Flavin-containing monooxygenases (FMOs) are NADPH-dependent flavoenzymes that catalyze the oxidation of heteroatom centers in numerous drugs and xenobiotics. FMO2, or "pulmonary" FMO, one of five forms of the enzyme identified in mammals, is expressed predominantly in lung and differs from other FMOs in that it can catalyze the N-oxidation of certain primary alkylamines. We describe here the isolation and characterization of cDNAs for human FMO2. Analysis of the sequence of the cDNAs and of a section of the corresponding gene revealed that the major FMO2 allele of humans encodes a polypeptide that, compared with the orthologous protein of other mammals, lacks 64 amino acid residues from its C terminus. Heterologous expression of the cDNA revealed that the truncated polypeptide was catalytically inactive. The nonsense mutation that gave rise to the truncated polypeptide, a C 3 T transition in codon 472, is not present in the FMO2 gene of closely related primates, including gorilla and chimpanzee, and must therefore have arisen in the human lineage after the divergence of the Homo and Pan clades. Possible mechanisms for the fixation of the mutation in the human population and the potential significance of the loss of functional FMO2 in humans are discussed.

National Institute for Health and Clinical Excellence guidelines recommend the use of 'Track and Trigger' systems to identify early clinical deterioration. The Standardised Early Warning Score (SEWS) is used in the Royal Infirmary of Edinburgh. Previous work, suggested that the frequency and accuracy of SEWS documentation varied throughout the hospital. A prospective study was performed over a 14-night period looking at SEWS documentation in patients causing clinical concern requiring medical review, or triggering a SEWS of 4 (the 'trigger' score). SEWS charts were examined the following morning. In the ward arc, SEWS documentation was correct in only 21% of cases. The most frequent errors were one or more observations omitted (64%), SEWS total not calculated (55%) or incorrectly calculated (21%). Up to five errors per chart were noted. The observations most frequently omitted were respiratory rate, temperature and neurological status. In contrast, SEWS documentation was correct in 68% of patients in the combined assessment unit (CAU). This study demonstrates significant deficiencies in the overnight use of SEWS, particularly on the ward arc. This is particularly concerning as this study was limited only to patients already causing clinical concern, and highlights that basic observations are often incomplete, and the SEWS chart poorly understood and acted upon. SEWS recording and documentation was significantly better in CAU (P < 0.001, FET), where there is a dedicated, ongoing SEWS education programme for nursing and medical staff. We recommend this is rolled out across the hospital. Alternative methods of improving the use of SEWS are considered.

BackgroundIn 2010, the acute admissions unit (AAU) at Stirling Royal Infirmary had the highest number of cardiac arrests of any ward. A quality improvement project was undertaken to reduce this to <1/1000 admissions by December 2011.MethodsIn January 2011, based on initial needs assessment, we selected three initiatives to improve cardiac arrest rate: (1) structured response to deteriorating patients; (2) analysis of adverse events; and (3) improved end-of-life decision-making. We performed a failure modes effects analysis to identify reasons for the failure of early recognition and response. Ward staff conducted weekly safety meetings to engage unit staff and promote a safety culture of continuous improvement. Additionally, in July 2011 the unit adopted a ward-based clinical team structure with twice daily consultant ward rounds. Our primary outcome measure, cardiac arrests per 1000 admissions, was measured from January 2011 to August 2012.ResultsOver 17 months, the number of cardiac arrests per 1000 admissions fell from a baseline of 2.8/1000 admissions to 0.8/1000 admissions (71% reduction), referrals to palliative care increased by 22 to 37/1000 admissions per month (68% increase) and the 30-day mortality of patients admitted to the AAU fell from 6.3% to 4.8% (24% relative reduction).ConclusionsThrough adoption of a shared goal, application of improvement methodology including the model for improvement to test new innovations, and promotion of a safety culture in the AAU, cardiac arrests were successfully reduced to <1/1000 admissions per month with an associated significant fall in mortality. This was achieved with negligible cost.

This is the first study that we are aware of directly comparing out-of-hours performance before and after the implementation of H@N. Significant improvements in both patient and system outcomes were observed, with no adverse effects noted.