The quality of care delivered to residents in long-term care in Australia: an indicator-based review of resident records (CareTrack Aged study).

BACKGROUND: This study estimated the prevalence of evidence-based care received by a population-based sample of Australian residents in long-term care (LTC) aged ≥ 65 years in 2021, measured by adherence to clinical practice guideline (CPG) recommendations. METHODS: Sixteen conditions/processes of care amendable to estimating evidence-based care at a population level were identified from prevalence data and CPGs. Candidate recommendations (n = 5609) were extracted from 139 CPGs which were converted to indicators. National experts in each condition rated the indicators via the RAND-UCLA Delphi process. For the 16 conditions, 236 evidence-based care indicators were ratified. A multi-stage sampling of LTC facilities and residents was undertaken. Trained aged-care nurses then undertook manual structured record reviews of care delivered between 1 March and 31 May 2021 (our record review period) to assess adherence with the indicators. RESULTS: Care received by 294 residents with 27,585 care encounters in 25 LTC facilities was evaluated. Residents received care for one to thirteen separate clinical conditions/processes of care (median = 10, mean = 9.7). Adherence to evidence-based care indicators was estimated at 53.2% (95% CI: 48.6, 57.7) ranging from a high of 81.3% (95% CI: 75.6, 86.3) for Bladder and Bowel to a low of 12.2% (95% CI: 1.6, 36.8) for Depression. Six conditions (skin integrity, end-of-life care, infection, sleep, medication, and depression) had less than 50% adherence with indicators. CONCLUSIONS: This is the first study of adherence to evidence-based care for people in LTC using multiple conditions and a standardised method. Vulnerable older people are not receiving evidence-based care for many physical problems, nor care to support their mental health nor for end-of-life care. The six conditions in which adherence with indicators was less than 50% could be the focus of improvement efforts.

The future of health systems to 2030: a roadmap for global progress and sustainability.

Most research on health systems examines contemporary problems within one, or at most a few, countries. Breaking with this tradition, we present a series of case studies in a book written by key policymakers, scholars and experts, looking at health systems and their projected successes to 2030. Healthcare Systems: Future Predictions for Global Care includes chapters on 52 individual countries and five regions, covering a total of 152 countries. Synthesised, two key contributions are made in this compendium. First, five trends shaping the future healthcare landscape are analysed: sustainable health systems; the genomics revolution; emerging technologies; global demographics dynamics; and new models of care. Second, nine main themes arise from the chapters: integration of healthcare services; financing, economics and insurance; patient-based care and empowering the patient; universal healthcare; technology and information technology; aging populations; preventative care; accreditation, standards, and policy; and human development, education and training. These five trends and nine themes can be used as a blueprint for change. They can help strengthen the efforts of stakeholders interested in reform, ranging from international bodies such as the World Health Organization, the International Society for Quality in Health Care and the World Bank, through to national bodies such as health departments, quality and safety agencies, non-government organisations (NGO) and other groups with an interest in improving healthcare delivery systems. This compendium offers more than a glimpse into the future of healthcare-it provides a roadmap to help shape thinking about the next generation of caring systems, extrapolated over the next 15 years.

Quality of Health Care for Children in Australia, 2012-2013.

Importance: The quality of routine care for children is rarely assessed, and then usually in single settings or for single clinical conditions. Objective: To estimate the quality of health care for children in Australia in inpatient and ambulatory health care settings. Design, Setting, and Participants: Multistage stratified sample with medical record review to assess adherence with quality indicators extracted from clinical practice guidelines for 17 common, high-burden clinical conditions (noncommunicable [n = 5], mental health [n = 4], acute infection [n = 7], and injury [n = 1]), such as asthma, attention-deficit/hyperactivity disorder, tonsillitis, and head injury. For these 17 conditions, 479 quality indicators were identified, with the number varying by condition, ranging from 9 for eczema to 54 for head injury. Four hundred medical records were targeted for sampling for each of 15 conditions while 267 records were targeted for anxiety and 133 for depression. Within each selected medical record, all visits for the 17 targeted conditions were identified, and separate quality assessments made for each. Care was evaluated for 6689 children 15 years of age and younger who had 15 240 visits to emergency departments, for inpatient admissions, or to pediatricians and general practitioners in selected urban and rural locations in 3 Australian states. These visits generated 160 202 quality indicator assessments. Exposures: Quality indicators were identified through a systematic search of local and international guidelines. Individual indicators were extracted from guidelines and assessed using a 2-stage Delphi process. Main Outcomes and Measures: Quality of care for each clinical condition and overall. Results: Of 6689 children with surveyed medical records, 53.6% were aged 0 to 4 years and 55.5% were male. Adherence to quality of care indicators was estimated at 59.8% (95% CI, 57.5%-62.0%; n = 160 202) across the 17 conditions, ranging from a high of 88.8% (95% CI, 83.0%-93.1%; n = 2638) for autism to a low of 43.5% (95% CI, 36.8%-50.4%; n = 2354) for tonsillitis. The mean adherence by condition category was estimated as 60.5% (95% CI, 57.2%-63.8%; n = 41 265) for noncommunicable conditions (range, 52.8%-75.8%); 82.4% (95% CI, 79.0%-85.5%; n = 14 622) for mental health conditions (range, 71.5%-88.8%); 56.3% (95% CI, 53.2%-59.4%; n = 94 037) for acute infections (range, 43.5%-69.8%); and 78.3% (95% CI, 75.1%-81.2%; n = 10 278) for injury. Conclusions and Relevance: Among a sample of children receiving care in Australia in 2012-2013, the overall prevalence of adherence to quality of care indicators for important conditions was not high. For many of these conditions, the quality of care may be inadequate.

Accomplishing reform: successful case studies drawn from the health systems of 60 countries.

Healthcare reform typically involves orchestrating a policy change, mediated through some form of operational, systems, financial, process or practice intervention. The aim is to improve the ways in which care is delivered to patients. In our book 'Health Systems Improvement Across the Globe: Success Stories from 60 Countries', we gathered case-study accomplishments from 60 countries. A unique feature of the collection is the diversity of included countries, from the wealthiest and most politically stable such as Japan, Qatar and Canada, to some of the poorest, most densely populated or politically challenged, including Afghanistan, Guinea and Nigeria. Despite constraints faced by health reformers everywhere, every country was able to share a story of accomplishment-defining how their case example was managed, what services were affected and ultimately how patients, staff, or the system overall, benefited. The reform themes ranged from those relating to policy, care coverage and governance; to quality, standards, accreditation and regulation; to the organization of care; to safety, workforce and resources; to technology and IT; through to practical ways in which stakeholders forged collaborations and partnerships to achieve mutual aims. Common factors linked to success included the 'acorn-to-oak tree' principle (a small scale initiative can lead to system-wide reforms); the 'data-to-information-to-intelligence' principle (the role of IT and data are becoming more critical for delivering efficient and appropriate care, but must be converted into useful intelligence); the 'many-hands' principle (concerted action between stakeholders is key); and the 'patient-as-the-pre-eminent-player' principle (placing patients at the centre of reform designs is critical for success).

Combining C-reactive protein and quick sequential organ failure assessment (qSOFA) to improve prognostic accuracy for sepsis and mortality in adult inpatients: A systematic review.

Background and Aims: Infections are common in hospitals, and if mismanaged can develop into sepsis, a leading cause of death and disability worldwide. This study aimed to examine whether combining C-reactive protein (CRP) with the quick sequential organ failure assessment (qSOFA) improves its accuracy for predicting mortality and sepsis in adult inpatients. Methods: PubMed, MEDLINE, EMBASE, Scopus, Web of Science, Science Direct, CINAHL, Open Grey, Grey Literature Report, and the Clinical Trials registry were searched using CRP and qSOFA search terms. Title, abstract, and full-text screening were performed by two independent reviewers using pre-determined eligibility criteria, followed by data extraction and a risk of bias assessment using the Quality Assessment tool for Diagnostic Accuracy Studies 2 (QUADAS-2). Disagreements were settled through discussion and consultation with a third reviewer. Results: Four retrospective studies with a total of 2070 patients were included in this review. Adding CRP to qSOFA improved the Area Under the Receiver Operating Characteristic Curve up to 9.7% for predicting mortality and by 14.9% for identifying sepsis. The sensitivity and specificity of the combined score for mortality prediction were available in two studies. CRP improved the sensitivity of qSOFA by 43% and 71% while only decreasing the specificity by 12% and 7%, respectively. A meta-analysis was not performed due to study heterogeneity. Conclusion: This comprehensive review provided initial evidence that combining CRP with qSOFA may improve the accuracy of qSOFA alone in identifying sepsis or patients at risk of dying in hospital. The combined tool demonstrated the potential to improve patient outcomes, with implications for low-resource settings given its simplicity and low-cost.

Practitioner characteristics and the treatment of children and adolescents with attention deficit hyperactivity disorder.

AIM: To investigate whether recent Australian practice conforms to the draft 2009 National Health and Medical Research Council (NHMRC) guidelines on the management of attention deficit hyperactivity disorder. METHODS: Data from the 2007 Special Review on Attention Deficit Hyperactivity Disorder in Children and Adolescents in New South Wales (NSW) were examined. RESULTS: Two hundred seven approved stimulant prescribers in NSW responded to a detailed survey on treatment practice (including 121 paediatricians and 67 psychiatrists). Overall, the practice identified in this survey of NSW approved stimulant prescribers was consistent with that recommended in the draft NHMRC guidelines. Paediatricians were more likely to inform families of developmental therapies. Most prescribers (67%) considered stimulants to be the first line of treatment for at least half of their patients. Psychiatrists were more likely to use stimulants as first-line treatments, while those recently qualified were less likely to prescribe. Half of the prescribers were willing to consider prescribing for children 4 years of age and younger. Paediatricians were more likely to consider prescribing to this age group, while those recently qualified were less likely. There were no significant differences in prescribing practice between child and adult psychiatrists. Most prescribers (67-97%) routinely monitored patients on stimulants for weight, height, blood pressure and academic progress. Psychiatrists were less likely to review these parameters than paediatricians, with this difference being largely due to adult psychiatrists. CONCLUSIONS: There are significant differences in prescribing practice between paediatricians and psychiatrists. These variations may reflect differing training programs and patient populations, and merit close consideration in any review arising from the publication of the recent NHMRC guideline.

Does lactate enhance the prognostic accuracy of the quick Sequential Organ Failure Assessment for adult patients with sepsis? A systematic review.

OBJECTIVES: To investigate whether adding lactate to the quick Sequential (sepsis-related) Organ Failure Assessment (qSOFA) improves the prediction of mortality in adult hospital patients, compared with qSOFA alone. DESIGN: Systematic review in accordance with Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies guidelines. DATA SOURCES: Embase, Medline, PubMed, SCOPUS, Web of Science, CINAHL and Open Grey databases were searched in November 2020. ELIGIBILITY CRITERIA: Original research studies published after 2016 comparing qSOFA in combination with lactate (LqSOFA) with qSOFA alone in adult patients with sepsis in hospital. The language was restricted to English. DATA EXTRACTION AND SYNTHESIS: Title and abstract screening, full-text screening, data extraction and quality assessment (using Quality Assessment of Diagnostic Accuracy Studies-2) were conducted independently by two reviewers. Extracted data were collected into tables and diagnostic test accuracy was compared between the two tests. RESULTS: We identified 1621 studies, of which 11 met our inclusion criteria. Overall, there was a low risk of bias across all studies. The area under the receiver operating characteristic (AUROC) curve for qSOFA was improved by the addition of lactate in 9 of the 10 studies reporting it. Sensitivity was increased in three of seven studies that reported it. Specificity was increased in four of seven studies that reported it. Of the six studies set exclusively within the emergency department, five published AUROCs, all of which reported an increase following the addition of lactate. Sensitivity and specificity results varied throughout the included studies. Due to insufficient data and heterogeneity of studies, a meta-analysis was not performed. CONCLUSIONS: LqSOFA is an effective tool for identifying mortality risk both in adult inpatients with sepsis and those in the emergency department. LqSOFA increases AUROC over qSOFA alone, particularly within the emergency department. However, further original research is required to provide a stronger base of evidence in lactate measurement timing, as well as prospective trials to strengthen evidence and reduce bias. PROSPERO REGISTRATION NUMBER: CRD42020207648.

Outcomes from the first 2 years of the Australian National Hand Hygiene Initiative.

OBJECTIVE: To report outcomes from the first 2 years of the National Hand Hygiene Initiative (NHHI), a hand hygiene (HH) culture-change program implemented in all Australian hospitals to improve health care workers' HH compliance, increase use of alcohol-based hand rub and reduce the risk of health care-associated infections. DESIGN AND SETTING: The HH program was based on the World Health Organization 5 Moments for Hand Hygiene program, and included standardised educational materials and a regular audit system of HH compliance. The NHHI was implemented in January 2009. MAIN OUTCOME MEASURES: HH compliance and Staphylococcus aureus bacteraemia (SAB) incidence rates 2 years after NHHI implementation. RESULTS: In late 2010, the overall national HH compliance rate in 521 hospitals was 68.3% (168,641/246,931 moments), but HH compliance before patient contact was 10%-15% lower than after patient contact. Among sites new to the 5 Moments audit tool, HH compliance improved from 43.6% (6431/14,740) at baseline to 67.8% (106,851/157,708) (P < 0.001). HH compliance was highest among nursing staff (73.6%; 116,851/158,732) and worst among medical staff (52.3%; 17,897/34,224) after 2 years. National incidence rates of methicillin-resistant SAB were stable for the 18 months before the NHHI (July 2007-2008; P = 0.366), but declined after implementation (2009-2010; P = 0.008). Annual national rates of hospital-onset SAB per 10,000 patient-days were 1.004 and 0.995 in 2009 and 2010, respectively, of which about 75% were due to methicillin-susceptible S. aureus. CONCLUSIONS: The NHHI was associated with widespread sustained improvements in HH compliance among Australian health care workers. Although specific linking of SAB rate changes to the NHHI was not possible, further declines in national SAB rates are expected.

Evolution in the techniques and outcomes of aortic arch surgery: a 22 year single centre experience.

BACKGROUND: Aortic arch replacement is a complicated and high risk procedure. There have been many advances over recent years. We review the changes in our unit's techniques and outcomes over the past 22 years. METHODS: Data were collated from databases and medical records for all patients who underwent aortic arch replacement surgery from January 1989 to December 2010. The patients were divided into two groups - Group A (1989-2005) and Group B (2006-2010). Data were analysed to compare early and late series patients' outcomes. Logistic regression was used to identify variables that predicted mortality. RESULTS: Seventy-five eligible patients (56 males; mean age: 57.5 years; Group A: 40, Group B 35) were identified. There were great changes in the technique and the methods of cerebral protection. The overall mortality rate was 30.7% - Group A: 50% and Group B: 8.6% (p<0.001). Overall permanent neurological dysfunction was 23.7% - Group A: 40% and Group B: 11.8% (p=0.012). Cardiovascular disease and circulatory arrest time were significant predictors of mortality. CONCLUSIONS: Increased experience and volume and advances in techniques over 22 years have resulted in major improvements in outcomes for patients having aortic arch replacement, allowing the procedure to be performed with greatly improved outcomes.

Endothelial activation after coronary artery bypass surgery: comparison between on-pump and off-pump techniques.

BACKGROUND: The effects of off-pump coronary artery bypass (OPCAB) surgery on endothelial cell activation are poorly understood. Endothelial cell adhesion molecules (CAMs) are expressed and released when the endothelium is activated. We compared plasma CAMs (E-selectin, ICAM-1 and VCAM-1) and HUVEC expression of the same CAMs when exposed to plasma taken before, during and after OPCAB or on-pump coronary surgery (CABG). METHODS: Patients undergoing first time CABG (n=10) or OPCAB (n=10) had 6 blood samples taken before surgery and up to 24h post-operatively. Plasma samples were assayed for E-selectin, ICAM-1 and VCAM-1. The same plasma samples were exposed to HUVEC cultures and cell-surface expression of E-selectin, ICAM-1 and VCAM-1 measured. Data are expressed as mean+/-SEM of n subjects. RESULTS: Plasma E-selectin was unchanged. Plasma ICAM-1 and VCAM-1 were elevated 24h post-operatively in both groups (P<0.01), with no differences between the groups. Twenty-four hours post-OPCAB plasma increased basal and IL-1beta induced expression of endothelial VCAM-1 by 133+/-16% and 140+/-27% (P<0.05), respectively. Plasma taken 3h post-CABG decreased endothelial VCAM-1 expression by 76+/-10% (P<0.05). Peri-operative plasma had no effect on endothelial expression of E-selectin or ICAM-1 in either group. CONCLUSIONS: OPCAB and CABG with CPB appear to generate qualitatively different inflammatory responses with respect to endothelial activation, which may have clinical implications.

Quantitative and temporal differences in coagulation, fibrinolysis and platelet activation after on-pump and off-pump coronary artery bypass surgery.

BACKGROUND: With the increasing use of OPCAB, potentially devastating thromboembolic events, including graft thrombosis may become increasingly evident. We present a study of the quantitative and temporal differences of the coagulation system, fibrinolysis and platelet activation after coronary artery surgery with or without cardiopulmonary bypass. METHODS: Patients undergoing on-pump CABG (n=10) or OPCAB (n=10) had six blood samples taken before surgery and up to 24h post-operatively. Activation of the coagulation cascade (tissue factor pathway-factor VIIa), endothelial injury (von Willebrand Factor antigen), thrombin generation (prothrombin fragments FI+II), fibrinolysis (decreased plasminogen levels), fibrin degradation (D-Dimer), platelet counts and platelet activation (soluble P-selectin) were quantified. RESULTS: CABG caused earlier and more significant generation of thrombin, however OPCAB caused a late and sustained generation of thrombin. CABG caused intraoperative activation of fibrinolysis and fibrin degradation, however, at 24h these parameters were equally elevated in both groups. Platelet activation was significant in the CABG group, but did not occur in the OPCAB group. CONCLUSIONS: Late thrombin generation and reduced fibrinolysis in the presence of intact, functioning platelets may contribute to adverse thromboembolic events after OPCAB surgery. Thromboembolic prophylaxis and anti-platelet therapy may need to be more aggressive after OPCAB surgery.

Controlled pre-post, mixed-methods study to determine the effectiveness of a national delirium clinical care standard to improve the diagnosis and care of patients with delirium in Australian hospitals: a protocol.

INTRODUCTION: Delirium, an acute confusional state, affects up to 29% of acute inpatients aged 65 years and over. The Australian Delirium Clinical Care Standard (the Standard) contains evidence-based, multicomponent interventions, to identify and reduce delirium. This study aims to: (1) conduct a controlled, before-and-after study to assess the clinical effectiveness of the Standard to improve diagnosis and treatment of delirium; (2) conduct a cost-effectiveness study of implementing the Standard and (3) evaluate the implementation process. METHODS AND ANALYSIS: The study will use a controlled, preimplementation and postimplementation mixed-methods study design, including: medical record reviews, activity-based costing analysis and interviews with staff, patients and their family members. The study population will comprise patients 65 years and over, admitted to surgical, medical and intensive care wards in four intervention hospitals and one control hospital. The primary clinical outcome will be the incidence of delirium. Secondary outcomes include: length of stay, severity and duration of delirium, inhospital mortality rates, readmission rates and use of psychotropic drugs. Cost-effectiveness will be evaluated through activity-based costing analysis and outcome data, and the implementation process appraised through the qualitative results. ETHICS AND DISSEMINATION: Ethics approval has been received for two hospitals. Additional hospitals have been identified and ethics applications will be submitted once the tools in the pilot study have been tested.The results will be submitted for publication in peer-reviewed journals and presented to national and international conferences. Results seminars will provide a quality feedback mechanism for staff and health policy bodies.

Endovascular grafting of the thoracic aorta, an evolving therapy: ten-year experience in a single centre.

BACKGROUND: Surgical therapy for the thoracic aorta carries a high morbidity and mortality. Endovascular therapy for aneurysms and its adaptation to the thoracic aorta over the past 10 years is an exciting advance. This is a retrospective review of endovascular grafting of the thoracic aorta during the past decade at Royal Prince Alfred Hospital and the outcomes achieved over this period. METHODS: A retrospective review of all patients at our institution who underwent endovascular grafting of the thoracic aorta between March 1995 and March 2005 was carried out. Data were analysed using Stata version 8.0 (Stata corporation, College Station, TX, USA). RESULTS: Sixty-five patients underwent endovascular stent grafting of the thoracic aorta. The indications were degenerative aneurysm (31), Stanford type B dissection (23) both acute (12) and chronic (11), traumatic transection (9) and penetrating ulcer (2). There were no conversions to open repair. Twenty-two patients required additional procedures, six of which were unplanned. The median age was 65 (range 18-85), 68% of patients were men. The median procedure time was 115 min (range 55-240 min). Mean hospital stay was 9.8+/-7.3 days and high dependency/intensive care unit stay 1.5+/-3.2 days. Thirty-day mortality was 0 in 41 for elective cases (one patient (2.5%) died 37 days post-procedure) and 12% (3 of 25) for emergency cases. Complications occurred in 20 of 41 (49%) elective cases and 14 of 24 (58%) emergency cases within the first 30 days. The most frequent major complications were neurological including paraplegia (transient 2 of 65, permanent (2 of 65)) and stroke (4 of 65). Other complications included endoleak (12 of 65), acute renal failure (1 of 65), and brachial artery false aneurysm (1 of 65). The mean length of follow up was 22.5 months (range, 1-97 months). Six patients required further endovascular procedures for persistent endoleak or ongoing perfusion of chronic dissection. Late deaths (>30 days) related to the endovascular treatment occurred in two patients (3%). CONCLUSION: Endovascular grafting of the thoracic aorta is an evolution in the treatment of thoracic aortic pathology. The results of elective endovascular grafts were acceptable. Emergency procedures had a higher incidence of complications and death. Improvement in graft technology, design and deployment are required.

Corynebacterium diphtheriae endocarditis--surgery for some but not all!

Corynebacterium diphtheriae endocarditis was thought to be a rare disease. We reviewed our experience in four cases of this disease treated over a period of 10 years. Seventy cases reported in literature were reviewed. The outcome is good if cases are carefully selected for medical or surgical treatment. We conclude that infective endocarditis due to C. diphtheriae, is perhaps more common than expected. It may be recognized more frequently and on occasion may be an aggressive disease. Those patients with an abnormal valve (including prosthetic valves) should be subjected to surgery at the earliest available opportunity, whereas patients with normal valves may be carefully watched during the course of medical treatment as long as immediate surgery can occur if needed.

CareTrack Kids-part 2. Assessing the appropriateness of the healthcare delivered to Australian children: study protocol for a retrospective medical record review.

INTRODUCTION: Australian and international clinical practice guidelines are available for common paediatric conditions. Yet there is evidence that there are substantial variations between the guidelines, recommendations (appropriate care) and the care delivered. This paper describes a study protocol to determine the appropriateness of the healthcare delivered to Australian children for 16 common paediatric conditions in acute and primary healthcare settings. METHODS AND ANALYSIS: A random sample of 6000-8000 medical records representing a cross-section of the Australian paediatric population will be reviewed for appropriateness of care against a set of indicators within three Australian states (New South Wales, Queensland and South Australia) using multistage, stratified sampling. Medical records of children aged <16 years who presented with at least one of the study conditions during 2012 and 2013 will be reviewed. ETHICS AND DISSEMINATION: Human Research Ethics Committee approvals have been received from the Sydney Children's Hospital Network, Children's Health Queensland Hospital and Health Service and Women's and Children's Hospital Network (South Australia). An application is under review for the Royal Australian College of General Practitioners. The authors will submit the results of the study to relevant journals and offer oral presentations to researchers, clinicians and policymakers at national and international conferences.

CareTrack Kids-part 1. Assessing the appropriateness of healthcare delivered to Australian children: study protocol for clinical indicator development.

INTRODUCTION: Despite the widespread availability of clinical guidelines, considerable gaps remain between the care that is recommended (appropriate care) and the care provided. This protocol describes a research methodology to develop clinical indicators for appropriate care for common paediatric conditions. METHODS AND ANALYSIS: We will identify conditions amenable to population-level appropriateness of care research and develop clinical indicators for each condition. Candidate conditions have been identified from published research; burden of disease, prevalence and frequency of presentation data; and quality of care priority lists. Clinical indicators will be developed through searches of national and international guidelines, and formatted with explicit criteria for inclusion, exclusion, time frame and setting. Experts will review the indicators using a wiki-based approach and modified Delphi process. A formative evaluation of the wiki process will be undertaken. ETHICS AND DISSEMINATION: Human Research Ethics Committee approvals have been received from Sydney Children's Hospital Network, Children's Health Queensland Hospital and Health Service, and the Women's and Children's Health Network (South Australia). Applications are under review with Macquarie University and the Royal Australian College of General Practitioners. We will submit the results of the study to relevant journals and offer national and international presentations.

Haptoglobin elutes from human atherosclerotic coronary arteries--a potential marker of arterial pathology.

BACKGROUND: Molecules which egress from atherosclerotic arteries may function as plasma markers of arterial pathology, but such egress has not been proven with living human coronary arteries. We hypothesised that proteins eluting from the arterial wall may discriminate between atherosclerotic and non-atherosclerotic coronary arteries. METHODS AND RESULTS: During cardiac bypass surgery, 155 sequential fractions of antegradely flushed coronary cardioplegia solution were collected by balloon-cuffed catheter from the coronary sinus in subjects with angiographically extensive (n=30) or minor (n=7) coronary disease. Although plasma was the major source of protein in heavily blood-contaminated samples, under conditions of low blood contamination (<0.5 mg/ml red cell Haemoglobin) coronary circulation-derived protein was detected. N-terminal sequencing of a major 40 kDa band detected by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated 100% homology with beta chain of Haptoglobin (Hpt). Comparison of perfusates from patients with and without significant coronary disease found that the concentration of Hpt was markedly increased in perfusates from atherosclerotic coronary arteries (0.099+/-0.017 microg Hpt/microg Hb) relative to controls (0.016+/-0.008 microg Hpt/microg Hb, P=0.0027). Analysis of peripheral plasma samples of the same subjects, and of a separate cohort of patients, confirmed greater Hpt in those with angiographic coronary disease than in those without disease. CONCLUSIONS: Proteins such as Hpt elute from the human coronary vascular bed and may differentiate between arteries with minor or extensive atherosclerosis. Although the suitability of Hpt as a circulating plasma marker for atherosclerosis remains to be established, the approach used in the present study may permit identification of diverse plasma-detectable markers of atherosclerosis, and the subsequent non-invasive evaluation of in vivo arterial pathology.

Endothelial expression of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 is suppressed by postbypass plasma containing increased soluble intercellular adhesion molecule 1 and vascular cell adhesion molecule 1.

OBJECTIVE: Endothelial cell dysfunction has been implicated in the inflammatory response to cardiopulmonary bypass, and the upregulation of endothelial cell expression of adhesion molecules might promote leukocyte extravasation in vivo. Soluble endothelial cell adhesion molecules are increased after bypass. The aim of this study was to investigate the relationship between endothelial cell-surface expression of adhesion molecules and their concentration in plasma after coronary artery bypass grafting. METHODS: Ten patients undergoing coronary artery bypass with cardiopulmonary bypass had 5 plasma samples taken at defined intervals before, during, and after cardiopulmonary bypass. Plasma was incubated with human umbilical vein endothelial cell monolayers, and expression of E-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 on the surface of human umbilical vein endothelial cell monolayers was measured by means of enzyme-linked immunosorbent assay. Plasma soluble adhesion molecules, C-reactive protein, interleukin 8, interleukin 10, transforming growth factor beta1, and neutrophil counts were determined for each patient. RESULTS: Markers typical of acute inflammation (ie, interleukin 8, neutrophils, and C-reactive protein) were all increased after bypass. Soluble plasma intercellular and vascular cell adhesion molecule 1 (but not E-selectin) were increased after bypass. However, endothelial cell expression of vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 (but not E-selectin) were significantly decreased by exposure to postbypass plasma. Additionally, postbypass plasma inhibited interleukin 1beta-stimulated endothelial cell expression of vascular cell and intercellular adhesion molecule 1. Interleukin 10 and transforming growth factor beta1, both of which are known to inhibit endothelial cell adhesion molecule expression, were respectively increased 10-fold and 3-fold (P <.05) after bypass. CONCLUSIONS: Despite containing increased soluble intercellular and vascular cell adhesion molecule 1, postbypass plasma inhibits endothelial cell expression of intercellular and vascular cell adhesion molecule 1. Upregulated vascular expression of adhesion molecules might not be essential for endothelial activation after bypass.

Late quadriplegia after adult coarctation repair.

Quadriplegia developed suddenly 1 month after coarctation repair in a 53-year-old human. Cervical cord ischemia caused by thrombosis in an enlarged anterior spinal artery collateral was diagnosed on magnetic resonance scan and spinal angiography. After urgent cord decompression and anticoagulation there was neurologic improvement over a period of several months. Urgent investigation of neurologic abnormalities occurring late after coarctation repair may enable intervention to avert permanent neurologic sequelae.