Showing papers by "McMaster University published in 1998"

Sample size and optimal designs for reliability studies

Abstract: A method is developed to calculate the required number of subjects k in a reliability study, where reliability is measured using the intraclass correlation rho. The method is based on a functional approximation to earlier exact results. The approximation is shown to have excellent agreement with the exact results and one can use it easily without intensive numerical computation. Optimal design configurations are also discussed; for reliability values of about 40 per cent or higher, use of two or three observations per subject will minimize the total number of observations required.

Effects of Computer-Based Clinical Decision Support Systems on Physician Performance and Patient Outcomes: A Systematic Review

Abstract: Context.—Many computer software developers and vendors claim that their systems can directly improve clinical decisions. As for other health care interventions, such claims should be based on careful trials that assess their effects on clinical performance and, preferably, patient outcomes.Objective.—To systematically review controlled clinical trials assessing the effects of computer-based clinical decision support systems (CDSSs) on physician performance and patient outcomes.Data Sources.—We updated earlier reviews covering 1974 to 1992 by searching the MEDLINE, EMBASE, INSPEC, SCISEARCH, and the Cochrane Library bibliographic databases from 1992 to March 1998. Reference lists and conference proceedings were reviewed and evaluators of CDSSs were contacted.Study Selection.—Studies were included if they involved the use of a CDSS in a clinical setting by a health care practitioner and assessed the effects of the system prospectively with a concurrent control.Data Extraction.—The validity of each relevant study (scored from 0-10) was evaluated in duplicate. Data on setting, subjects, computer systems, and outcomes were abstracted and a power analysis was done on studies with negative findings.Data Synthesis.—A total of 68 controlled trials met our criteria, 40 of which were published since 1992. Quality scores ranged from 2 to10, with more recent trials rating higher (mean, 7.7) than earlier studies (mean, 6.4) (P<.001). Effects on physician performance were assessed in 65 studies and 43 found a benefit (66%). These included 9 of 15 studies on drug dosing systems, 1 of 5 studies on diagnostic aids, 14 of 19 preventive care systems, and 19 of 26 studies evaluating CDSSs for other medical care. Six of 14 studies assessing patient outcomes found a benefit. Of the remaining 8 studies, only 3 had a power of greater than 80% to detect a clinically important effect.Conclusions.—Published studies of CDSSs are increasing rapidly, and their quality is improving. The CDSSs can enhance clinical performance for drug dosing, preventive care, and other aspects of medical care, but not convincingly for diagnosis. The effects of CDSSs on patient outcomes have been insufficiently studied.

IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses.

Abstract: IL-6 is induced often together with the proinflammatory cytokines TNFalpha and IL-1 in many alarm conditions, and circulating IL-6 plays an important role in the induction of acute phase reactions. However, whether this endogenous IL-6 plays any additional pro- or antiinflammatory roles in local or systemic responses remains unclear. In this study, the role of IL-6 in acute inflammatory responses was investigated in animal models of endotoxic lung or endotoxemia by using IL-6+/+ and IL-6-/- mice. Aerosol exposure of endotoxin induced increased IL-6 and proinflammatory cytokines TNFalpha and MIP-2 and a neutrophilic response in the lung of IL-6+/+ mice. However, the levels of TNFalpha and MIP-2 and neutrophilia were significantly higher in the lung of IL-6-/- mice. The rate of neutrophil apoptosis in these mice was similar to that in IL-6+/+ mice. A low constitutive level of antiinflammatory cytokine IL-10 was not enhanced by endotoxin and remained similar in the lung in both IL-6+/+ and IL-6-/- mice. Systemically, intraperitoneal delivery of endotoxin resulted in much more pronounced circulating levels of TNFalpha, MIP-2, GM-CSF, and IFNgamma in IL-6-/- mice than in IL-6+/+ mice, and administration of recombinant IL-6 to IL-6-/- mice abolished these differences. In contrast, circulating IL-10 levels were induced to a similar degree in both IL-6+/+ and IL-6-/- mice. Thus, our studies reveal that endogenous IL-6 plays a crucial antiinflammatory role in both local and systemic acute inflammatory responses by controlling the level of proinflammatory, but not antiinflammatory, cytokines, and that these antiinflammatory activities by IL-6 cannot be compensated for by IL-10 or other IL-6 family members.

A Bond Path: A Universal Indicator of Bonded Interactions

Abstract: The quantum mechanics of proper open systems yields the physics that governs the local behavior of the electron density, ρ(r). The Ehrenfest force F(r) acting on an element of ρ(r) and the virial field ν(r) that determine its potential energy are obtained from equations of motion for the electronic momentum and virial operators, respectively. Each is represented by a “dressed” density, a distribution in real space that results from replacing the property in question for a single electron with a corresponding density that describes its average interaction with all of the remaining particles in the system. All bond paths, lines of maximum density linking neighboring nuclei in a system in stable electrostatic equilibrium, have a common physical origin in terms of F(r) and ν(r), regardless of the nature of the interaction. Each is homeomorphically mirrored by a virial path, a line of maximally negative potential energy density linking the same nuclei. The presence of a bond path and its associated virial path...

PROACT: A Phase II Randomized Trial of Recombinant Pro-Urokinase by Direct Arterial Delivery in Acute Middle Cerebral Artery Stroke

Abstract: Background and Purpose—To test the safety and recanalization efficacy of intra-arterial local delivery of plasminogen activators in acute ischemic stroke, a randomized trial of recombinant pro-urok...

A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns

Abstract: Idiopathic generalized epilepsies account for about 40% of epilepsy up to age 40 and commonly have a genetic basis. One type is benign familial neonatal convulsions (BFNC), a dominantly inherited disorder of newborns. We have identified a sub-microscopic deletion of chromosome 20q13.3 that co-segregates with seizures in a BFNC family. Characterization of cDNAs spanning the deleted region identified one encoding a novel voltage-gated potassium channel, KCNQ2, which belongs to a new KQT-like class of potassium channels. Five other BFNC probands were shown to have KCNQ2 mutations, including two transmembrane missense mutations, two frameshifts and one splice-site mutation. This finding in BFNC provides additional evidence that defects in potassium channels are involved in the mammalian epilepsy phenotype.

Incidence of and Risk Factors for Ventilator-Associated Pneumonia in Critically Ill Patients

Abstract: Background: Understanding the risk factors for ventilator-associated pneumonia can help to assess prognosis and devise and test preventive strategies Objective: To examine the baseline and time-de

Increased auditory cortical representation in musicians

Abstract: Acoustic stimuli are processed throughout the auditory projection pathway, including the neocortex, by neurons that are aggregated into 'tonotopic' maps according to their specific frequency tunings. Research on animals has shown that tonotopic representations are not statically fixed in the adult organism but can reorganize after damage to the cochlea or after training the intact subject to discriminate between auditory stimuli. Here we used functional magnetic source imaging (single dipole model) to measure cortical representations in highly skilled musicians. Dipole moments for piano tones, but not for pure tones of similar fundamental frequency (matched in loudness), were found to be enlarged by about 25% in musicians compared with control subjects who had never played an instrument. Enlargement was correlated with the age at which musicians began to practise and did not differ between musicians with absolute or relative pitch. These results, when interpreted with evidence for modified somatosensory representations of the fingering digits in skilled violinists, suggest that use-dependent functional reorganization extends across the sensory cortices to reflect the pattern of sensory input processed by the subject during development of musical skill.

Explaining nursing turnover intent: job satisfaction, pay satisfaction, or organizational commitment?

Abstract: A number of models have been developed to explain nurses' turnover behavior. The common theme that emerges from these models is that turnover behavior is a multistage process that includes attitudinal, decisional, and behavioral components. The purpose of this study was to assess both the direct and indirect impact of certain pay policies upon the turnover intentions of paediatric nurses. The two major questions addressed were: What was the relative impact of job satisfaction, pay satisfaction, and organizational commitment upon the turnover intentions of paediatric nurses eligible for these pay policies? What model accurately portrays the relationship among these three independent variables and turnover intentions? Exploration of the causal pathways among these variables and demographic factors revealed complex models of association. The results suggest that job satisfaction has only an indirect influence on the intention to quit, whereas organizational commitment has the strongest and most direct impact. A further finding that pay satisfaction had both direct and indirect effects on turnover intent was consistent with administrators' assumptions underlying the pay policies. Control variables such as having a degree, having children, and working 12-hour shifts were found to have both direct and indirect influences upon pay satisfaction and turnover intent. © 1998 John Wiley & Sons, Ltd.

Rating Health Information on the Internet Navigating to Knowledge or to Babel

Abstract: Context.—The rapid growth of the Internet has triggered an information revolution of unprecedented magnitude. Despite its obvious benefits, the increase in the availability of information could also result in many potentially harmful effects on both consumers and health professionals who do not use it appropriately.Objectives.—To identify instruments used to rate Web sites providing health information on the Internet, rate criteria used by them, establish the degree of validation of the instruments, and provide future directions for research in this area.Data Sources.—MEDLINE (1966-1997), CINHAL (1982-1997), HEALTH (1975-1997), Information Science Abstracts (1966 to September 1995), Library and Information Science Abstracts (1969-1995), and Library Literature (1984-1996); the search engines Lycos, Excite, Open Text, Yahoo, HotBot, Infoseek, and Magellan; Internet discussion lists; meeting proceedings; multiple Web pages; and reference lists.Instrument Selection.—Instruments used at least once to rate the quality of Web sites providing health information with their rating criteria available on the Internet.Data Extraction.—The name of the developing organization, Internet address, rating criteria, information on the development of the instrument, number and background of people generating the assessments, and data on the validity and reliability of the measurements.Data Synthesis.—A total of 47 rating instruments were identified. Fourteen provided a description of the criteria used to produce the ratings, and 5 of these provided instructions for their use. None of the instruments identified provided information on the interobserver reliability and construct validity of the measurements.Conclusions.—Many incompletely developed instruments to evaluate health information exist on the Internet. It is unclear, however, whether they should exist in the first place, whether they measure what they claim to measure, or whether they lead to more good than harm.

Genomic DNA transfer with a high-capacity adenovirus vector results in improved in vivo gene expression and decreased toxicity

Abstract: Many applications for human gene therapy would be facilitated by high levels and long duration of physiologic gene expression. Adenoviral vectors are frequently used for gene transfer because of their high cellular transduction efficiency in vitro and in vivo. Expression of viral proteins and the low capacity for foreign DNA limits the clinical application of first- and second-generation adenoviral vectors. Adenoviral vectors with all viral coding sequences deleted offer the prospect of decreased host immune responses to viral proteins, decreased cellular toxicity of viral proteins and increased capacity to accommodate large regulatory DNA regions. Currently most vectors used in vivo for preclinical and clinical studies express cDNAs under the control of heterologous eukaryotic or viral promoters. Using an adenoviral vector with all viral coding sequences deleted and containing the complete human alpha1-antitrypsin (PI) locus, we observed tissue-specific transcriptional regulation in cell culture and in vivo; intravenous injection in mice resulted in high levels of very stable expression for more than ten months and decreased acute and chronic toxicity. These results indicate significant advantages of regulated gene expression using genomic DNA for gene transfer and of adenoviral gene transfer vectors devoid of all viral coding sequences.

Analysis of multiblock and hierarchical PCA and PLS models

Abstract: Multiblock and hierarchical PCA and PLS methods have been proposed in the recent literature in order to improve the interpretability of multivariate models. They have been used in cases where the number of variables is large and additional information is available for blocking the variables into conceptually meaningful blocks. In this paper we compare these methods from a theoretical or algorithmic viewpoint using a common notation and illustrate their differences with several case studies. Undesirable properties of some of these methods, such as convergence problems or loss of data information due to deflation procedures, are pointed out and corrected where possible. It is shown that the objective function of the hierarchical PCA and hierarchical PLS methods is not clear and the corresponding algorithms may converge to different solutions depending on the initial guess of the super score. It is also shown that the results of consensus PCA (CPCA) and multiblock PLS (MBPLS) can be calculated from the standard PCA and PLS methods when the same variable scalings are applied for these methods. The standard PCA and PLS methods require less computation and give better estimation of the scores in the case of missing data. It is therefore recommended that in cases where the variables can be separated into meaningful blocks, the standard PCA and PLS methods be used to build the models and then the weights and loadings of the individual blocks and super block and the percentage variation explained in each block be calculated from the results. © 1998 John Wiley & Sons, Ltd.

A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group.

Abstract: Background Critically ill patients who require mechanical ventilation are at increased risk for gastrointestinal bleeding from stress ulcers. There are conflicting data on the effect of histamine H2-receptor antagonists and the cytoprotective agent sucralfate on rates of gastrointestinal bleeding, ventilator-associated pneumonia, and mortality. Methods In a multicenter, randomized, blinded, placebo-controlled trial, we compared sucralfate with the H2-receptor antagonist ranitidine for the prevention of upper gastrointestinal bleeding in 1200 patients who required mechanical ventilation. Patients received either nasogastric sucralfate suspension (1 g every six hours) and an intravenous placebo or intravenous ranitidine (50 mg every eight hours) and a nasogastric placebo. Results The patients in the two groups had similar base-line characteristics. Clinically important gastrointestinal bleeding developed in 10 of 596 (1.7 percent) of the patients receiving ranitidine, as compared with 23 of 604 (3.8 percent...

Technical note: improved DNA extraction from ancient bones using silica-based spin columns

Abstract: We describe a simple method for extracting polymerase chain reaction-amplifiable DNA from ancient bones without the use of organic solvents. Bone powders are digested with proteinase K, and the DNA is purified directly using silica-based spin columns (QIAquick3, QIAGEN). The efficiency of this protocol is demonstrated using human bone samples ranging in age from 15 to 5,000 years old.

Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group.

Abstract: PURPOSETo determine the relative efficacy of an intensive cyclophosphamide, epirubicin, and fluorouracil (CEF) adjuvant chemotherapy regimen compared with cyclophosphamide, methotrexate, and fluorouracil (CMF) in node-positive breast cancer.PATIENTS AND METHODSPremenopausal women with node-positive breast cancer were randomly allocated to receive either cyclophosphamide 100 mg/m2 orally days 1 through 14; methotrexate 40 mg/m2 intravenously (i.v.) days 1 and 8; and fluorouracil 600 mg/m2 i.v. days 1 and 8 or cyclophosphomide 75 mg/m2 orally days 1 through 14; epirubicin 60 mg/m2 i.v. days 1 and 8; and fluorouracil 500 mg/m2 i.v. days 1 and 8. Each cycle was administered monthly for 6 months. Patients administered CEF received antibiotic prophylaxis with cotrimoxazole two tablets twice a day for the duration of chemotherapy.RESULTSThe median follow-up was 59 months. One hundred sixty-nine of the 359 CMF patients developed recurrence compared with 132 of the 351 CEF patients. The corresponding 5-year relaps...

Risk of fatal pulmonary embolism in patients with treated venous thromboembolism.

Abstract: Context.—The most serious complication of deep vein thrombosis (DVT) or nonfatal pulmonary embolism (PE) is fatal PE. However, reliable estimates as to the risk of fatal PE in patients with treated DVT or PE are lacking.Objective.—To provide reliable estimates of the risk of fatal PE and the case-fatality rate of recurrent DVT or PE among patients presenting with symptomatic DVT or PE, during and following 3 months of anticoagulant therapy.Data Sources.—A MEDLINE literature search was performed to identify prospective studies in which patients with symptomatic DVT or PE were treated with 5 to 10 days of heparin and 3 months of oral anticoagulants. We searched the years 1966 to September 1997 using the search terms thrombophlebitis, diagnosis, drug therapy, and prognosis. Current Contents and bibliographies were also scanned.Data Extraction.—Of 137 retrieved studies, 25 studies satisfied predetermined methodologic criteria and were included in the analysis.Data Synthesis.—Among patients presenting with DVT, the rate of fatal PE during anticoagulant therapy was 0.4% (95% confidence interval [CI], 0.2%-0.6%); following anticoagulant therapy it was 0.3 per 100 patient-years (95% CI, 0.1-0.8). The case-fatality rate of recurrent DVT or PE during anticoagulant therapy was 8.8% (95% CI, 5.0%-14.1%); following anticoagulant therapy it was 5.1% (95% CI, 1.4%-12.5%). Among patients presenting with PE, the rate of fatal PE during anticoagulant therapy was 1.5% (95% CI, 0.9%-2.2%); following anticoagulant therapy it was 0 per 265 patient-years (95% CI, 0-3.6). The case-fatality rate of recurrent DVT or PE among patients presenting with PE was 26.4% (95% CI, 16.7%-38.1%).Conclusion.—Among patients with symptomatic PE or DVT who are treated with anticoagulants for 3 months, fatal PE is rare during and following anticoagulant therapy. Patients presenting with PE are more likely to die of recurrent PE or DVT than are patients presenting with DVT.

Protein Phylogenies and Signature Sequences: A Reappraisal of Evolutionary Relationships among Archaebacteria, Eubacteria, and Eukaryotes

Abstract: The presence of shared conserved insertion or deletions (indels) in protein sequences is a special type of signature sequence that shows considerable promise for phylogenetic inference. An alternative model of microbial evolution based on the use of indels of conserved proteins and the morphological features of prokaryotic organisms is proposed. In this model, extant archaebacteria and gram-positive bacteria, which have a simple, single-layered cell wall structure, are termed monoderm prokaryotes. They are believed to be descended from the most primitive organisms. Evidence from indels supports the view that the archaebacteria probably evolved from gram-positive bacteria, and I suggest that this evolution occurred in response to antibiotic selection pressures. Evidence is presented that diderm prokaryotes (i.e., gram-negative bacteria), which have a bilayered cell wall, are derived from monoderm prokaryotes. Signature sequences in different proteins provide a means to define a number of different taxa within prokaryotes (namely, low G+C and high G+C gram-positive, Deinococcus-Thermus, cyanobacteria, chlamydia-cytophaga related, and two different groups of Proteobacteria) and to indicate how they evolved from a common ancestor. Based on phylogenetic information from indels in different protein sequences, it is hypothesized that all eukaryotes, including amitochondriate and aplastidic organisms, received major gene contributions from both an archaebacterium and a gram-negative eubacterium. In this model, the ancestral eukaryotic cell is a chimera that resulted from a unique fusion event between the two separate groups of prokaryotes followed by integration of their genomes.

Barriers and bridges to evidence based clinical practice

Abstract: This is the fourth in a series of eight articles analysing the gap between research and practice Series editors: Andrew Haines and Anna Donald Clinicians and healthcare planners who want to improve the quality and efficiency of healthcare services will find help in research evidence. This evidence is increasingly accessible through information services that combine high quality evidence with information technology. However, there are several barriers to the successful application of research evidence to health care. We discuss both the prospects for harnessing evidence to improve health care and the problems that readers—clinicians, planners, and patients—will need to overcome to enjoy the benefits of research(box). View this table: Problems in implementing evidence based medicine and possible solutions The aim of evidence based health care is to provide the means by which current best evidence from research can be judiciously and conscientiously applied in the prevention, detection, and care of health disorders.1 This aim is decidedly ambitious given how slowly important new treatments are disseminated into practice2–%4and how resistant practitioners are to withdrawing established treatments from practice even once their utility has been disproved.5 ### Summary points The barriers to the dissemination and timely application of research findings in the making of decisions about health care are complex and have been little studied. They include many factors beyond the control of the practitioner …

Family-Centred Service

Abstract: Family-centred service (FCS) is a popular phrase widely used to encompass a set of ideas about service delivery to children and their families. Despite the increasing adoption of the concepts of FCS, however, many clinicians may remain uncertain about exactly what FCS means. This review article has four purposes. The first section presents a brief review of the history and ideas behind FCS. Second, the authors present a new framework of FCS, blending the elements of this approach into a set of ideas that have immediate clinical applicability. The third focus of this paper is to review the research evidence that supports FCS and to point to areas where further research is needed. Finally we consider the implications for service providers of the move to FCS, and the potential uses of the FCS framework as a guide for teaching and research.

Methodology and reports of systematic reviews and meta-analyses: a comparison of Cochrane reviews with articles published in paper-based journals.

Abstract: Context.—Review articles are important sources of information to help guide decisions by clinicians, patients, and other decision makers. Ideally, reviews should include strategies to minimize bias and to maximize precision and be reported so explicitly that any interested reader would be able to replicate them.Objective.—To compare the methodological and reporting aspects of systematic reviews and meta-analyses published by the Cochrane Collaboration with those published in paper-based journals indexed in MEDLINE.Data Sources.—The Cochrane Library, issue 2 of 1995, and a search of MEDLINE restricted to 1995.Study Selection.—All 36 completed reviews published in the Cochrane Database of Systematic Reviews and a randomly selected sample of 39 meta-analyses or systematic reviews published in journals indexed by MEDLINE in 1995.Data Extraction.—Number of authors, trials, and patients; trial sources; inclusion and exclusion criteria; language restrictions; primary outcome; trial quality assessment; heterogeneity testing; and effect estimates. Updating by 1997 was evaluated.Results.—Reviews found in MEDLINE included more authors (median, 3 vs 2; P<.001), more trials (median, 13.5 vs 5; P<.001), and more patients (median, 1280 vs 528; P <.001) than Cochrane reviews. More Cochrane reviews, however, included a description of the inclusion and exclusion criteria (35/36 vs 18/39; P<.001) and assessed trial quality (36/36 vs 12/39; P<.001). No Cochrane reviews had language restrictions (0/36 vs 7/39; P<.01). There were no differences in sources of trials, heterogeneity testing, or description of effect estimates. By June 1997, 18 of 36 Cochrane reviews had been updated vs 1 of 39 reviews listed in MEDLINE.Conclusions.—Cochrane reviews appear to have greater methodological rigor and are more frequently updated than systematic reviews or meta-analyses published in paper-based journals.

Does This Patient Have Deep Vein Thrombosis

Abstract: ContextOutpatients with suspected deep vein thrombosis (DVT) have nonspecific signs and symptoms. Missed DVT diagnosis may result in fatal pulmonary embolism. Since many patients may have DVT, a selective and efficient diagnostic process is needed.ObjectiveTo systematically review trials that determined the prevalence of DVT using clinical prediction rules either with or without D-dimer, for the diagnosis of DVT.Data SourcesEnglish- and French-language studies were identified from MEDLINE from 1990 to July 2004 and supplemented by a review of all relevant bibliographies.Study SelectionWe included studies that prospectively enrolled consecutive, unselected outpatients with suspected DVT and applied clinical prediction rules before D-dimer testing or diagnostic imaging. All studies included sufficient information to allow the calculation of the prevalence of DVT for at least 1 of the 3 clinical probability estimates (low, moderate, or high). We required that patients be followed up for a minimum 3-month period. Unless the clinical model incorporated prior DVT, studies were excluded if patients with a history of prior DVT were enrolled.Data ExtractionTwo reviewers independently reviewed and abstracted data for estimating the prevalence of DVT, sensitivity, specificity, and likelihood ratios (LRs) of D-dimer in each of the 3 clinical probability estimates. Data for the D-dimer in all studies were pooled and analyzed as high-sensitivity/low-specificity test or a moderate-sensitivity/moderate-specificity test.Data SynthesisFourteen studies involving more than 8000 patients used 1 clinical prediction rule for diagnosing DVT, of which 11 incorporated D-dimer testing in the diagnostic algorithm. The prevalence of DVT in the low, moderate, and high clinical probability groups was 5.0% (95% CI, 4.0%-8.0%), 17% (95% CI, 13%-23%), and 53% (95% CI, 44%-61%), respectively. The overall prevalence of DVT was 19% (95% CI, 16%-23%). Pooling all studies, the sensitivity, specificity, and negative LRs of D-dimer testing in the low probability group were 88% (95% CI, 81%-92%), 72% (95% CI, 65%-78%), and 0.18% (95% CI, 0.12-0.18); in the moderate probability group: 90% (95% CI, 80%-95%), 58% (95% CI, 49%-67%), and 0.19% (95% CI, 0.11-0.32); and in the high probability group: 92% (95% CI, 85%-96%), 45% (95% CI, 37%-52%), and 0.16% (95% CI, 0.09-0.30). The LRs for a normal result on a high or moderately sensitive D-dimer assay among patients with: (1) low clinical suspicion were 0.10 (95% CI, 0.03-0.37) and 0.20 (95% CI, 0.12-0.31); (2) moderate clinical suspicion were 0.05 (95% CI, 0.01-0.21) and 0.23 (95% CI, 0.13-0.39); and (3) high clinical suspicion were 0.07 (95% CI, 0.03-0.18) and 0.15 (95% CI, 0.10-0.38).ConclusionsDiagnostic accuracy for DVT improves when clinical probability is estimated before diagnostic tests. Patients with low clinical probability on the predictive rule have prevalence of DVT of less than 5%. In low-probability patients with negative D-dimer results, diagnosis of DVT can be excluded without ultrasound; in patients with high clinical suspicion for DVT, results should not affect clinical decisions.

Interpreting treatment effects in randomised trials

Abstract: The need to measure the impact of treatments on health related quality of life has led to a rapid increase in the variety of instruments available and in their use as measures of outcome in clinical trials. One limitation of instruments that purport to measure health related quality of life is difficulty interpreting their results. In the past decade, investigators have progressed in making these questionnaire results interpretable. For example, we have shown that when questionnaires present response options in the form of seven point scales with verbal descriptions for each option (see box), the smallest difference that patients consider important is often approximately 0.5 per question. A moderate difference corresponds to a change of approximately 1.0 per question, and changes of greater than 1.5 can be considered large. Thus, for example, in a domain with four items, patients will consider a 1 point change in two or more items as important. This finding applies across different areas of function, including dyspnoea, fatigue, and emotional function in patients with chronic airflow limitation1; and symptoms, emotional function, and activity limitations in adults2 and children3 with asthma, parents of children with asthma,4 and adults with rhinoconjunctivitis.5 Initially, we used comparisons in the same patient to establish this difference, but more recently we have replicated this finding using differences between patients.6 #### Summary points Several questionnaires on quality of life related to health are available, but interpreting their results may be difficult For some questionnaires, we now know that the smallest change in score that patients consider important is 0.5 Even if the mean difference between a treatment and a control is appreciably less than the smallest change that is important, treatment may have an important impact on many patients A method for estimating the proportion of patients who …

Health care contingent valuation studies : a review and classification of the literature

Abstract: Purpose: The contingent valuation method (CVM) is a survey-based approach for eliciting consumer's monetary valuations for programme benefits for use in cost-benefit analysis (CBA). We used the conceptual framework of O'Brien and Gafni (1996) to classify and critically appraise health care CVM studies. Methods: Search of computerized health care and economic citation databases (e.g. MEDLINE, ECONLIT) and manual search for papers published between 1984–1996 reporting primary data valuing health programme benefits in monetary units by CVM using willingness-to-pay (WTP) or accept (WTA). We classified studies using both empirical (i.e. who was surveyed and how) and conceptual criteria (i.e. which measure of consumer utility was measured and why). Results: 48 CVM studies were retrieved; the majority (42) undertook money valuation in the context of cost benefit analysis (CBA), with the remainder being pricing/demand studies. Among the 42 CBA studies, the consumer utility being measured (i.e. compensating (CV) vs. equivalent variation (EV) was explicitly stated in only three (7%) studies). WTP was measured in 95% of studies and WTA in 5%. By cross-tabulation, 42 (91%) studies were designed as WTP/CV, two (4%) were WTP/EV, two (4%) were WTA/CV and no studies used WTA/EV. Most studies were administered by mail (52%) with 38% being in-person interviews. Value elicitation techniques included open-ended questions (38%), payment cards (19%) discrete choice questions (26%) or bidding games (29%). Some form of construct validation tests, particularly associations between WTP and income, were done in 21 studies (50%). Conclusions: (i) The number of health care CVM studies is growing rapidly and the majority are done in the context of CBA; (ii) there is wide variation among health care CVM studies in terms of the types of questions being posed and the elicitation formats being used; (iii) classification and appraisal of the literature is difficult because reporting of methods and their relationship with the conceptual framework of CBA is poor; (iii) the applicability to health care of the CVM guidelines issued by the National Oceanic and Atmospheric Administration (NOAA) panel for environmental economics is unclear. © 1998 John Wiley & Sons, Ltd.

Critical appraisal of the health research literature: prevalence or incidence of a health problem.

Abstract: This article identifies and discusses criteria that can be used by health professionals to critically appraise research articles that estimate the prevalence or incidence of a disease or health problem. These guidelines will help determine the validity and usefulness of such community assessment studies. The criteria relate to the validity of the study methods (design, sampling frame, sample size, outcome measures, measurement and response rate), interpretation of the results and applicability of the findings. The research question "What is the prevalence of dementia in Canada?" is used as an example for this paper.

Muscle performance and enzymatic adaptations to sprint interval training

Abstract: Our purpose was to examine the effects of sprint interval training on muscle glycolytic and oxidative enzyme activity and exercise performance. Twelve healthy men (22 +/- 2 yr of age) underwent intense interval training on a cycle ergometer for 7 wk. Training consisted of 30-s maximum sprint efforts (Wingate protocol) interspersed by 2-4 min of recovery, performed three times per week. The program began with four intervals with 4 min of recovery per session in week 1 and progressed to 10 intervals with 2.5 min of recovery per session by week 7. Peak power output and total work over repeated maximal 30-s efforts and maximal oxygen consumption (VO2 max) were measured before and after the training program. Needle biopsies were taken from vastus lateralis of nine subjects before and after the program and assayed for the maximal activity of hexokinase, total glycogen phosphorylase, phosphofructokinase, lactate dehydrogenase, citrate synthase, succinate dehydrogenase, malate dehydrogenase, and 3-hydroxyacyl-CoA dehydrogenase. The training program resulted in significant increases in peak power output, total work over 30 s, and VO2 max. Maximal enzyme activity of hexokinase, phosphofructokinase, citrate synthase, succinate dehydrogenase, and malate dehydrogenase was also significantly (P < 0.05) higher after training. It was concluded that relatively brief but intense sprint training can result in an increase in both glycolytic and oxidative enzyme activity, maximum short-term power output, and VO2 max.

Synchronization of batch trajectories using dynamic time warping

Abstract: The application of dynamic time warping (DTW) to the analysis and monitoring of batch processes is presented. This dynamic-programming-based technique has been used in the area of speech recognition for the recognition of isolated and connected words. DTW has the ability to synchronize two trajectories by appropriately translating, expanding, and contracting localized segments within both trajectories to achieve a minimum distance between the trajectories. Batch processes often are characterized by unsynchronized trajectories, due to the presence of batch-to-batch disturbances and the existence of physical constraints. To compare these batch histories and apply statistical analysis one needs to reconcile the timing differences among these trajectories. This can be achieved using DTW with only a minimal amount of process knowledge. The combination of DTW and a monitoring method based on Multiway PCA/PLS is used for both off-line and on-line implementation. Data fiom an industrial polymerization reactor are used to illustrate the implementation and the performance of this method.