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D Cook

Publications and source records attributed to D Cook.

At least 127 records · Page 7Linked to original sources
PubMed1995

Basic statistics for clinicians: 4. Correlation and regression.

Correlation and regression help us to understand the relation between variables and to predict patients' status in regard to a particular variable of interest. Correlation examines the strength of the relation between two variables, neither of which is considered the variable one is trying to predict (the target variable). Regression analysis examines the ability of one or more factors, called independent variables, to predict a patient's status in regard to the target or dependent variable. Independent and dependent variables may be continuous (taking a wide range of values) or binary (dichotomous, yielding yes-or-no results). Regression models can be used to construct clinical prediction rules that help to guide clinical decisions. In considering regression and correlation, clinicians should pay more attention to the magnitude of the correlation or the predictive power of the regression than to whether the relation is statistically significant.

Data Interpretation, Statistical↗
PubMed1995

Basic statistics for clinicians: 3. Assessing the effects of treatment: measures of association.

In the third of a series of four articles the authors show the calculation of measures of association and discuss their usefulness in clinical decision making. From the rates of death or other "events" in experimental and control groups in a clinical trial, we can calculate the relative risk (RR) of the event after the experimental treatment, expressed as a percentage of the risk without such treatment. The absolute risk reduction (ARR) is the difference in the risk of an event between the groups. The relative risk reduction is the percentage of the baseline risk (the risk of an event in the control patients) removed as a result of therapy. The odds ratio (OR), which is the measure of choice in case-control studies, gives the ratio of the odds of an event in the experimental group to those in the control group. The OR and the RR provide limited information in reporting the results of prospective trials because they do not reflect changes in the baseline risk. The ARR and the number needed to treat, which tells the clinician how many patients need to be treated to prevent one event, reflect both the baseline risk and the relative risk reduction. If the timing of events is important--to determine whether treatment extends life, for example--survival curves are used to show when events occur over time.

Case-Control Studies↗
PubMed1995

Basic statistics for clinicians: 2. Interpreting study results: confidence intervals.

In the second of four articles, the authors discuss the "estimation" approach to interpreting study results. Whereas, in hypothesis testing, study results lead the reader to reject or accept a null hypothesis, in estimation the reader can assess whether a result is strong or weak, definitive or not. A confidence interval, based on the observed result and the size of the sample, is calculated. It provides a range of probabilities within which the true probability would lie 95% or 90% of the time, depending on the precision desired. It also provides a way of determining whether the sample is large enough to make the trial definitive. If the lower boundary of a confidence interval is above the threshold considered clinically significant, then the trial is positive and definitive, if the lower boundary is somewhat below the threshold, the trial is positive, but studies with larger samples are needed. Similarly, if the upper boundary of a confidence interval is below the threshold considered significant, the trial is negative and definitive. However, a negative result with a confidence interval that crosses the threshold means that trials with larger samples are needed to make a definitive determination of clinical importance.

Clinical Trials as Topic↗
PubMed1995

Basic statistics for clinicians: 1. Hypothesis testing.

In the first of a series of four articles the authors explain the statistical concepts of hypothesis testing and p values. In many clinical trials investigators test a null hypothesis that there is no difference between a new treatment and a placebo or between two treatments. The result of a single experiment will almost always show some difference between the experimental and the control groups. Is the difference due to chance, or is it large enough to reject the null hypothesis and conclude that there is a true difference in treatment effects? Statistical tests yield a p value: the probability that the experiment would show a difference as great or greater than that observed if the null hypothesis were true. By convention, p values of less than 0.05 are considered statistically significant, and investigators conclude that there is a real difference. However, the smaller the sample size, the greater the chance of erroneously concluding that the experimental treatment does not differ from the control--in statistical terms, the power of the test may be inadequate. Tests of several outcomes from one set of data may lead to an erroneous conclusion that an outcome is significant if the joint probability of the outcomes is not taken into account. Hypothesis testing has limitations, which will be discussed in the next article in the series.

Clinical Trials as Topic↗
PubMed1995

Transient induction of a peroxidase gene in Medicago truncatula precedes infection by Rhizobium meliloti.

Although key determinative events of the Rhizobium-legume symbiosis are likely to precede bacterial infection, no plant genes have been identified that are expressed strongly prior to infection and nodule morphogenesis. A subtractive hybridization-polymerase chain reaction technique was used to enrich for genes induced during the early phases of the R. meliloti-Medicago truncatula symbiosis. One gene so identified encodes a putative plant peroxidase protein, which we have named Rip1 for Rhizobium-induced peroxidase. The accumulation of rip1 transcript was rapidly and transiently induced by R. meliloti and by the corresponding lipooligosaccharide signal molecule Nod factor RmIV, which was both necessary and sufficient for rip1 induction. The duration of maximal rip1 expression coincided with the preinfection period: transcript levels for rip1 were near maximal by 3 hr postinoculation and declined by 48 hr, coincident with early infection events and the onset of nodule morphogenesis. Furthermore, although rip1 induction preceded bacterial infection by at least 24 hr, the transcript was localized to epidermal cells in the differentiating root zone that was subsequently infected by Rhizobium. Thus, a defining feature of the Rhizobium infection court is the prior induction of rip1 expression.

Amino Acid Sequence↗
PubMed1995

Measurements of blood pressure, oedema and proteinuria in a pregnant population of New Zealand.

This is the first report of the largest study of blood pressure measurement in pregnancy in a New Zealand population using standardized definitions and methodology. Over 3,800 women who delivered in an 8-month period in the Wellington region were included in the study. Blood pressure measurement and the presence of oedema and proteinuria were recorded from booking until delivery and in the puerperium. Only 2.7% of women were unable to be contacted after delivery for details on outcomes. The results established normal ranges for blood pressure throughout pregnancy. The data show that blood pressure greater than 140/90 until 35 weeks' gestation is outside 2 standard deviations at all gestations and justifies using these measurements as the definition of hypertension in pregnancy. The fall in blood pressure in the 2nd trimester was less than 1 mm Hg per week in both the systolic and diastolic pressures. This fall was smaller than previously recorded in other studies. Gestational hypertension was the commonest blood pressure abnormality occurring in 15.2% of the population. This represented 69% of the pregnant women with a hypertensive disorder. The overall incidence of both gestational hypertension and preeclampsia was 18.5% which is higher than reported in other parts of the world. In this study obesity was significantly associated with hypertensive disorders in pregnancy. An arm circumference of > 33 cm, one of the measurements of obesity, was found in 6.8% of the study population. Even after the effect of arm circumference was taken into account, hypertensive disorders were also more common in Pacific Island women.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1995

Interobserver variation in the computed tomographic evaluation of mediastinal lymph node size in patients with potentially resectable lung cancer. Canadian Lung Oncology Group.

OBJECTIVE: To measure the reliability of the assessment of mediastinal lymph node size in computed tomographic (CT) scans of the thorax. DESIGN: Observer agreement study in which radiologists, blinded to one anothers' interpretation, were randomized to read 30 scans each. POPULATION: Sixty scans from patients with apparently operable non-small cell carcinoma of the lung were read by radiologists responsible for clinical interpretation (clinical radiologists) and four radiologists with a special interest in thoracic CT (study radiologists). MEASUREMENTS: Radiologists measured the size of left and right superior mediastinal nodes, aortic nodes, and the subcarinal nodes and, on the basis of whether any nodes accessible to mediastinoscopy were greater than 1 cm, recommended whether mediastinoscopy be undertaken. Agreement was quantified using kappa, a measure of chance-corrected agreement. RESULTS: Among all radiologists, agreement on whether there were any nodes larger than 1 cm for right superior mediastinal nodes was 0.68; for left superior mediastinal nodes it was 0.28; for aortic pulmonary nodes it was 0.62; for subcarinal nodes it was 0.58; and for any node greater than 1 cm and accessible to mediastinoscopy it was 0.61. The agreement was very similar when the analysis was restricted to the study radiologists. CONCLUSION: Although the good level of overall agreement suggests that CT provides useful information in the evaluation of mediastinal lymph node size, the disagreement was sufficient that it likely contributes to suboptimal sensitivity and specificity of CT in detecting tumor spread reported in previous studies.

Carcinoma, Non-Small-Cell Lung↗
PubMed1995

Problem-based learning: its role in undergraduate surgical education.

OBJECTIVE: To familiarize the surgeon with problem-based learning (PBL) and to discuss the current and future role of PBL in undergraduate surgical education. DATA SOURCES: Two meta-analyses comparing the outcome of a PBL curriculum with a traditional curriculum and other studies in the English-language literature. STUDY SELECTION: Data on the effectiveness of PBL can best be assessed by a meta-analysis in which the conclusions of many studies are reviewed and combined to provide a more comprehensive picture. The studies chosen represent those from the only two recent meta-analyses of the problem that have appeared in reputable journals. DATA EXTRACTION: Results reported are those obtained using appropriate techniques and published in reputable journals. Information relevant to the major issues in undergraduate surgical training was selected for inclusion. DATA SYNTHESIS: PBL depends on self-directed learning, triggered by a clinical problem. The students meet in small groups led by a facilitator and discuss carefully designed clinical cases. At the conclusion, the students will have encountered all the information necessary to solve the case and, in so doing, will have gained knowledge that in a conventional curriculum would usually have been disseminated by lecture. There were only small differences between graduates from the two types of curricula. Those from a PBL curriculum had comparable examination results to those from a traditional curriculum on both basic science and clinically based examinations but were happier with their educational experiences. CONCLUSIONS: Centres that have adopted a PBL approach have found improved student motivation and enjoyment, but there has been no convincing evidence of improved learning. An intelligent combination of both traditional and PBL approaches will likely provide the most effective training for undergraduate surgical clerks.

Canada↗
PubMed1995

Lazaroids and deferoxamine attenuate the intracellular effects of oxyhaemoglobin in vascular smooth muscle.

OBJECTIVES: While it is probable that the cerebrovascular spasm which occurs after subarachnoid haemorrhage results from the action of haemoglobin, the mechanism of that process remains unclear. These studies were thus designed to test the hypothesis that the action of oxyhaemoglobin results from the iron-catalyzed formation of free radicals and subsequent lipid peroxidation resulting in intracellular changes in the second messengers for contraction. METHODS: Levels of intracellular calcium and of inositol (1,4,5)-trisphosphate were measured in cultured vascular smooth muscle cells derived from primate cerebral arteries. Contractility of rings of canine cerebral vessels were examined in vitro using standard pharmacological techniques. Vessels in spasm were obtained from the "two haemorrhage" canine model and the presence of vasospasm was confirmed angiographically. In each case, the effects of oxyhaemoglobin and sometimes of free radicals generated from iron salts were examined in the presence and in the absence of free-radical scavenging agents or the iron chelating agent, deferoxamine. RESULTS: Oxyhaemoglobin produces a slowly-developing sustained contraction of arterial rings which is accompanied by a sustained elevation of intracellular calcium. It also produces a transient but significant elevation of inositol (1,4,5)-trisphosphate, but this is not correlated with the development of sustained constriction. Deferoxamine and the lazaroid compounds U-74389G and U-83836E were effective in preventing the effects of oxyhaemoglobin and free radicals in the models tested, although in vessels in spasm, all effects were smaller. CONCLUSIONS: The present study provides results which are consistent with the hypothesis that the actions of haemoglobin on vascular smooth muscle are mediated by the formation of free radicals which subsequently affect intracellular calcium concentrations. This also implies that agents which impair free radical production or other processes leading to iron-catalyzed lipid peroxidation, are of potential value in cerebrovascular spasm.

Animals↗
PubMed1994

Spectrum of quality of life impairment in hypothyroidism.

The aim of this study is to evaluate the frequency and relative importance of different aspects of health related quality of life (HRQOL) impairment in patients with hypothyroidism. A survey of 200 patients with treated hypothyroidism was undertaken. Patients were identified and questionnaires distributed through family physicians, endocrinologists, and regional branches of the Thyroid Foundation of Canada. Frequency of importance of patients' symptoms attributed to hypothyroidism and resolved or improved with treatment were measured. Establishing the wide variety of patient-specific complaints associated with hypothyroidism provides guidance for clinicians dealing with hypothyroid patients, and investigators interested in HRQOL impairment in these patients.

Humans↗
PubMed1994

Cerebral vascular smooth muscle potassium channels and their possible role in the management of vasospasm.

One of the promising therapeutic uses of the potassium channel openers is in the management of cerebral vasospasm, a prolonged vasoconstriction of major cerebral arteries which follows aneurysmal subarachnoid haemorrhage. In this review, we first summarize the properties of potassium channels in cerebral vascular smooth muscle. Calcium-activated and ATP-dependent potassium channels are the major potassium channels identified in the cerebrovascular smooth muscle and both are believed to play a role in the regulation of cerebrovascular smooth muscle tone. The calcium-activated potassium channels can be activated by depolarization, by elevation of internal calcium and by some vasodilators. Some neuropeptides and potassium channel openers open the ATP-dependent potassium channels and produce vasodilation. We then review the effects of both synthetic and endogenous potassium channel openers in the cerebrovascular system, discuss their efficacy in the management of models of cerebrovascular spasm, and outline the clinical promise of these agents.

Adenosine Triphosphate↗
PubMed1994

Effect of increasing doses of beta agonists on spirometric parameters, exercise capacity, and quality of life in patients with chronic airflow limitation.

BACKGROUND: A study was undertaken to determine the impact of different doses of inhaled terbutaline on peak flow rates, spirometric parameters, functional exercise capacity, and quality of life in patients with chronic airflow limitation. METHODS: A double blind, randomised, placebo controlled, multiple crossover trial was conducted with treatment periods of one week. Patients with a clinical diagnosis of chronic airflow limitation and FEV1 below 70% predicted after administration of bronchodilator were recruited from secondary care respiratory practices, and the effect of 500, 1000, and 1500 micrograms inhaled terbutaline four times daily on spirometric parameters (FEV1, FVC), maximum inspiratory pressures, six minute walking distance, and health-related quality of life (Chronic Respiratory Disease Questionnaire, Quality of Well Being, Standard Gamble) was measured. RESULTS: Twenty five patients completed the trial. Peak flow rates and FEV1 showed statistically significant but clinically trivial improvement on the higher drug doses. Results of maximum inspiratory pressure measurements, walk test distance, and quality of life measures showed minimal differences on the different dosages, and none of the differences approached conventional statistical significance. CONCLUSIONS: Regular use of beta agonists in doses higher than two puffs four times a day is very unlikely to provide additional functional or symptomatic benefit to patients with chronic airflow limitation.

Aged↗
PubMed1994

Antagonism of eicosanoid-induced contraction of rat aorta by sulphonylureas.

Glibenclamide and other sulphonylureas are extensively used as specific blockers for ATP-dependent potassium channels in vascular smooth muscle. However, glibenclamide has recently been shown to inhibit actions of some prostanoids in vascular smooth muscle. We extend our previous study by examining the relaxant actions of five different sulphonylureas in rat aorta. The inhibitory effects of sulphonylureas on the contractions induced by prostaglandins F2 alpha, E2 and D2, norepinephrine, 5-hydroxytryptamine (5-HT) or potassium chloride (KCl) were examined. Glibenclamide significantly inhibited the contractions produced by prostaglandins F2 alpha, E2 and D2 but was without effect on responses to norepinephrine, 5-HT or KCl. Glimepiride produced significant attenuation of the responses to all agents tested (5-HT, norepinephrine, KCl), although the inhibition of the responses to prostaglandin F2 alpha was most pronounced. Glipizide and tolbutamide had activities similar to that of glibenclamide, while chlorpropamide was devoid of any antagonist action in rat aorta. In rat aorta precontracted with norepinephrine, glibenclamide inhibited the relaxant responses to lemakalim and pinacidil. Thus, in addition to the effect on ATP-dependent potassium channels, glibenclamide inhibits responses to prostaglandins F2 alpha, E2 and D2 but not to other agents. This effect is shared by glimepiride, tolbutamide and glipizide.

Animals↗