Development and validation of a cost-utility model for Type 1 diabetes mellitus.

AIMS: To develop a health economic model to evaluate the cost-effectiveness of new interventions for Type 1 diabetes mellitus by their effects on long-term complications (measured through mean HbA1c ) while capturing the impact of treatment on hypoglycaemic events. METHODS: Through a systematic review, we identified complications associated with Type 1 diabetes mellitus and data describing the long-term incidence of these complications. An individual patient simulation model was developed and included the following complications: cardiovascular disease, peripheral neuropathy, microalbuminuria, end-stage renal disease, proliferative retinopathy, ketoacidosis, cataract, hypoglycemia and adverse birth outcomes. Risk equations were developed from published cumulative incidence data and hazard ratios for the effect of HbA1c , age and duration of diabetes. We validated the model by comparing model predictions with observed outcomes from studies used to build the model (internal validation) and from other published data (external validation). We performed illustrative analyses for typical patient cohorts and a hypothetical intervention. RESULTS: Model predictions were within 2% of expected values in the internal validation and within 8% of observed values in the external validation (percentages represent absolute differences in the cumulative incidence). CONCLUSIONS: The model utilized high-quality, recent data specific to people with Type 1 diabetes mellitus. In the model validation, results deviated less than 8% from expected values.

Sepsis associated with central vein catheters in critically ill patients.

In 440 critically ill patients, the association between different central vein catheter insertion sites, the duration of catheter insertion and catheter-associated sepsis was examined. Of 780 catheter tips studied, 19% were colonized by microorganisms. The incidence of colonization varied with the different insertion sites. The lowest percentage of colonized catheters occurred with catheters inserted via the subclavian vein (15%) and the highest, at the femoral vein insertion site (34%, p less than 0.01). The percentage of catheters colonized increased as the duration of insertion increased, at all insertion sites studied. Catheter colonization was closely related to the development of bacteraemia and was associated with approximately 10% of colonized catheters. Our results suggest that the subclavian site is associated with the lowest infective complication rate. To minimize catheter associated sepsis, catheters at all insertion sites should be used with parsimony and only kept in place for the minimum amount of time that their continuing use is necessary.

Experimental model of left ventricular failure.

A model of chronic cardiac failure has undergone extensive hemodynamic investigation. Under anesthesia the homonymous and second diagonal coronary arteries of sheep have been ligated. The resulting myocardial infarction caused significant acute hemodynamic impairment (paired two-tailed t tests), mean pulmonary artery pressure increasing from 7.31 +/- 0.94 to 13.80 +/- 1.19 mm Hg (p less than 0.001), pulmonary artery diastolic pressure increasing from 4.94 +/- 1.03 to 11.13 +/- 1.27 mm Hg (p less than 0.001), and directly measured left ventricular end-diastolic pressure increasing from 9.31 +/- 1.52 to 17.42 +/- 1.82 mm Hg (p less than 0.001) after infarction documented with invasive monitoring. There was a hemodynamically significant left ventricular aneurysm (paired two-tailed t tests) in animals studied 3 months later, with increased mean pulmonary artery pressure from 7.20 +/- 1.15 to 13.80 +/- 2.00 mm Hg (p = 0.009), an increase in pulmonary artery diastolic pressure from 4.60 +/- 1.30 to 12.10 +/- 2.06 mm Hg (p = 0.006), and an increase in left ventricular end-diastolic pressure from 11.00 +/- 1.94 mm Hg before infarction to 17.00 +/- 2.69 mm Hg (p = 0.038). We conclude that this is a useful model of chronic left ventricular failure that is reproducible and applicable to investigations of therapeutic options in chronic heart failure.

Dynamic cardiomyoplasty in chronic left ventricular failure: an experimental model.

Dynamic cardiomyoplasty continues to attract interest as a therapeutic option in the management of heart failure. In a large animal model of ischemic heart failure, we have compared dynamic cardiomyoplasty with both adynamic cardiomyoplasty and a control group. Heart failure was induced by coronary artery ligation in sheep, and under the same anesthetic dynamic cardiomyoplasty (n = 5), adynamic cardiomyoplasty (n = 4), or no further procedure was performed (n = 5). After recovery the animals were housed for a further 3 months. The dynamic cardiomyoplasty underwent a recognized muscle transformation protocol during this period. At terminal studies, the animals were hemodynamically assessed, both under baseline conditions and after colloid volume loading. The data at baseline were compared with unpaired t tests, and the function curves created by volume loading were compared by analysis of variance. Although the changes at baseline were small, there were highly significant improvements in the function curves in the dynamic cardiomyoplasty group when the stimulators were turned on compared with stimulators off (p = 0.005) for cardiac output; p = 0.035 for left ventricular end-diastolic pressure; p = 0.002 for pulmonary artery capillary wedge pressure; p = 0.004 for stroke volume; and p = 0.003 for cardiac power). There were also significant improvements in indices of cardiac performance when the dynamic cardiomyoplasty group was compared with both the control and adynamic cardiomyoplasty groups. We conclude that there is experimental evidence that cardiomyoplasty augments cardiac function in a model of chronic left ventricular failure.

Incidence and effects of increased cerebral blood flow velocity after severe head injury: a transcranial Doppler ultrasound study I. Prediction of post-traumatic vasospasm and hyperemia.

Cerebral blood flow velocity was monitored in 50 patients with severe head injury (GCS 8 or less) within 24 h of injury and at least once daily thereafter, using transcranial Doppler ultrasonography (TCD). Delayed post-traumatic vasospasm occurred in 20, and cerebral hyperemia in another 15. Doppler velocities were higher in vasospasm, which also lasted significantly longer than hyperemia. The presence of visible blood on an early CT scan was of some value in predicting vasospasm only (accuracy 59%). Xenon-133 cerebral blood flow (CBF) was also measured within 24 h of injury. An abnormal early cerebral blood flow level, either above or below a narrow central range, was more effective than CT in predicting vasospasm or hyperemia (accuracy 80%), while the combination of an abnormal blood flow and hemorrhagic findings on CT scan helped to determine which of these would occur later. Patients with an abnormal early cerebral blood flow and hemorrhagic findings on CT were more likely to develop vasospasm--accuracy for prediction of vasospasm 73%. This distinction may be of great importance, since these different groups of patients may well need different management.

Transcranial Doppler ultrasound in brain death: experience in 140 patients.

The interpretation of clinical tests for brain death is often complicated by the presence of facial trauma, or the use of barbiturate therapy for reduction of intracranial pressure. We propose a non-invasive technique--transcranial Doppler (TCD) sonography for the diagnosis of brain death. One hundred and forty comatose patients, 111 of whom were believed to be brain dead underwent TCD examinations. TCD assessments of the middle cerebral arteries (MCAs) and the basilar artery were performed before formal clinical testing for brain death. The TCD spectra recorded in the brain dead (BD) patients consisted of short, sharp systolic peaks followed by retrograde flow during diastole or just systolic peaks with absent flow in either direction. There were no survivors among patients who displayed these two TCD patterns. The 29 comatose control patients always showed flow throughout the cardiac cycle--no retrograde flow was ever recorded in these patients all of whom survived. Of particular interest were the basilar artery results. In nine BD patients no MCA signals could be obtained while good quality signals were recorded from the basilar artery. The TCD results agreed essentially with 100% accuracy with clinical testing and four vessel cerebral angiography. This paper illustrates the usefulness of TCD examination of the MCAs and especially the basilar artery in the diagnosis of brain death.

Meningococcal infection in patients with the human immunodeficiency virus and acquired immunodeficiency syndrome.

Meningococcal infection is believed to be rare in HIV-positive individuals. We present 2 cases from our reference caseload within the last 10 years.

The use of transcranial Doppler sonography in the diagnosis of brain death.

The diagnosis of brain death is important for many reasons. Clinical testing may not be feasible, so that cerebral angiography is needed to confirm circulatory arrest. Angiography is, however, cumbersome and expensive. We present the results of transcranial Doppler (TCD) studies on the middle cerebral arteries of 40 patients with brain death. In six, no cranial signals could be obtained. All except two of the remaining patients had typical TCD appearances, with a reverberating pattern and little or no net forward flow. One patient had this appearance on one side and a carotid-cavernous fistula on the other side, and another had preserved middle cerebral artery flow. Sixteen control patients all had quite different signals, with some showing evidence of raised intracranial pressure and some of vasospasm. There were thus few false-negative results, and more importantly no false-positives. Refinement of this technique, especially looking to a numerical value for the net flow velocity below which circulatory arrest is certain, is needed. The possibility of a changing pattern on serial studies, with prediction of brain death before it actually occurs, is also to be explored.

Potential for cadaveric organ retrieval in New South Wales.

OBJECTIVES: To measure the potential for cadaver organ retrieval in New South Wales and to determine the reasons for potential donors failing to become actual donors. DESIGN: Prospective audit of all patients dying in five hospitals in New South Wales between 1 December 1989 and 30 November 1990; quality assurance of the data by independent medical specialist and if disagreement by study committee. PATIENTS: 2879 patients (100% of all deaths) yielding 364 patients with coma and 181 potential donors. OUTCOME MEASURES: Realistic medically suitable potential donor rate, missed potential donor rate, rate of potential donors with permission refused, donor rate, reasons for realistic medically suitable potential donors failing to become actual donors. RESULTS: 2879 deaths yielded 73 medically suitable potential donors, resulting in 19 actual donors, 30 missed potential donors, 19 potential donors with permission refused, and five in whom adequate resuscitation failed. The most common reason for a potential donor failing to become an actual donor was a decision by the senior medical practitioner to withdraw or not to institute ventilatory or haemodynamic support (26/73). The second major obstacle was refusal of permission by the next of kin (17/73). Assuming that the potential donor rate was that implied by the observed donor rate (13/million population/year) the projected missed potential donor rate was 9/million population/year (95% confidence interval 4 to 15) and the projected rate of potential donors with permission refused was 13/million population/year (95% confidence interval 5 to 22). Assuming that the rate of potential donors in the study hospitals was the same as in the other New South Wales hospitals, the projected donor rate for New South Wales was 18/million population/year (10 to 26); the projected missed potential donor rate was 15/million population/year (7 to 23); and the projected rate of potential donors with permission refused was 18/million population/year (10 to 27). CONCLUSIONS: The donor rate could be increased 70%-80% by overcoming the reluctance of medical practitioners to resuscitate missed potential donors and increased further by gaining permission for organ retrieval from the next of kin.

Towards consensus: history of the Australian Veterinary Association to 2000.

From its earliest beginnings in Australia in the latter part of the 19th century, the veterinary profession has striven to achieve a national voice. Well-known veterinarians were involved in the eventual establishment of the Australian Veterinary Association (AVA) in 1921. Today, all states are represented and the AVA has close contact with state and federal governments, and producer organisations. With the growth in the number of special interest groups, the AVA more than ever provides unity in diversity in order to fulfil its mission to promote the profession for the benefit of animals, the environment and the community.

Porokeratosis in association with lymphoedema.

We describe four patients in whom porokeratosis coexisted with lympoedema of the legs. A possible pathogenetic link between the two disorders is discussed, as well as the therapeutic implications and the novel physical sign of lymphoedema bulging through the porokeratotic lesions.