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Biomedical subjects

M K Gould

Publications and source records attributed to M K Gould.

At least 19 recordsLinked to original sources
PubMed2005

Accuracy of transbronchial needle aspiration for mediastinal staging of non-small cell lung cancer: a meta-analysis.

BACKGROUND: The reported accuracy of transbronchial needle aspiration (TBNA) for mediastinal staging in non-small cell lung cancer (NSCLC) varies widely. We performed a meta-analysis to estimate the accuracy of TBNA for mediastinal staging in NSCLC. METHODS: Medline, Embase, and the bibliographies of retrieved articles were searched for studies evaluating TBNA accuracy with no language restriction. Meta-analytical methods were used to construct summary receiver-operating characteristic curves and to pool sensitivity and specificity. RESULTS: Thirteen studies met inclusion criteria, including six studies that surgically confirmed all TBNA results and enrolled at least 10 patients with and without mediastinal metastasis (tier 1). Methodological quality varied but did not affect diagnostic accuracy. In tier 1 studies the median prevalence of mediastinal metastasis was 34%. Using a random effects model, the pooled sensitivity and specificity were 39% (95% CI 17 to 61) and 99% (95% CI 96 to 100), respectively. Compared with tier 1 studies, the median prevalence of mediastinal metastasis (81%; p = 0.002) and pooled sensitivity (78%; 95% CI 71 to 84; p = 0.009) were higher in non-tier 1 studies. Sensitivity analysis confirmed that the sensitivity of TBNA depends critically on the prevalence of mediastinal metastasis. The pooled major complication rate was 0.3% (95% CI 0.01 to 4). CONCLUSIONS: When properly performed, TBNA is highly specific for identifying mediastinal metastasis in patients with NSCLC, but sensitivity depends critically on the study methods and patient population. In populations with a lower prevalence of mediastinal metastasis, the sensitivity of TBNA is much lower than reported in recent lung cancer guidelines.

Biopsy, Needle↗
PubMed2005

Health-related quality of life in patients with idiopathic pulmonary fibrosis: a systematic review.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) profoundly affects the quality of patients' lives. A systematic review was performed to evaluate critically the published literature and to examine what is known about health-related quality of life (HRQL) in patients with IPF. METHODS: The MEDLINE, EMBASE, Health and Psychosocial Instruments, and Cochrane Library databases were searched to 1 April 2004. Abstracts and bibliographies of published articles were scanned and contact was made with investigators. Included studies analysed HRQL (or quality of life) in at least 10 patients with IPF. Two reviewers independently selected studies, evaluated their quality according to predetermined criteria, and abstracted data on study design, patients' demographic and clinical characteristics, and quality of life outcome measures. RESULTS: Seven studies met the inclusion criteria. The studies enrolled 512 patients with IPF and used three different instruments to measure HRQL. All studies had important limitations in methodological quality; none measured longitudinal changes in HRQL over time. Patients reported substantially impaired HRQL, especially in domains that measured physical health and level of independence. Patients with IPF appear to have similar impairments in HRQL to those with chronic obstructive pulmonary disease. Measures of dyspnoea were moderately correlated with scores from domains that measured physical health (R2 = 0.03-0.66) and energy/fatigue/pep (R2 = 0.19-0.55), but measures of pulmonary function and gas exchange did not correlate as strongly with these and other domains. CONCLUSION: Studies of HRQL in patients with IPF suggest that, in addition to the obvious effect on physical health, general health, energy level, respiratory symptoms, and level of independence are also impaired. Variability in HRQL among patients is not fully explained by measures of dyspnoea or pulmonary function, suggesting that HRQL measures provide unique information. More research is needed to identify or design appropriate measurement instruments for patients with IPF and to examine changes in HRQL over time or in response to specific treatments.

Aged↗
PubMed2001

Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis.

CONTEXT: Focal pulmonary lesions are commonly encountered in clinical practice, and positron emission tomography (PET) with the glucose analog 18-fluorodeoxyglucose (FDG) may be an accurate test for identifying malignant lesions. OBJECTIVE: To estimate the diagnostic accuracy of FDG-PET for malignant focal pulmonary lesions. DATA SOURCES: Studies published between January 1966 and September 2000 in the MEDLINE and CANCERLIT databases; reference lists of identified studies; abstracts from recent conference proceedings; and direct contact with investigators. STUDY SELECTION: Studies that examined FDG-PET or FDG with a modified gamma camera in coincidence mode for diagnosis of focal pulmonary lesions; enrolled at least 10 participants with pulmonary nodules or masses, including at least 5 participants with malignant lesions; and presented sufficient data to permit calculation of sensitivity and specificity were included in the analysis. DATA EXTRACTION: Two reviewers independently assessed study quality and abstracted data regarding prevalence of malignancy and sensitivity and specificity of the imaging test. Disagreements were resolved by discussion. DATA SYNTHESIS: We used a meta-analytic method to construct summary receiver operating characteristic curves. Forty studies met inclusion criteria. Study methodological quality was fair. Sample sizes were small and blinding was often incomplete. For 1474 focal pulmonary lesions of any size, the maximum joint sensitivity and specificity (the upper left point on the receiver operating characteristic curve at which sensitivity and specificity are equal) of FDG-PET was 91.2% (95% confidence interval, 89.1%-92.9%). In current practice, FDG-PET operates at a point on the summary receiver operating characteristic curve that corresponds approximately to a sensitivity and specificity of 96.8% and 77.8%, respectively. There was no difference in diagnostic accuracy for pulmonary nodules compared with lesions of any size (P =.43), for semiquantitative methods of image interpretation compared with qualitative methods (P =.52), or for FDG-PET compared with FDG imaging with a modified gamma camera in coincidence mode (P =.19). CONCLUSIONS: Positron emission tomography with 18-fluorodeoxyglucose is an accurate noninvasive imaging test for diagnosis of pulmonary nodules and larger mass lesions, although few data exist for nodules smaller than 1 cm in diameter. In current practice, FDG-PET has high sensitivity and intermediate specificity for malignancy.

Glucose-6-Phosphate↗
PubMed2001

Occupational inhalant exposure and respiratory disorders among never-smokers referred to a hospital pulmonary function laboratory.

BACKGROUND: Multiple reports have described associations between occupational inhalant exposure and lung disease. Previous occupational lung disease investigations have studied populations consisting of both smokers and nonsmokers. Smoking complicates interpretation of toxicant exposure-response relationships. The objective of this study was to determine whether, among never-smokers, occupational exposure to gases, dusts, or fumes is associated with a history of respiratory disorders and pulmonary function test defined obstructive lung disease. METHODS: We performed a retrospective analysis of 517 never-smoker patients who underwent pulmonary function testing in our clinical laboratory between 1986 and 1999. We calculated the relative risks of developing adverse respiratory health outcomes given a history of exposure to occupational inhalants. RESULTS: Compared with persons with a negative occupational exposure history, exposed persons had an increased risk of reporting a history of bronchitis [relative risk (RR), 1.59; 95% confidence interval (CI), 1.20-2.12], recurrent lung infections (RR, 2.09; 95% CI, 1.14-3.82), and bronchodilator use (RR, 1.61; 95% CI, 1.26-2.06). There was also a statistically significant association between a history of inhalant exposure and the finding of an obstructive ventilatory defect on pulmonary function testing (RR, 1.79; 95% CI, 1.12-2.85). A history of inhalant exposure was not associated with self-reported asthma (RR, 1.08; 95% CI, 0.83-1.41). The population attributable risk estimates for respiratory disorders due to inhalant exposure were: bronchitis, 23.6%; recurrent lung infection, 36.3%; bronchodilator use, 24.3%; and obstructive lung disease, 29.6%. CONCLUSIONS: Occupational inhalant exposure is a strong risk factor for lung disease in this population of never smokers. A significant burden of respiratory disease in this population may be attributable to occupational inhalant exposure.

Adolescent↗
PubMed1999

Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A cost-effectiveness analysis.

BACKGROUND: Low-molecular-weight heparins are effective for treating venous thrombosis, but their cost-effectiveness has not been rigorously assessed. OBJECTIVE: To evaluate the cost-effectiveness of low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. DESIGN: Decision model. DATA SOURCES: Probabilities for clinical outcomes were obtained from a meta-analysis of randomized trials. Cost estimates were derived from Medicare reimbursement and other sources. TARGET POPULATION: Two hypothetical cohorts of 60-year-old men with acute deep venous thrombosis. TIME HORIZON: Patient lifetime. PERSPECTIVE: Societal. INTERVENTION: Fixed-dose low-molecular-weight heparin or adjusted-dose unfractionated heparin. OUTCOME MEASURES: Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. An in-patient hospital setting was used for the base-case analysis. Secondary analyses examined outpatient treatment with low-molecular-weight heparin. RESULTS OF BASE-CASE ANALYSIS: Total costs for inpatient treatment were $26,516 for low-molecular-weight heparin and $26,361 for unfractionated heparin. The cost of initial care was higher in patients who received low-molecular-weight heparin, but this was partly offset by reduced costs for early complications. Low-molecular-weight heparin treatment increased quality-adjusted life expectancy by approximately 0.02 years. The incremental cost-effectiveness of inpatient low-molecular-weight heparin treatment was $7820 per QALY gained. Treatment with low-molecular-weight heparin was cost saving when as few as 8% of patients were treated at home. RESULTS OF SENSITIVITY ANALYSIS: When late complications were assumed to occur 25% less frequently in patients who received unfractionated heparin, the incremental cost-effectiveness ratio increased to almost $75,000 per QALY gained. When late complications were assumed to occur 25% less frequently in patients who received low-molecular-weight heparin, this treatment resulted in a net cost savings. Inpatient low-molecular-weight heparin treatment became cost saving when its pharmacy cost was reduced by 31% or more, when it reduced the yearly incidence of late complications by at least 7%, when as few as 8% of patients were treated entirely as outpatients, or when at least 13% of patients were eligible for early discharge. CONCLUSIONS: Low-molecular-weight heparins are highly cost-effective for inpatient management of venous thrombosis. This treatment reduces costs when small numbers of patients are eligible for outpatient management.

Anticoagulants↗
PubMed1999

Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A meta-analysis of randomized, controlled trials.

BACKGROUND: Low-molecular-weight heparins may simplify the management of deep venous thrombosis. A critical clinical issue is whether this more convenient therapy is as safe and effective as treatment with unfractionated heparin. PURPOSE: To compare the safety and efficacy of low-molecular-weight heparins with those of unfractionated heparin for treatment of acute deep venous thrombosis. DATA SOURCES: Reviewers identified studies by searching MEDLINE, reviewing references from retrieved articles, scanning abstracts from conference proceedings, and contacting investigators and pharmaceutical companies. STUDY SELECTION: Randomized, controlled trials that compared a low-molecular-weight heparin preparation with unfractionated heparin for treatment of acute deep venous thrombosis. DATA EXTRACTION: Two reviewers extracted data independently. Reviewers evaluated study quality using a validated four-item instrument. DATA SYNTHESIS: Eleven of 37 studies met inclusion criteria for three major outcomes. Most studies used proper randomization procedures, but only one was double-blinded. Compared with unfractionated heparin, low-molecular-weight heparins reduced mortality rates over 3 to 6 months of patient follow-up (odds ratio, 0.71 [95% CI, 0.53 to 0.94]; P = 0.02). For major bleeding complications, the odds ratio favored low-molecular-weight heparins (0.57 [CI, 0.33 to 0.99]; P = 0.047), but the absolute risk reduction was small and not statistically significant (0.61% [CI, -0.04% to 1.26%]; P = 0.07). For preventing thromboembolic recurrences, low-molecular-weight heparins seemed as effective as unfractionated heparin (odds ratio, 0.85 [CI, 0.63 to 1.14]; P > 0.2). CONCLUSIONS: Low-molecular-weight heparin treatment reduces mortality rates after acute deep venous thrombosis. These drugs seem to be as safe as unfractionated heparin with respect to major bleeding complications and appear to be as effective in preventing thromboembolic recurrences.

Analysis of Variance↗
PubMed1999

Usefulness of positron emission tomography imaging in the management of lung cancer.

Positron emission tomography imaging is useful for the characterization of the solitary pulmonary nodule and mediastinal staging. Potential future applications include extrathoracic staging to help to determine the ideal site for possible tissue diagnosis, to guide treatment plans, and to monitor the response to therapy and recurrence. Positron emission tomography may also predict prognosis. This review discusses the uses of positron emission tomography, the current literature, and the clinical guidelines for positron emission tomography imaging.

Carcinoma, Non-Small-Cell Lung↗
PubMed1998

Strategy and cost in investigating solitary pulmonary nodules.

OBJECTIVE: To compare the probability of cancer in a solitary pulmonary nodule using standard criteria with Bayesian analysis and result of 2-[F-18] fluoro-2-deoxy-D-glucose-positron emission tomographic (FDG-PET) scan. SETTING: A university hospital and a teaching Veteran Affairs Medical Center. METHODS: Retrospective analysis of 52 patients who had undergone both CT scan of the chest and a FDG-PET scan for evaluation of a solitary pulmonary nodule. FDG-PET scan was classified as abnormal or normal. Utilizing Bayesian analysis, the probability of cancer using "standard criteria" available in the literature, based on patient's age, history of previous malignancy, smoking history, size and edge of nodule, and presence or absence of calcification were calculated and compared to the probability of cancer based on an abnormal or normal FDG-PET scan. Histologic study of the nodules was the gold standard. RESULTS: The likelihood ratios for malignancy in a solitary pulmonary nodule with an abnormal FDG-PET scan was 7.11 (95% confidence interval [CI], 6.36 to 7.96), suggesting a high probability for malignancy, and 0.06 (95% CI, 0.05 to 0.07) when the PET scan was normal, suggesting a high probability for benign nodule. FDG-PET scan as a single test alone was more accurate than the standard criteria and standard criteria plus PET scan in correctly classifying nodules as malignant or benign. CONCLUSION: FDG-PET scan as a single test was a better predictor of malignancy in solitary pulmonary nodules than the standard criteria using Bayesian analysis. FDG-PET scan can be a useful adjunct test in the evaluation of solitary pulmonary nodules.

Cost-Benefit Analysis↗
PubMed1997

Lung cancer.

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Carcinoma, Bronchogenic↗
PubMed1992

Potential oxyradical damage and energy status in individual muscle fibres from degenerating muscle diseases.

Inherited degenerating muscle diseases result in disintegration of muscle fibres, which is initiated by a lack of or alteration to a muscle protein. In Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) the protein is known to be dystrophin. The cellular function of dystrophin is not known in any detail but its absence appears to lead to a weakening of the sarcolemma. It has been proposed by Murphy and Kehrer that this leads ultimately to increased oxyradical production which may accelerate the degeneration. Studies have been carried out on individual muscle fibres derived from biopsy samples from patients with a number of degenerative muscle diseases. The glutathione cycling components, in particular glutathione and glutathione peroxidase, are significantly elevated in DMD, BMD and other diseases. Glutathione reductase is also elevated in some of these diseases. Energy producing systems are also affected particularly in intact fibres of muscle derived from muscle at an advanced stage of the disease. These results suggest that oxyradical damage may occur as a secondary consequence of muscle degenerating disease, leading to a breakdown in the glycogenolytic energy producing system.

Adenosine Diphosphate↗
PubMed1986

Inhibitory effect of anoxia on 125I-insulin binding by rat hepatocytes.

We have examined the possibility that 125I-insulin binding by isolated rat hepatocytes is modulated by cellular ATP levels. To avoid complications due to ATP-dependent internalization of bound insulin, 125I-insulin binding was determined at 10 degrees C; at this temperature, equilibrium binding was achieved after incubation for 4-6 h. When hepatocytes were incubated at 37 degrees C under anaerobic conditions, ATP levels and 125I-insulin binding were both lowered by about 65%. Anoxia inhibited the association of 125I-insulin with the hepatocyte receptor; the dissociation of insulin from hepatocytes was not affected. Cellular ATP levels and 125I-insulin binding were both restored when anaerobic cells were incubated further at 37 degrees C under aerobic conditions. When anaerobic cells were incubated in air at 10 degrees C during the insulin binding assay, 125I-insulin binding recovered completely, but ATP levels were unaffected. The inhibitory effect of anoxia on 125I-insulin binding was not due to any effect on 125I-insulin degradation or on cell viability. We conclude (1) that the ability of hepatocytes to bind insulin can be modulated on a short-term basis in response to the metabolic status of the cell, and (2) that modulation of the liver cell insulin receptor is not a function of cellular ATP levels.

Anaerobiosis↗