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Biomedical subjects

Petra Macaskill

Publications and source records attributed to Petra Macaskill.

13 recordsLinked to original sources

Effect of study design and quality on unsatisfactory rates, cytology classifications, and accuracy in liquid-based versus conventional cervical cytology: a systematic review.

BACKGROUND: Liquid-based cytology is reported to increase the sensitivity of cervical cytology and the proportion of slides that are satisfactory for assessment, in comparison with conventional cytology. Although some countries have changed to liquid-based cytology for cervical screening, controversy remains. We reviewed the published work to assess the performance of liquid-based cytology relative to conventional cytology in primary studies assessed to be of low, medium, or high methodological quality. METHODS: 56 primary studies were reviewed and assessed with strict methodological criteria. Liquid-based cytology and conventional cytology were compared in terms of the percentage of slides classified as unsatisfactory, the percentage of slides classified in each cytology category, and the accuracy of detection of high-grade disease. Data were examined for studies overall and in strata to examine the effect of study quality on results. FINDINGS: The median difference in the percentage of unsatisfactory slides between liquid-based cytology and conventional cytology was 0.17%. Only one small study was a randomised controlled trial. The classification of high-grade squamous epithelial lesion varied according to study quality (p=0.04), with conventional cytology classifying more slides in this category than did liquid-based cytology in high-quality studies (n=3) only. In medium-quality (n=30) and high-quality studies, liquid-based cytology classified more slides as atypical squamous cells of unknown significance than did conventional cytology when compared with low-quality studies (n=17; p=0.05). Only four studies provided sufficient verified data to allow estimation of sensitivity and specificity and comparison of test accuracy. INTERPRETATION: We saw no evidence that liquid-based cytology reduced the proportion of unsatisfactory slides, or detected more high-grade lesions in high-quality studies, than conventional cytology. This review does not lend support to claims of better performance by liquid-based cytology. Large randomised controlled trials are needed.

Cytological Techniques↗

New methods give better estimates of changes in diagnostic accuracy when prior information is provided.

OBJECTIVE: Whether tests such as imaging should be read with or without access to prior clinical information is controversial. Naïve comparisons may suggest that the provision of prior information improves test accuracy, whereas in fact the opposite may be true. This is because provision of clinical background may actually bias test readers to over- or underinterpret relevant test findings, and they may suboptimally integrate the previous and current evidence. We propose comparing the combined accuracy of prior information and a test read (i) with or (ii) without knowledge of prior information. Analysis methods include simple decision rules and logistic regression. STUDY DESIGN AND SETTING: A study of cancer detection in women presenting with breast symptoms, in whom ultrasound could be read with or without reviewing prior mammography. RESULTS: Naïve analysis gave an area under the receiver operating characteristics curve (AUC) for ultrasound read with mammography on view that was 4.6% higher (P < .01) than without mammography on view. Our approach, comparing the combined accuracy of mammography and ultrasound read i) with and ii) without knowledge of mammographic findings, showed much smaller differences. CONCLUSION: Our approach is more appropriate than naïve analyses. The particular choice of analytic method depends on the study size and the diagnostic accuracy of combinations of the prior information and the test reading.

Adult↗

Intraocular lens power in bilateral cataract surgery: whether adjusting for error of predicted refraction in the first eye improves prediction in the second eye.

PURPOSE: To assess whether the retrospectively calculated intraocular lens (IOL) position value in the first eye reduces the error of predicted refraction in the second. SETTING: Prince of Wales Hospital, Sydney, Australia. METHODS: One hundred twenty-one consecutive patients who had bilateral cataract surgery with the same IOL (SI-30NB, Advanced Medical Optics) were identified. The case-derived A-constant in the first eye was calculated from the postoperative refraction. This value was used to calculate the adjusted error of predicted refraction in the second eye and compared against the unadjusted error in that eye (calculated using manufacturer's A-constant). RESULTS: Axial length (r = 0.97), corneal power (r = 0.97), and IOL power (r = 0.90) were strongly correlated between eyes with no statistically significant mean interocular difference. Although there was no significant interocular difference in the mean error of predicted refraction (SRK/T), there was only a moderate correlation between eyes (r = 0.40). Using the axial length vergence formula, the mean adjusted error of predicted refraction in the second eye (-0.66 diopter [D]) was significantly larger than the mean unadjusted error (-0.47 D) (P = .029). The standard deviation of the adjusted error of predicted refraction (SRK/T) in the second eye (0.85 D) was greater than the standard deviation of the unadjusted error (0.79). Similarly, the adjusted mean absolute error of predicted refraction (0.65 D) was greater than the unadjusted error (0.63 D). CONCLUSION: Adjusting the IOL power in the second eye by the amount of overprediction or underprediction in the first eye did not improve prediction accuracy because the error of predicted refraction varied independently between the 2 eyes of an individual.

Cataract Extraction↗

The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed.

BACKGROUND AND OBJECTIVE: Publication bias and other sample size effects are issues for meta-analyses of test accuracy, as for randomized trials. We investigate limitations of standard funnel plots and tests when applied to meta-analyses of test accuracy and look for improved methods. METHODS: Type I and type II error rates for existing and alternative tests of sample size effects were estimated and compared in simulated meta-analyses of test accuracy. RESULTS: Type I error rates for the Begg, Egger, and Macaskill tests are inflated for typical diagnostic odds ratios (DOR), when disease prevalence differs from 50% and when thresholds favor sensitivity over specificity or vice versa. Regression and correlation tests based on functions of effective sample size are valid, if occasionally conservative, tests for sample size effects. Empirical evidence suggests that they have adequate power to be useful tests. When DORs are heterogeneous, however, all tests of funnel plot asymmetry have low power. CONCLUSION: Existing tests that use standard errors of odds ratios are likely to be seriously misleading if applied to meta-analyses of test accuracy. The effective sample size funnel plot and associated regression test of asymmetry should be used to detect publication bias and other sample size related effects.

Diagnostic Errors↗

Risk factors for HIV infection in a gynaeco-obstetric population in Vietnam--a case-control study.

BACKGROUND: Vietnam has an emerging HIV epidemic, particularly in male drug injectors. Data on HIV infections in women in the general population, and their risk factors, are scanty. METHODS: A case-control study was performed in a large gynaeco-obstetric hospital in Haiphong city in 1998-2001. The sample was 22000 attendees. The medical records of 58 HIV-seropositive cases were compared with 422 randomly chosen HIV-seronegative controls for potential risk factors. RESULTS: A multivariate analysis found that HIV infection was associated with young age, past/current history of sexually transmitted infections (STI) and being unemployed. Patients aged 21-30 years were 10-fold less likely to be infected than women aged <20 years (OR 0.11, 95% CI 0.04-0.33). Women with a past/current history of STI had over 20 times the risk of those who did not (95% CI 6.7-62.3). Unemployed women had at least twice the risk of infection of any other occupational group. CONCLUSIONS: We have identified risk factors in women that have not been highlighted previously in Vietnam. Our study suggests that all antenatal women, especially those who are young or unemployed (or, with a current/past history of STI), should be offered free HIV tests, counselling and management.

Adolescent↗

Adjustment for baseline measurement error in randomized controlled trials induces bias.

When estimating the treatment effect in a randomized controlled trial, it is common to have a continuous outcome which is also observed at baseline. These observations are often prone to measurement error, for example due to within-patient variability. Controversy exists in the literature about whether baseline measurement error should be adjusted for in this context. Computer simulations were used to compare the biases in the estimated treatment effect, with and without adjusting for measurement error, and for different levels of observed baseline imbalance. The impacts of sample size (30 per group and 300 per group) and reliability coefficient (0.6, 0.8 and 1) were also assessed. The results show that in randomized controlled trials, the ordinary least squares (OLS) estimator without adjusting for measurement error is unbiased. On the contrary, adjusting for measurement error leads to bias, especially when sample sizes are small and/or measurement error is large. The treatment effect adjusting for measurement error is on average overestimated when the baseline mean of the control group is larger than that of the treated group. It is underestimated when the control group has a smaller baseline mean.

Analysis of Variance↗

Empirical Bayes estimates generated in a hierarchical summary ROC analysis agreed closely with those of a full Bayesian analysis.

BACKGROUND AND OBJECTIVE: A range of fixed-effect and random-effects meta-analytic methods are available to obtain summary estimates of measures of diagnostic test accuracy. The hierarchical summary receiver operating characteristic (HSROC) model proposed by Rutter and Gatsonis in 2001 represents a general framework for the meta-analysis of diagnostic test studies that allows different parameters to be defined as a fixed effect or random effects within the same model. The Bayesian method used for fitting the model is complex, however, and the model is not widely used. The objective of this report is to show how the model may be fitted using the SAS procedure NLMIXED and to compare the results to the fully Bayesian analysis using an example. METHODS: The HSROC model, its assumptions, and its interpretation are described. The advantages of this model over the usual summary ROC (SROC) regression model are outlined. A complex example is used to compare the estimated SROC curves, expected operating points, and confidence intervals using the alternative approaches to fitting the model. RESULTS: The empirical Bayes estimates obtained using NLMIXED agree closely with those obtained using the fully Bayesian analysis. CONCLUSION: This alternative and more straightforward method for fitting the HSROC model makes the model more accessible to meta-analysts.

Bayes Theorem↗

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↗

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↗

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↗

Epidemiology of physical activity participation among New South Wales school students.

OBJECTIVE: To examine the prevalence and socio-demographic distribution of physical activity among New South Wales school students in Years 8 and 10. METHODS: Cross-sectional survey of 2,026 randomly selected NSW high school students in 1997. The survey participants self-reported their physical activity participation during a normal week in summer and winter school terms. RESULTS: During summer school terms, 80.9% and 85.9% of Year 8 and Year 10 boys, respectively, and 80.8% and 77.7% of Year 8 and Year 10 girls, respectively, were adequately active. During winter school terms, 75.6% and 84.0% of Year 8 and Year 10 boys, respectively, and 69.4% and 66.0% of Year 8 and Year 10 girls, respectively, were adequately active. The associations between socio-economic status, urban/rural place of residence and physical activity participation were neither strong nor consistent. There were complex relationships between physical activity participation and cultural background among boys, and large differences between different cultural groups of girls and large declines in participation from Year 8 to Year 10 among girls. CONCLUSIONS: Although the majority of boys and girls are adequately active, it is clear that a smaller proportion of girls than boys are vigorously active, particularly during winter. There were no clear differences across tertiles of SES or place of residence, but there were significant differences between girls from different cultural backgrounds. IMPLICATIONS: Efforts to increase the proportion of young people who are vigorously active should emphasise the needs and interests of girls, particularly those from Middle-Eastem and Asian cultural backgrounds.

Adolescent↗

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↗