Spinal anaesthesia for spinal surgery.
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Adult↗
Biomedical subjects
M Goddard
Publications and source records attributed to M Goddard.
Octogenarians undergoing cardiac surgery outlive their peers: a case for early referral.
OBJECTIVE: To examine short and long term outcomes of octogenarians having heart operations and to analyse the interaction between patient and treatment factors. METHODS: Multivariate analysis of prospectively collected data and a survival comparison with an age and sex matched national population. The outcomes were base in-hospital mortality, risk stratified by logistic EuroSCORE (European system for cardiac operative risk evaluation), and long term survival. RESULTS: 12,461 consecutive patients (706 over 80 years) operated on between 1996 and 2003 in a regional UK unit were studied. Octogenarians more often had impaired ventricular function, pulmonary hypertension, and valve operations. They also included a higher proportion of women, had a higher serum creatinine concentration, and had a trend towards more unstable angina. Younger patients had a higher prevalence of previous cardiac operation, previous myocardial infarction, and diabetes. The in-hospital mortality rate was 3.9% for all patients (EuroSCORE predicted 6.1%, p < 0.001) and 9.8% for octogenarians (predicted 14.1%, p = 0.002). Long bypass time and non-elective surgery increased the risk of death above EuroSCORE prediction in both groups. A greater proportion of octogenarians stayed in intensive care more than 24 hours (37% v 23%, p < 0.001). Long term survival was significantly better in the study patients than in a general population with the same age-sex distribution (survival rate at five years 82.1% v 55.9%, p < 0.001). CONCLUSIONS: Cardiac surgery in a UK population of octogenarians produced excellent results. Elective referrals should be encouraged in all age groups.
Age Factors↗
Artificial selection and maintenance of genetic variance in the global dairy cow population.
Genetic improvement of dairy cows, which has increased the milk yield of cows in the UK by 1200 kg per lactation in 12 years, is an excellent example of the application of quantitative genetics to agriculture. The most important traits of dairy cattle are expressed only in females, but the main opportunity for selection is in males. Despite this, genetic improvement was achieved by the invention of a new statistical methodology, called 'best linear unbiased prediction' to estimate the breeding value of bulls. Intense selection of the best bulls, combined with the worldwide use of these bulls through artificial insemination and frozen semen, has created a global population and caused concern that the genetic variation available in the future will be reduced. Maintenance of genetic variation and long-term genetic gains would be aided by rational payment systems, use of crossbreeding where profitable, inclusion of all economically important traits in the breeding objective, recognition of genotype by environment interactions and the use of selection algorithms that balance estimated breeding value against the average relationship among the selected animals. Fortunately, all of these things are happening to some degree.
Animals↗
Improved survival with VATS pleurectomy-decortication in advanced malignant mesothelioma.
AIMS: Malignant mesothelioma is increasing in incidence and no current therapy significantly prolongs survival. Previous surgical strategies involved high-risk open procedures without achieving histologically clear resection margins. We present the results of VATS debulking pleurectomy-decortication in advanced disease. METHODS: A consecutive series of patients with suspected malignant mesothelioma underwent thoracoscopic assessment to determine the feasibility of decortication, where this was not possible a biopsy alone was taken. Post-operative radiotherapy was administered to port sites, but no other adjuvant therapy was given. The two groups (biopsy only and pleurectomy-decortication) were composed of patients with histologically confirmed mesothelioma [28 and 51 patients, respectively]. The primary endpoint was comparison of actuarial patient survival. Secondary endpoints included post-operative air leak and duration of hospital stay. RESULTS: The overall actuarial survival was 288 days and 67% of patients had died at the time of data analysis. The groups were matched for patient and tumour-related characteristics including age (66, 64 years, p=0.39) and tumour stage (median IMIG stage 3 [IQR 2-3] both groups, p=0.54). The biopsy only group had fewer air leaks (57, 84%, p=0.01) and a shorter hospital stay (4, 8 days, p=0.03). However, the pleurectomy-decortication group had favourable actuarial survival relative to the biopsy only group (416, 127 days, p<0.001). Multivariate analysis showed early stage (p<0.001), absence of pre-operative fever (p=0.03) and pleurectomy-decortication (p<0.001) as independent predictors of survival. CONCLUSION: VATS pleurectomy-decortication is feasible in the majority of cases and independently improves survival for patients with advanced malignant mesothelioma.
Actuarial Analysis↗
Multi-sequence in vivo MRI can quantify fibrous cap and lipid core components in human carotid atherosclerotic plaques.
OBJECTIVES: Risk of thrombo-embolic stroke is thought to be better reflected by carotid plaque composition than by luminal stenosis. We set out to determine whether high resolution MRI was a valid method of quantifying plaque components in vivo. DESIGN: A prospective cohort study validating in vivo MRI against histological analysis of excised carotid plaques. MATERIALS: Twenty-five recently symptomatic patients with severe internal carotid artery stenosis underwent pre-operative in vivo multi-sequence MRI of the carotid artery using a 1.5 T system. METHODS: Individual plaque constituents were characterized on axial MR images according to net signal intensities. Analysis of fibrous cap and lipid core content was quantified proportional to overall plaque area. Bland-Altman plots were generated, and intra-class coefficients computed to determine the level of agreement between the two methods and inter-observer variability. RESULTS: The intra-class correlation coefficients between two MR readers were 0.94 and 0.88 for quantifying fibrous cap and lipid core components, respectively. There was good agreement between MR and histology derived quantification of both fibrous cap and lipid core content; the mean % difference for fibrous cap was 0.75% (+/-2.86%) and for lipid core was 0.86% (+/-1.76%). CONCLUSION: High resolution carotid MRI can be used to quantify plaque components and may prove useful in risk stratification.
Aged↗
Ventricular assist surprise: giant cell myocarditis or sarcoidosis?
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Adult↗
Lethal mesenteric ischaemia after cardiopulmonary bypass: a common complication?
OBJECTIVES: The purpose of the study was twofold: (1) to identify the incidence of acute mesenteric ischaemia (A.M.Isc.) following cardiopulmonary bypass and (2) to identify factors associated with its development. METHODS: A retrospective review of all autopsy reports from 1st January 1994 to 31st December 2000 was undertaken. Fifty-two patients were identified with acute mesenteric ischaemia at post-mortem following cardiac surgery. Demographic, pre-, intra- and post-operative variables were collected from their case notes. Four age, sex and period matched controls [n=208 (4 x 52)] were randomly selected for each case. Conditional logistic regression was used to compare the cases and controls. RESULTS: A total of 11,202 patients underwent surgery requiring cardiopulmonary bypass (CPB) during the study period with an overall mortality rate of 3%. The autopsy rate was 95% throughout the study period. From autopsy reports 52 patients (corrected for autopsy rate: 0.49% of group) were identified with A.M.Isc. Comparing controls with A.M.Isc. cases by univariate analysis, significant associations (P</=0.001) with A.M.Isc. were identified. These included: (1) peripheral vascular disease [15 (7%) vs. 14 (27%)]; (2) intraaortic balloon pump (IABP) use [5 (2%) vs. 22 (42%)]; (3) post-operative renal failure [2 (1%) vs. 32 (61%)]; (4) operation type (coronary artery bypass graft (CABG) alone [143 (69%) vs. 25 (48%)], valve alone [35 (17%) vs. 5 (10%)], valve+CABG [23 (11%) vs. 11 (21%)], major cardiac [7 (3%) vs. 11 (21%)]); (5) priority of operation (elective [155 (75%) vs. 27 (52%) emergency 52 (25%) vs. 25 (48%)]; and (6) smoking 12 (7%) vs. 9 (17%). CPB and cross-clamp times (minutes) were also significantly different between the groups [median (inter-quartile range (IQR)); 72 (55,96) vs. 100 (76,128) and 39 (30,54) vs. 56 (37,84), respectively]. Neither diabetes 23 (11%) vs. 6 (12%) nor hypertension 102 (49%) vs. 26 (50%) achieved significance (P<0.001). CONCLUSION: The incidence of acute mesenteric ischaemia is 0.49% of all cases undergoing CPB. A.M.Isc. is a common association with death following CPB (11%). It appears to be significantly associated with the presence of peripheral vascular disease, IABP use, the development of post-operative renal failure, operation type and priority, smoking, duration of CPB and cross-clamp time. Surprisingly, it was not linked to general risk factors for vascular disease.
Acute Disease↗
Macrophage function and stability of the atherosclerotic plaque: progress report of a European project.
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ATP-Binding Cassette Transporters↗
Impact of published clinical outcomes data: case study in NHS hospital trusts.
OBJECTIVE: To examine the impact of the publication of clinical outcomes data on NHS Trusts in Scotland to inform the development of similar schemes elsewhere. DESIGN: Case studies including semistructured interviews and a review of background statistics. SETTING: Eight Scottish NHS acute trusts. PARTICIPANTS: 48 trust staff comprising chief executives, medical directors, stroke consultants, breast cancer consultants, nurse managers, and junior doctors. MAIN OUTCOME MEASURES: Staff views on the benefits and drawbacks of clinical outcome indicators provided by the clinical resource and audit group (CRAG) and perceptions of the impact of these data on clinical practice and continuous improvement of quality. RESULTS: The CRAG indicators had a low profile in the trusts and were rarely cited as informing internal quality improvement or used externally to identify best practice. The indicators were mainly used to support applications for further funding and service development. The poor effect was attributable to a lack of professional belief in the indicators, arising from perceived problems around quality of data and time lag between collection and presentation of data; limited dissemination; weak incentives to take action; a predilection for process rather than outcome indicators; and a belief that informal information is often more useful than quantitative data in the assessment of clinical performance. CONCLUSIONS: Those responsible for developing clinical indicator programmes should develop robust datasets. They should also encourage a working environment and incentives such that these data are used to improve continuously.
Attitude of Health Personnel↗
Defect in insulin-like growth factor-1 survival mechanism in atherosclerotic plaque-derived vascular smooth muscle cells is mediated by reduced surface binding and signaling.
Apoptosis of vascular smooth muscle cells (VSMCs) is increased in atherosclerosis compared with normal vessels, where it may contribute to plaque rupture. We have previously found that human plaque-derived VSMCs (pVSMCs) are intrinsically sensitive to apoptosis and not responsive to the protective effects of insulin-like growth factor-1 (IGF-1). We therefore examined the mechanism underlying this defect. Human pVSMCs showed <25% (125)I-IGF-1 surface binding, <20% IGF-1 receptor (IGF-1R) expression than that of normal medial VSMCs, and <40% Akt kinase activity in response to IGF-1. pVSMCs expressed and secreted high levels of IGF-1 binding proteins (IGFBPs), and the IGF-1 analogues, long R3 and Des 1,3 IGF-1, which do not bind to IGFBPs, were able to increase pVSMC survival to normal medial VSMC levels. The long R3 survival effect was phosphatidylinositol 3-kinase-mediated, but it was not dependent on Akt activity alone. Intimal pVSMCs in vivo showed reduced IGF-1R expression compared with medial VSMCs, in particular at the shoulder regions of plaques. We conclude that human pVSMCs show an intrinsic sensitivity to apoptosis caused in part by defective expression of IGF-1R, impaired IGF-1-mediated survival signaling and increased IGFBP secretion. This impaired IGF-1 protection against apoptosis may promote VSMC loss and plaque instability in atherosclerosis.
Androstadienes↗
Improving performance in public hospitals: a role for comparative costs?
In order to encourage performance improvements, the English government has set targets for acute hospitals to reduce their unit costs. Targets are based on analysis of costs across all acute hospitals. This policy has parallels with that of 'yardstick competition', advocated as a means to encourage efficiency in industries that lack competitive pressures. However, the prospect of cost improvements may not be realised in England. Firstly, there are insufficient incentives to respond appropriately to the provision of comparative cost information. Secondly, there is more than one index purporting to measure relative hospital costs. As comparison of unit costs is highly dependent on the measurement technique adopted, caution should be exercised when setting performance targets.
Benchmarking↗
Equity of access to health care services: theory and evidence from the UK.
The pursuit of equity of access to health care is a central objective of many health care systems. This paper first sets out a general theoretical framework within which equity of access can be examined. It then applies the framework by examining the extent to which research evidence has been able to detect systematic inequities of access in UK, where equity of access has been a central focus in the National Health Service since its inception in 1948. Inequity between socio-economic groups is used as an illustrative example, and the extent of inequity of access experienced is explored in each of five service areas: general practitioner consultations; acute hospital care; mental health services; preventative medicine and health promotion; and long-term health care. The paper concludes that there appear to be important inequities in access to some types of health care in the UK, but that the evidence is often methodologically inadequate, making it difficult to draw firm conclusions. In particular, it is difficult to establish the causes of inequities which in turn limits the scope for recommending appropriate policy to reduce inequities of access. The theoretical framework and the lessons learned from the UK are of direct relevance to researchers from other countries seeking to examine equity of access in a wide variety of institutional settings.
Health Services Accessibility↗
Erratum to 'Measuring appropriate use of acute beds: A systematic review of methods and results'.
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Journal Article↗
Neuroprotective gene therapy for Huntington's disease using a polymer encapsulated BHK cell line engineered to secrete human CNTF.
Huntington's disease (HD) is an autosomal dominant genetic disease with devastating clinical effects on cognitive, psychological, and motor functions. These clinical symptoms primarily relate to the progressive loss of medium-spiny GABA-ergic neurons of the striatum. There is no known treatment to date. Several neurotrophic factors have, however, demonstrated the capacity to protect striatal neurons in various experimental models of HD. This includes the ciliary neurotrophic factor (CNTF), the substance examined in this protocol. An ex vivo gene therapy approach based on encapsulated genetically modified BHK cells will be used for the continuous and long-term intracerebral delivery of CNTF. A device, containing up to 106 human CNTF-producing BHK cells surrounded by a semipermeable membrane, will be implanted into the right lateral ventricle of 6 patients. Capsules releasing 0.15-0.5 microg CNTF/day will be used. In this phase I study, the principal goal will be the evaluation of the safety and tolerability of the procedure. As a secondary goal, HD symptoms will be analyzed using a large battery of neuropsychological, motor, neurological, and neurophysiological tests and the striatal pathology monitored using MRI and PET-scan imaging. It is expected that the gene therapy approach described in this protocol will mitigate the side effects associated with the peripheral administration of recombinant hCNTF and allow a well-tolerated, continuous intracerebroventricular delivery of the neuroprotective factor.
Animals↗
Long-term survival of nonhuman primates receiving life-supporting transgenic porcine kidney xenografts.
BACKGROUND: Recently, there has been a resumed interest in clinical xenotransplantation using pig organs. However, no data are available yet regarding the capacity of porcine organs to sustain the life of a primate beyond the first month. We have attempted to obtain long-term survival of nonhuman primates using human decay-accelerating factor (hDAF) transgenic pig organs and an immunosuppressive strategy particularly aimed at neutralizing the humoral component of the immune response. METHODS: hDAF transgenic or control kidneys were transplanted into 14 bilaterally nephrectomized cynomolgus monkeys (Macaca fascicularis) that underwent splenectomy and were immunosuppressed with cyclosporine A, cyclophosphamide, and steroids. All animals also received recombinant erythropoietin. Postoperatively, the primates were monitored daily. Laboratory evaluations included serum biochemistry, hematology, and measurements of hemolytic antipig antibodies. To assess the role of splenectomy in the control of humoral response, historical data were also used from a group of monkeys (n=7) that received the same immunosuppressive regimen and an hDAF transgenic porcine kidney but did not have splenectomy or receive recombinant erythropoietin. RESULTS: This immunosuppressive approach obtained the longest survival time (78 days) described to date of a primate receiving a life-supporting porcine renal xenograft. Furthermore, four of nine animals in this series survived for 50 days or more. Most biochemical measurements in this study (including plasma urea, creatinine, sodium, and potassium concentrations) remained within normal ranges for several weeks in all of the longest-surviving animals. CONCLUSIONS: Normalization of renal function (urea and creatinine) in primate recipients of porcine renal xenografts suggests that pig kidneys may be suitable for future clinical xenotransplantation. Additional immunosuppressive approaches, specifically designed to prevent humorally mediated immunological damage, should be explored to further prolong survival of primates that have received porcine xenografts.
Animals↗
Enhancing performance in health care: a theoretical perspective on agency and the role of information.
This paper examines the role of information in securing control of health care systems. The discussion focuses on the impact of the proposed 'Performance Framework', which entails a significant increase in the importance attached to formal performance indicators in the management of the UK National Health Service. The paper starts with a discussion of the role of performance data in securing organizational control within health care systems and summarizes recent research into the behavioural consequences of seeking to control health care agents using such information. A theoretical principal/agent model is then used to illustrate the incentives that exist for dysfunctional behaviour within health care when only imperfect information systems are available. The theoretical results are then examined in the context of a qualitative empirical study, which elicited the perceptions of managers and health care professionals connected with eight NHS hospitals. The study confirmed the existence and importance of serious dysfunctional consequences arising from the use of information as a means of control, and concludes that the Performance Framework will be successful only if it is used in careful conjunction with other means of control.
Delivery of Health Care↗
Measuring appropriate use of acute beds. A systematic review of methods and results.
A systematic review of the methods used to assess appropriateness of acute bed use and the evidence on the scale of inappropriate use in different patient groups is presented. Issues of generalisability of the findings are also addressed. Criteria based tools are the accepted way of measuring inappropriate days of stay and admissions, although opinion based classification is very common. While a number of tools exist, few have been adequately tested for reliability and validity. The Appropriateness Evaluation Protocol (AEP) is the most commonly used tool, and has been tested more widely. It appears to be both reliable and valid. An estimated 29% of admissions to acute psychiatric may be inappropriate. Regarding days of care after admission, between 24 and 58% of stays were not judged to be appropriate for continued stay on an acute ward. The need for continued acute psychiatric care may become lower as patients experience continued stay in the acute setting. A lack of housing and community support was the most commonly cited reason preventing discharge. Rates of inappropriate use appear to be higher for older patients than for the general population. Wide variation in rates of inappropriate days of stay was found, but it may be safe to assume that inappropriate use is greater than 20% across a wide variety of settings. Reasons for older patients to remain in an acute hospital bed after medically necessary are typically moderate nursing care needs (i.e. long-term care). The estimates of inappropriate use in other groups was found to be highly variable. Before definitive conclusions on the inappropriate use of acute beds can be made, future research needs to take into account the methodological problems discussed here.
Acute Disease↗
Clinical versus actual outcome in cardiac surgery: a post-mortem study.
BACKGROUND: Clinical attribution of the cause of death can be misleading, with the only true outcome measure being post-mortem analysis. Despite this there is very little published data on post-mortems following cardiac surgery. METHODS: Prospective consecutive post-mortem data were collected on 167 patients (84.4% of all in-hospital cardiac surgical deaths) in a single institution. Clinical diagnoses were compared with post-mortem findings. RESULTS: The mean age at death was 69.8 with 67.6% male. The proportion undergoing coronary artery bypass graft (CABG) alone was 52.1%, valve surgery 18.6%, valve+CABG 19.2% and other procedures 10.1%. The mean time to death was 7.9 days (range 0-87). The causes of death were cardiac 67.7%, gastrointestinal 9.6%, respiratory 8.4%, haemorrhage/technical failure 4.8%, stroke (cerebrovascular accident) 3.6%, multiorgan failure 3.0%, sepsis 1.8%, malignancy 0. 6% and trauma 0.6%. Post-mortem revealed an unsuspected cause of death in 19 (11.4%). These were gastrointestinal (infarction nine, perforation two), cardiac three, adult respiratory distress syndrome two, technical two and pulmonary embolus one. In addition, an unsuspected lung cancer was found in 1 patient who died of cardiac causes. When cardiac deaths were compared with non-cardiac causes the Parsonnet score was higher 20.0 (+/-1.4) vs. 15.3 (+/-1.6), P=0. 07; and a greater proportion tended to have poor ejection fractions (34 vs. 15%), P=0.12. There was no significant difference between the groups in terms of age, sex, operation, hypertension, diabetes, creatinine and body mass. CONCLUSIONS: Post-mortem can determine unsuspected diagnoses in a significant proportion of cases. Pre-operative risk factors do not correlate with eventual cause of death. Post-mortem still has an important role to play in cardiac surgery.
Aged↗