Countess of Chester Hospital

Abstract The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

BACKGROUND: Inflammation (assessed by C-reactive protein [CRP]) and the metabolic syndrome (MetS) are associated with cardiovascular disease (CVD), but population-based data are limited. METHODS AND RESULTS: We assessed the cross-sectional relations of CRP to the MetS (National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, Adult Treatment Panel III definition) in 3037 subjects (1681 women; mean age, 54 years) and the utility of CRP and the MetS to predict new CVD events (n=189) over 7 years. MetS (> or =3 of 5 traits) was present in 24% of subjects; mean age-adjusted CRP levels for those with 0, 1, 2, 3, 4, or 5 MetS traits were 2.2, 3.5, 4.2, 6.0, or 6.6 mg/L, respectively (P trend <0.0001). In persons with MetS, age-adjusted CRP levels were higher in women than men (7.8 versus 4.6 mg/L; P<0.0001). MetS and baseline CRP were individually related to CVD events (for MetS: age-sex-adjusted hazard ratio [HR], 2.1; 95% CI, 1.5 to 2.8; for highest versus lowest CRP quartile: HR, 2.2; 95% CI, 1.4 to 3.5). Greater risk of CVD persisted for MetS and CRP even after adjustment in a model including age, sex, MetS (HR, 1.8; 95% CI, 1.4 to 2.5), and CRP (HR, 1.9; 95% CI, 1.2 to 2.9). The c-statistic associated with the age- and sex-adjusted model including CRP was 0.72; including MetS, 0.74; and including CRP and MetS, 0.74. CONCLUSIONS: Elevated CRP levels are related to insulin resistance and the presence of the MetS, especially in women. Although discrimination of subjects at risk of CVD events using both MetS and CRP is not better than using either phenotype alone, both CRP and MetS are independent predictors of new CVD events.

BACKGROUND: The erosion of the early mortality advantage of elective endovascular aneurysm repair (EVAR) compared with open repair of abdominal aortic aneurysm remains without a satisfactory explanation. METHODS: An individual-patient data meta-analysis of four multicentre randomized trials of EVAR versus open repair was conducted to a prespecified analysis plan, reporting on mortality, aneurysm-related mortality and reintervention. RESULTS: The analysis included 2783 patients, with 14 245 person-years of follow-up (median 5·5 years). Early (0-6 months after randomization) mortality was lower in the EVAR groups (46 of 1393 versus 73 of 1390 deaths; pooled hazard ratio 0·61, 95 per cent c.i. 0·42 to 0·89; P = 0·010), primarily because 30-day operative mortality was lower in the EVAR groups (16 deaths versus 40 for open repair; pooled odds ratio 0·40, 95 per cent c.i. 0·22 to 0·74). Later (within 3 years) the survival curves converged, remaining converged to 8 years. Beyond 3 years, aneurysm-related mortality was significantly higher in the EVAR groups (19 deaths versus 3 for open repair; pooled hazard ratio 5·16, 1·49 to 17·89; P = 0·010). Patients with moderate renal dysfunction or previous coronary artery disease had no early survival advantage under EVAR. Those with peripheral artery disease had lower mortality under open repair (39 deaths versus 62 for EVAR; P = 0·022) in the period from 6 months to 4 years after randomization. CONCLUSION: The early survival advantage in the EVAR group, and its subsequent erosion, were confirmed. Over 5 years, patients of marginal fitness had no early survival advantage from EVAR compared with open repair. Aneurysm-related mortality and patients with low ankle : brachial pressure index contributed to the erosion of the early survival advantage for the EVAR group. Trial registration numbers: EVAR-1, ISRCTN55703451; DREAM (Dutch Randomized Endovascular Aneurysm Management), NCT00421330; ACE (Anévrysme de l'aorte abdominale, Chirurgie versus Endoprothèse), NCT00224718; OVER (Open Versus Endovascular Repair Trial for Abdominal Aortic Aneurysms), NCT00094575.

When microbial strain-typing methods are compared, the most important characteristics are typeability, reproducibility, and discriminatory power. While typeability and reproducibility can be presented as numerical values, indices of discriminatory power have only recently been described. This paper examines the relationship between reproducibility and indices of discriminatory power. In an individual typing method, an inverse relationship between reproducibility and discriminatory power appears as the number of test differences required in order to distinguish between strains is increased. A method of standardizing the discriminatory power of a typing method to a predetermined reproducibility is presented. In this way the discriminatory powers of different typing methods can be compared while being standardized for the effect of reproducibility.

with conventional cuprophane membranes.4 Haemodialysis with high flux dialysers and polysulfone or polyacrylonitrile membranes lowers t32 microglobulin concentrations, and an improvement in shoulder pain in patients changed to high flux dialysers has been reported.5 The mechanism of the improvement is not clear; possibly amyloid is no longer deposited and the associated inflammation decreases. The improved biocompatibility of these membranes is known to be associated with reduced activation of some mediators of the inflammatory response.

after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

The metabolic syndrome and insulin resistance have been related to incident cardiovascular disease (CVD), but it is uncertain if metabolic syndrome predicts CVD independent of insulin resistance. Our study sample included 2,898 people without diabetes or CVD at baseline. Metabolic syndrome was defined by the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria. Insulin resistance was defined by the homeostasis model assessment (HOMA-IR) and by Gutt et al.'s insulin sensitivity index (ISI(0,120)). Age- and sex-adjusted proportional hazards regression models assessed the association of baseline metabolic syndrome and insulin resistance to 7-year CVD risk (186 events). Metabolic syndrome and both measures of insulin resistance were individually related to incident CVD (age- and sex-adjusted hazard ratio [HR] for metabolic syndrome [present versus absent]: 2.0 [95% CI 1.5-2.6], P = 0.0001; for HOMA-IR: 1.9 [1.2-2.9], P = 0.003; and for ISI(0,120) [both highest versus lowest quartile]: 0.5 [0.3-0.7], P = 0.001). In models adjusted for age, sex, LDL cholesterol, and smoking status and including metabolic syndrome, ISI(0,120) levels were independently related to incident CVD (0.5 [0.3-0.8], P = 0.004), whereas HOMA-IR levels were not (1.3 [0.8-2.1], P = 0.24); metabolic syndrome was associated with increased CVD risk in both models (HR 1.6, P < or = 0.007 in both). In conclusion, metabolic syndrome and ISI(0,120) but not HOMA-IR independently predicted incident CVD. Metabolic syndrome may not capture all the CVD risk associated with insulin resistance.

Safe vascular access is integral to anaesthetic and critical care practice, but procedures are a frequent source of patient adverse events. Ensuring safe and effective approaches to vascular catheter insertion should be a priority for all practitioners. New technology such as ultrasound and other imaging has increased the number of tools available. This guidance was created using review of current practice and literature, as well as expert opinion. The result is a consensus document which provides practical advice on the safe insertion and removal of vascular access devices.

CONTEXT: The athlete's heart (AH) remains a popular topic of study. Controversy related to training-specific cardiac adaptation in male athletes, and continuing developments in imaging technology and scaling prompted this systematic review and meta-analysis. OBJECTIVE: To provide new insight in relation to: 1) cardiac adaptation to divergent training patterns in male athletes, 2) a developing research database using cardiac magnetic resonance (CMR) in athletes; 3) functional data derived from tissue-Doppler analysis as well as right ventricular (RV) and left atrial (LA) measurements in athletes; and 4) an awareness of the impact of body size on cardiac dimensions. STUDY DESIGN: Systematic review and meta-analysis of prospective trials. Data extraction performed by two researchers. DATA SOURCES: Pub Med, Medline, Scopus and ISI Web of knowledge scholarly data base. STUDY SELECTION: Prospective studies were included if they were echocardiographic or CMR trials of elite young male athletes, with clear indication of type of sports and passed a quality criteria checklist. RESULTS: All left ventricular (LV) structural parameters were higher in athletes than in controls. Only LV end-diastolic diameter and volume were higher in endurance athletes than in resistance athletes: 54.8 mm (95% CI 54.1 to 55.6) vs 52.4 mm (95% CI 51.2 to 53.6); p<0.001 and 171 ml (95% CI 157 to 185) vs 131 ml (95% CI 120 to 142); p<0.001, respectively. RV end-diastolic volume, mass and LA diameter were higher in endurance athletes than controls. LV end-diastolic volume was larger when CMR was used rather than echocardiography: 178 ml (95% CI Q7 162 to 194) vs 135 ml (95% CI 128 to 142); p<0.001. Meta-analysis regression models demonstrated positive and significant associations between body surface area (BSA) and LV mass, RV mass and LA diameter. CONCLUSIONS: Morphological features of the male AH were noted in both athlete groups. A training-specific pattern of concentric hypertrophy was not discerned in resistance athletes. Both imaging mode and BSA can have a significant impact on the interpretation of AH data.

OBJECTIVES: To determine the incidence and study the causes and outcome of congenital brachial palsy (CBP). DESIGN: Active surveillance of newborn infants using the British Paediatric Surveillance Unit notification system and follow up study of outcome at 6 months of age. SETTING: The United Kingdom and Republic of Ireland. PARTICIPANTS: Newborn infants presenting with a flaccid paresis of the arm (usually one, rarely both) born between April 1998 and March 1999. MAIN OUTCOME MEASURES: Extent of the lesion at birth and degree of recovery at 6 months of age. FINDINGS: There were 323 confirmed cases giving an incidence of 0.42 per 1000 live births (1 in 2300). Significant associated risk factors in comparison with the normal population were shoulder dystocia (60% v 0.3%), high birth weight with 53% infants weighing more than the 90th centile, and assisted delivery (relative risk (RR) 3.4, 95% confidence interval (CI) 2.9 to 3.9, p = 0.0001). There was a considerably lower risk of CBP in infants delivered by caesarean section (RR 7, 95% CI 2 to 56, p = 0.002). At about 6 months of age, about half of the infants had recovered fully, but the remainder showed incomplete recovery including 2% with no recovery. The relative risk of partial or no recovery in infants with extensive lesions soon after birth compared with those with less extensive lesions was 11.28 (95% CI 2.38 to 63.66, p = 0.000005). CONCLUSIONS: The incidence of CBP in the United Kingdom and Republic of Ireland is strikingly similar to that previously reported nearly 40 years ago. Most cases are due to trauma at delivery, which is not necessarily excessive or inappropriate. Given the uncertainty about the appropriate management of these infants, serious consideration should be given to a formal clinical trial of microsurgical nerve repair.

Human epidermal growth factor receptor 2 (HER2) overexpression is present in approximately 15% of early invasive breast cancers, and is an important predictive and prognostic marker. The substantial benefits achieved with anti-HER2 targeted therapies in patients with HER2-positive breast cancer have emphasised the need for accurate assessment of HER2 status. Current data indicate that HER2 test accuracy improved following previous publication of guidelines and the implementation of an external quality assessment scheme with a decline in false-positive and false-negative rates. This paper provides an update of the guidelines for HER2 testing in the UK. The aim is to further improve the analytical validity and clinical utility of HER2 testing by providing guidelines of test performance parameters, and recommendations on the postanalytical interpretation of test results. HER2 status should be determined in all newly diagnosed and recurrent breast cancers. Testing involves immunohistochemistry with >10% complete strong membrane staining defining a positive status. In situ hybridisation, either fluorescent or bright field chromogenic, is used either upfront or in immunohistochemistry borderline cases to detect the presence of HER2 gene amplification. Situations where repeat HER2 testing is advised are outlined and the impact of genetic heterogeneity is discussed. Strict quality control and external quality assurance of validated assays are essential. Testing laboratories should perform ongoing competency assessment and proficiency tests and ensure the reliability and accuracy of the assay. Pathologists, oncologists and surgeons involved in test interpretation and clinical use should adhere to published guidelines and maintain accurate performance and consistent interpretation of test results.

Dyspraxia is an enigma to many people, both professional and lay alike--what is it, how does it relate to developmental coordination disorder and associated conditions, how common is it, how is it recognised and diagnosed and how should it be managed? This article attempts to unravel this enigma by: dealing with the terminology of coordination difficulties from the "clumsy child syndrome" through "dyspraxia" to "developmental coordination disorder (DCD)"; briefly examining the debate as to whether dyspraxia or DCD should be regarded as a medical or social disorder; discussing the differential diagnosis of dyspraxia or DCD; considering the assessment of children with dyspraxia or DCD; reviewing the range of current treatment approaches in the UK.

EMPD is a rare condition that poses difficulties of diagnosis and management. Suspicious skin lesions not responding to topical therapy after four to six weeks should be biopsied to exclude EMPD. There is an associated malignancy in 20% to 30% of cases and a detailed investigation of the patient should be carried out at presentation to exclude invasive disease. Surgery remains the mainstay of treatment for EMPD but carries a 40% local recurrence rate. As a result of this, other treatment modalities have been used mostly on an experimental basis to treat EMPD, including radiotherapy, topical and systemic chemotherapy, Mohs' micrographic surgery (MMS), laser therapy and PDT. The British Society for the Study of Vulval Disease (http://www.bssvd.fsnet.co. uk) has established a national register of cases and patients may benefit from referral to centres of expertise in treating vulval conditions. Because EMPD is so rare, there is currently a lack of appropriately controlled clinical trials comparing the various methods of treatment and the precise role of each modality of treatment in the management of this condition has yet to be elucidated. Nevertheless, it is clear that follow up of treated EMPD must be long term whatever the primary mode of treatment, because of the propensity of this condition to recur. Multicentre randomised controlled trials are required to compare different treatments. © RCOG 2004.

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are effective for obese patients with type 2 diabetes mellitus (T2DM) because they concomitantly target obesity and dysglycaemia. Considering the high prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with T2DM, we determined the impact of 6 months' GLP-1 RA therapy on intrahepatic lipid (IHL) in obese, T2DM patients with hepatic steatosis, and evaluated the inter-relationship between changes in IHL with those in glycosylated haemoglobin (HbA(1)c), body weight, and volume of abdominal visceral and subcutaneous adipose tissue (VAT and SAT). We prospectively studied 25 (12 male) patients, age 50±10 years, BMI 38.4±5.6 kg/m(2) (mean ± SD) with baseline IHL of 28.2% (16.5 to 43.1%) and HbA(1)c of 9.6% (7.9 to 10.7%) (median and interquartile range). Patients treated with metformin and sulphonylureas/DPP-IV inhibitors were given 6 months GLP-1 RA (exenatide, n = 19; liraglutide, n = 6). IHL was quantified by liver proton magnetic resonance spectroscopy ((1)H MRS) and VAT and SAT by whole body magnetic resonance imaging (MRI). Treatment was associated with mean weight loss of 5.0 kg (95% CI 3.5,6.5 kg), mean HbA(1c) reduction of 1·6% (17 mmol/mol) (0·8,2·4%) and a 42% relative reduction in IHL (-59.3, -16.5%). The relative reduction in IHL correlated with that in HbA(1)c (ρ = 0.49; p = 0.01) but was not significantly correlated with that in total body weight, VAT or SAT. The greatest IHL reduction occurred in individuals with highest pre-treatment levels. Mechanistic studies are needed to determine potential direct effects of GLP-1 RA on human liver lipid metabolism.

BACKGROUND: A large number of scoring systems for assessing a patient's risk of complications or death has been developed over recent years. This is a review of those that are of relevance to general surgeons. METHODS: A Medline literature search was performed to identify all articles concerning 'severity of illness', 'morbidity', 'mortality' and 'postoperative complications' in the field of surgery from 1966 to 1997. Further searches were performed to find papers about specific identified scoring systems, and relevant articles from the reference lists of these were also sought. RESULTS AND CONCLUSION: The advantages of an accurate assessment of a patient's risk include, on an individual level, the opportunity to give a more accurate prognosis and choose the most appropriate treatment. If the risk of an adverse outcome is known for a group of patients, the actual outcome can be compared with the predicted outcome, and comparison can be made between groups in different surgical units for the purposes of audit or research. The Physiological and Operative Severity Score for enUmeration of Mortality and morbidity (POSSUM) is the most appropriate of the currently available scores for general surgical practice.

Abstract Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown 1 to be highly efficient for discovery of genetic associations 2 . Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group 3 . Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling ( JAK1 ), monocyte–macrophage activation and endothelial permeability ( PDE4A ), immunometabolism ( SLC2A5 and AK5 ), and host factors required for viral entry and replication ( TMPRSS2 and RAB2A ).

BACKGROUND: Research questions To compare the efficacy of nintedanib and pirfenidone in the treatment of progressive pulmonary fibrosis; and to compare the efficacy of anti-fibrotic therapy (grouping nintedanib and pirfenidone together) in patients with IPF versus patients with progressive lung fibrosis not classified as IPF. STUDY DESIGN AND METHODS: A search of databases including MEDLINE, EMBASE, PubMed, and clinicaltrials.gov was conducted. Studies were included if they were randomised controlled trials of pirfenidone or nintedanib in adult patients with IPF or non-IPF patients, and with extractable data on mortality or decline in forced vital capacity (FVC). Random effects meta-analyses were performed on changes in FVC and where possible on mortality in the selected studies. RESULTS: 13 trials of antifibrotic therapy were pooled in a meta-analysis (with pirfenidone and nintedanib considered together as anti-fibrotic therapy). The change in FVC was expressed as a standardised difference to allow pooling of percentage and absolute changes. The mean effect size in the IPF studies was - 0.305 (SE 0.043) (p < 0.001) and in the non-IPF studies the figures were - 0.307 (SE 0.063) (p < 0.001). There was no evidence of any difference between the two groups for standardised rate of FVC decline (p = 0.979). Pooling IPF and non-IPF showed a significant reduction in mortality, with mean risk ratio of 07.01 in favour of antifibrotic therapy (p = 0.008). A separate analysis restricted to non-IPF did not show a significant reduction in mortality (risk ratio 0.908 (0.547 to 1.508), p = 0.71. INTERPRETATION: Anti-fibrotic therapy offers protection against the rate of decline in FVC in progressive lung fibrosis, with similar efficacy shown between the two anti-fibrotic agents currently in clinical use. There was no significant difference in efficacy of antifibrotic therapy whether the underlying condition was IPF or non-IPF with progressive fibrosis, supporting the hypothesis of a common pathogenesis. The data in this analysis was insufficient to be confident about a reduction in mortality in non-IPF with anti-fibrotic therapy. Trial Registration PROSPERO, registration number CRD42021266046.

OBJECTIVE: Cyanoacrylate (CA) embolization of refluxing great saphenous veins (GSVs) has been previously described. The outcomes from a multicenter study are still lacking. METHODS: A prospective multicenter study was conducted in seven centers in four European countries to abolish GSV reflux by endovenous CA embolization. Neither tumescent anesthesia nor postinterventional compression stockings were used. Varicose tributaries remained untreated until at least 3 months after the index treatment. Clinical examination, quality of life assessment, and duplex ultrasound evaluation were performed at 2 days and after 1, 3, 6, and 12 months. RESULTS: In 70 patients, of whom 68 (97.1%) were available for 12-month follow-up, 70 GSVs were treated. Two-day follow-up showed one proximal and one distal partial recanalization. Three additional proximal recanalizations were observed at 3-month (n = 2) and 6-month (n = 1) follow-up. Cumulative 12-month survival free from recanalization was 92.9% (95% confidence interval, 87.0%-99.1%). Mean (standard deviation) Venous Clinical Severity Score improved from 4.3 ± 2.3 at baseline to 1.1 ± 1.3 at 12 months. Aberdeen Varicose Vein Questionnaire score showed an improvement from 16.3 at baseline to 6.7 at 12 months (P < .0001). Side effects were generally mild; a phlebitic reaction occurred in eight cases (11.4%) with a median duration of 6.5 days (range, 2-12 days). Pain without a phlebitic reaction was observed in five patients (8.6%) for a median duration of 1 day (range, 0 -12 days). No serious adverse event occurred. Paresthesia was not observed. CONCLUSIONS: Endovenous CA embolization of refluxing GSVs is safe and effective without the use of tumescent anesthesia or compression stockings.

In this retrospective pilot study we examine the feasibility of establishing a confidential enquiry into why some patients die after emergency admission to hospital. After excluding those who died in the first hour or who were admitted for palliative care, pairs of physicians were able to collect quantitative and qualitative data on 200 consecutive deaths. Both physicians reported shortfalls of care in 14 patients and one of the pair in 25 patients whose deaths would not have been the expected outcome. In 25, the shortfalls of care may have contributed to their deaths. Major problems were delays in seeing doctors, inaccurate diagnoses, delays in investigations and initiation of treatment. They occurred mostly in those admitted at night. It is possible that establishing the correct diagnosis and starting appropriate treatment may have been delayed in 64% of the 200 patients. The headline figures appear worse than some previous external assessment studies but this study did concentrate on those in whom problems were more likely. Nevertheless, the frequency is too high to be overlooked. In this feasibility study we have demonstrated that it is practicable for local staff to collect and assess data in hospitals and that the types of problems identified are relevant to anyone planning how to organise emergency care. A larger definitive study should be performed.