This meta-analysis of publications over an approximate ten-year period from 2002-12 looked at mortality after coronary presentations.A total of 487 reports were studied and 48 were assessed for the impact of nominal 'off hours' (night and weekends) presentation for catheter-based revascularisation for ST elevation myocardial infarction (STEMI).Smaller studies tended to show increased mortality off hours, larger samples little or no adverse effect.The net impact, using a random effect meta-analysis model, was a statistically significant 2-4% mortality excess.This was linked by the authors to an increase in hospital 'door to balloon' times.

The European Working Time Directive (EWTD) limits excessive night shifts and restricts the working week to no more than 48 hours. The underlying rationale is to minimise the health risks to all workers. Here we debate the impact of night rotas for doctors-in-training on patient safety and medical education; when the EWTD was agreed these topics may not have been considered, either systematically or objectively. The impacts of diurnal rhythms on human functions affect all night workers, but the nature of rostered medical and surgical work has little precedent in other industries or even in the contracts of other healthcare staff. For example, rostered night duties need to be distinguished from permanent night shift work. On-call medical night work from training doctors is generally required for short periods and usually involves fewer patients. It is an important time in training, where clinical responsibility and decision-making can be matured in a supervised setting. To comply with the EWTD most hospitals have adopted rota patterns that aim to cover the clinical needs, while ensuring no doctor works for more than 48 hours in an average working week. To monitor this process longterm studies are necessary to evaluate effects on a doctor's health and on patient care generally. The EWTD has also led to a loss of continuity of patient care; does this really matter?

High quality decision-making for individual patients is at the heart of integrated medical care and has little correlation to the level of activity undertaken. There has been a rise in diagnostic indecision in recent years as practitioners increasingly rely on ‘doing a lot’ rather than ‘doing it right’. This is evident in the expanding use of ‘rapid’ or ‘open access’ systems and ‘rule out’ testing to diagnose diseases, rather than reliance on basic high quality medical diagnostic acumen, based on knowledge and triage expertise. The National Health Service (NHS) needs to be cost-effective and it is unacceptable to provide or commission services in isolation on the basis of expediency, demand or popularity without reference to their effectiveness.

In this issue, we include a pilot study which examined the completeness of physical examination of inpatients referred for specialist neurological assessment. 1 The findings, based upon patient recollection of diagnostic tools used during their initial medical assessment, suggest significant omissions in basic examination which have the potential to compromise the quality and safety of care delivered. In publishing this paper, we recognise it is based on a small scale study, with limitations, but believe these preliminary findings have wider implications for all in medicine, remind us of the importance of conducting physical examination 2 and could be of value

Nonesterified fatty acids (NEFA) and insulin have been implicated in the pathogenesis of diabetes mellitus (Type 2 diabetes) and coronary artery disease (CAD). We hypothesized that intracardiac levels of insulin and NEFA within the aortic root, coronary sinus and systemic venous levels would be different in patients with coronary atherosclerosis and/or diabetes. We also studied the metabolic cardiac response following percutaneous coronary intervention (PCI).A total of 67 subjects (42 males; mean age 60 +/- 11 years) were recruited, of which three groups were identified: Group I - those with no CAD or Type 2 diabetes (n = 17); Group II - those with CAD but no Type 2 diabetes (n = 40); and Group III - patients with Type 2 diabetes and CAD (n = 10). Of the whole cohort, 34 patients (51%) proceeded to PCI. NEFA and insulin levels were analysed using enzymatic colorimetric and a monoclonal immuno-autoanalyser techniques, respectively. Subsequently, fractional extraction (FFE) of both variables was calculated.Nonesterified fatty acids and insulin concentrations were lower in the aortic root versus coronary sinus (both P < 0.05). FFE of NEFA was 2x higher in Group I (P < 0.01) with a sevenfold reduction in insulin FFE in Group III. Following PCI, systemic NEFA levels increased significantly (P < 0.05) with no significant change seen within the coronary sinus (P = NS), whilst a reduction in insulin concentrations at all three sites was observed (all P < 0.01). No significant difference in FFE of NEFA was seen after PCI when comparing Groups II and III. There was a drop in insulin extraction in Group II (nondiabetic subjects, from 12% to -4%, P = 0.04), compared with an increase seen in Group III (Type 2 diabetes patients, from -4% to 3%, P = 0.03).There is an intracardiac gradient of NEFA and insulin in Groups I-III. Cardiac NEFA metabolism was higher in those with mild CAD compared with those with obstructive CAD whereas intracardiac insulin extraction was lower in Group III (diabetic) patients. PCI was associated with a systemic rise in NEFA, with a reduction in insulin levels and cardiac utilization, but these effects were blunted in diabetic patients.

ABSTRACT Background Acute exercise has been associated with activation of thrombosis, and this risk may be accentuated in patients with heart failure. Given the relation of platelets to atherothrombosis, we tested the hypothesis that acute exercise would adversely affect platelet indices and platelet activation markers in patients with systolic and diastolic heart failure. Materials and methods We studied 20 patients with systolic heart failure (17 men, 3 women; mean age 64 ± 10 years, all with ejection fraction (EF) ≤ 40%) and 20 patients with diastolic heart failure (14 men, 6 women; mean age 64 ± 8 years, mean EF = 66%) who were exercised to maximal intensity, who were compared to 13 healthy controls (6 men, 7 women; mean age 60 ± 4 years, mean EF = 73%). We measured platelet indices (platelet volume, mass and component) and platelet activation markers (platelet‐bound CD62P%G, CD63%G and CD40L%G using flow cytometry, as well as plasma sCD40L and soluble P‐selectin (sP‐sel) levels). Results Baseline Mean Platelet Volume (MPV), sP‐sel, CD40L%G and CD63%G levels were significantly higher in patients with systolic and diastolic heart failure, when compared with controls. The mean exercise duration and VO 2 peak in patients with systolic and diastolic heart failure were not significantly different, but lower than that seen in healthy controls. Following exercise, mean haematocrit, CD62P%G, and CD63%G significantly increased in all three subject groups (all P < 0·05). The proportional change in CD62P%G and CD63%G were not significantly different between healthy controls and heart failure patients ( P > 0·05). Conclusion Acute maximal graded exercise increases platelet activation markers, with no disproportionate differences between heart failure patients and healthy controls, despite the former group having a lower exercise tolerance and VO 2 peak.

Background: Anderson-Fabry Disease (AFD) is an inherited metabolic disease associated with premature death secondary to cardiovascular and renal disease. Patients with AFD develop progressive left ventricular (LV) remodelling and heart failure. We hypothesized that altered extracellular matrix (ECM) turnover contributes to the pathophysiology of cardiac disease in AFD. Methods and Results: Twenty-nine consecutive patients (44.1 +/- 11.7 years, 15 male) with AFD and 21 normal controls (39.7 +/- 11.3 years, 10 male) had serum analysed for matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix metalloproteinase-1 and -2 (TIMP-1, TIMP-2). All patients underwent clinical assessment, echocardiography and Mainz Severity Score Index (MSSI) measurement, a validated severity score in AFD. MMP-9 levels were significantly higher in patients than controls (1003.8 +/- 337.8 ng/ml vs 576.7 +/- 276.3 ng/ml respectively, p < 0.001). There were no differences in TIMP levels between patients and controls. There was a positive correlation between MMP-9 levels and MSSI (r = 0.5, p = 0.01). There was a negative correlation between MMP-9 and endocardial fractional shortening (FS) (r = -0.5, p = 0.01) and mid-wall FS (r = -0.6, p = 0.001). There was no correlation between other echocardiographic parameters and MMP-9 levels. These relations were independent of age and sex using stepwise linear regression analysis. Conclusions: Patients with AFD have abnormal ECM turnover compared to normal controls. The correlation between MMP-9 levels and systolic function suggests that altered ECM turnover is important in cardiac remodelling. The association between MMP-9 and overall disease severity suggests that circulating levels of MMP-9 may provide a useful marker for assessing the response of patients with AFD to enzyme replacement treatment.

Endothelial injury and subsequent damage/dysfunction are crucial processes in the pathogenesis of coronary artery disease (CAD). The quantification of circulating endothelial cells (CECs) from whole blood is an advancing and novel method of assessing endothelial injury [1]. These CECs represent endothelial cells that have become detached from the endothelial monolayer in response to endothelial damage [1]. Increased CECs have been linked to a variety of cardiovascular disease (CVD) states and have been linked to worsening CVD outcomes [1, 2]. However, patients with CAD invariably have widespread peripheral as well as coronary atherosclerosis. Consequently, the proportion of CECs in these patients that actually represent coronary endothelial injury is uncertain. This study has two main hypotheses: (i) CEC counts and plasma von Willebrand factor (VWF, an established plasma marker of endothelial damage/dysfunction) levels would be significantly higher in the coronary sinus (CS, which drains the heart) compared with the aortic root (AR) or femoral vein (FV) in patients with CAD; (ii) percutaneous coronary intervention (PCI, coronary angioplasty ± stenting) would cause a significant acute rise in CECs and VWF levels from the CS and not from the AR or FV samples. To test these hypotheses, we performed a cross-sectional study comparing CEC counts and VWF levels from the AR, CS and FV in a cohort of CAD patients undergoing coronary angiography, and determined the effects of PCI in a subset of these subjects. We recruited a cohort of 41 patients aged > 35 years, either scheduled for elective diagnostic cardiac catheterization or clinically stable following an acute syndrome. We excluded patients with atrial fibrillation, valvular heart disease, previous coronary artery bypass surgery and/or with recent (< 3 months) stroke, and patients with coexistent infection, renal or hepatic impairment, known cancer, known inflammatory disease and those on hormone replacement therapy were also excluded. The study was approved by the local research and Ethics Committee and all patients gave their written informed consent. Central access was achieved using five and six French sheaths (Cordis Ltd, Warren, NJ, USA) in the FV and artery, respectively. A pigtail catheter was used for AR blood sampling and an Amplatz AL-1 catheter (Cordis Ltd) or modified Sims (Cook Ltd, Letchworth, UK) was used to cannulate the CS under fluoroscopy. All catheters and sheaths were flushed with a solution of 0.5% heparinized normal saline. A standard series of coronary angiographic images was defined in all cases. Samples were acquired from the AR, CS and the FV in quick succession. Post-PCI blood samples were taken immediately post procedure and prior to the use of any vascular closure device. The first 5 mL of aspirated blood was discarded each time prior to assay sampling. In a subgroup of 12 patients, we additionally investigated the effects of contrast on coronary ostium CEC/VWF release by repeating the baseline counts immediately following complete left coronary injections. CEC and VWF analyses were performed by independent operators who were blinded to the site of vascular sampling. CEC analysis was performed using the immunobead technique as previously described [3]. VWF levels were measured in duplicate by enzyme-linked immunosorbent assay from batched frozen (−70 °C) citrated plasma, as previously well described [2]. Based on a recent paper [4], which noted a 50% increase in peripheral blood CECs following PCI (n = 15), coupled with previous CEC data among similar patient groups with CAD [1], we calculated that a sample size of 20 patients in each group had an 80% power to detect a 50% increase in mean CECs (pre vs. post angioplasty). This sample size would also provide 80% power to detect a 15% increase in mean VWF levels at a significance level (alpha) of 0.05 (one-tailed). Data were analyzed using graphpad instat version 3.05 (http://www.graphpad.com). The Kolmogorov–Smirnov test (for normality) determined our data to be normally distributed. Consequently, data are presented as the mean ± SD. Comparisons within groups were performed using repeated measures anova and paired t-test used for comparisons between paired samples. A P-value < 0.05 was considered statistically significant for all comparisons. The patient demographics are shown in Table 1. There were no significant differences in baseline CEC counts (P = 0.89) or VWF levels (P = 0.59) between the AR, CS and right femoral vein (FV; Table 2). 'Urgent' patients had higher CEC counts than 'elective' cases (all P < 0.05). In a subgroup of 12 patients, there were no changes in coronary ostium CECs (P = 0.39) or VWF (P = 0.81) levels with contrast injection (full data not shown). From the total cohort of 41 patients, 26 patients subsequently underwent PCI (Table 1). PCI led to significant increases in CEC counts mL−1 across all three sites (pre-PCI vs. post-PCI): AR (P = 0.02), CS (P = 0.0005) and RFV (P = 0.01) There was no significant change in VWF levels following PCI, irrespective of sampling site (Table 3). There were no significant relationships between Gensini scores (extent of coronary disease), number of stents, type of stent, volume of contrast, and screening time on either absolute/Δ VWF levels or CEC counts, for any of the three sites sampled (data not shown). Furthermore, we found no significant correlations between CECs and VWF at any of the sampled sites (data not shown). This is the first paper to define the relationship between baseline and PCI-related CEC counts and plasma VWF levels across multiple vascular territories. We observed no apparent differences in VWF levels or CEC counts on concurrent samples taken from the AR, CS and FV. However, we have documented that PCI was associated with significant increases in CEC counts, but not VWF levels. These changes were evident regardless of the site of sampling. In the only other paper reporting comparative CEC counts from the CS and peripheral blood, Yu et al. [5] found significantly higher CEC counts in the CS compared with the periphery in 20 patients with 'unstable angina' and 17 patients with symptomatically stable CAD. However, in this unblinded study, using a different method of CEC isolation, the effects of PCI on CEC counts or other endothelial markers were not investigated [5]. Dignat-George et al. [6] reported similar CEC counts in the FV vs. femoral artery following PCI (n = 10). In a further small study (n = 15), these investigators noted a significant increase in peripheral blood CECs, on comparing blood taken immediately post-PCI (15.9 ± 3.7 cells mL−1; P = 0.001) compared with preprocedural counts (2.4 ± 0.9 CEC mL−1) [5]. The observed broadly similar rise in CEC counts, following PCI, regardless of the sample site, would appear to suggest that PCI leads either to widespread endothelial perturbation and/or a rapid equilibration of responses. Contrary to our initial hypothesis, we cannot presume that the increased CEC counts represent specific coronary artery endothelial shedding. Passage of the coronary guide catheter, angioplasty guide wire and/or balloon (±stent) into the aorta and coronary vasculature may have resulted in generalized CEC release, but we found no significant change in coronary os CECs/VWF with contrast. As CEC and VWF sampling was only performed at two time points (immediately pre-PCI and post-PCI) we cannot excluded the possibility that we may have missed an abrupt rise in local release of VWF that may have been detected by more frequent and protracted sampling post-PCI. Finally, the autonomic procedural stress might engender a disseminated endothelial shedding response throughout the endothelium circulation. In conclusion, this study showed no significant differences in baseline CEC counts or VWF levels between the AR, CS and RFV. However, PCI was associated with a significant increase in CECs, but not VWF, across all three sampling sites. We thank Dr A. D. Blann for helpful advice. We acknowledge the support of Immunicon Corp, Huntingdon Valley, PA, USA and the Sandwell and West Birmingham Hospitals NHS Trust for the Haemostasis Thrombosis and Vascular Biology Unit.

The quantity of referrals to secondary care is increasing. That the quality of medical referrals is decreasing is a common allegation yet has rarely been assessed. We report a time-limited, cross-sectional survey evaluating cardiological referral information quality. Referral letters (n = 218, excluding direct access pro formas) from GPs to the Cardiology Department at City Hospital, Birmingham, were collated and analysed over 2 months. A subset (n = 49) of these patients completed questionnaires assessing their knowledge and patient communication of the referral. Information quality was poor (length, diagnosis, expectation, prior treatment and investigation) with almost half of all letters containing only outline symptomatic complaints without diagnosis. The majority of patients referred had not been investigated or treated in any way before referral. Despite lack of understanding of the reason for referral, typically the majority of patients expressed themselves as satisfied with the process. Given most referrals are seen as appropriate, information exchange between secondary and primary care is crucial. By contrast, the standard of even basic clinical assessment communicated between primary care and secondary care was severely limited. The reason(s) why medical assessment is lacking are unclear but must be explored to give more support to primary care to complete basic medical task particularly if investment is to flow into this source.