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Biomedical subjects

D A Cook

Publications and source records attributed to D A Cook.

At least 19 recordsLinked to original sources
PubMed2007

Improving the quality of patient care using reliability measures: a classification tree approach.

This paper considers the application and interpretation of new reliability measures for a classification tree-based medical risk assessment tool. Following the construction of a classification tree reliability measures may then be used to provide an estimate of the precision of the classification and the probability in each terminal node of the classification tree. Identification of unreliable nodes (those that have low precision) in this application may indicate patient groups requiring closer monitoring or scenarios in which further information about the patient is required, thereby providing medical practitioners with an avenue for more informed decision making.

Biometry↗
PubMed2006

Methods to assess performance of models estimating risk of death in intensive care patients: a review.

Models that estimate the probability of death of intensive care unit patients can be used to stratify patients according to the severity of their condition and to control for casemix and severity of illness. These models have been used for risk adjustment in quality monitoring, administration, management and research and as an aid to clinical decision making. Models such as the Mortality Prediction Model family, SAPS II, APACHE II, APACHE III and the organ system failure models provide estimates of the probability of in-hospital death of ICU patients. This review examines methods to assess the performance of these models. The key attributes of a model are discrimination (the accuracy of the ranking in order of probability of death) and calibration (the extent to which the model's prediction of probability of death reflects the true risk of death). These attributes should be assessed in existing models that predict the probability of patient mortality, and in any subsequent model that is developed for the purposes of estimating these probabilities. The literature contains a range of approaches for assessment which are reviewed and a survey of the methodologies used in studies of intensive care mortality models is presented. The systematic approach used by Standards for Reporting Diagnostic Accuracy provides a framework to incorporate these theoretical considerations of model assessment and recommendations are made for evaluation and presentation of the performance of models that estimate the probability of death of intensive care patients.

APACHE↗
PubMed2003

Comparison of perceived comfort differences between standard and experimental load carriage systems.

The current popularity of backpack-type load carriage systems (LCS) by students has precipitated a prevalence of postural abnormalities and pain. This study compared subjective perceptual comfort in standard and vertically loaded LCSs. Sixteen females ages 18-23 years rated their personal LCSs for perceived shoulder, neck, and lower back comfort and for overall comfort, each day for two weeks using 100 mm visual analogue scales (VAS). Each scale contained polar extremities of 'very comfortable' to 'very uncomfortable' and a vertical mark placed on the 100 mm line by the participants indicated their perception of comfort. Following two weeks, participants were given LCSs that distributed the weight vertically and were asked to rate the system in the same way for an additional two-week period. Statistical analysis revealed significant differences in shoulder (p=0.015), neck (p=0.005), and lower back (p=0.036) comfort and overall comfort (p=0.001) between the participants' personal LCSs and the experimental LCS. In conclusion, vertical load placement may redistribute the load in a manner that reduces symptoms of selected anatomical discomfort.

Adolescent↗
PubMed2002

Prospective independent validation of APACHE III models in an Australian tertiary adult intensive care unit.

Evaluation of the performance of the APACHE III (Acute Physiology and Chronic Health Evaluation) ICU (intensive care unit) and hospital mortality models at the Princess Alexandra Hospital, Brisbane is reported. Prospective collection of demographic, diagnostic, physiological, laboratory, admission and discharge data of 5681 consecutive eligible admissions (1 January 1995 to 1 January 2000) was conducted at the Princess Alexandra Hospital, a metropolitan Australian tertiary referral medical/surgical adult ICU ROC (receiver operating characteristic) curve areas for the APACHE III ICU mortality and hospital mortality models demonstrated excellent discrimination. Observed ICU mortality (9.1%) was significantly overestimated by the APACHE III model adjusted for hospital characteristics (10.1%), but did not significantly differ from the prediction of the generic APACHE III model (8.6%). In contrast, observed hospital mortality (14.8%) agreed well with the prediction of the APACHE III model adjusted for hospital characteristics (14.6%), but was significantly underestimated by the unadjusted APACHE III model (13.2%). Calibration curves and goodness-of-fit analysis using Hosmer-Lemeshow statistics, demonstrated that calibration was good with the unadjusted APACHE III ICU mortality model, and the APACHE III hospital mortality model adjusted for hospital characteristics. Post hoc analysis revealed a declining annual SMR (standardized mortality rate) during the study period. This trend was present in each of the non-surgical, emergency and elective surgical diagnostic groups, and the change was temporally related to increased specialist staffing levels. This study demonstrates that the APACHE III model performs well on independent assessment in an Australian hospital. Changes observed in annual SMR using such a validated model support an hypothesis of improved survival outcomes 1995-1999.

APACHE↗
PubMed2001

Targeting acute ischemic stroke with a calcium-sensitive opener of maxi-K potassium channels.

During ischemic stroke, neurons at risk are exposed to pathologically high levels of intracellular calcium (Ca++), initiating a fatal biochemical cascade. To protect these neurons, we have developed openers of large-conductance, Ca++-activated (maxi-K or BK) potassium channels, thereby augmenting an endogenous mechanism for regulating Ca++ entry and membrane potential. The novel fluoro-oxindoles BMS-204352 and racemic compound 1 are potent, effective and uniquely Ca++-sensitive openers of maxi-K channels. In rat models of permanent large-vessel stroke, BMS-204352 provided significant levels of cortical neuroprotection when administered two hours after the onset of occlusion, but had no effects on blood pressure or cerebral blood flow. This novel approach may restrict Ca++ entry in neurons at risk while having minimal side effects.

Animals↗
PubMed2001

The polycationic aminoglycosides modulate the vasoconstrictive effects of endothelin: relevance to cerebral vasospasm.

1. The vasoactive peptide endothelin (ET) has been implicated in the pathogenesis of cerebral vasospasm following subarachnoid haemorrhage. In these studies we investigated the involvement of protein kinase C (PKC) in sustained vasoconstriction induced by ET-1 in canine cerebral arteries. We also examined the ability of the aminoglycoside antibiotics to reverse the effects mediated by ET-1 in canine cerebrovascular smooth muscle cells (CVSMC). 2. The ET(A) receptor antagonist, BQ-123, showed a competitive inhibition of the ET-1 responses. 3. The vasoconstrictor action of both ET-1 (0.5 nM) and phorbol myristate acetate (PMA) (160 nM) was reversed by a selective PKC inhibitor, Ro-32-0432. 4. In cerebral arteries precontracted with ET-1 the aminoglycosides caused a concentration-dependent relaxation. The EC(50s) for the relaxation were as follows: 0.54+/-0.05, 0.63+/-0.01, 1.88+/-0.46 and 2.3+/-0.92 mM for gentamicin, neomycin, streptomycin and kanamycin, respectively. 5. Gentamicin caused a concentration-dependent decrease of the PMA-induced responses in calcium free medium. 6. PKC activity was elevated in CVSMC exposed to ET-1 (170%) and PMA (167%) for a period of time (60 min) corresponding to maximum tonic contraction induced by these agents in arterial rings. 7. The administration of the aminoglycosides to CVSMC, in concentrations corresponding to the EC(50s) from contractility studies, reduced the effects of both ET-1 and PMA on PKC activity to the levels not different from controls. 8. These results show that the aminoglycosides are able to inhibit sustained vasoconstriction induced by ET-1, an effect which is due, at least in part, to the inhibition of PKC.

Animals↗
PubMed2001

Role of opioid receptors in neurogenic dural vasodilation and sensitization of trigeminal neurones in anaesthetized rats.

Migraine headache is thought to be caused by a distension of meningeal blood vessels, the activation of trigeminal sensory neurones and the the development of a central sensitization within the trigeminal nucleus caudalis (TNC). It has been proposed that clinically effective 5-HT(1B/1D) agonists act peripherally to inhibit the release of calcitonin gene-related peptide (CGRP) and neurogenic dural vasodilation, and to attenuate nociceptive neurotransmission within the TNC. Since opioids are also effective anti-migraine agents the present studies investigated the role of opioids within the trigemino-vascular system in anaesthetised rats. Electrical stimulation of the dura mater evoked neurogenic dural vasodilation which was significantly inhibited by morphine (1 mg kg(-1)) the selective mu-opioid agonist DAGO (10 microg kg(-1)) and the mixed agonist/antagonist butorphanol (1 mg kg(-1)) but not by the kappa- and delta-opioid agonists (+/-) U50488H (100 microg kg(-1)) and DPDPE (1 mg kg(-1)). Morphine had no effect on CGRP-evoked dural vasodilation. In electrophysiological studies morphine (1 - 10 mg kg(-1)) significantly attenuated brainstem neuronal activity in response to electrical stimulation of the dura by 65% at 10 mg kg(-1). Morphine (3 mg kg(-1)) also inhibited the TNC neuronal sensitization following CGRP-evoked dilation. The present studies have demonstrated that opioids block the nociceptive neurotransmission within the trigeminal nucleus caudalis and in addition inhibit neurogenic dural vasodilation via an action on mu-opioid receptors located on trigeminal sensory fibres innervating dural blood vessels. These peripheral and central actions are similar to those of the 'triptan' 5-HT(1B/1D) agonists and could account for the anti-migraine actions of opioids.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2001

Antenatal seroprevalence of herpes simplex virus type 2 (HSV-2) in Canadian women: HSV-2 prevalence increases throughout the reproductive years.

BACKGROUND: This study sought to provide the first population estimates of herpes simplex type 2 (HSV-2) seroprevalence in Canada. GOAL: To measure the antenatal seroprevalence of HSV-2 antibodies in reproductive age women. STUDY DESIGN: An anonymous unlinked seroprevalence study used stored sera collected from pregnant women in British Columbia during 1999. Randomized sampling within age strata selected a total of 1215 subjects, ages 15 to 44 years. Serologic testing used the Gull Meridian Test. Overall prevalence was directly standardized to the 1999 Canadian female population. RESULTS: The age-adjusted prevalence for HSV-2 was 17.3% (95% CI, 15.2-19.4). Prevalence ranged from 7.1% (ages, 15-19 years) to 28.1% (ages, 40-44 years), with the largest increases after the age of 24 years. CONCLUSIONS: The HSV-2 seroprevalence among pregnant women in British Columbia is similar to that in the United States and other countries. Seroprevalence continues to rise through the later reproductive years. This observation may relate to continued transmission, an age cohort effect, or both.

Adolescent↗
PubMed2000

Performance of APACHE III models in an Australian ICU.

STUDY OBJECTIVE: Evaluation of the performance of the APACHE (acute physiology and chronic health evaluation) III ICU and hospital mortality models at an Australian tertiary adult ICU. DESIGN: Noninterventional, observational study. SETTING: Metropolitan, Australian, tertiary referral medical/surgical ICU. PATIENTS: A total of 3,398 consecutive eligible admissions from January 1, 1995, to December 31, 1997. MEASUREMENTS: Prospective collection of demographic, diagnostic, physiologic, laboratory, admission, and discharge data. RESULTS: The patient sample was younger and more commonly male, with more comorbidities and a different operative and referral source mix, compared to the APACHE III development sample. Receiver operating characteristic curve areas for ICU (0.92) and hospital mortality (0.90) demonstrated excellent discrimination. Observed ICU mortality (9.9%) did not significantly differ from the prediction of the APACHE III model (8.9%) or the APACHE III model adjusted for hospital characteristics (10.5%). The hospital mortality (16.0%) was underestimated by the APACHE III model [13.6%; chi(2)(1) = 7.4; p = 0.01]. With proprietary adjustments for hospital characteristics (14.9%) or referenced to the US database (15.6%), agreement was closer. Good calibration was found with all models except the unadjusted hospital mortality model. CONCLUSION: In contrast to other non-American studies, this Australian study demonstrates that the APACHE III can perform well on independent assessment. As perfect discrimination and calibration cannot coexist in a probabilistic model with dichotomous outcomes, performance of APACHE III models with proprietary adjustment for hospital characteristic provide a good compromise for use in quality surveillance.

APACHE↗
PubMed2000

In vivo animal models of cerebral vasospasm: a review.

BACKGROUND: Cerebral vasospasm is delayed-onset cerebral arterial narrowing in response to blood clots left in the subarachnoid space after spontaneous aneurysmal subarachnoid hemorrhage (SAH). Ideally, studies on the pathogenesis and treatment of cerebral vasospasm in humans should be conducted using human cerebral arteries. Because in vivo experiments using human vessels are not possible, and postmortem pathological examination of human arteries in vasospasm provides only a limited amount of information, a number of animal models of vasospasm have been developed. METHODS: The literature was searched to find all references to in vivo animal models of SAH and vasospasm. An online search of the medical database MEDLINE was initially performed using the key words "cerebral," "vasospasm," "subarachnoid," "hemorrhage," "animal," and "model." References were checked to determine the first description of each in vivo animal model. RESULTS: Fifty-seven models of SAH and vasospasm were identified. These models used one of three techniques to simulate SAH: 1) an artery was punctured allowing blood to escape and collect around the artery and its neighbors; 2) an artery was surgically exposed, and autologous blood obtained from another site was placed around the artery; or 3) blood from another site was injected into the subarachnoid space and was allowed to collect around arteries. Each technique has advantages and disadvantages. The majority of animal models of SAH and vasospasm use intracranial arteries; however, extracranial arteries have also been used recently in vasospasm experiments. These studies seem easier and less costly to perform, but concerns exist regarding the physiological dissimilarity between systemic and cerebral arteries. CONCLUSION: The model of SAH and vasospasm used most frequently is the canine "two-hemorrhage" model, in which two injections of blood into the dog's basal cistern performed 48 hours apart result in greater arterial vasoconstriction than that effected by a single injection of blood. On the basis of its ability to accurately predict what occurs in human SAH, the best model of vasospasm seems to be the primate model in which a blood clot is surgically placed around the large cerebral vessels at the base of the monkey's brain.

Animals↗
PubMed1999

Long-term effects of in vivo angioplasty in normal and vasospastic canine carotid arteries: pharmacological and morphological analyses.

OBJECT: A canine model of hemorrhagic vasospasm of the high cervical internal carotid artery (ICA) was used to study the long-term effects of transluminal balloon angioplasty (TBA) on the structure and function of the arterial wall. METHODS: Forty dogs underwent surgical exposure of both distal cervical ICAs, followed by baseline angiographic studies on Day 0. Dogs in Group A (20 animals) underwent simple exposure of one ICA and placement of a silicone elastomer cuff around a segment of the opposite artery. These animals underwent repeated angiography on Day 7, and then TBA was performed on the uncuffed ICA; the cuff was removed from the opposite vessel. For dogs in Group B (20 animals), blood clot-filled cuffs were placed around both ICAs, and on Day 7 angiography was repeated and TBA was performed on one randomly selected ICA. Four animals were then killed from each group, and in the remaining animals the cuffs were removed from both ICAs. On Days 14, 21, 28, and 56, four animals from each group underwent repeated angiography and were then killed to permit pharmacological and morphological analyses of the ICAs. This protocol yielded five study categories: cuffed nonblood-coated arteries not subjected to TBA, blood-coated arteries not subjected to TBA, blood-coated arteries subjected to TBA, normal arteries subjected to TBA, and control arteries obtained from the proximal ICA in each animal. The contractile responses of isolated arterial rings obtained from each ICA were recorded after treatment with potassium chloride, noradrenaline, and serotonin, whereas relaxations in response to the calcium ionophore A23187 and papaverine were recorded after tonic contraction to noradrenaline had been established. Morphological analysis was performed using scanning electron microscopy. Arteries surrounded by an empty cuff exhibited no angiographic, pharmacological, or morphological differences compared with normal arteries on any study day. Arteries surrounded by blood developed angiographically confirmed vasospasm on Day 7, with characteristic pharmacological and morphological features; resolution of these symptoms occurred by Day 21. Vasospastic arteries subjected to TBA on Day 7 remained dilated on angiographic studies, exhibited impaired responses to pharmacological agents (except for papaverine), and showed altered morphological features until Day 28. Normal arteries subjected to TBA on Day 7 remained dilated on angiographic studies, exhibited impaired responses to pharmacological agents (except for papaverine), and displayed altered morphological features until Day 14. CONCLUSIONS: These results indicate that the canine high cervical ICA model produces consistent and reproducible vasospasm that follows a similar time course to that seen in humans. When TBA is performed in vasospastic arteries, it results in an immediate functional impairment of vascular smooth muscle that lasts for 2 weeks, with resolution at 3 weeks; morphological changes are mostly resolved 3 weeks post-TBA. In normal vessels, TBA causes functional impairment and morphological alterations that are not as severe or as long-lasting as those seen in vasospastic arteries.

Angioplasty, Balloon↗
PubMed1998

Routine prenatal screening for HIV in a low-prevalence setting.

BACKGROUND: The objectives of this study were to assess the effect of British Columbia's June 1994 guidelines for prenatal HIV screening on the rate of maternal-fetal HIV transmission and to estimate the cost-effectiveness of such screening. METHODS: The authors conducted a retrospective review of pregnancy and delivery statistics, HIV screening practices, laboratory testing volume, prenatal and labour management decisions of HIV-positive women, maternal-fetal transmission rates and associated costs. RESULTS: Over 1995 and 1996, 135,681 women were pregnant and 92,645 carried to term. The rate of HIV testing increased from 55% to 76% of pregnancies on chart review at one hospital between November 1995 and November 1996. On the basis of seroprevalence studies, an estimated 50.2 pregnancies and 34.3 (95% confidence interval 17.6 to 51.0) live births to HIV-positive women were expected. Of 42 identified mother-infant pairs with an estimated date of delivery during 1995 or 1996, 25 were known only through screening. Of these 25 cases, there were 10 terminations, 1 spontaneous abortion and 14 cases in which the woman elected to carry the pregnancy to term with antiretroviral therapy. There was one stillbirth. One instance of maternal-fetal HIV transmission occurred among the 13 live births. The net savings attributable to prevented infections among babies carried to term were $165,586, with a saving per prevented case of $75,266. INTERPRETATION: A routine offer of pregnancy screening for HIV in a low-prevalence setting reduces the rate of maternal-fetal HIV transmission and may rival other widely accepted health care expenditures in terms of cost-effectiveness.

British Columbia↗
PubMed1998

Salmeterol improves quality of life in patients with asthma requiring inhaled corticosteroids. Salmeterol Quality of Life Study Group.

BACKGROUND: Traditional clinical outcomes have demonstrated that salmeterol improves pulmonary function and reduces asthma symptoms. However, they do not evaluate how patients perceive the effect of therapeutic intervention on day-to-day functioning and well-being. OBJECTIVE: We sought to evaluate the impact of salmeterol on disease-specific quality of life with the Asthma Quality-of-Life Questionnaire, as well as the efficacy and safety of salmeterol in patients with stable asthma who were symptomatic despite daily use of inhaled corticosteroids. METHODS: This was a randomized, double-blind, placebo-controlled, parallel-group study of 506 patients. Patients were treated with 42 microg salmeterol or placebo twice daily for 12 weeks delivered through a metered dose inhaler. RESULTS: Mean change from baseline in asthma quality-of-life scores was significantly greater (p < or = 0.006) after 12 weeks of treatment with salmeterol compared with placebo ("as-needed" albuterol) in global scores (1.08 vs 0.61) and individual domains (activity limitations, 0.91 vs 0.54; asthma symptoms, 1.28 vs 0.71; emotional function, 1.17 vs 0.65; and environmental exposure, 0.84 vs 0.47). Patients treated with salmeterol experienced significantly greater improvements from baseline to week 12 compared with placebo in FEV1 (0.42 L vs 0.15 L, p < 0.001), morning peak expiratory flow (47 L/min vs 14 L/min, p < 0.001), evening peak expiratory flow (29 L/min vs 11 L/min, p < 0.001), and asthma symptom scores (daytime scores reduced by 0.55 vs 0.30, p < 0.001). Patients treated with salmeterol used significantly less supplemental albuterol (reduced by 3 puffs/day vs 1 puff/day, p < 0.001). CONCLUSION: Salmeterol provided significantly greater improvement in quality-of-life outcomes in patients whose asthma symptoms are not well controlled with inhaled corticosteroids. These results demonstrate that the benefits of salmeterol are not limited to conventional clinical measures of efficacy.

Administration, Inhalation↗