Showing papers by "McMaster University published in 2002"

Revisiting the Quantitative-Qualitative Debate: Implications for Mixed-Methods Research

Abstract: Health care research includes many studies that combine quantitative and qualitative methods. In this paper, we revisit the quantitative-qualitative debate and review the arguments for and against using mixed-methods. In addition, we discuss the implications stemming from our view, that the paradigms upon which the methods are based have a different view of reality and therefore a different view of the phenomenon under study. Because the two paradigms do not study the same phenomena, quantitative and qualitative methods cannot be combined for cross-validation or triangulation purposes. However, they can be combined for complementary purposes. Future standards for mixed-methods research should clearly reflect this recommendation.

Methods to explain the clinical significance of health status measures.

Abstract: One can classify ways to establish the interpretability of quality-of-life measures as anchor based or distribution based. Anchor-based measures require an independent standard or anchor that is itself interpretable and at least moderately correlated with the instrument being explored. One can further classify anchor-based approaches into population-focused and individual-focused measures. Population-focused approaches are analogous to construct validation and rely on multiple anchors that frame an individual's response in terms of the entire population (eg, a group of patients with a score of 40 has a mortality of 20%). Anchors for population-based approaches include status on a single item, diagnosis, symptoms, disease severity, and response to treatment. Individual-focused approaches are analogous to criterion validation. These methods, which rely on a single anchor and establish a minimum important difference in change in score, require 2 steps. The first step establishes the smallest change in score that patients consider, on average, to be important (the minimum important difference). The second step estimates the proportion of patients who have achieved that minimum important difference. Anchors for the individual-focused approach include global ratings of change within patients and global ratings of differences between patients. Distribution-based methods rely on expressing an effect in terms of the underlying distribution of results. Investigators may express effects in terms of between-person standard deviation units, within-person standard deviation units, and the standard error of measurement. No single approach to interpretability is perfect. Use of multiple strategies is likely to enhance the interpretability of any particular instrument.

Interventions to Enhance Patient Adherence to Medication Prescriptions

Abstract: ADHERENCE MAY BE DEFINED AS the extent to which a patient’s behavior (in terms of taking medication, following a diet, modifying habits, or attending clinics) coincides with medical or health advice. If a patient is prescribed an antibiotic for an infection to be taken as 1 tablet 4 times a day for a week but takes only 2 tablets a day for 5 days, the adherence would be 36% (10/28). The term adherence is intended to be nonjudgmental, a statement of fact rather than of blame of the prescriber, patient, or treatment. Compliance and concordance are synonyms for adherence. This simple definition of adherence belies the difficulties that many medical regimens present for patients. For example, the regimen described for type 2 diabetes mellitus in a previous article includes a special diet, increased exercise, smoking cessation, oral hypoglycemic drugs, and risk factor management, usually involving additional drugs. Such regimens fulfill theoretical, physiological, and empirical considerations about optimal care, while ignoring practical patient-centered concerns, such as the nature, nurture, culture, and stereotyping of the patient, and the inconvenience, cost, and adverse effects of the treatment. Indeed, low adherence with prescribed treatments is very common. Typical adherence rates for prescribed medications are about 50% with a range of 0% to more than 100%.

Interventions to enhance patient adherence to medication prescriptions: scientific review.

Abstract: ContextLow adherence with prescribed treatments is ubiquitous and undermines treatment benefits.ObjectiveTo systematically review published randomized controlled trials (RCTs) of interventions to assist patients' adherence to prescribed medications.Data SourcesA search of MEDLINE, CINAHL, PSYCHLIT, SOCIOFILE, IPA, EMBASE, The Cochrane Library databases, and bibliographies was performed for records from 1967 through August 2001 to identify relevant articles of all RCTs of interventions intended to improve adherence to self-administered medications.Study Selection and Data ExtractionStudies were included if they reported an unconfounded RCT of an intervention to improve adherence with prescribed medications for a medical or psychiatric disorder; both adherence and treatment outcome were measured; follow-up of at least 80% of each study group was reported; and the duration of follow-up for studies with positive initial findings was at least 6 months. Information on study design features, interventions, controls, and findings (adherence rates and patient outcomes) were extracted for each article.Data SynthesisStudies were too disparate to warrant meta-analysis. Forty-nine percent of the interventions tested (19 of 39 in 33 studies) were associated with statistically significant increases in medication adherence and only 17 reported statistically significant improvements in treatment outcomes. Almost all the interventions that were effective for long-term care were complex, including combinations of more convenient care, information, counseling, reminders, self-monitoring, reinforcement, family therapy, and other forms of additional supervision or attention. Even the most effective interventions had modest effects.ConclusionsCurrent methods of improving medication adherence for chronic health problems are mostly complex, labor-intensive, and not predictably effective. The full benefits of medications cannot be realized at currently achievable levels of adherence; therefore, more studies of innovative approaches to assist patients to follow prescriptions for medications are needed.

Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement

Abstract: Background The Quality of Reporting of Meta-analyses (QUOROM) conference was convened to address standards for improving the quality of reporting of meta-analyses of clinical randomised controlled trials (RCTs). Methods The QUOROM group consisted of 30 clinical epidemiologists, clinicians, statisticians, editors, and researchers. In conference, the group was asked to identify items they thought should be included in a checklist of standards. Whenever possible, checklist items were guided by research evidence suggesting that failure to adhere to the item proposed could lead to biased results. A modified Delphi technique was used in assessing candidate items. Findings The conference resulted in the QUOROM statement, a checklist, and a flow diagram. The checklist describes our preferred way to present the abstract, introduction, methods, results, and discussion sections of a report of a meta-analysis. It is organised into 21 headings and subheadings regarding searches, selection, validity assessment, data abstraction, study characteristics, and quantitative data synthesis, and in the results with ‘trial flow’, study characteristics, and quantitative data synthesis; research documentation was identified for eight of the 18 items. The flow diagram provides information about both the numbers of RCTs identified, included, and excluded and the reasons for exclusion of trials. Interpretation We hope this report will generate further thought about ways to improve the quality of reports of meta-analyses of RCTs and that interested readers, reviewers, researchers, and editors will use the QUOROM statement and generate ideas for its improvement. © 2000 British Journal of Surgery Society Ltd

Managing An Organizational Learning System By Aligning Stocks and Flows

Abstract: This paper considers the relationship between the stocks and flows of learning across levels in an overall organizational learning system. A survey instrument based on the Strategic Learning Assessment Map (SLAM) was administered to 15 individuals representing senior-, middle- and non-management levels from each of 32 organizations, resulting in a total sample of 480 respondents. This research supports the premise that there is a positive relationship between the stocks of learning at all levels and business performance. Furthermore, the proposition that the misalignment of stocks and flows in an overall organizational learning system is negatively associated with business performance is also supported.

Prognosis for gross motor function in cerebral palsy: creation of motor development curves.

Abstract: ContextLack of a valid classification of severity of cerebral palsy and the absence of longitudinal data on which to base an opinion have made it difficult to consider prognostic issues accurately.ObjectiveTo describe patterns of gross motor development of children with cerebral palsy by severity, using longitudinal observations, as a basis for prognostic counseling with parents and for planning clinical management.DesignLongitudinal cohort study of children with cerebral palsy, stratified by age and severity of motor function and observed serially for up to 4 years during the period from 1996 to 2001.SettingNineteen publicly funded regional children's ambulatory rehabilitation programs in Ontario.ParticipantsA total of 657 children aged 1 to 13 years at study onset, representing the full spectrum of clinical severity of motor impairment in children with cerebral palsy.Main Outcome MeasuresSeverity of cerebral palsy, classified with the 5-level Gross Motor Function Classification System; function, formally assessed with the Gross Motor Function Measure (GMFM).ResultsBased on a total of 2632 GMFM assessments, 5 distinct motor development curves were created; these describe important and significant differences in the rates and limits of gross motor development among children with cerebral palsy by severity. There is substantial within-stratum variation in gross motor development.ConclusionsEvidence-based prognostication about gross motor progress in children with cerebral palsy is now possible, providing parents and clinicians with a means to plan interventions and to judge progress over time. Further work is needed to describe motor function of adolescents with cerebral palsy.

Interventions for helping patients to follow prescriptions for medications

Abstract: Background People who are prescribed self-administered medications typically take less than half the prescribed doses. Efforts to assist patients with adherence to medications might improve the benefits and efficiency of health care, but also might increase its adverse effects. Objectives To update a review summarising the results of randomised controlled trials (RCTs) of interventions to help patients follow prescriptions for medications for medical problems, focusing on trials that measured both adherence and clinical outcomes. Search strategy Computerised searches to August 2001 in MEDLINE, CINAHL, The Cochrane Library, International Pharmaceutical Abstracts (IPA) PsychInfo, and Sociofile; bibliographies in articles on patient adherence; articles in the reviewers' personal collections; and contact with authors of original and review articles on the topic. Selection criteria Articles were selected if they reported an unconfounded RCT of an intervention to improve adherence with prescribed medications, measuring both medication adherence and treatment outcome, with at least 80% follow-up of each group studied and, for long-term treatments, at least six months follow-up for studies with positive initial findings. Data collection and analysis Information on study design features, interventions and controls, and results were extracted by one reviewer and confirmed by at least one other reviewer. The studies were too disparate to warrant meta-analysis. Main results For short-term treatments, one of three interventions reported in three RCTs showed an effect on both adherence and clinical outcome. Eighteen of 36 interventions for long-term treatments reported in 30 RCTs were associated with improvements in adherence, but only 16 interventions led to improvements in treatment outcomes. Almost all of the interventions that were effective for long-term care were complex, including combinations of more convenient care, information, reminders, self-monitoring, reinforcement, counselling, family therapy, and other forms of additional supervision or attention by a health care provider (physician, nurse, pharmacist or other). Even the most effective interventions did not lead to large improvements in adherence and treatment outcomes. Two studies showed that telling patients about adverse effects of treatment did not affect their adherence. Authors' conclusions The full benefits of medications cannot be realised at currently achievable levels of adherence. Current methods of improving adherence for chronic health problems are mostly complex and not very effective. Innovations to assist patients to follow medication prescriptions are needed.

Participation in the occupations of everyday life.

Abstract: Participation or involvement in everyday occupations is vital for all humans. As described by the World Health Organization, participation has a positive influence on health and well-being. The presence of disability has been found to lead to participation that is less diverse, is located more in the home, involves fewer social relationships, and includes less active recreation. Occupational therapy is in a unique position to contribute to the development and fulfillment of participation for persons with and without disabilities. This article describes the nature and outcomes of participation. Characteristics to define and measure meaningful participation are outlined. Information about time use will help to develop an understanding of patterns of participation across locations, gender, culture, and the life span. Factors that affect participation within the environment, family, and persons are summarized. Occupational therapy research is needed to examine the complex relationship among person, environment, and participation in occupations. In practice and education, knowledge about participation can enhance the client-centered and evidence-based nature of occupational therapy services.

Helping Patients Follow Prescribed Treatment: Clinical Applications

Abstract: Low adherence to prescribed medical regimens is a ubiquitous problem. Typical adherence rates are about 50% for medications and are much lower for lifestyle prescriptions and other more behaviorally demanding regimens. In addition, many patients with medical problems do not seek care or drop out of care prematurely. Although accurate measures of low adherence are lacking for many regimens, simple measures, such as directly asking patients and watching for appointment nonattendance and treatment nonresponse, will detect most problems. For short-term regimens (≤2 weeks), adherence to medications is readily achieved by giving clear instructions. On the other hand, improving adherence to long-term regimens requires combinations of information about the regimen, counseling about the importance of adherence and how to organize medication taking, reminders about appointments and adherence, rewards and recognition for the patient's efforts to follow the regimen, and enlisting social support from family and friends. Successful interventions for long-term regimens are all labor-intensive but ultimately can be cost-effective.

Preferential transformation of human neuronal cells by human adenoviruses and the origin of HEK 293 cells.

Abstract: The 293 cell line was derived by transformation of primary cultures of human embryonic kidney (HEK) cells with sheared adenovirus (Ad)5 DNA. A combination of immunostaining, immunoblot, and microarray analysis showed that 293 cells express the neurofilament (NF) subunits NF-L, NF-M, NF-H, and a-internexin as well as many other proteins typically found in neurons. Three other independently derived HEK lines, two transformed by Ad5 and one by Ad12, also expressed NFs, as did one human embryonic retinal cell line transformed with Ad5. Two rodent kidney lines transformed with Ad12 were also found to express NF proteins, although several rodent kidney cell lines transformed by Ad5 DNA and three HEK cell lines transformed by the SV40 early region did not express NFs. These results suggest that human Ads preferentially transform human neuronal lineage cells. We also demonstrate that the widely used HEK293 cells have an unexpected relationship to neurons, a finding that may require reinterpretation of many previous studies in which it was assumed that HEK293 cells resembled more typical kidney epithelial cells.

Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update

Abstract: Cardiac surgery with cardiopulmonary bypass (CPB) induces an acute phase reaction that has been implicated in the pathogenesis of several postoperative complications. Recent data indicate that a complex sequence of events leads to the final activation of leukocytes and endothelial cells (EC), which is responsible for cell dysfunction in different organs. Activation of the contact system, endotoxemia, ischemia and reperfusion injury and surgical trauma are all potential triggers of inflammation following CPB. Different pro- and anti-inflammatory mediators (cytokines, adhesion molecules) are involved and their release is mediated by intracellular transcription factors (nuclear factor-kappa B, NF-kappa B). In this review, we examine recent advances in the understanding of the pathophysiology of the CPB-induced acute phase reaction and evaluate the different pharmacological, technical and surgical strategies used to reduce its effects. Emphasis is given to the central role of transcription factor NF-kappa B in the complex mechanism of the inflammatory reaction and to the effects of compounds such as heparin and glycosaminoglycans, phosphodiesterase inhibitors and protease inhibitors whose role as anti-inflammatory agent has only recently been recognized.

Intellectual capital ROI: a causal map of human capital antecedents and consequents

Abstract: This report describes the results of a ground‐breaking research study that measured the antecedents and consequents of effective human capital management. The research sample consisted of 76 senior executives from 25 companies in the financial services industry. The results of the study yielded a holistic causal map that integrated constructs from the fields of intellectual capital, knowledge management, human resources, organizational behaviour, information technology and accounting. The integration of both quantitative and qualitative measures in an overall conceptual model yielded several research implications. The resulting structural equation model allows participating organizations and researchers to gauge the effectiveness of an organization’s human capital capabilities. This will allow practitioners and researchers to more efficiently allocate resources with regard to human capital management. The potential outcomes of the study are limitless, since a program of consistent re‐evaluation can lead to the establishment of causal relationships between human capital management and economic and business results.

The biotic ligand model : a historical overview

Abstract: During recent years, the biotic ligand model (BLM) has been proposed as a tool to evaluate quantitatively the manner in which water chemistry affects the speciation and biological availability of metals in aquatic systems. This is an important consideration because it is the bioavailability and bioreactivity of metals that control their potential to cause adverse effects. The BLM approach has gained widespread interest amongst the scientific, regulated and regulatory communities because of its potential for use in developing water quality criteria (WQC) and in performing aquatic risk assessments for metals. Specifically, the BLM does this in a way that considers the important influences of site-specific water quality. This journal issue includes papers that describe recent advances with regard to the development of the BLM approach. Here, the current status of the BLM development effort is described in the context of the longer-term history of advances in the understanding of metal interactions in the environment upon which the BLM is based. Early developments in the aquatic chemistry of metals, the physiology of aquatic organisms and aquatic toxicology are reviewed first, and the degree to which each of these disciplines influenced the development of water quality regulations is discussed. The early scientific advances that took place in each of these fields were not well coordinated, making it difficult for regulatory authorities to take full advantage of the potential utility of what had been learned. However, this has now changed, with the BLM serving as a useful interface amongst these scientific disciplines, and within the regulatory arena as well. The more recent events that have led to the present situation are reviewed, and consideration is given to some of the future needs and developments related to the BLM that are envisioned. The research results that are described in the papers found in this journal issue represent a distinct milestone in the ongoing evolution of the BLM approach and, more generally, of approaches to performing ecological assessments for metals in aquatic systems. These papers also establish a benchmark to which future scientific and regulatory developments can be compared. Finally, they demonstrate the importance and usefulness of the concept of bioavailability and of evaluative tools such as the BLM.

A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer

Abstract: Background Esophagectomy is a standard treatment for resectable esophageal cancer but relatively few patients are cured. Combining neoadjuvant chemoradiation with surgery may improve survival but treatment morbidity is a concern. We performed a meta-analysis of randomized controlled trials (RCTs) that compared the use of neoadjuvant chemoradiation and surgery with the use of surgery alone for esophageal cancer. Methods Medline and manual searches were done to identify all published RCTs that compared neoadjuvant chemoradiation and surgery with surgery alone for esophageal cancer. A random-effects model was used and the odds ratio (OR) was the principal measure of effect. Systematic quantitative review was done for outcomes unique to the neoadjuvant chemoradiation treatment group, such as pathological complete response. Results Nine RCTs that included 1,116 patients were selected with quality scores ranging from 1 to 3 (5-point Jadad scale). Odds ratio (95% confidence interval [CI]; P value), expressed as chemoradiation and surgery versus surgery alone (treatment versus control; values Conclusions Compared with surgery alone, neoadjuvant chemoradiation and surgery improved 3-year survival and reduced local-regional cancer recurrence. It was associated with a lower rate of esophageal resection, but a higher rate of complete (R0) resection. There was a nonsignificant trend toward increased treatment mortality with neoadjuvant chemoradiation. Concurrent administration of neoadjuvant chemotherapy and radiotherapy was superior to sequential chemoradiation treatment scheduling.

The architecture of diagnostic research

Abstract: This is the second in a series of five articles Considerable effort has been expended at the interface between clinical medicine and scientific methods to achieve the maximum validity and usefulness of diagnostic tests. This article focuses on the specific kinds of questions that arise in diagnostic research and the study architectures (the conversions of these clinical questions into appropriate research designs) used to answer them. As an example we shall take shall take assessment of the value of the plasma concentration of B-type natriuretic peptide (BNP) in the diagnosis of left ventricular dysfunction.1 Randomised controlled trials are dealt with elsewhere. As in other forms of clinical research, there are several different ways studying the potential or real diagnostic value of a physical sign or laboratory test, and each is appropriate to one kind of question and inappropriate for others. Among the possible questions about the relation between a putative diagnostic test and a target disorder (for example, the concentration of BNP and left ventricular dysfunction), four are most relevant. #### Summary points Diagnostic studies should match methods to diagnostic questions The keys to validity in diagnostic test studies are Both specificity and sensitivity may change as the same diagnostic test is applied in primary, …

Myogenic specification of side population cells in skeletal muscle.

Abstract: Skeletal muscle contains myogenic progenitors called satellite cells and muscle-derived stem cells that have been suggested to be pluripotent. We further investigated the differentiation potential of muscle-derived stem cells and satellite cells to elucidate relationships between these two populations of cells. FACS® analysis of muscle side population (SP) cells, a fraction of muscle-derived stem cells, revealed expression of hematopoietic stem cell marker Sca-1 but did not reveal expression of any satellite cell markers. Muscle SP cells were greatly enriched for cells competent to form hematopoietic colonies. Moreover, muscle SP cells with hematopoietic potential were CD45 positive. However, muscle SP cells did not differentiate into myocytes in vitro. By contrast, satellite cells gave rise to myocytes but did not express Sca-1 or CD45 and never formed hematopoietic colonies. Importantly, muscle SP cells exhibited the potential to give rise to both myocytes and satellite cells after intramuscular transplantation. In addition, muscle SP cells underwent myogenic specification after co-culture with myoblasts. Co-culture with myoblasts or forced expression of MyoD also induced muscle differentiation of muscle SP cells prepared from mice lacking Pax7 gene, an essential gene for satellite cell development. Therefore, these data document that satellite cells and muscle-derived stem cells represent distinct populations and demonstrate that muscle-derived stem cells have the potential to give rise to myogenic cells via a myocyte-mediated inductive interaction.

De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases.

Abstract: Objective Neonatal-onset multisystem inflammatory disease (NOMID; also known as chronic infantile neurologic, cutaneous, articular [CINCA] syndrome) is characterized by fever, chronic meningitis, uveitis, sensorineural hearing loss, urticarial skin rash, and a characteristic deforming arthropathy. We investigated whether patients with this disorder have mutations in CIAS1, the gene which causes Muckle-Wells syndrome and familial cold autoinflammatory syndrome, two dominantly inherited disorders with some similarities to NOMID/CINCA syndrome. Methods Genomic DNA from 13 patients with classic manifestations of NOMID/CINCA syndrome and their available parents was screened for CIAS1 mutations by automated DNA sequencing. Cytokine messenger RNA (mRNA) levels were assessed by real-time polymerase chain reaction on peripheral blood leukocyte mRNA, and serum cytokine levels were assayed by enzyme-linked immunosorbent assay. Protein expression was assessed by Western blotting of lysates from plastic-adherent peripheral blood mononuclear cells. Results In 6 of the 13 patients, we found 6 heterozygous missense substitutions in CIAS1. Five of the 6 mutations are novel. None of these sequence changes was observed in a panel of >900 chromosomes from healthy controls. Two distinct nucleotide changes in a single codon in unrelated patients resulted in the same amino acid change. In 4 mutation-positive children whose parental DNA was available, no mutation was found in the parental DNA, supporting the conclusion that the mutations arose de novo. Consistent with the recently discovered role of CIAS1 in the regulation of interleukin-1 (IL-1), we found evidence of increased IL-1β, as well as tumor necrosis factor, IL-3, IL-5, and IL-6, but not transforming growth factor β, in a mutation-positive patient compared with normal controls. Conclusion Our data increase the total number of known germline mutations in CIAS1 to 20, causing a spectrum of diseases ranging from familial cold autoinflammatory syndrome to Muckle-Wells syndrome to NOMID/CINCA syndrome. Mutations in CIAS1 were only found in ∼50% of the cases identified clinically as NOMID/CINCA syndrome, which raises the possibility of genetic heterogeneity. IL-1 regulation by CIAS1 suggests that IL-1 receptor blockade may constitute a rational approach to the treatment of NOMID/CINCA syndrome.

Postactivation potentiation: role in human performance.

Abstract: Postactivation potentiation (PAP) is the transient increase in muscle contractile performance after previous contractile activity. This review describes the features and mechanism of PAP, assesses its potential role in endurance and strength/speed performance, considers strategies for exploiting PAP, and outlines how PAP might be affected by training.

Cutover peatlands: A persistent source of atmospheric CO2

Abstract: [i] Peatlands represent an important component of the global carbon cycle, storing 23 g C m -2 yr -1 . Peatland mining eliminates the carbon sink function of the peatland. In this paper we measure the total ecosystem respiration in a natural, 2 and 3 year (young) and 7 and 8 year (old) postcutover peatland near Sainte-Marguerite-Marie, Quebec, during the summers of 1998 and 1999. Although the natural site was a source of CO 2 during the dry 1998 study season (138 g C m -2 ), CO 2 emissions were between 260 and 290% higher in the cutover sites (363 and 399 g C m -2 for young and old, respectively). Cutover site CO 2 emissions were only 88 and 112 g CO 2 .C m -2 at the young and old sites during the wet 1999 study season. Total ecosystem respiration was more dependent on the water table position than on changes in the thermal regime or the labile carbon of the peat in a dry summer, but the opposite was the case in a wet summer. CO 2 emissions increased with postharvest time regardless of a decrease in labile carbon, demonstrating that cutover peatlands are a large persistent source of atmospheric CO 2 . Direct measurement of the net ecosystem CO 2 exchange in cutover peatlands, as opposed to determining the loss of carbon from bulk density determinations, provides a better understanding of how peat drainage and harvesting operations affect the carbon balance in peatlands.

Configural Face Processing Develops more Slowly than Featural Face Processing

Abstract: Expertise in face processing takes many years to develop. To determine the contribution of different face-processing skills to this slow development, we altered a single face so as to create sets of faces designed to measure featural, configural, and contour processing. Within each set, faces differed only in the shape of the eyes and mouth (featural set), only in the spacing of the eyes and mouth (spacing set), or only in the shape of the external contour (contour set). We presented adults, and children aged 6, 8, and 10 years, with pairs of upright and inverted faces and instructed them to indicate whether the two faces were the same or different. Adults showed a larger inversion effect for the spacing set than for the featural and external contour sets, confirming that the spacing set taps configural processing. On the spacing set, all groups of children made more errors than adults. In contrast, on the external contour and featural sets, children at all ages were almost as accurate as adults, with no significant difference beginning at age 6 on the external contour set and beginning at age 10 on the featural set. Overall, the results indicate that adult expertise in configural processing is especially slow to develop.

Properties of the summary receiver operating characteristic (SROC) curve for diagnostic test data.

Abstract: The summary receiver operating characteristic (SROC) curve has been recommended to represent the performance of a diagnostic test, based on data from a meta-analysis. However, little is known about the basic properties of the SROC curve or its estimate. In this paper, the position of the SROC curve is characterized in terms of the overall diagnostic odds ratio and the magnitude of inter-study heterogeneity in the odds ratio. The area under the curve (AUC) and an index Q(*) are discussed as potentially useful summaries of the curve. It is shown that AUC is maximized when the study odds ratios are homogeneous, and that it is quite robust to heterogeneity. An upper bound is derived for AUC based on an exact analytic expression for the homogeneous situation, and a lower bound based on the limit case Q(*), defined by the point where sensitivity equals specificity: Q(*) is invariant to heterogeneity. The standard error of AUC is derived for homogeneous studies, and shown to be a reasonable approximation with heterogeneous studies. The expressions for AUC and its standard error are easily computed in the homogeneous case, and avoid the need for numerical integration in the more general case. SE(AUC) and SE(Q(*)) are found to be numerically close, with SE(Q(*)) being larger if the odds ratio is very large. The methods are illustrated using data for the Pap smear screening test for cervical cancer, and for three tests for the diagnosis of metastases in cervical cancer patients.

Significant variability in response to inhaled corticosteroids for persistent asthma

Abstract: Background: A clinical model is needed to compare inhaled corticosteroids (ICSs) with respect to efficacy. Objective: The purpose of this investigation was to compare the relative beneficial and systemic effects in a dose-response relationship for 2 ICSs. Methods: A 24-week, parallel, open-label, multicenter trial examined the benefit-risk ratio of 2 ICSs in persistent asthma. Benefit was assessed by improvements in FEV 1 and PC 20 ; risk was assessed by overnight plasma cortisol suppression. Thirty subjects were randomized to either beclomethasone dipropionate (BDP) 168, 672, and 1344 μg/day (n = 15) or fluticasone propionate (FP) 88, 352, and 704 μg/day (n = 15), both administered by means of a metered dose inhaler (MDI) with chlorofluorocarbon propellant via a spacer, in 3 consecutive 6-week intervals; this was followed by 3 weeks of FP dry powder inhaler (DPI) 2000 μg/day. Results: Maximum FEV 1 response occurred with the low dose for FP-MDI and the medium dose for BDP-MDI and was not further increased by treatment with FP-DPI. Near-maximum methacholine PC 20 improvement occurred with the low dose for FP-MDI and the medium dose for BDP-MDI. Both BDP-MDI and FP-MDI caused dose-dependent cortisol suppression. Responsiveness to ICS treatment was found to vary markedly among subjects. Good (>15%) FEV 1 response, in contrast to poor ( 1 /forced vital capacity ratio (0.63 vs 0.73) before treatment. Excellent (>3 doubling dilutions) improvement in PC 20 , in contrast to poor ( Conclusions: Near-maximal FEV 1 and PC 20 effects occurred with low-medium dose for both ICSs in the subjects studied. High-dose ICS therapy did not significantly increase the efficacy measures that were evaluated, but it did increase the systemic effect measure, overnight cortisol secretion. Significant intersubject variability in response occurred with both ICSs. It is possible that higher doses of ICSs are necessary to manage more severe patients or to achieve goals of therapy not evaluated in this study, such as prevention of asthma exacerbations. (J Allergy Clin Immunol 2002;109:410-8.)

Readiness for organizational change: A longitudinal study of workplace, psychological and behavioural correlates

Abstract: To examine factors influencing readiness for healthcare organizational change, 654 randomly selected hospital staff completed questionnaires measuring the logistical and occupational risks of change, ability to cope with change and to solve jobrelated problems, social support, measures of Karasek's (1979) active vs. passive job construct (job demand× decision latitude) and readiness for organizational change. Workers in active jobs (Karasek, 1979) which afforded higher decision latitude and control over challenging tasks reported a higher readiness for organizational change scores. Workers with an active approach to job problem-solving with higher job change self-efficacy scores reported a higher readiness for change. In hierarchical regression analyses, active jobs, an active job problem-solving style and job-change self-efficacy contributed independently to the prediction of readiness for organizational change. Time 1 readiness for organizational change scores and an active approach to job problem-solving were the best predictors of participation in redesign activities during a year-long re-engineering programme.