for emergency admissions. Further investigation is needed to evaluate whole-system secular change during the implementation of 7 day services. Policy makers should exercise caution before attributing the weekend effect mainly to differences in specialist staffing. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme.

Characterisation of the DNA sequence specificity, cellular toxicity and cross-linking properties of novel bispyridine-based dinuclear platinum complexes.

BACKGROUND: The anti-tumour activity of cisplatin is thought to be a result of its capacity to form DNA adducts which prevent cellular processes such as DNA replication and transcription. These DNA adducts can effectively induce cancer cell death, however, there are a range of clinical side effects and drug resistance issues associated with its use. In this study, the biological properties of three novel dinuclear platinum-based compounds (that contain alkane bridging linkers of eight, ten and twelve carbon atoms in length) were characterised to assess their potential as anticancer agents. METHODS: The properties of these compounds were determined using a DNA template containing seven tandem telomeric repeat sequences. A linear amplification reaction was used in combination with capillary electrophoresis to quantify the sequence specificity of DNA adducts formed by these compounds at base pair resolution. The DNA cross-linking ability of these compounds was assessed using denaturing agarose gel electrophoresis and cytotoxicity was determined in HeLa cells using a colorimetric cell viability assay. RESULTS: The dinuclear compounds were found to preferentially form DNA adducts at guanine bases and they exhibited different damage intensity profiles at the telomeric repeat sequences compared to that of cisplatin. The dinuclear compounds were found to exhibit a low level of cytotoxicity relative to cisplatin and their cytotoxicity increased as the linker length increased. Conversely, the interstrand cross-linking efficiency of the dinuclear compounds increased as the linker length decreased and the compound with the shortest alkane linker was six-fold more effective than cisplatin. CONCLUSIONS: Since the bifunctional compounds exhibit variation in sequence specificity of adduct formation and a greater ability to cross-link DNA relative to cisplatin they warrant further investigation towards the goal of developing new cancer chemotherapeutic agents.