Siew F Chan

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.

Accuracy of reading liquid based cytology slides using the ThinPrep Imager compared with conventional cytology: prospective study

Objective To compare the accuracy of liquid based cytology using the computerised ThinPrep Imager with that of manually read conventional cytology. Design Prospective study. Setting Pathology laboratory in Sydney, Australia. Participants 55 164 split sample pairs (liquid based sample collected after conventional sample from one collection) from consecutive samples of women choosing both types of cytology and whose specimens were examined between August 2004 and June 2005. Main outcome measures Primary outcome was accuracy of slides for detecting squamous lesions. Secondary outcomes were rate of unsatisfactory slides, distribution of squamous cytological classifications, and accuracy of detecting glandular lesions. Results Fewer unsatisfactory slides were found for imager read cytology than for conventional cytology (1.8% v 3.1%; P<0.001). More slides were classified as abnormal by imager read cytology (7.4% v 6.0% overall and 2.8% v 2.2% for cervical intraepithelial neoplasia of grade 1 or higher). Among 550 patients in whom imager read cytology was cervical intraepithelial neoplasia grade 1 or higher and conventional cytology was less severe than grade 1, 133 of 380 biopsy samples taken were high grade histology. Among 294 patients in whom imager read cytology was less severe than cervical intraepithelial neoplasia grade 1 and conventional cytology was grade 1 or higher, 62 of 210 biopsy samples taken were high grade histology. Imager read cytology therefore detected 71 more cases of high grade histology than did conventional cytology, resulting from 170 more biopsies. Similar results were found when one pathologist reread the slides, masked to cytology results. Conclusion The ThinPrep Imager detects 1.29 more cases of histological high grade squamous disease per 1000 women screened than conventional cytology, with cervical intraepithelial neoplasia grade 1 as the threshold for referral to colposcopy. More imager read slides than conventional slides were satisfactory for examination and more contained low grade cytological abnormalities.

Comparative Accuracy of Renal Duplex Sonographic Parameters in the Diagnosis of Renal Artery Stenosis: Paired and Unpaired Analysis

OBJECTIVE The purpose of this study was to evaluate the test performance of duplex sonographic parameters in screening for hemodynamically significant renal artery stenosis, which occurs in approximately 5% of persons with hypertension. MATERIALS AND METHODS A comprehensive literature search was conducted to find studies on the diagnosis of renal artery stenosis in which duplex sonography and intraarterial angiography were compared and in which sensitivity and specificity were calculated. MEDLINE (1966-2005), EMBASE (1988-2005), and reference lists were searched and the authors contacted. Data were subjected to meta-analysis according to the hierarchical summary receiver operating characteristic curve model. Heterogeneity in test performance relating to population and design features was investigated. RESULTS From 1,357 titles, 88 studies involving 9,974 arteries in 8,147 patients were included. The following four parameters were evaluated: peak systolic velocity (21 studies), acceleration time (13 studies), acceleration index (13 studies), and renal-aortic ratio (13 studies). The corresponding diagnostic odds ratios (ORs) were 60.9 (95% CI, 28.3-131.2), 28.9 (95% CI, 7.1-117.2), 16.0 (95% CI, 5.1-50.6), and 29.3 (95% CI, 12.7-67.7). Results based on studies in which parameters were directly compared showed that peak systolic velocity had greater accuracy than renal-aortic ratio (relative diagnostic OR, 1.8; p = 0.03; nine studies) and acceleration index (relative diagnostic OR, 5.3; p < 0.001; five studies). Acceleration time versus acceleration index showed no evidence of a difference in accuracy (relative diagnostic OR, 1.1; p = 0.65; nine studies). Analysis of peak systolic velocity used in combination with other parameters compared with peak systolic velocity alone (seven studies) showed evidence of a shift in test positivity (p < 0.001) but only weak evidence of improvement in accuracy (relative diagnostic OR, 1.6; p = 0.09). CONCLUSION Sonography is a moderately accurate screening test for renal artery stenosis. The single measurement, peak systolic velocity, has the highest performance characteristics, an expected sensitivity of 85% and specificity of 92%. Additional measurements do not increase accuracy.

Absolute and relative accuracy of rapid urine tests for urinary tract infection in children: a meta-analysis

Rapid urine tests, such as microscopy, for bacteria and white cells, and dipsticks, for leucocyte esterase and nitrites, are often used in children that are unwell to guide early diagnosis and treatment of urinary tract infection. We aimed to establish whether these tests were sufficiently sensitive to avoid urine culture in children with negative results and to compare the accuracy of dipsticks with microscopy. Medline, Embase, and reference lists were searched. Studies were included if urine culture results were compared with rapid tests in children. Data were analysed to obtain absolute and relative accuracy estimates. Data from 95 studies in 95 703 children were analysed. Summary estimates for sensitivity and specificity for microscopy for Gram-stained bacteria were 91% (95% CI 80-96) and 96% (92-98), for unstained bacteria were 88% (75-94) and 92% (84-96), for urine white cells were 74% (67-80) and 86% (82-90), for leucocyte esterase or nitrite positive dipstick were 88% (82-91) and 79% (69-87), and for nitrite-only positive dipstick were 49% (41-57) and 98% (96-99). Microscopy for bacteria with Gram stain had higher accuracy than other laboratory tests with relative diagnostic odds ratio compared with bacteria without Gram stain of 8.7 (95% CI 1.8-41.1), white cells of 14.5 (4.7-44.4), and nitrite of 22.0 (0.7-746.3). Microscopy for white cells should not be used for the diagnosis of urinary tract infection because its accuracy is no better than that of dipstick, laboratory facilities are needed, and results are delayed. Rapid tests are negative in around 10% of children with a urinary tract infection and cannot replace urine culture. If resources allow, microscopy with Gram stain should be the single rapid test used.

Most bowel cancer symptoms do not indicate colorectal cancer and polyps: a systematic review

BackgroundBowel symptoms are often considered an indication to perform colonoscopy to identify or rule out colorectal cancer or precancerous polyps. Investigation of bowel symptoms for this purpose is recommended by numerous clinical guidelines. However, the evidence for this practice is unclear. The objective of this study is to systematically review the evidence about the association between bowel symptoms and colorectal cancer or polyps.MethodsWe searched the literature extensively up to December 2008, using MEDLINE and EMBASE and following references. For inclusion in the review, papers from cross sectional, case control and cohort studies had to provide a 2×2 table of symptoms by diagnosis (colorectal cancer or polyps) or sufficient data from which that table could be constructed. The search procedure, quality appraisal, and data extraction was done twice, with disagreements resolved with another reviewer. Summary ROC analysis was used to assess the diagnostic performance of symptoms to detect colorectal cancer and polyps.ResultsColorectal cancer was associated with rectal bleeding (AUC 0.66; LR+ 1.9; LR- 0.7) and weight loss (AUC 0.67, LR+ 2.5, LR- 0.9). Neither of these symptoms was associated with the presence of polyps. There was no significant association of colorectal cancer or polyps with change in bowel habit, constipation, diarrhoea or abdominal pain. Neither the clinical setting (primary or specialist care) nor study type was associated with accuracy.Most studies had methodological flaws. There was no consistency in the way symptoms were elicited or interpreted in the studies.ConclusionsCurrent evidence suggests that the common practice of performing colonoscopies to identify cancers in people with bowel symptoms is warranted only for rectal bleeding and the general symptom of weight loss. Bodies preparing guidelines for clinicians and consumers to improve early detection of colorectal cancer need to take into account the limited value of symptoms.

Psychosocial outcomes of three triage methods for the management of borderline abnormal cervical smears: an open randomised trial

Objective To assess which of three triage strategies for women with borderline abnormal cervical smear results in the best psychosocial outcomes. Design Pragmatic, non-blinded, multicentre, randomised controlled trial. Setting 18 family planning clinics across Australia, covering both urban and rural areas, between January 2004 and October 2006. Participants Women aged 16-70 years (n=314) who attended routine cervical screening and received a borderline cervical smear. Interventions Patients were randomly assigned to human papillomavirus (HPV) DNA testing (n=104), a repeat smear test at six months (n=106), or the patient’s informed choice of either test supported by a decision aid (n=104). Psychosocial outcomes were assessed at multiple time points over 12 months by postal questionnaire. Main outcome measures We assessed health related quality of life (SF36 mental health subscale), cognitive effects (such as perceived risk of cervical cancer, intrusive thoughts), affective outcomes (general anxiety [state-trait anxiety inventory]), specific anxiety about an abnormal smear (cervical screening questionnaire), and behavioural outcomes (sexual health behaviour and visits to the doctor) over 12 months of follow-up. Results At two weeks, some psychosocial outcomes were worse for women allocated to HPV testing compared with those in the smear testing group (SF36 vitality subscale: t=−1.63, df=131, P=0.10; intrusive thoughts χ2=8.14, df=1, P<0.01). Over 12 months, distress about the abnormal smear was lowest in women allocated to HPV testing and highest in the repeat smear testing group (t=−2.89, df=135, P<0.01). Intrusive thoughts were highest in patients allocated to HPV testing (25%, compared with 13% in the informed choice group; difference=12%, 95% CI −1.1% to 25.1%). Women in the HPV DNA group and the informed choice group were more satisfied with their care than women allocated to repeat smear testing. Conclusions Although the psychosocial effect was initially worse for women allocated to HPV triage, over the full year of follow-up this intervention was better for women’s psychosocial health than repeat smear testing. Offering informed choice could have a small advantage for cognitive outcomes, but in view of the additional effort and logistical complexity that this intervention requires, HPV testing alone can be justified for most women.Trial Registration actr.org.au Identifier: 12605000111673

Determining the Impact of Informed Choice : Separating Treatment Effects from the Effects of Choice and Selection in Randomized Trials

Background. The Rucker 2-stage randomized trial (RCT) design and method allows treatment, preference, and selection effects to be estimated separately in clinical trials. Objective. To understand the effect of patient choice on patient outcomes, the authors applied the Rucker design and analysis method. Design. They used data from a trial of management strategies for women with atypical cells of undetermined significance (ASCUS) detected at routine cervical screening, in which informed choice using a decision aid was compared to no choice. Setting. Women’s health clinics across Australia. Patients. Women aged 18 to 70 years (n = 314) with ASCUS. Intervention. Women were randomized to either an informed choice of human papillomavirus (HPV) triage testing or repeat Pap testing or to no choice with random allocation to management by either option. Measurements. Health-related quality of life (SF36) and satisfaction were measured over the course of management and up to 1 year after triage. Results. Using the Rucker analysis, patients who received their choice had higher quality of life scores than those who did not choose (SF36 MCS, 6% higher, 6.0; 95% confidence interval: −0.6 to 12.9; P = 0.07; effect size 0.61 [moderate]). In contrast, the traditional RCT analysis suggested there was little difference in quality of life between the choice and no-choice trial arms. Limitations. The Rucker method assumes that the declared preferences for treatment in the choice arm are representative of the preferences that would have been observed in the no-choice arms if choice was available. Conclusions. The Rucker method should be used to estimate treatment, preference, and selection effects in randomized trials, as it adds to our understanding of the effect of choice on patient outcomes.

Who needs colonoscopy to identify colorectal cancer? Bowel symptoms do not add substantially to age and other medical history

Aliment Pharmacol Ther 2010; 32: 270–281

HPV testing versus repeat Pap testing for the management of a minor abnormal Pap smear: evaluation of a decision aid to support informed choice.

OBJECTIVE To examine womens informed preference for the management of a mildly abnormal Pap smear and the impact of a decision aid. METHODS Women (n=106) were given a choice of management supported by a decision aid and surveyed before, and after decision making to evaluate predictors of choice and decision aid impact. RESULTS HPV triage was preferred by most women (65%) although a substantial minority selected repeat Pap testing (35%). Women who chose HPV triage were more likely to have had children, have had a previous abnormal Pap smear and were more distressed than women who chose a repeat Pap test. In total, 68% of women made an informed choice. Rapid timing of follow-up was important for women choosing HPV testing. The lower chance of colposcopy and greater opportunity for regression, were rated as important by women choosing Pap testing. Decisional conflict was lower among women who chose HPV triage. No other differences in short-term psychological outcomes were found. CONCLUSION The decision aid supported informed choice among the majority of women. Women tailored their choice to their practical, health and psychological needs. PRACTICE IMPLICATIONS Offering women an informed choice for a mildly abnormal Pap smear may enable women to select the management that best suits their circumstances.

Ordering of renal tract imaging by paediatricians after urinary tract infection.

Aim:  To describe paediatricians’ reported ordering of renal tract imaging of children following urinary tract infection.