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Biomedical subjects

L A Moran

Publications and source records attributed to L A Moran.

At least 19 recordsLinked to original sources
PubMed2001

Establishing the minimal number of items for a responsive, valid, health-related quality of life instrument.

Reducing the number of items in a health-related quality of life instrument will enhance efficiency. However, it is important to maintain measurement properties. We determined the effect of reducing items from each domain (dyspnea, fatigue, emotion and mastery) of the 20-item Chronic Respiratory Questionnaire (CRQ). Three randomized trials of respiratory rehabilitation provided data. We removed items one at a time from each domain in three orders: by item impact, item responsiveness, and at random. Responsiveness, test-retest reliability and construct validity were evaluated at each step. Responsiveness and reliability, evaluated by intraclass correlation coefficients (ICC), were reduced marginally as the number of items was reduced to two items per domain. The deterioration was greatest when reducing from two items to one. To detect a particular effect, sample size would increase by about 10% when reducing the number of items in a domain to 2. Construct validity showed a more marked deterioration. Reducing to two items per domain would maintain responsiveness and reliability of the CRQ at an acceptable level, with a trade-off of reduced construct validity and increase in sample size requirements.

Factor Analysis, Statistical↗
PubMed2000

Development and testing of a utility measure for major, unipolar depression (McSad).

OBJECTIVE: To develop and test a direct utility measure (McSad) for major, unipolar depression. METHODS: A depression specific, multi-attribute health state classification system was created; clinical validity was evaluated by experts using specially designed structured exercises; a cross-sectional survey was conducted to obtain directly measured utilities for depression health states. SETTING: Tertiary care, university medical centre. PARTICIPANTS: Three psychiatrists, 3 psychiatric nurses and 3 social workers assessed depression health state clinical validity. Survey participants were referred by psychiatrists and consisted of 105 outpatients, currently in remission with at least one episode of major, unipolar depression in the past two years. SURVEY RESULTS: Respondent self-health state utility (mean and 95% confidence interval (CI)) was 0.79 (0.74-0.83). Utilities for hypothetical, untreated depression health states were: mild depression, 0.59 (0.55-0.62); moderate depression, 0.32 (0.29-0.34); severe depression, 0.04 (0.01-0.07). Fifty-six percent of respondents rated severe depression worse than being dead. Utilities for the hypothetical health states were not correlated with self-health utility. The intra-class correlation coefficient (ICC) was satisfactory for 13 of the 14 health states assessed. CONCLUSIONS: McSad was feasible and acceptable in patients with a history of major unipolar depression. The utilities for mild, moderate and severe untreated depression show the low health-related quality of life associated with depression. Initial assessments of test-retest reliability and validity yielded satisfactory results but further studies are needed to extend our knowledge of the measurement properties of McSad.

Adult↗
PubMed1999

A database designed for utilization management in diagnostic imaging.

The methods and tools of health services research have been applied to a diverse number of health care areas. Surprisingly, they have been adopted only recently in diagnostic imaging, by a small number of professionals, in response to the severe fiscal constraints and widespread structural changes in the health industry, as well as to a growing concern that the value of social and individual investment in high-cost imaging services could not be validated objectively. As a result of the need for accountability for the use of scarce resources, regulators and payers of health services increasingly demand that a reasoned and objective evaluative process be adopted. To undertake a statistically driven evaluative approach that stands up to objective assessment of methodological rigour, an organized data-collection system is needed. Without this fundamental cornerstone, evaluators are left with little more than anecdotal evidence and professional and personal opinion to guide decision-making. It then becomes difficult to learn from both the successes and failures that are routinely experienced during times of rapid and fundamental change. This article describes the efforts made to integrate health services research in radiology into the routine daily activities and supporting systems of a large academic health system, the Hamilton Health Sciences Corporation and McMaster University Department of Radiology, in an attempt to move in the direction of evidence-based decision-making. The authors hope this will allow others to learn and improve on this work. Radiologists may then move the vast data systems and infrastructure associated with all imaging services to an evidence-based model for managing and guiding the vast resources entrusted to our collective stewardship.

Academic Medical Centers↗
PubMed1999

Use of dexrazoxane as a cardioprotectant in patients receiving doxorubicin or epirubicin chemotherapy for the treatment of cancer. The Provincial Systemic Treatment Disease Site Group.

GUIDELINE QUESTIONS: 1) Should dexrazoxane be used routinely in patients with advanced or metastatic cancer who are at risk of developing cardio toxicity when receiving chemotherapy containing doxorubicin or epirubicin? 2) Do the available data support the use of dexrazoxane when anthracyclines are being used in the adjuvant setting for patients at risk of developing cardiotoxicity? OBJECTIVE: To make recommendations regarding the use of dexrazoxane to prevent cardiotoxicity in patients with nonhematological malignancies who are receiving anthracycline- containing chemotherapy. OUTCOMES: Clinical and subclinical cardiotoxicity, noncardiac toxicity and impact on efficacy outcomes such as response and overall survival are considered. PERSPECTIVE (VALUES): Evidence was selected, reviewed and synthesized by 2 members of Cancer Care Ontario's Systemic Treatment Disease Site Group (STDSG), formerly the Systemic Treatment Program Committee. Drafts of this document have been circulated and reviewed by members of the STDSG. The STDSG comprises medical oncologists, pharmacists, supportive care personnel and administrators. Community representatives did not participate in the development of this guideline, but they will be included in future guidelines. QUALITY OF EVIDENCE: Seven randomized controlled trials (RCTs), 2 with placebo control, were available for analysis. BENEFITS: Data for clinical cardiotoxicity from 6 trials were pooled (n = 1070). The meta-analysis indicated that the risk of experiencing clinical cardiotoxicity was significantly reduced by dexrazoxane (risk ratio 0.24; 95% confidence interval [CI] 0.11 to 0.52; p = 0.00031). There was no significant benefit shown in individual trials for objective response or survival. HARMS: One of the RCTs revealed a significantly lower objective response rate in the dexrazoxane arm. However, a meta-analysis of objective response across 5 trials of breast cancer patients (n = 818) did not confirm this effect (odds ratio 0.85; 95% CI 0.61 to 1.18; p = 0.33). The use of dexrazoxane increased the incidence of myelosuppression and other noncardiac toxicities, but these were generally mild. PRACTICE GUIDELINE: The evidence supports the use of dexrazoxane to provide protection against the cardiotoxicity associated with conventional-dose doxorubicin in patients with advanced but anthracycline-sensitive cancer, in whom the continued use of anthracycline-containing chemotherapy is indicated in the opinion of the treating physician and who have received 300 mg/m2 or more of doxorubicin. The evidence supports the use dexrazoxane to provide protection against the cardiotoxicity associated with conventional-dose epirubicin in patients with advanced but anthracycline-sensitive cancer, in whom the continued use of anthracycline-containing chemotherapy is indicated in the opinion of the treating physicians. There are no data indicating the optimal cumulative dose of epirubicin at which dexrazoxane should be instituted. For doxorubicin, use of dexrazoxane is recommended after the cumulative dose reaches 300 mg/m2 (i.e., 55% of the recommended maximum). A similar formula could be used for epirubicin, that is, institution of dexrazoxane when the cumulative dose of epirubicin reaches 550 mg/m2, as the recommended maximum cumulative dose in Canada is 1000 mg/m2. Preclinical studies did not show any cardioprotectant effect for dexrazoxane when used with mitoxantrone, and no clinical studies have been done. Therefore, dexrazoxane is not recommended for use with mitoxantrone. There is no evidence for or against the use of dexrazoxane in the adjuvant setting for any tumour type. Because of concerns that dexrazoxane may reduce the efficacy of anthracyclines, and because data are not yet available on long-term toxicities, further studies should be performed before the drug is used in this setting.

Aged↗
PubMed1997

Health state utilities in knee replacement surgery: the development and evaluation of McKnee.

OBJECTIVE: 1. To develop McKnee, a classification system and direct utility measure for health states associated with knee replacement (KR) surgery. 2. To apply McKnee in a before-after study of KR surgery to: (i) gain experience with McKnee in an elderly population; (ii) confirm the practicality and usefulness of the McKnee system; (iii) assess self-health utility one week before and 3 mo after surgery; (iv) evaluate the stability of 3 clinical marker health states describing mild, moderate, and severe knee disability; (v) compare self-health utility scores with Short Form 36 (SF-36). METHODS: 1. Instrument development: The McKnee modified Health Utilities Index was developed and used to describe self-health and clinical marker health states: the clinical validity of the clinical marker states was evaluated by 5 clinicians involved in the care off KR patients. 2. Instrument evaluation: McKnee and the SF-36 were administered to 48 patients with osteoarthritis one week before and 3 mo after KR surgery. RESULTS: Before-after study: McKnee was feasible and acceptable in the older patient group studied (mean age in years, SD: 69.9, 8.6). No change in self-health utility (mean, SD) was observed at 3 mo postsurgery: before -0.78, 0.17; after -0.78, 0.21. On the SF-36, only the change scores for pain and health transition were statistically significant. Utilities (mean, SD) for the clinical marker health states were: mild -0.80, 0.20; moderate -0.55, 0.28; and severe -0.48, 0.31. The clinical marker mean utility scores were stable between the baseline and 3 mo assessment, but the intraclass correlation coefficients for individual scores were low. CONCLUSION: McKnee provides a preference based measure of health related quality of life that can be used to obtain and interpret clinically the knee disability utility scorers needed for cost-utility studies and medical decision-making models about KR surgery. The McKnee system provides a practical and useful method for classifying knee disability health states and obtaining direct measurements of utility scores for selected health states.

Aged↗
PubMed1997

Erythropoietin in the management of patients with nonhematologic cancer receiving chemotherapy. Systemic Treatment Program Committee.

GUIDELINE QUESTIONS: 1) Does erythropoietin (EPO) reduce the need for transfusion of red blood cells in patients receiving chemotherapy for a nonhematologic cancer? 2) Does the administration of EPO improve the quality of life of these cancer patients? OBJECTIVE: To make recommendations regarding the use of EPO to reduce the need for transfusion of red blood cells in patients receiving chemotherapy for a nonhematologic cancer. OUTCOMES: First transfusion requirement from the start of chemotherapy is the main outcome of interest. Quality of life and costs are also considered. PERSPECTIVE (VALUES): Evidence was selected and reviewed by 5 members of the Ontario Cancer Treatment Practice Guidelines Initiative (OCTPGI) and the Systemic Treatment Program Committee (STPC). Drafts of this document have been circulated to and reviewed by members of the STPC. The STPC comprises medical oncologists, pharmacists, supportive care personnel and administrators. No community representative participated in the development of this practice guideline. QUALITY OF EVIDENCE: Eleven randomized controlled trials (RCTs), most placebo-controlled, were available for review. A meta-analysis was performed with 8 trials that shared a clinically relevant outcome measure. Only 1 trial assessed quality of life. BENEFITS: The meta-analysis showed a relative risk for transfusion among EPO patients of 0.64 (95% confidence interval 0.53-0.78), which translates into a 36% relative reduction in the proportion of patients requiring transfusion (p = 0.00001). Reduction in transfusion requirements was similar across strata defined by methodological quality, EPO dose, hematologic status, tumour type at trial entry and chemotherapy regimen. In the 1 trial that assessed quality of life, EPO was associated with improved quality of life. HARMS: Hypertension has been noted rarely in EPO-treated cancer patients. The RCTs did not report adverse effects in EPO-treated patients compared with control patients during the follow-up period. Long-term adverse effects are unknown. EPO is more costly than transfusion, but formal cost-effectiveness studies are unavailable. PRACTICE GUIDELINE: For patients receiving chemotherapy for nonhematologic cancer in whom symptoms of anemia are expected and in whom transfusion of red blood cells is not considered an acceptable treatment option, EPO can be recommended as a safe, effective treatment alternative. The evidence in support of using EPO is stronger for patients receiving platinum-based chemotherapy regimens that for those receiving non-platinum-based regimens. CLINICAL PRACTICE GUIDELINE DATE: Apr. 4, 1997.

Anemia↗
PubMed1996

Workplace organizational correlates of lost-time accident rates in manufacturing.

We report the results of a questionnaire survey of manufacturing workplaces related to the lost-time frequency rates (LTFR) for Workers' Compensation claims. Six types of industry were chosen.' metal articles, plastic articles, grain products, textile manufacturing, printing, and automobile manufacturing. LTFR were standardized by type of industry. Stratifying simultaneously by number of employees and LTFR category, we sampled 718 workplaces. A mail questionnaire to labor and management representatives provided at least some information on 58%. Response rates were similar across LTFR categories, and telephone interviews of non-responders showed little difference in their replies from those obtained in completed questionnaires. A large number of variables were examined. Apart from statistical significance, we looked for consistency in trends across LTFR categories and in patterns for similar questions. Significant associations grouped into several areas. Lower LTFR were associated with: concrete demonstration by management of its concern for the workforce; greater involvement of workers in general decision-making; greater willingness of the Joint Health and Safety Committee to solve problems internally; and greater experience of the workforce. Variables that were not significant included profitability and financial performance. A final stepwise multiple regression explained 19% of the variance in LTFR, although this analysis suffered from several limitations.

Absenteeism↗
PubMed1996

Immediate and delayed effects of laparoscopic Nissen fundoplication on pulmonary function.

BACKGROUND: An effort was made to assess the respiratory outcomes of laparoscopic Nissen fundoplication (LNF). METHODS: Prospective follow-up of 69 patients undergoing LNF for gastroesophageal reflux disease. Outcomes included pulmonary function testing, 24-h pH recording, esophageal manometry, and symptom assessment. RESULTS: There was an improvement (p < 0.0001) in heartburn and cough scores. There was a significant fall in spirometry (p < 0001), diffusing capacity (p < 0.0001), and respiratory muscle strength (p < 0.0001) 36 h after surgery, which had returned to baseline by 1 month. At 6 months, the patients (n = 16) with impaired preoperative diffusing capacity showed improvement (17.8 +/- 3.7 to 19.8 +/- 4.6 ml/min/mmHg, p = 0.0245). CONCLUSION: Patients undergoing LNF have impaired gas exchange before surgery which tends to improve 6 months after surgery. There is an early reversible impairment in respiratory function due to diaphragm dysfunction. Patients with a preoperative 1-s forced expired volume > 1.5, or 50% predicted, are unlikely to develop significant early respiratory complication.

Adult↗
PubMed1994

Structure and expression of an inducible HSP70-encoding gene from Mus musculus.

We have determined the nucleotide sequence of a stress-inducible mouse Hsp70-encoding gene named hsp70A1. The gene encodes a 641-amino-acid protein whose deduced sequence is similar to those of other members of the HSP70 family. The 5' end (tsp) of a heat-inducible mRNA is 225 bp upstream from the start codon, and several consensus recognition sequences for transcription factors lie upstream from this tsp. There are 17 putative binding sites for heat-shock transcription factor (HSF), including three clusters of multiple binding sites. We show that this upstream region is sufficient to direct heat-inducible expression of a hsp70A1::cat hybrid gene in mouse and human cells.

Amino Acid Sequence↗
PubMed1990

An essential member of the HSP70 gene family of Saccharomyces cerevisiae is homologous to immunoglobulin heavy chain binding protein.

Immunoglobulin heavy chain binding protein (BiP) is present in the lumen of the mammalian endoplasmic reticulum, where it associates transiently with a variety of newly synthesized secretory and membrane proteins or permanently with mutant proteins that are incorrectly folded. We describe a unique member of the Saccharomyces cerevisiae 70-kDa heat shock protein gene family (HSP70) that encodes a protein homologous to mammalian BiP. The DNA sequence contains a 2046-nucleotide open reading frame devoid of introns, and examination of the predicted amino acid sequence reveals features not found in most other yeast HSP70 proteins but which are present in BiP. Most notable are a 42-residue sequence at the N terminus that exhibits characteristics of a cleavable signal sequence and a C-terminal sequence, -His-Asp-Glu-Leu, that is involved in determining endoplasmic reticulum localization in yeast. The 5' flanking region of this gene contains two overlapping sequences between nucleotides -146 and -169 that closely resemble consensus heat shock elements. The yeast BiP gene is strongly heat shock-inducible, whereas the BiP genes in various other species are either weakly or non-heat-inducible. We demonstrate that a functional BiP gene is essential for vegetative growth. An evolutionary comparison of amino acid sequences of 34 HSP70 proteins from 17 species suggests that BiP genes share a common ancestor, which diverged from other HSP70 genes near the time when eukaryotes first appeared.

Amino Acid Sequence↗
PubMed1989

Inducible expression of an hsp68-lacZ hybrid gene in transgenic mice.

Transgenic mice have been generated that express the E. coli beta-galactosidase gene under the control of the promoter from the mouse heat-shock gene, hsp68. Sequences from -664 to +113 relative to the start of transcription of the hsp68 gene were sufficient to direct stress-induced expression of the beta-galactosidase gene in adult tail tissue and various tissues of fetal stages of development. Expression was detected in situ by staining with the chromogenic substrate, X-gal. The hybrid gene was refractory to induction in preimplantation embryos until the blastocyst stage of development, as reported for the endogenous hsp68 gene. No constitutive expression was observed by in situ staining or Northern analysis at any stage of development, even in tissues that constitutively express the endogenous hsp68 gene. We conclude that the hsp68 promoter region included in the construct contains sufficient sequence information for heat and arsenite inducibility, but it does not contain sequences controlling tissue-specific expression during development. This tightly regulated inducible promoter may provide a useful tool for short-term inducible gene expression in transgenic mice.

Animals↗
PubMed1987

Cell-lineage-specific expression of the mouse hsp68 gene during embryogenesis.

Transcription of the mouse hsp68 and hsc70 genes in embryonal carcinoma cells, various embryonic and extraembryonic tissues, and some adult tissues has been assessed using cloned probes to the mouse hsp68 gene. The results from Northern blots showed that both F9 and P19 cells respond in the expected manner to a heat shock. Hsp68 expression was only detected in heat-induced F9 and P19 cells. Hsc70 transcripts were present in uninduced cells and their levels increased after induction. In adult tissues, the hsp68 gene was expressed constitutively in the kidney. A different hsp68-like transcript was detected at significant levels in adult testes. Constitutive expression of hsp68 was observed in both the placenta (beginning at Day 8.5) and yolk sac (beginning at Day 11.5). No hsp68 expression was detected in embryonic tissues until Day 15.5. Expression of the mouse hsp68 gene during embryogenesis suggests that it may play some role in development.

Animals↗
PubMed1987

Isolation of a mouse heat-shock gene (hsp68) by recombinational screening.

We have used cloned fragments from a Drosophila melanogaster hsp70 gene and a mouse hsp68 cDNA in recombinational screens of mouse genomic libraries. Using the mouse probe we have isolated two overlapping recombinant lambda phages comprising 22 kb of cloned DNA. Southern analysis has localized the homology with the Drosophila hsp70 coding region to a 2.2-kb fragment containing the mouse heat-shock gene. Insertion accompanying recombinational screening can disrupt interesting sequences; we have overcome this inconvenience by developing a simple one-step genetic selection for phage which have precisely excised the microplasmid probe.

Animals↗
PubMed1986

Molecular cloning and analysis of DNA complementary to three mouse Mr = 68,000 heat shock protein mRNAs.

The construction and isolation of three recombinant DNAs complementary to different mouse L-cell Mr = 68,000 heat shock protein (hsp68) mRNAs is described. cDNA libraries derived from heat-shocked mouse L-cell poly(A)+ RNA by the vector-linked primer strategy of cDNA synthesis and cloning of Okayama and Berg (Okayama, H., and Berg, P. (1982) Mol. Cell. Biol. 2, 161-170) were screened first with a Drosophila hsp70 heterologous probe and subsequently with a cDNA probe isolated from the first screening. Positive clones were assigned to one of three sets based on their restriction map, and the largest member of each group was chosen for further analysis. All three cDNAs hybrid-select mRNA for the mouse major heat shock protein (hsp68) as assayed by in vitro translation and hybridize preferentially to two heat shock-induced hsp68 mRNAs on Northern blots. The coding regions of the cDNAs are almost identical and closely resemble other HSP70 genes but the 3' untranslated regions diverge considerably. Differences in the lengths of the untranslated regions are responsible for the two different sized induced hsp68 mRNAs in mouse L-cells. The physical maps of these cDNA clones and the limited number of mouse genomic DNA fragments detected on Southern blots suggest that there are at least three closely related heat shock-inducible members of the mouse HSP70 gene family. None of the cloned cDNAs are derived from the two related cognate genes known to be present in the mouse genome.

Animals↗
PubMed1985

Expression of heat shock genes in fetal and maternal rabbit brain.

Cloned fragments of members of the Drosophila and mouse major heat shock (hsp70) gene family were used to demonstrate that homologous sequences are present in the rabbit genome. After a physiologically relevant increase in body temperature of 3 degrees C, transcription of inducible hsp70 genes is detected in both the fetal and maternal brain and kidney. The induced hsp70 gene transcripts decay rapidly after whole body hyperthermia subsides. Transcripts of constitutively expressed member(s) of the hsp70 gene family, the heat shock cognate genes (hsc70), are detected in unstressed fetal and maternal rabbit tissues.

Animals↗