Tara Selman

Diagnostic accuracy of tests for lymph node status in primary cervical cancer: a systematic review and meta-analysis

Background: Lymph node status is the key to determining the prognosis and treatment of cervical cancer. However, it cannot be assessed clinically, and testing for nodal metastasis is controversial. We sought to systematically review the diagnostic accuracy literature on sentinel node biopsy, positron emission tomography, magnetic resonance imaging and computed tomography to evaluate the accuracy of each index test in determining lymph node status in patients with cervical cancer. Methods: We searched MEDLINE (1966–2006), EMBASE (1980–2006), Medion (1980–2006) and the Cochrane library (Issue 2, 2006) for relevant articles. We also manually searched the reference lists from primary articles and reviews, and we contacted experts in the field for conference abstracts and unpublished studies. We performed random-effects meta-analysis of accuracy indices, and we performed meta-regression analysis to test the effect of study quality on diagnostic accuracy and to identify other sources of heterogeneity. Results: We included 72 relevant primary studies, involving a total of 5042 women, in our analysis. We found that, in determining lymph node status, sentinel node biopsy had a pooled positive likelihood ratio of 40.8 (95% confidence interval [CI] 24.6–67.6) and a pooled negative likelihood ratio of 0.18 (95% CI 0.14–0.24). The pooled positive likelihood ratios (and 95% CI) were 15.3 (7.9–29.6) for positron emission tomography, 6.4 (4.9–8.3) for magnetic resonance imaging and 4.3 (3.0–6.2) for computed tomography. The pooled negative likelihood ratios (and 95% CIs) were 0.27 (0.11–0.66) for positron emission tomography, 0.50 (0.39–0.64) for magnetic resonance imaging and 0.58 (0.48–0.70) for computed tomography. Using a 27% pretest probability of lymph node metastasis among all cases (regardless of stage), we found that a positive sentinel node biopsy result increased post-test probability to 94% (95% CI 90%–96%), whereas a positive finding on positron emission tomography increased it to 85% (75%–92%). Interpretation: Sentinel node biopsy has greater accuracy in determining lymph node status among women with primary cervical cancer than current commonly used imaging methods.

Laparoscopic Uterosacral Nerve Ablation for Alleviating Chronic Pelvic Pain: A Randomized Controlled Trial

CONTEXT Chronic pelvic pain is a common condition with a major effect on health-related quality of life, work productivity, and health care use. Operative interruption of nerve trunks in the uterosacral ligaments by laparoscopic uterosacral nerve ablation (LUNA) is a treatment option for patients with chronic pelvic pain. OBJECTIVE To assess the effectiveness of LUNA in patients with chronic pelvic pain. DESIGN, SETTING, AND PARTICIPANTS Randomized controlled trial of 487 women with chronic pelvic pain lasting longer than 6 months without or with minimal endometriosis, adhesions, or pelvic inflammatory disease, who were recruited to the study by consultant gynecological surgeons from 18 UK hospitals between February 1998 and December 2005. Follow-up was conducted by questionnaires mailed at 3 and 6 months and at 1, 2, 3, and 5 years. INTERVENTION Bilateral LUNA or laparoscopy without pelvic denervation (no LUNA); participants were blinded to the treatment allocation. MAIN OUTCOME MEASURES The primary outcome was pain, which was assessed by a visual analogue scale. Data concerning the 3 types of pain (noncyclical pain, dysmenorrhea, and dyspareunia) were analyzed separately as was the worst pain level experienced from any of these 3 types of pain. The secondary outcome was health-related quality of life, which was measured using a generic instrument (EuroQoL EQ-5D and EQ-VAS). RESULTS After a median follow-up of 69 months, there were no significant differences reported on the visual analogue pain scales for the worst pain (mean difference between the LUNA group and the no LUNA group, -0.04 cm [95% confidence interval {CI}, -0.33 to 0.25 cm]; P = .80), noncyclical pain (-0.11 cm [95% CI, -0.50 to 0.29 cm]; P = .60), dysmenorrhea (-0.09 cm [95% CI, -0.49 to 0.30 cm]; P = .60), or dyspareunia (0.18 cm [95% CI, -0.22 to 0.62 cm]; P = .40). No differences were observed between the LUNA group and the no LUNA group for quality of life. CONCLUSION Among women with chronic pelvic pain, LUNA did not result in improvements in pain, dysmenorrhea, dyspareunia, or quality of life compared with laparoscopy without pelvic denervation. TRIAL REGISTRATION controlled-trials.com Identifier: ISRCTN41196151.

A systematic review of tests for lymph node status in primary endometrial cancer

BackgroundThe lymph node status of a patient is a key determinate in staging, prognosis and adjuvant treatment of endometrial cancer. Despite this, the potential additional morbidity associated with lymphadenectomy makes its role controversial. This study systematically reviews the accuracy literature on sentinel node biopsy; ultra sound scanning, magnetic resonance imaging (MRI) and computer tomography (CT) for determining lymph node status in endometrial cancer.MethodsRelevant articles were identified form MEDLINE (1966–2006), EMBASE (1980–2006), MEDION, the Cochrane library, hand searching of reference lists from primary articles and reviews, conference abstracts and contact with experts in the field. The review included 18 relevant primary studies (693 women). Data was extracted for study characteristics and quality. Bivariate random-effect model meta-analysis was used to estimate diagnostic accuracy of the various index tests.ResultsMRI (pooled positive LR 26.7, 95% CI 10.6 – 67.6 and negative LR 0.29 95% CI 0.17 – 0.49) and successful sentinel node biopsy (pooled positive LR 18.9 95% CI 6.7 – 53.2 and negative LR 0.22, 95% CI 0.1 – 0.48) were the most accurate tests. CT was not as accurate a test (pooled positive LR 3.8, 95% CI 2.0 – 7.3 and negative LR of 0.62, 95% CI 0.45 – 0.86. There was only one study that reported the use of ultrasound scanning.ConclusionMRI and sentinel node biopsy have shown similar diagnostic accuracy in confirming lymph node status among women with primary endometrial cancer than CT scanning, although the comparisons made are indirect and hence subject to bias. MRI should be used in preference, in light of the ASTEC trial, because of its non invasive nature.

Systematic review and meta-analysis of the test accuracy of ductus venosus Doppler to predict compromise of fetal/neonatal wellbeing in high risk pregnancies with placental insufficiency

OBJECTIVE To evaluate the test accuracy of ductus venosus Doppler for prediction of compromise of fetal/neonatal wellbeing. STUDY DESIGN The search strategy employed searching of electronic databases (Medline, Embase, Cochrane library, Medion) from inception to May 2009, hand searching of journal and reference lists, contact with experts. Two reviewers independently selected articles in which the results of ductus venosus Doppler were associated with the occurrence of compromise of fetal/neonatal wellbeing. There were no language restrictions applied. Data were extracted on study characteristics, quality and results to construct 2 x 2 tables. Likelihood ratios for positive and negative test results, sensitivity, specificity and their 95% confidence intervals were generated for the different indices and thresholds. RESULTS Eighteen studies, testing 2267 fetuses met the selection criteria, all performed in a high risk population with placental insufficiency in second/third trimester. Meta-analysis showed moderate predictive accuracy. The best result was for the prediction of perinatal mortality, positive likelihood ratio 4.21 (95% CI 1.98-8.96) and negative likelihood ratio 0.43 (95% CI 0.30-0.61). For prediction of adverse perinatal outcome the results were positive likelihood ratio 3.15 (95% CI 2.19-4.54) and negative likelihood ratio 0.49 (95% CI 0.40-0.59). CONCLUSION Abnormal ductus venosus Doppler showed moderate predictive accuracy for compromise of fetal/neonatal wellbeing overall and perinatal mortality in high risk pregnancies with placental insufficiency.

The quality of reporting of primary test accuracy studies in obstetrics and gynaecology: application of the STARD criteria

BackgroundIn obstetrics and gynaecology there has been a rapid growth in the development of new tests and primary studies of their accuracy. It is imperative that such studies are reported with transparency allowing the detection of any potential bias that may invalidate the results. The objective of this study was to determine the quality of reporting in diagnostic test accuracy studies in obstetrics and gynaecology using the Standards for Reporting of Diagnostic Accuracy - STARD checklist.MethodsThe included studies of ten systematic reviews were assessed for compliance with each of the reporting criteria. Using appropriate statistical tests we investigated whether there was an improvement in reporting quality since the introduction of the STARD checklist, whether a correlation existed between study sample size, country of origin of study and reporting quality.ResultsA total of 300 studies were included (195 for obstetrics, 105 for gynaecology). The overall reporting quality of included studies to the STARD criteria was poor. Obstetric studies reported adequately > 50% of the time for 62.1% (18/29) of the items while gynaecologic studies did the same 51.7% (15/29). There was a greater mean compliance with STARD criteria in the included obstetric studies than the gynaecological (p < 0.0001). There was a positive correlation, in both obstetrics (p < 0.0001) and gynaecology (p = 0.0123), between study sample size and reporting quality. No correlation between geographical area of publication and compliance with the reporting criteria could be demonstrated.ConclusionsThe reporting quality of papers in obstetrics and gynaecology is improving. This may be due to initiatives such as the STARD checklist as well as historical progress in awareness among authors of the need to accurately report studies. There is however considerable scope for further improvement.

Gynaecologic surgery from uncertainty to science: evidence-based surgery is no passing fad

BACKGROUND The randomized controlled trial (RCT) is the least biased measure of the effectiveness of interventions, including surgical interventions. The aim was to review the available evidence base in gynaecologic surgery, to assess what progress has been made and to determine gaps in the evidence for clinical decision-making. METHODS Systematic reviews involving gynaecological surgery interventions were extracted from the Cochrane Database of Systematic Reviews (Issue 2, 2007) and data were extracted for key primary outcomes from each of the randomized trials in the reviews. The reviews were categorized as to whether they had provided evidence of effectiveness for pre-defined outcomes of most relevance to patients. RESULTS Of 371 reviews or protocols published on the Cochrane Database of Systematic Reviews (Issue 2, 2007), only 30 were completed reviews assessing surgical interventions. Seven reviews concluded there was evidence of a significant effect (whether beneficial or harmful) of the interventions studied for pre-defined primary outcomes; 11 reviews concluded there was some evidence of significant effects for primary outcomes along with some gaps for primary outcomes; 12 reviews concluded insufficient evidence of effectiveness. Common themes of unique methodological challenges and pitfalls with trials of surgical interventions were apparent. CONCLUSIONS Cochrane reviews have gone a long way to establishing a sound evidence base in gynaecologic surgery: some gaps in the evidence have been eliminated and others highlighted. In general, gynaecology has been a specialty where surgical interventions have been well exposed to the scrutiny of RCTs compared with other surgical specialties.

Gynaecologic surgery from uncertainty to science: evolution of randomized control trials

BACKGROUND It is now accepted that both medical and surgical practice should be based on reliable and sound clinical evidence. However, randomized control trials comparing surgical interventions have been associated with many problems. The aim of this review is to assess if there has been progress made in establishing the evidence base for surgical interventions in gynaecology. METHODS Relevant reviews were identified from Cochrane Database of Systematic Reviews (Issue , 2006) and data from individual randomized control trials extracted. Chi-squared test was used to compare quality pre- and post-Consolidated Standards of Reporting Trials (CONSORT) statement. Meta-regression analyses were performed to test the hypothesis that effect size decreased over time. Further multiple linear regression analyses were used to test the hypothesis that precision increased over time and finally a logistic regression model was used to estimate whether treatment effects differed between trials with and without allocation concealment. RESULTS Twenty-three relevant reviews were identified, including 94 trials. The proportion of studies reporting allocation concealment significantly increased after the introduction of the CONSORT statement (P = 0.002). There was a trend towards improvement in precision over time. Similarly, there was a reduction in size of treatment effect over time (log of the ratio of odds ratios per year 0.96; 95% confidence interval 0.93-0.99, P = 0.04). CONCLUSIONS Gynaecologic surgical practice appears to be benefiting from improvement in its research base in a subject where practitioners do not participate readily in randomized evaluation.

Quality of information accompanying on-line marketing of home diagnostic tests

Objective To assess the quality of information provided to consumers by websites marketing medical home diagnostic tests. Design A cross-sectional analysis of a database developed from searching targeted websites. Setting Data sources were websites written in English which marketed medical home diagnostic tests. Main outcome measures A meta-search engine was used to identify the first 20 citations for each type of home diagnostic medical test. Relevant websites limited to those written in English were reviewed independently and in triplicate, with disputes resolved by two further reviewers. Information on the quality of these sites was extracted using a pre-piloted performer. Results 168 websites were suitable for inclusion in the review. The quality of these sites showed marked variation. Only 24 of 168 (14.2%) complied with at least three-quarters of the quality items and just over half (95 of 168, 56.5%) reported official approval or certification of the test. Information on accuracy of the test marketed was reported by 87 of 168 (51.7%) websites, with 15 of 168 (8.9%) providing a scientific reference. Instructions for use of the product were found in 97 of 168 (57.9%). However, the course of action to be taken after obtaining the test result was stated in only 63 of 168 (37.5%) for a positive result and 43 of 168 (25.5%) for a negative result. Conclusions The quality of information posted on commercial websites marketing home tests online is unsatisfactory and potentially misleading for consumers.

Methodological quality of test accuracy studies included in systematic reviews in obstetrics and gynaecology: sources of bias

BackgroundObstetrics and gynaecology have seen rapid growth in the development of new tests with research on these tests presented as diagnostic accuracy studies. To avoid errors in judgement it is important that the methodology of these studies is such that bias is minimised. Our objective was to determine the methodological quality of test accuracy studies in obstetrics and gynaecology using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) checklist and to assess sources of bias.MethodsA prospective protocol was developed to assess the impact of QUADAS on ten systematic reviews performed over the period 2004-2007.We investigated whether there was an improvement in study quality since the introduction of QUADAS, whether a correlation existed between study sample size, country of origin of study and its quality. We also investigated whether there was a correlation between reporting and methodological quality and by the use of meta-regression analyses explored for items of quality that were associated with bias.ResultsA total of 300 studies were included. The overall quality of included studies was poor (> 50% compliance with 57.1% of quality items). However, the mean compliance with QUADAS showed an improvement post-publication of QUADAS (54.9% versus 61.4% p = 0.002). There was no correlation with study sample size. Gynaecology studies published from the United States of America showed higher quality (USA versus Western Europe p = 0.002; USA versus Asia p = 0.004). Meta-regression analysis showed that no individual quality item had a significant impact on accuracy. There was an association between reporting and methodological quality (r = 0.51 p < 0.0001 for obstetrics and r = 0.56 p < 0.0001 for gynaecology).ConclusionsA combination of poor methodological quality and poor reporting affects the inferences that can be drawn from test accuracy studies. Further compliance with quality checklists is required to ensure that bias is minimised.

Management of twin-to-twin transfusion syndrome

Twin-to-twin transfusion (TTTS) syndrome complicates approximately 10–15% of all monochorionic twin pregnancies. The pathogenesis of this condition is primarily placental in origin, with unidirectional arteriovenous anastomoses being implicated in the development of the condition and secondary fetoplacental endocrine disturbance compounding the clinical presentation. If untreated, this condition ends in pregnancy loss in over 90% of cases by 26 weeks, and survivors have high rates of neurodevelopmental delay. Fetoscopic laser ablation is the treatment of choice in severe TTTS and increases perinatal survival significantly, while reducing long-term neurodevelopmental morbidity in childhood survivors. Such monochorionic twin pregnancies though, even after ‘successful therapy’, remain high risk in utero and the need for specialist and careful ultrasound surveillance and multidisciplinary care is mandatory. Monochorionic twin pregnancies constitute 20–30% of all twin pregnancies but compared with dichorionic twins are associated with up to a 10-fold increase in fetal loss rates, perinatal mortality and morbidity.1 2 All monochorionic placentae have intertwin vascular anastomoses, which may predispose the twins to acute and chronic haemodynamic disequilibrium increasing perinatal mortality and morbidity.3 However, in between 10% and 15% of monochorionic twins, the intertwin vascular anastomoses are ‘unidirectional’ leading to relative hyperperfusion within the ‘recipient twin’ causing polyuria, hydramnios and cardiac dysfunction while the co-twin, the ‘donor’, is hypoperfused, with oliguria, oligohydramnios with features of increased fetoplacental impedence.4 It is these clinical features, diagnosed using ultrasound that constitutes the diagnosis of TTTS, a condition if untreated (or unrecognised) that is associated with over 90% perinatal loss and neurodevelopmental morbidity in over 50% of cases.5 This morbid prenatal condition (rarely associated with an intertwin discordancy of haemoglobin concentration) is to be contrasted with acute haemodynamic shifts through placental anastomoses, often associated with uterine contractions, and leading to profound haemodynamic and haemoglobin differences between the fetuses noted at …