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Biomedical subjects

Les Irwig

Publications and source records attributed to Les Irwig.

29 records · Page 2Linked to original sources
PubMed2004

The number needed to treat (NNT) can be adjusted for bias when the outcome is measured with error.

BACKGROUND AND OBJECTIVE: We consider the number needed to treat (NNT) when the event of interest is defined by dichotomizing a continuous response at a threshold level. If the response is measured with error, the resulting NNT is biased. We consider methods to reduce this bias. METHODS: Bias adjustment was studied using simulations in which we varied the distributions of the underlying response and measurement error, including both normal and nonnormal distributions. We studied a maximum likelihood estimate (MLE) based on normality assumptions, and also considered a simulation-extrapolation estimate (SIMEX) without such assumptions. The treatment effect across all potential thresholds was summarized using an NNT threshold curve. RESULTS: Crude NNT estimation was substantially biased due to measurement error. The MLE performed well under normality, and it continued to perform well with nonnormal measurement error, but when the underlying response was nonnormal the MLE was unacceptably biased and was outperformed by the SIMEX estimate. The simulation results were also reflected in empirical data from a randomized study of cholesterol-lowering therapy. CONCLUSION: Ignoring measurement error can lead to substantial bias in NNT, which can have an important practical effect on the interpretation of analyses. Analysis methods that adjust for measurement error bias can be used to assess the sensitivity of NNT estimates to this effect.

Bias↗
PubMed2004

A randomized crossover trial of PAPNET for primary cervical screening.

OBJECTIVE: To develop and demonstrate efficient methods to estimate the relative true positive and false positive rates of two cervical screening tests (conventional cytology and PAPNET). METHODS: We designed the study to meet stringent methodologic criteria for comparison of two tests while simultaneously minimizing the numbers requiring reference standard verification. We used a cytology reference standard and also assessed histology when available. For the primary analysis, slides with discordant results around the test threshold (CIN 1) were reviewed by a panel of two cytopathologists, blind to previous results, to establish the reference standard result (reference standard threshold for abnormality CIN2). Where histology was available, a secondary analysis was conducted with the reference standard based on the highest grade lesion (either cytology or histology). RESULTS: Among 21,747 Pap smears, 372 were discordant around the test threshold, requiring verification. In the primary analysis PAPNET detected four more true positives than conventional reading; difference in sensitivity 1.29% (95%CI -5.79 to 8.36%, P=.40). There were two extra false positives using PAPNET; difference in the false positive rate 0.0097% (95%CI -0.122 to 0.142%, P=.47). The results of the combined cytology and histology analysis were similar; difference in true positive rate 0.29% (95%CI -6.76 to 7.34%, P=.50) and difference in false positive rate 0.024% (95%CI -0.098 to 0.15%, P=.39). CONCLUSION: This is an efficient and valid study design where the objective is to examine the comparative accuracy of two tests. The design provides an efficient means of estimating the difference between true positive and false positive detection by the two tests, which often is sufficient information for policy decisions.

Adolescent↗
PubMed2004

The influence of clinical information on the accuracy of diagnostic mammography.

OBJECTIVE: This study examined the influence of knowledge of clinical information on the accuracy of mammography in women referred for investigation of breast symptoms. METHODS: Subjects were sampled from all women consecutively attending a symptomatic breast clinic and aged 25-55 years. This included all 240 women shown to have breast cancer and 240 age-matched women shown not to have cancer. Mammography films were prospectively reported by two radiologists independently of each other in a blinded manner and without knowledge of any clinical information. The films were then re-read with information about the type and site of symptoms (and without knowledge of the level of suspicion of cancer on clinical examination). The accuracy of reading with and without information on symptoms was compared using sensitivity and specificity and receiver operating characteristic (ROC) curves. The effect of age on changes in test accuracy was examined. RESULTS: Reporting the mammogram with knowledge of clinical information (compared to without any information) significantly improved sensitivity (75.8 vs. 71.3%, P = 0.003) for one radiologist, with a non-significant reduction in specificity (85.4 vs. 87.1%, P = 0.22). For the other radiologist, it resulted in non-significant improvement in both sensitivity (75.4 vs. 73.8%, P = 0.13) and specificity (89.2 vs. 87.9%, P = 0.25). Age did not have a statistically significant effect on changes in test accuracy in our data. ROC curves for both radiologists showed that reporting mammography with knowledge of clinical information resulted in small (about 2%) but significant improvement in overall test accuracy. CONCLUSION: Our findings support the provision of clinical information relating to patients' presentation to radiologists reporting diagnostic mammography.

Adult↗
PubMed2003

Oxygen-saturation targets and outcomes in extremely preterm infants.

BACKGROUND: Physiological studies have shown that chronic hypoxemia may occur in preterm infants who require supplemental oxygen for extended periods and that this hypoxemia may contribute to poor growth and development. Anecdotal reports and uncontrolled observational studies have suggested that a higher oxygen-saturation range may be beneficial in terms of growth and development. METHODS: We conducted a multicenter, double-blind, randomized, controlled trial involving 358 infants born at less than 30 weeks of gestation who remained dependent on supplemental oxygen at 32 weeks of postmenstrual age. They were randomly assigned to a target functional oxygen-saturation range of either 91 to 94 percent (standard-saturation group) or 95 to 98 percent (high-saturation group); this target was maintained for the duration of supplemental-oxygen therapy. The primary outcomes were growth and neurodevelopmental measures at a corrected age of 12 months. RESULTS: There were no significant differences between the groups in weight, length, or head circumference at a corrected age of 12 months. The frequency of major developmental abnormalities also did not differ significantly between the standard-saturation group and the high-saturation group (24 percent and 23 percent, respectively, P=0.85). There were six deaths due to pulmonary causes in the high-saturation group and one such death in the standard-saturation group (P=0.12). The high-saturation group received oxygen for a longer period after randomization (median, 40 days vs. 18 days; P<0.001) and had a significantly higher rate of dependence on supplemental oxygen at 36 weeks of postmenstrual age and a significantly higher frequency of home-based oxygen therapy. CONCLUSIONS: Targeting a higher oxygen-saturation range in extremely preterm infants who were dependent on supplemental oxygen conferred no significant benefit with respect to growth and development and resulted in an increased burden on health services.

Double-Blind Method↗
PubMed2003

Sydney Breast Imaging Accuracy Study: Comparative sensitivity and specificity of mammography and sonography in young women with symptoms.

OBJECTIVE: We examined the age-specific sensitivity and specificity of mammography and sonography in symptomatic women to determine the age below which sonography may be the more accurate imaging test, which may guide the choice of initial breast imaging examination based on the woman's age. MATERIALS AND METHODS: Four hundred eighty subjects were sampled from all women consecutively attending a symptomatic breast clinic between 1994 and 1996 and ranging in age from 25 to 55 years. We included all 240 women shown to have breast cancer (thus avoiding selection bias) and 240 age-matched women shown not to have cancer. Mammograms and sonograms were prospectively interpreted independently and without knowledge of age by two radiologists in a blinded manner, with a third radiologist arbitrating disagreements. Sensitivity and specificity of each imaging test in relation to age were examined using logistic regression modeling, and accuracy was compared using the chi-square test for paired proportions. RESULTS: Sensitivity and specificity of each test were not linearly associated with age; however, the sensitivity of mammography increased substantially in women older than 50 years. Sonographic sensitivity of 81.7% was not significantly greater than mammographic sensitivity of 75.8% (chi(2)(1) = 2.06, p = 0.15). However, in women 45 years old or younger, the sensitivity of sonography was 13.2% (95% confidence interval, 2.1-24.3%) greater than that of mammography. The specificity of both tests was approximately 88.0%. CONCLUSION: These data show that sonography is the more accurate imaging test in women 45 years old or younger who present with breast symptoms and may be an appropriate initial imaging examination.

Adult↗
PubMed2002

Assessing the gain in diagnostic performance when combining two diagnostic tests.

Combining dichotomous (or dichotomized) results of two diagnostic tests will result in a trade-off in sensitivity and specificity of the combined test relative to the component tests. Because of this inherent trade-off, likelihood ratios provide a clinically relevant means of comparing the combined test with one of its components. The likelihood ratios depend on both sensitivity and specificity and hence take into account the trade-off between them. A graphical approach is used to assess whether the combined test is superior to a component test, or vice versa. Asymptotic standard errors are derived for comparing likelihood ratios when a paired study design is used. The trade-off in the expected number of additional true positive and false positive results (or true negative and false negative results) is used as the basis for deciding whether to use tests in combination when neither the combined nor a component test shows superior test performance based on their likelihood ratios. These methods are illustrated with an example that considers the combined use of Pap and HPV testing.

Diagnostic Tests, Routine↗
PubMed2002

Analytic methods for comparing two dichotomous screening or diagnostic tests applied to two populations of differing disease prevalence when individuals negative on both tests are unverified.

Two dichotomous screening tests may be compared by applying both tests to all members of a sampled population. For individuals with a positive result on either test the disease status may be verified by a reference standard, but for individuals negative on both tests the disease status may be unverified because the probability of disease is so low that further investigation is costly, unacceptable and perhaps unethical. If the tests have been applied to samples from two populations which have different disease prevalences then unbiased estimates of the true positive and false positive rates of each test, the prevalences in the two populations, and two parameters representing dependence between the two tests can be estimated using maximum likelihood methods. The methods are based on the assumption that the sensitivities and specificities of the two tests, and the dependencies between the tests, are independent of prevalence. A test of goodness of fit provides a test of this.

Adult↗
PubMedDate not supplied

Combining carbohydrate-deficient transferrin and gamma-glutamyltransferase to increase diagnostic accuracy for problem drinking.

AIM: To examine methods for combining quantitative results for serum carbohydrate deficient transferrin (CDT), gamma-glutamyltransferase (GGT) and/or aspartate aminotransferase (AST), and refining these by inclusion of patient characteristics. METHODS: Data from 1684 subjects, recruited from the general population, abstainer groups and alcohol treatment centres (participants in the five nations WHO/ISBRA study of biological markers of alcohol use), were used to develop clinical rules for combining results of GGT, AST and CDT. The algorithm derived by Sillanaukee and Olsson was tested, and compared with new algorithms derived by logistic regression and discriminant analysis. Diagnostic accuracy was assessed by area underneath the receiver operator characteristic curve. Effects of adding gender and clinical information to the algorithm were estimated. RESULTS: The predictive ability of combination rules derived from the two studies and by two different statistical techniques was remarkably consistent. For men, combining lnCDT and lnGGT provided the best accuracy for detecting daily consumption of 60 g ethanol or more in the past 30 days. For women, GGT alone provided the best accuracy for that consumption level. Clinical variables added significantly to the diagnostic accuracy of the models for both men and women, and conversely the test results modified the probability of problem drinking as assessed from clinical data alone. A graphic method was produced to help clinicians estimate probabilities for consumption of 60 g or more per day. CONCLUSIONS: Combining biochemical markers enhances detection of problem drinking in men but not in women. Information on clinical variables increases the ability to correctly detect problem drinking.

Adolescent↗
PubMedDate not supplied

The influence of knowledge of mammography findings on the accuracy of breast ultrasound in symptomatic women.

Breast ultrasound is generally interpreted with knowledge of the mammographic examination. This study examined the influence of knowledge of mammography findings on the accuracy of ultrasound in women with breast symptoms. Subjects were sampled from all women 25-55 years of age consecutively attending a breast clinic. This included all 240 women shown to have breast cancer and 240 age-matched women shown not to have cancer. Ultrasound films were prospectively reviewed and reported by two radiologists independent of each other and in a blinded manner. A two-phase design was used. In the first phase, the radiologists provided an opinion on the ultrasound films. In the second phase, the ultrasound films were reread with consideration of the corresponding mammographic examination. The accuracy of reading the ultrasound with and without knowledge of the findings on mammography was compared using sensitivity and specificity, and receiver operating characteristics (ROC) curves. Reporting the ultrasound with knowledge of mammography (compared to without mammography) improved sensitivity and reduced specificity for both radiologists. For one reader, sensitivity increased from 77.5% to 86.7% (p = 0.0002) and specificity decreased from 89.7% to 85.4% (p = 0.04). For the other reader, sensitivity increased from 81.3% to 87.5% (p = 0.0023) and specificity decreased from 87.1% to 85.0% (p = 0.27). ROC curves for both radiologists showed that reporting ultrasound with knowledge of mammography resulted in small (about 3%), but significant improvement in the area under the ROC curve. Our study indicates that knowledge of the findings of mammography improves the interpretation of breast ultrasound in symptomatic women.

Adult↗