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Biomedical subjects

L Griffith

Publications and source records attributed to L Griffith.

At least 37 records · Page 2Linked to original sources
PubMed1999

The attributable morbidity and mortality of ventilator-associated pneumonia in the critically ill patient. The Canadian Critical Trials Group.

To evaluate the attributable morbidity and mortality of ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients, we conducted a prospective, matched cohort study. Patients expected to be ventilated for > 48 h were prospectively followed for the development of VAP. To determine the excess ICU stay and mortality attributable to VAP, we matched patients with VAP to patients who did not develop clinically suspected pneumonia. We also conducted sensitivity analyses to examine the effect of different populations, onset of pneumonia, diagnostic criteria, causative organisms, and adequacy of empiric treatment on the outcome of VAP. One hundred and seventy-seven patients developed VAP. As compared with matched patients who did not develop VAP, patients with VAP stayed in the ICU for 4.3 d (95% confidence interval [CI]: 1.5 to 7. 0 d) longer and had a trend toward an increase in risk of death (absolute risk increase: 5.8%; 95% CI: -2.4 to 14.0 d; relative risk (RR) increase: 32.3%; 95% CI: -20.6 to 85.1%). The attributable ICU length of stay was longer for medical than for surgical patients (6. 5 versus 0.7 d, p < 0.004), and for patients infected with "high risk" organisms as compared with "low risk" organisms (9.1 d versus 2.9 d). The attributable mortality was higher for medical patients than for surgical patients (RR increase of 65% versus -27.3%, p = 0. 04). Results were similar for three different VAP diagnostic criteria. We conclude that VAP prolongs ICU length of stay and may increase the risk of death in critically ill patients. The attributable risk of VAP appears to vary with patient population and infecting organism.

Critical Illness↗
PubMed1998

Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment.

Novel anti-neoplastic agents such as gene targeting vectors and encapsulated carriers are quite large (approximately 100-300 nm in diameter). An understanding of the functional size and physiological regulation of transvascular pathways is necessary to optimize delivery of these agents. Here we analyze the functional limits of transvascular transport and its modulation by the microenvironment. One human and five murine tumors including mammary and colorectal carcinomas, hepatoma, glioma, and sarcoma were implanted in the dorsal skin-fold chamber or cranial window, and the pore cutoff size, a functional measure of transvascular gap size, was determined. The microenvironment was modulated: (i) spatially, by growing tumors in subcutaneous or cranial locations and (ii) temporally, by inducing vascular regression in hormone-dependent tumors. Tumors grown subcutaneously exhibited a characteristic pore cutoff size ranging from 200 nm to 1.2 microm. This pore cutoff size was reduced in tumors grown in the cranium or in regressing tumors after hormone withdrawal. Vessels induced in basic fibroblast growth factor-containing gels had a pore cutoff size of 200 nm. Albumin permeability was independent of pore cutoff size. These results have three major implications for the delivery of therapeutic agents: (i) delivery may be less efficient in cranial tumors than in subcutaneous tumors, (ii) delivery may be reduced during tumor regression induced by hormonal ablation, and (iii) permeability to a molecule is independent of pore cutoff size as long as the diameter of the molecule is much less than the pore diameter.

Adenocarcinoma↗
PubMed1998

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

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) of those receiving sucralfate (relative risk, 0.44; 95 percent confidence interval, 0.21 to 0.92; P=0.02). In the ranitidine group, 114 of 596 patients (19.1 percent) had ventilator-associated pneumonia, as compared with 98 of 604 (16.2 percent) in the sucralfate group (relative risk, 1.18; 95 percent confidence interval, 0.92 to 1.51; P=0.19). There was no significant difference between the groups in mortality in the intensive care unit (ICU) (23.5 percent in the ranitidine group and 22.9 percent in the sucralfate group) or the duration of the stay in the ICU (median, nine days in both groups). CONCLUSIONS: Among critically ill patients requiring mechanical ventilation, those receiving ranitidine had a significantly lower rate of clinically important gastrointestinal bleeding than those treated with sucralfate. There were no significant differences in the rates of ventilator-associated pneumonia, the duration of the stay in the ICU, or mortality.

Aged↗
PubMed1998

"Incomplete resection" in non-small cell lung cancer: need for a new definition. Canadian Lung Oncology Group.

BACKGROUND: This study was designed to determine the prognostic value of positive surgical resection margin or highest nodal station sampled at thoracotomy in patients with non-small cell lung cancer. METHODS: Two reviewers independently examined the surgical records and pathologic reports from a randomized trial comparing computed tomography versus mediastinoscopy for staging of lung cancer. They recorded pathologic findings at the surgical resection margin, the highest mediastinal nodal station sampled at thoracotomy, histologic type, tumor size, N status, and evidence of vascular or lymphatic invasion. These variables formed the independent variables in logistic regression models to predict recurrence. RESULTS: Except for 1 patient, follow-up at 3 years for 399 included patients was complete. Significant predictors of recurrence were tumor size (odds ratio [OR], 1.2 (per centimeter); 99% CI [confidence interval], 1.1 to 1.4), and N status (compared with N0, N1: OR, 1.6; CI, 0.8 to 3.1; N2: OR, 3.2; CI, 1.4 to 7.5). Other variables, including positive surgical resection margin, did not predict early recurrence or death. CONCLUSIONS: In patients with non-small cell lung cancer, surgical resection margin or highest nodal station sampled at thoracotomy that are involved by carcinoma do not predict recurrence. The current definition of incomplete resection has limited prognostic significance.

Aged↗
PubMed1998

Adjudicating ventilator-associated pneumonia in a randomized trial of critically ill patients.

PURPOSE: The purpose of this study was to evaluate an adjudication strategy for diagnosing ventilator-associated pneumonia (VAP) in a randomized trial. MATERIALS AND METHODS: In a double-blind trial of sucralfate versus ranitidine, one of four pairs of adjudicators examined each case of clinically suspected VAP. Nurse and physician notes and all relevant laboratory data were allocated to each adjudication pair in groups of five patients. Each reader in the pair decided whether the patient had VAP; differences were resolved by consensus discussion. RESULTS: The overall unadjusted study odds ratio for VAP was 0.82 (P = .21) representing a trend toward less pneumonia with sucralfate compared with ranitidine. The odds ratio adjusted for adjudication pair was 0.85 (P = .27). The proportion of charts adjudicated as VAP positive among pairs ranged from 50% to 92%; crude agreement between readers in each pair varied from 50% to 82%. When adjudicators disagreed, the final consensus was split evenly between the two adjudicators' initial opinions in two pairs; in the other two pairs, the final decision reflected one dominant initial opinion. Personnel time to adjudicate all patients with a suspicion of VAP was 74 days. CONCLUSIONS: Though adjudication of outcomes such as VAP is time-consuming, consistent decision-making requires strict criteria, training, and calibration. Patients should be assigned to adjudication teams through random allocation.

Anti-Ulcer Agents↗
PubMed1998

Development of a health-related quality-of-life questionnaire (PCOSQ) for women with polycystic ovary syndrome (PCOS).

OBJECTIVE: To develop a self-administered questionnaire for measuring health-related quality of life (HRQL) in women with polycystic ovary syndrome (PCOS). METHODS: We identified a pool of 182 items potentially relevant to women with PCOS through semistructured interviews with PCOS patients, a survey of health professionals who worked closely with PCOS women, and a literature review. One hundred women with PCOS completed a questionnaire in which they told us whether the 182 items were relevant to them and, if so, how important the issue was in their daily lives. We included items endorsed by at least 50% of women in the analysis plus additional items considered crucial by clinicians and an important subgroup of patients in a factor analysis. We chose items for the final questionnaire taking into account both item impact (the frequency and importance of the items) and the results of the factor analysis. RESULTS: Over 50% of the women with PCOS labelled 47 items as important to them. Clinicians chose 5 additional items from the infertility domain, 4 of which were identified as important by women who were younger, less educated, married, and African-American. The Cattell's Scree plot from a factor analysis of these 51 items suggested 5 factors that made intuitive sense: emotions, body hair, weight, infertility, and menstrual problems. We chose the highest impact items from these 5 domains to construct a final questionnaire, the Polycystic Ovary Syndrome Questionnaire (PCOSQ), which includes a total of 26 items and takes 10-15 minutes to complete. CONCLUSIONS: We have used established principles to construct a questionnaire that promises to be useful in measuring health-related quality of life. The questionnaire should be tested prior to, or concurrent with, its use in randomized trials of new treatment approaches.

Adult↗
PubMed1998

Prenatal alcohol exposure and communication, behavior, and nonverbal intelligence of 3 school-age children.

Associations of prenatal alcohol exposure in speech, language, behavioral, and intellectual development were investigated in three school-aged children diagnosed with Fetal Alcohol Syndrome, accompanied by Attention Deficit Hyperactivity Disorder. Each child showed similar patterns of moderate-to-severe dysfunctional behavior; however, their scores on speech, language and nonverbal intellectual measures were highly variable.

Attention Deficit Disorder with Hyperactivity↗
PubMed1997

Meta-analysis of prophylactic treatments against Pneumocystis carinii pneumonia and toxoplasma encephalitis in HIV-infected patients.

In a meta-analysis, we examined the efficacy of aerosolized pentamidine, trimethoprim-sulfamethoxazole, and dapsone or dapsone/pyrimethamine for the prevention of Pneumocystis carinii pneumonia and toxoplasma encephalitis in patients with HIV infection. Of 22 trials, 13 compared trimethoprim-sulfamethoxazole with aerosolized pentamidine, nine compared dapsone alone or in combination with pyrimethamine with aerosolized pentamidine, and eight compared trimethoprim-sulfamethoxazole with dapsone/pyrimethamine. In total, 1484 patients were treated with trimethoprim-sulfamethoxazole, 1548 patients with dapsone/pyrimethamine or dapsone, and 1800 patients with aerosolized pentamidine. For dapsone/pyrimethamine versus aerosolized pentamidine, the risk ratio for P. carinii pneumonia was 0.90 (95% confidence interval [CI], 0.71-1.15), and for toxoplasma encephalitis it was 0.72 (95% CI, 0.54-0.97). For trimethoprim-sulfamethoxazole versus aerosolized pentamidine, the risk ratio of P. carinii pneumonia was 0.59 (95% CI, 0.45-0.76), and for toxoplasma encephalitis it was 0.78 (95% CI, 0.55-1.11). For trimethoprim-sulfamethoxazole versus dapsone/pyrimethamine, the risk ratio of P. carinii pneumonia was 0.49 (95% CI, 0.26-0.92), and for toxoplasma encephalitis it was 1.17 (95% CI, 0.68-2.04). Although current evidence does not allow a definitive recommendation, administration of trimethoprim-sulfamethoxazole for prophylaxis of P. carinii pneumonia and toxoplasmosis in patients with HIV infection is consistent with the available data.

AIDS-Related Opportunistic Infections↗
PubMed1997

Attitudes toward the use of gender-inclusive language among residency trainees. The McMaster Residency Training Program Directors.

OBJECTIVE: To explore postgraduate medical trainees' attitudes toward the use of gender-inclusive language. DESIGN: Self-administered questionnaire. SETTING: Seven residency training programs at McMaster University, Hamilton, Ont., from July 1993 to June 1994. PARTICIPANTS: Of 225 residents in the programs, 186 responded to the survey, for a response rate of 82.7%. Men and women were equally represented among the respondents. OUTCOME MEASURES: Categorization of attitudes about the use of language as gender-inclusive or gender-exclusive; characteristics predicting a gender-inclusive attitude. RESULTS: Factor analysis and Cronbach's alpha (0.90) supported the existence of a construct related to attitudes about language use, the poles of which were categorized as gender-inclusive and gender-exclusive. The authors classified residents with respect to their attitudes to language use from their responses to the questionnaire. In univariate analyses, sex, residency program and country of graduation significantly predicted a gender-inclusive attitude (p < 0.01). Only the first 2 variables were significant in a multivariate model; residency program explained 18% of the variance and sex 3%. Residents in obstetrics and gynecology and psychiatry had the most gender-inclusive attitudes, whereas residents in surgery and anesthesia had the most gender-exclusive attitudes. CONCLUSIONS: Residents' values are reflected in the language they choose to use. Language use may provide an index of underlying attitudes that may create hostile environments for female trainees.

Adult↗
PubMed1997

Glycogenosis type II: a juvenile-specific mutation with an unusual splicing pattern and a shared mutation in African Americans.

The recessively inherited deficiency of acid alpha-glucosidase (GAA) called Glycogenosis Type II is expressed as three different phenotypes: infantile, juvenile, and adult. At the molecular level, infantile and adult forms of the disease have been extensively studied, but little is known regarding the genetic defects associated with the juvenile form. We describe a novel mutation that defines the intermediate juvenile phenotype in a compound heterozygous patient. A transversion of t to g in intron 6 at position -22 creates a cryptic acceptor site and results in unusual splicing abnormality: insertion of 21 nucleotides of the intronic sequence into mRNA and removal of exon 6 without disruption of the reading frame. The second mutation, Arg854Stop in exon 18, had been previously identified in another African-American patient (Hermans et al., 1993a). Family study indicates that a silent allele harboring the Arg854Stop mutation in our patient is inherited from the patient's father, who is also African-American, thus suggesting a common mutation in this population.

Base Sequence↗
PubMed1996

Does treatment with L-thyroxine influence health status in middle-aged and older adults with subclinical hypothyroidism?

OBJECTIVE: To determine if health-related quality of life (HRQL) in patients of middle age and older with elevated thyroid-stimulating hormone (TSH) and normal total thyroid hormone levels-subclinical hypothyroidism-improves with L-thyroxine replacement therapy. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Outpatient clinic. PATIENTS: Thirty-seven patients with subclinical hypothyroidism, most with symptoms consistent with hypothyroidism, over 55 years of age. INTERVENTIONS: Placebo or L-thyroxine replacement therapy to achieve normal TSH level. MEASUREMENTS AND MAIN RESULTS: Disease-specific and general HRQL, cognitive function, bone mineral density, lipid levels. The mean daily dose of L-thyroxine replacement in the active group was 68 +/- 21 micrograms. TSH decreased by 8.6 mIU/L (95% confidence interval [CI] 4.1 to 13.1) and T4 increased by 27.9 nmol/L (95% CI 14.8 to 41.2). There was a statistically significant improvement in a composite psychometric memory score in treated versus control patients; all other outcomes showed similar findings in the two groups. Although confidence intervals for most measures did not exclude an important improvement in HRQL with thyroid replacement, no measure of symptoms or HRQL either showed clinically important trends in favor of treatment, or approached conventional levels of statistical significance. CONCLUSIONS: In middle-aged and older patients with elevated TSH and normal T4, it may not be harmful to follow biochemical and clinical status even in the presence of nonspecific symptoms potentially associated with hypothyroidism.

Aged↗
PubMed1996

Effects of electroconvulsive therapy on peripheral adrenoceptors, plasma, noradrenaline, MHPG and cortisol in depressed patients.

BACKGROUND: The mechanism of the antidepressant action of electroconvulsive therapy (ECT) remains unknown. Based on previous work with antidepressant drugs and their effects on the noradrenergic system, we undertook this study to further determine the effects of ECT on selected indices of peripheral adrenoceptor function in depressed patients. METHODS: Binding parameters (Bmax and Kd) of platelet alpha 2- and leukocyte beta 2-adrenoceptors, plasma noradrenaline (NA), 3-methoxy-4-hydroxy-phenylglycol (MHPG) and cortisol levels were determined in 18 patients, prior to treatment and 14 days after the last of a series of ECTs, and compared with samples obtained from 18 matched control subjects. RESULTS: Platelet alpha 2-adrenoceptor sites were significantly elevated in untreated patients compared with controls (P < 0.03), but leukocyte beta 2-adrenoceptor numbers did not differ. Treatment with ECT led to a significant reduction in platelet alpha 2-adrenoceptor numbers, whereas leukocyte beta 2-adrenoceptor densities increased. Pre-ECT plasma NA, MHPG, and cortisol levels were elevated in patients, compared with controls, and decreased following ECT, but these differences were not statistically significant. Post-ECT plasma NA and beta 2-adrenoceptor numbers were significantly, negatively correlated (P < 0.05). CONCLUSIONS: These results suggest that platelet alpha 2-adrenoceptors are supersensitive in depressed patients and treatment with ECT results in down-regulation of these receptors, which may be interpreted as a primary therapeutic, "normalising' effect. The post-ECT changes in leukocyte beta 2-adrenoceptors are probably only secondary to the lower circulating plasma NA levels.

Adult↗
PubMed1995

Measuring patient and relative satisfaction with level or aggressiveness of care and involvement in care decisions in the context of life threatening illness.

The objective of the study was to develop valid and reliable discriminative indices which measure patient and relative satisfaction with two closely related aspects of medical care: the level of care received and their involvement in decisions regarding care. We generated items by literature review and interviews with patients, relatives, and health care providers. In the final questionnaires, we included the items identified most frequently as sources of dissatisfaction and rated most important by 102 patients and 153 relatives. To measure reliability and validity we administered the instruments to 105 patients and 75 relatives of competent patients and 89 relatives of incompetent patients. We constructed three questionnaires: the Patient Satisfaction Index with 23 items, the Relative of Competent Patient Satisfaction Index with 34 items, and the Relative of Incompetent Patient Satisfaction Index with 29 items. We found mean scores of 75-80% of the maximum possible score, with a wide range of scores. The intraclass correlation for the instruments varied from 0.86 to 0.94. Correlations with global ratings were high (0.59-0.75) and similar to predictions. Correlations with caregiver ratings were lower than predicted (0.18-0.22). For both patients and relatives, our instruments discriminate between those with higher and lower satisfaction with the level of medical care and with their involvement with decision-making.

Aged↗
PubMed1995

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

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

Carcinoma, Non-Small-Cell Lung↗
PubMed1994

Quality of life after myocardial infarction.

The objective of this work was to develop and test a questionnaire to measure health-related quality of life for patients after myocardial infarction (MI). In a cross-sectional survey, 63 patients identified the most frequent and important problems following acute myocardial infarction. The Quality of Life after Myocardial Infarction (QLMI) instrument was developed on the basis of these most frequent and important problems. The QLMI was administered, along with instruments measuring health utilities, social function, and emotional function, in a randomized trial of rehabilitation versus conventional care. The most frequent and important problems fell into areas of symptoms, restriction, confidence, self-esteem, and emotions, each of which is represented in the 26-item QLMI. Effect sizes of the overall QLMI in differentiating between rehabilitation and control groups (0.35), and in detecting improvement over 12 months (1.22) were comparable or larger than any other instrument. The Pearson's correlation coefficient between QLMI administered at 8 and 12 months following AMI varied between 0.75 and 0.87 for the five domains and the overall score. We found substantial correlations of the QLMI with other measures with moderate concordance with predictions about how the instrument should behave if it is a valid measure of health-related quality of life. The QLMI demonstrates a high degree of reliability, and is more responsive than other questionnaires. Relations between the QLMI and other measures provide moderate to strong evidence of its validity in discriminating between patients following AMI according to their health-related quality of life, and in measuring changes in health-related quality of life over time.

Female↗
PubMed1994

Primary prevention of child physical abuse and neglect: a critical review. Part I.

This paper (Part I) and its companion paper (Part II) provide an overview of the primary prevention of child maltreatment. Part I reviews the effectiveness of interventions aimed at the primary prevention of child physical abuse and neglect. Prospective controlled trials published between January 1979 and May 1993 were systematically identified. The quality of each study was determined using criteria which assessed methodological rigor. Interventions aimed at the prevention of physical abuse and neglect were classified into six main categories within the broad group of perinatal and early childhood programs. While many of these programs did not show a reduction in physical abuse or neglect, there is evidence that extended home visitation can prevent physical abuse and neglect among disadvantaged families.

Adolescent↗
PubMed1994

Primary prevention of child sexual abuse: a critical review. Part II.

This paper (Part II) and the previous paper (Part I) provide an overview of the primary prevention of child maltreatment. Part II focuses on the effectiveness of interventions aimed at the primary prevention of child sexual abuse. It includes prospective controlled trials published between January 1979 and May 1993. These studies were systematically identified and the quality of each trial was determined using criteria which assessed methodological rigor. Interventions aimed at the prevention of sexual abuse were classified into eight main categories based on the method of intervention. All programs had education as the primary focus. There is evidence that educational programs can improve safety skills and knowledge of children about sexual abuse but no study has produced data that education actually reduces the occurrence of sexual abuse.

Adolescent↗