Showing papers by "McMaster University published in 1995"

American college of rheumatology preliminary definition of improvement in rheumatoid arthritis

Abstract: Objective. Trials of rheumatoid arthritis (RA) treatments report the average response in multiple outcome measures for treated patients. It is more clinically relevant to test whether individual patients improve with treatment, and this identifies a single primary efficacy measure. Multiple definitions of improvement are currently in use in different trials. The goal of this study was to promulgate a single definition for use in RA trials. Methods. Using the American College of Rheumatology (ACR) core set of outcome measures for RA trials, we tested 40 different definitions of improvement, using a 3-step process. First, we performed a survey of rheumatologists, using actual patient cases from trials, to evaluate which definitions corresponded best to rheumatologists' impressions of improvement, eliminating most candidate definitions of improvement. Second, we tested 20 remaining definitions to determine which maximally discriminated effective treatment from placebo treatment and also minimized placebo response rates. With 8 candidate definitions of improvement remaining, we tested to see which were easiest to use and were best in accord with rheumatologists' impressions of improvement. Results. The following definition of improvement was selected: 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: patient and physician global assessments, pain, disability, and an acutephase reactant. Additional validation of this definition was carried out in a comparative trial, and the results suggest that the definition is statistically powerful and does not identify a large percentage of placebo-treated patients as being improved. Conclusion. We present a definition of improvement which we hope will be used widely in RA trials.

Heparin-Induced Thrombocytopenia in Patients Treated with Low-Molecular-Weight Heparin or Unfractionated Heparin

Abstract: Background Heparin-induced thrombocytopenia, defined by the presence of heparin-dependent IgG antibodies, typically occurs five or more days after the start of heparin therapy and can be complicated by thrombotic events. The frequency of heparin-induced thrombocytopenia and of heparin-dependent IgG antibodies, as well as the relative risk of each in patients given low-molecular-weight heparin, is unknown. Methods We obtained daily platelet counts in 665 patients in a randomized, double-blind clinical trial comparing unfractionated heparin with low-molecular-weight heparin as prophylaxis after hip surgery. Heparin-induced thrombocytopenia was defined as a decrease in the platelet count below 150,000 per cubic millimeter that began five or more days after the start of heparin therapy, and a positive test for heparin-dependent IgG antibodies. We also tested a representative subgroup of 387 patients for heparin-dependent IgG antibodies regardless of their platelet counts. Results Heparin-induced thrombocytope...

Multivariate SPC charts for monitoring batch processes

Abstract: The problem of using time-varying trajectory data measured on many process variables over the finite duration of a batch process is considered. Multiway principal-component analysis is used to compress the information contained in the data trajectories into low-dimensional spaces that describe the operation of past batches. This approach facilitates the analysis of operational and quality-control problems in past batches and allows for the development of multivariate statistical process control charts for on-line monitoring of the progress of new batches. Control limits for the proposed charts are developed using information from the historical reference distribution of past successful batches. The method is applied to data collected from an industrial batch polymerization reactor.

W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity

Abstract: The pacemaker activity in the mammalian gut is responsible for generating anally propagating phasic contractions. The cellular basis for this intrinsic activity is unknown. The smooth muscle cells of the external muscle layers and the innervated cellular network of interstitial cells of Cajal, which is closely associated with the external muscle layers of the mammalian gut, have both been proposed to stimulate pacemaker activity. The interstitial cells of Cajal were identified in the last century but their developmental origin and function have remained unclear. Here we show that the interstitial cells of Cajal express the Kit receptor tyrosine kinase. Furthermore, mice with mutations in the dominant white spotting (W) locus, which have cellular defects in haematopoiesis, melanogenesis and gametogenesis as a result of mutations in the Kit gene, also lack the network of interstitial cells of Cajal associated with Auerbach's nerve plexus and intestinal pacemaker activity.

Herpes simplex virus turns off the TAP to evade host immunity

Abstract: Many viruses have evolved mechanisms to avoid detection by the host immune system. Herpes simplex virus (HSV) expresses an immediate early protein, ICP47, which blocks presentation of viral peptides to MHC class I-restricted cells. The properties of the newly synthesized class I molecules in HSV-infected cells resemble those of cell lines deficient in the transporter associated with antigen processing (TAP) in that class I molecules are retained in the endoplasmic reticulum, and the heavy chain and beta 2-microglobulin subunits dissociate in detergent extracts but the complex can be stabilized by peptides. We show here that ICP47 binds to TAP and prevents peptide translocation into the endoplasmic reticulum.

Methotrexate for the Treatment of Crohn's Disease

Abstract: Background Although corticosteroids are highly effective in improving symptoms of Crohn's disease, they may have substantial toxicity. In some patients, attempts to discontinue corticosteroids are ...

Users' Guides to the Medical Literature: IX. A Method for Grading Health Care Recommendations

Abstract: THE ULTIMATE PURPOSE of applied health research is to improve health care. Summarizing the literature to adduce recommendations for clinical practice is an important part of the process. Recently, the health sciences community has reduced the bias and imprecision of traditional literature summaries and their associated recommendations through the development of rigorous criteria for both literature overviews 1-3 and practice guidelines. 4,5 Even when recommendations come from such rigorous approaches, however, it is important to differentiate between those based on weak vs strong evidence. Recommendations based on inadequate evidence often require reversal when sufficient data become available, 6 while timely implementation of recommendations based on strong evidence can save lives. 6 In this article, we suggest an approach to classifying strength of recommendations. We direct our discussion primarily at clinicians who make treatment recommendations that they hope their colleagues will follow. However, we believe that any clinician who attends to

Multi-attribute health status classification systems. Health Utilities Index.

Abstract: In this article, multi-attribute approaches to the assessment of health status are reviewed with a special focus on 2 recently developed systems, the Health Utilities Index (HUI) Mark II and Mark III systems. The Mark II system consists of 7 attributes: sensation, mobility, emotion, cognition, self-care, pain and fertility. The Mark III system contains 8 attributes: vision, hearing, speech, ambulation, dexterity, emotion, cognition and pain. Each attribute consists of multiple levels of functioning. A combination of levels across the attributes constitutes a health state. The HUI systems are deliberately focused on the fundamental core attributes of health status, and on the capacity of individuals to function with respect to these attributes. Thus, the measure obtained constitutes a pure description of health status, uncontaminated by differential opportunity or preference. Multi-attribute systems provide a compact but comprehensive framework for describing health status for use in population health and programme evaluation studies. An important advantage of such systems is their ability to simultaneously provide detail on an attribute-by-attribute basis and to capture combinations of deficits among attributes. An additional advantage is their compatibility with multi-attribute preference functions, which provide a method for computing a summary health-related quality-of-life score for each health state.

Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of the literature.

Abstract: ObjectiveTo determine the effect of corticosteroid therapy on morbidity and mortality in patients with sepsis.Data SourcesWe searched for published and unpublished research using MEDLINE, EMBASE, and the Science Citation Index, manual searching of Index Medicus, citation review of relevant primary a

Neonatal thrombosis: report of a prospective Canadian and international registry.

Abstract: Objective. We sought to obtain representative data on the risk factors, diagnosis, current management, and short-term outcome of neonatal thrombosis. Research Design. A case registry was established at McMaster University. Standardized questionnaires were mailed to collaborators at participating centers every 4 to 6 months. Setting. Eighty-five level III and modified level II neonatal units in North America, Europe, and Australia were invited to join the registry. Patients. Eligible infants were born between January 1990 and June 1993. Large-vessel thrombosis was diagnosed during the first month of life or up to 44 weeks post-conception after premature birth. The clinical impression of thrombotic vessel obstruction was confirmed using at least one imaging technique. Results. Physicians in 64 centers expressed their willingness to participate. A total of 97 cases (excluding stroke) were registered from 29 centers. Spontaneous renal venous thrombosis (n = 21) was diagnosed at a median age of 2 days. The other venous (n = 39), arterial (n = 33), and mixed (n = 4) thromboses presented later; 89% of them were associated with an intravascular catheter and 29% with systemic infection. Doppler ultrasonography was the definitive diagnostic test in 68% of cases; contrast angiography was performed infrequently (14%). A third of all patients (but 62% of infants with renal venous thrombosis) received supportive therapy only. Thrombolytic agents were prescribed for 28% of catheter-associated venous thromboses and 30% of all arterial thromboses. The remainder of the patients were given heparin. Most patients (82%) survived to hospital discharge. Mortality rates were highest among infants with aortic thrombosis or central venous line-associated thrombosis affecting the right atrium or the superior vena cava (33%). Conclusions. Neonatal thrombosis is diagnosed fairly rarely. With the exception of spontaneous renal venous thrombosis, almost all cases are associated with indwelling catheters. Doppler ultrasound techniques are the most popular means of confirming the diagnosis in virtually all centers. Treatment varies greatly among different centers, probably because of the lack of scientific evidence about the optimum management of affected infants.

Multi-attribute preference functions. Health Utilities Index.

Abstract: SummaryMulti-attribute utility theory. an extension of conventional utility theory, can be applied to model preference scores for health slates defined by multi-attribute health status classification systems. The type of preference independence among the attributes determines the type of preference function required: additive, multiplicative or multilinear. In addition, the type of measurement instrument used determines the type of preference score obtained: value or utility.

Methods for construction of adenovirus vectors.

Abstract: Adenoviruses are attracting increasing attention as general purpose mammalian cell expression vectors, as recombinant vaccines, and potentially as vectors for gene therapy. Not only is the adenovirus genome relatively easy to manipulate by recombinant DNA techniques, but adenovirus vectors are relatively stable, grow to high titers, and can transduce a variety of cell types in cell culture and in vivo. Vectors can be designed that are either replication competent or replication defective and, in the latter case, are highly efficient at delivering and expressing genes in mammalian cells without resulting in cell killing. Methods are described for growing, titrating, and purifying adenoviruses, for extracting viral DNA from purified virions and from infected cells, for rescuing inserts of foreign DNA into the viral genome, and for assessing expression of inserted genes in adenovirus vectors.

The chirplet transform: physical considerations

Abstract: We consider a multidimensional parameter space formed by inner products of a parameterizable family of chirp functions with a signal under analysis. We propose the use of quadratic chirp functions (which we will call q-chirps for short), giving rise to a parameter space that includes both the time-frequency plane and the time-scale plane as 2-D subspaces. The parameter space contains a "time-frequency-scale volume" and thus encompasses both the short-time Fourier transform (as a slice along the time and frequency axes) and the wavelet transform (as a slice along the time and scale axes). In addition to time, frequency, and scale, there are two other coordinate axes within this transform space: shear in time (obtained through convolution with a q-chirp) and shear in frequency (obtained through multiplication by a q-chirp). Signals in this multidimensional space can be obtained by a new transform, which we call the "q-chirplet transform" or simply the "chirplet transform". The proposed chirplets are generalizations of wavelets related to each other by 2-D affine coordinate transformations (translations, dilations, rotations, and shears) in the time-frequency plane, as opposed to wavelets, which are related to each other by 1-D affine coordinate transformations (translations and dilations) in the time domain only.

Large group community-based parenting programs for families of preschoolers at risk for disruptive behaviour disorders: utilization, cost effectiveness, and outcome.

Abstract: A significant percentage of children with disruptive behavior disorders do not receive mental health assistance. Utilization is lowest among groups whose children are at greatest risk. To increase the availability, accessibility, and cost efficacy of parent training programs, this prospective randomized trial compared a large group community-based parent training program to a clinic-based individual parent training (PT) programs. All families of junior kindergartners in the Hamilton public and separate school boards were sent a checklist regarding problems at home. Those returning questionnaires above the 90th percentile were block randomly assigned to: (1) a 12-week clinic-based individual parent training (Clinic/Individual), (2) a 12-week community-based large group parent training (Community/Group), or (3) a waiting list control condition. Immigrant families, those using English as a second language, and parents of children with severe behaviour problems were significantly more likely to enroll in Community/Groups than Clinic/Individual PT. Parents in Community/Groups reported greater improvements in behaviour problems at home and better maintenance of these gains at 6-month follow-up. A cost analysis showed that, with groups of 18 families, Community/Groups are more than six times as cost effective as Clinic/Individual programs.

The MyoD family of transcription factors and skeletal myogenesis

Abstract: Gene targeting has allowed the dissection of complex biological processes at the genetic level. Our understanding of the nuances of skeletal muscle development has been greatly increased by the analysis of mice carrying targeted null mutations in the Myf-5, MyoD and myogenin genes, encoding members of the myogenic regulatory factor (MRF) family. These experiments have elucidated the hierarchical relationships existing between the MRFs, and established that functional redundancy is a feature of the MRF regulatory network. Either MyoD or Myf-5 is sufficient for the formation or survival of skeletal myoblasts. Myogenin acts later in development and plays an essential in vivo role in the terminal differentiation of myotubes.

Client-Centred Practice: What does it Mean and Does it Make a Difference?

Abstract: During the past 15 years, occupational therapists in Canada, through the Canadian Association of Occupational Therapists, have worked to develop and implement guidelines for practice of a client-centred approach to occupational therapy. One of the difficulties with the current Guidelines for the Client-Centred Practice of Occupational Therapy is the lack of a definition and discussion of the concepts and issues fundamental to client-centred practice. In this paper, key concepts of client-centred practice: individual autonomy and choice, partnership, therapist and client responsibility, enablement, contextual congruence, accessibility and respect for diversity are discussed. Two practice examples are used to illustrate these ideas and raise issues about obstacles to the practice of client-centred occupational therapy. Research evidence about the effectiveness of client-centred concepts in enhancing client satisfaction, functional outcomes and adherence to health service programmes is reviewed.

The WHO analgesic ladder for cancer pain management. Stepping up the quality of its evaluation

Abstract: Objective. —To perform a systematic review of studies evaluating the effectiveness of the World Health Organization (WHO) analgesic ladder as an intervention for cancer pain management. Data Sources. —Systematic search of MEDLINE from 1982 to 1995, hand search of textbooks and meeting proceedings, reference lists, and direct contact with authors. Study Selection. —Studies of any methodological design were included if they evaluated patients with cancer pain treated according to the WHO analgesic ladder and if the studies provided enough information to estimate the proportion of patients who achieved adequate analgesia with the use of the ladder. The strength of the evidence provided by each study was assessed separately by both authors using current concepts. Data Extraction. —From the hard copy of each study report, the first author's name, publication year, study design, number of dropouts per study, and proportion of patients with adequate analgesia in each study were extracted. Data Synthesis. —Eight studies purporting to evaluate the effectiveness of the WHO ladder were included in the review. Meta-analysis was not performed because the studies were case series with no control groups. The studies had other limitations: none provided information on the conditions in which pain was assessed; two were retrospective; one had short follow-up periods; three had high withdrawal rates; and one had variable follow-up periods. Analgesia was adequate in 69% to 100% of patients analyzed in the studies. Conclusions. —The studies available provide valuable information on the course of cancer pain and its treatment. However, the evidence they provide is insufficient to estimate confidently the effectiveness of the WHO analgesic ladder for the management of cancer pain. Until results from carefully designed controlled trials are available, it would be inappropriate to judge the performance of clinicians, programs, and institutions or to design policies based on such evidence. ( JAMA . 1995;274:1870-1873)

A Simple Simulational Algorithm for Generating Progressive Type-II Censored Samples

Abstract: We establish an independence result concerning a progressive Type-II censored sample from the uniform distribution. This result is used to present a simple and efficient simulational algorithm for generating a progressive Type-II censored sample from any continuous distribution.

Users' Guides to the Medical Literature: VIII. How to Use Clinical Practice Guidelines A. Are the Recommendations Valid?

Abstract: CLINICAL SCENARIO You are relieved to find that the last patient in your busy primary care clinic is a previously well 48-year-old woman with acute dysuria. There has been no polydipsia, fever, or hematuria; the physical examination reveals suprapubic tenderness; and urinalysis shows pyuria but no casts. You arrange cultures and antibiotic treatment for a lower urinary tract infection. On her way out the door, your patient observes that her friend has just started taking "female hormones," and she wonders whether she should too. Her menstrual periods stopped 6 months ago and she has never had cervical, ovarian, uterine, breast, or cardiovascular problems, but her mother had a mastectomy at age 57 for postmenopausal breast cancer. You give the same general advice you have offered similar patients in the past, but suggest that the matter be discussed at greater length when she returns after completing the antibiotic treatment. Later, as