POSSUM predicts hospital mortality and long-term survival in patients with hip fractures.

BACKGROUND: Each year, some 18,000 Dutch residents, most of them elderly, suffer a hip fracture. These patients constitute a major, and increasing, healthcare problem with high mortality. In an ageing population, not only the incidence of hip fractures will increase but also comorbidity. Comorbidity is a major cause of high mortality. The physiologic and operative severity score for the enumeration of mortality and morbidity (POSSUM) system predicts mortality and morbidity in surgical patients using physiologic and operative factors. METHODS: For 272 consecutive patients who were treated in our hospital for hip fractures, all complications were registered, and orthopedic POSSUM was performed. Total survival was registered with a mean follow-up of 58 months. Discriminating performance of POSSUM was estimated using receiver-operating curves. After validation, patients were divided into three equal large groups, termed low-risk group, intermediate-risk group, and high-risk group. Kaplan-Meier survival curves were made of each group. RESULTS: Orthopedic POSSUM performed well in predicting mortality with an area under the curve of 0.83 (95% confidence interval 0.76-0.89) and morbidity with an area under the curve of 0.83 (95% confidence interval 0.76-0.90). Three groups that composed of 92 (low risk), 93 (intermediate risk), and 87 (high risk) patients differed significantly in inhospital mortality, all complications, severe complications, and total survival. CONCLUSION: This study has shown that the orthopedic POSSUM is an excellent predictor of inhospital mortality and long-term survival in patients suffering from hip fractures. It is a reasonable predictor of severe postoperative complications. The orthopedic POSSUM is a useful risk stratification and audit tool.

Statistical models for quantifying diagnostic accuracy with multiple lesions per patient.

We propose random-effects models to summarize and quantify the accuracy of the diagnosis of multiple lesions on a single image without assuming independence between lesions. The number of false-positive lesions was assumed to be distributed as a Poisson mixture, and the proportion of true-positive lesions was assumed to be distributed as a binomial mixture. We considered univariate and bivariate, both parametric and nonparametric mixture models. We applied our tools to simulated data and data of a study assessing diagnostic accuracy of virtual colonography with computed tomography in 200 patients suspected of having one or more polyps.

Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews.

BACKGROUND AND OBJECTIVES: Studies of diagnostic accuracy most often report pairs of sensitivity and specificity. We demonstrate the advantage of using bivariate meta-regression models to analyze such data. METHODS: We discuss the methodology of both the summary Receiver Operating Characteristic (sROC) and the bivariate approach by reanalyzing the data of a published meta-analysis. RESULTS: The sROC approach is the standard method for meta-analyzing diagnostic studies reporting pairs of sensitivity and specificity. This method uses the diagnostic odds ratio as the main outcome measure, which removes the effect of a possible threshold but at the same time loses relevant clinical information about test performance. The bivariate approach preserves the two-dimensional nature of the original data. Pairs of sensitivity and specificity are jointly analyzed, incorporating any correlation that might exist between these two measures using a random effects approach. Explanatory variables can be added to the bivariate model and lead to separate effects on sensitivity and specificity, rather than a net effect on the odds ratio scale as in the sROC approach. The statistical properties of the bivariate model are sound and flexible. CONCLUSION: The bivariate model can be seen as an improvement and extension of the traditional sROC approach.

Sources of variation and bias in studies of diagnostic accuracy: a systematic review.

BACKGROUND: Studies of diagnostic accuracy are subject to different sources of bias and variation than studies that evaluate the effectiveness of an intervention. Little is known about the effects of these sources of bias and variation. PURPOSE: To summarize the evidence on factors that can lead to bias or variation in the results of diagnostic accuracy studies. DATA SOURCES: MEDLINE, EMBASE, and BIOSIS, and the methodologic databases of the Centre for Reviews and Dissemination and the Cochrane Collaboration. Methodologic experts in diagnostic tests were contacted. STUDY SELECTION: Studies that investigated the effects of bias and variation on measures of test performance were eligible for inclusion, which was assessed by one reviewer and checked by a second reviewer. Discrepancies were resolved through discussion. DATA EXTRACTION: Data extraction was conducted by one reviewer and checked by a second reviewer. DATA SYNTHESIS: The best-documented effects of bias and variation were found for demographic features, disease prevalence and severity, partial verification bias, clinical review bias, and observer and instrument variation. For other sources, such as distorted selection of participants, absent or inappropriate reference standard, differential verification bias, and review bias, the amount of evidence was limited. Evidence was lacking for other features, including incorporation bias, treatment paradox, arbitrary choice of threshold value, and dropouts. CONCLUSIONS: Many issues in the design and conduct of diagnostic accuracy studies can lead to bias or variation; however, the empirical evidence about the size and effect of these issues is limited.

The diagnostic odds ratio: a single indicator of test performance.

Diagnostic testing can be used to discriminate subjects with a target disorder from subjects without it. Several indicators of diagnostic performance have been proposed, such as sensitivity and specificity. Using paired indicators can be a disadvantage in comparing the performance of competing tests, especially if one test does not outperform the other on both indicators. Here we propose the use of the odds ratio as a single indicator of diagnostic performance. The diagnostic odds ratio is closely linked to existing indicators, it facilitates formal meta-analysis of studies on diagnostic test performance, and it is derived from logistic models, which allow for the inclusion of additional variables to correct for heterogeneity. A disadvantage is the impossibility of weighing the true positive and false positive rate separately. In this article the application of the diagnostic odds ratio in test evaluation is illustrated.

POSSUM predicts decreased overall survival in curative resection for colorectal cancer.

PURPOSE: Poor condition at operation determined by the physiologic POSSUM score is related to postoperative mortality and morbidity of colorectal cancer surgery. This study was designed to analyze the relationship between condition of patients with colorectal cancer at operation and long-term overall survival. METHODS: A total of 542 patients survived a radical resection for Stages I, II, or III colorectal cancer. Physiologic POSSUM score at surgery, exclusive of age, was calculated for all patients. Mean physiologic POSSUM score was used as cutoff point to determine low-risk and high-risk group patients. A Cox proportional hazard analysis was performed to study the effect of low-risk and high-risk group on overall survival and to identify independent risk factors. RESULTS: Five-year overall survival was significantly higher in low-risk group patients than in high-risk group patients (low-risk group 66.6 percent vs. high-risk group 48.5 percent; P < 0.001). Differences in overall survival also were found when patients in Stages I, II, and III were analyzed separately. Risk factors for overall survival were advanced stage of disease, poor tumor differentiation, mucinous adenocarcinoma, older than age 70 years, and poor condition of the patient at time of operation. CONCLUSIONS: Poor condition at operation, as determined by physiologic POSSUM score, is a risk indicator for long-term overall survival in colorectal cancer patients.

Case-control and two-gate designs in diagnostic accuracy studies.

BACKGROUND: In some diagnostic accuracy studies, the test results of a series of patients with an established diagnosis are compared with those of a control group. Such case-control designs are intuitively appealing, but they have also been criticized for leading to inflated estimates of accuracy. METHODS: We discuss similarities and differences between diagnostic and etiologic case-control studies, as well as the mechanisms that can lead to variation in estimates of diagnostic accuracy in studies with separate sampling schemes ("gates") for diseased (cases) and nondiseased individuals (controls). RESULTS: Diagnostic accuracy studies are cross-sectional and descriptive in nature. Etiologic case-control studies aim to quantify the effect of potential causal exposures on disease occurrence, which inherently involves a time window between exposure and disease occurrence. Researchers and readers should be aware of spectrum effects in diagnostic case-control studies as a result of the restricted sampling of cases and/or controls, which can lead to changes in estimates of diagnostic accuracy. These spectrum effects may be advantageous in the early investigation of a new diagnostic test, but for an overall evaluation of the clinical performance of a test, case-control studies should closely mimic cross-sectional diagnostic studies. CONCLUSIONS: As the accuracy of a test is likely to vary across subgroups of patients, researchers and clinicians might carefully consider the potential for spectrum effects in all designs and analyses, particularly in diagnostic accuracy studies with differential sampling schemes for diseased (cases) and nondiseased individuals (controls).

Expression of estrogen receptor, progesterone receptor, and insulin-like growth factor receptor-1 and of MIB-1 in patients with recurrent pleomorphic adenoma of the parotid gland.

BACKGROUND: Patients with recurrent pleomorphic adenomas of the parotid gland are difficult to manage without considerable risk of facial nerve injury. The prognostic significance of progesterone receptor (PR) and estrogen receptor (ER) reported in these adenomas was evaluated in patients with recurrent pleomorphic adenomas, comparing the results in a group of patients with primary adenomas without recurrences during 10 years of follow-up. METHODS: Paraffin embedded tumor samples from 52 patients with recurrent pleomorphic adenoma of the parotid gland were collected and stained immunohistochemically. Expression of PR, ER, Ki-67 antigen, and insulin-like growth factor receptor-1 (IGFR-1) was analyzed in resected samples of recurrent tumors and was compared with samples from a control group of patients with primary pleomorphic adenoma. RESULTS: A difference (P < 0.05) in the type of tumor was observed between the recurrent group (more cell-poor variants) and the control group. ER expression was low in both groups (19% and 17%, respectively), but immunoreactivity for ER was higher (48%) in normal parotid gland tissue. PR expression in the recurrent group (96%) was higher compared with PR expression in the control group (61%; P < 0.001). PR expression and IGFR-1 expression were correlated weakly (correlation coefficient = 0.660; P = 0.053) in the recurrent group. The expression of growth fraction (Ki-67 score) and IGFR-1 was similar in both groups but was more extensive compared with normal parotid gland tissue. CONCLUSIONS: PR seems to be a prognostic factor in recurrent pleomorphic adenoma of the parotid gland. The PR pathway can be considered a potential target for hormone treatment in patients with these recurrent adenomas.

Practical implementation of a multiplex PCR for acute respiratory tract infections in children.

Molecular testing for acute respiratory infections (ARIs) has documented value but limited implementation due to questions that typically slow the acceptance of new tests. This study sought to address these questions and achieve implementation. Rhinovirus was added to a nested multiplex PCR (M-PCR), increasing its diagnostic yield. Over one winter, three hospital pediatric departments used the M-PCR to complement their direct fluorescent-antibody assay (DFA) for respiratory syncytial virus (RSV). Clinicians recorded "pretest probability estimates" (using continuous scales for various pathogen groups) for comparison with test results; treatments and test turnaround times were also recorded. Transnasal and throat swabs, with or without nasopharyngeal aspirate (NPA), were M-PCR tested. NPA-containing sample sets found to be RSV positive by DFA were not further tested. Single PCR for human metapneumovirus (hMPV) was performed retrospectively. Of 178 ARI episodes representing 172 patients, NPA was included in 97 sample sets; 54 (56%) were determined to be RSV positive. The other NPA-containing sample sets (n = 43) yielded 27 findings (63%), and the swab-only sets (n = 81) yielded 47 findings (58%); rhinovirus was found most often. Testing for hMPV yielded seven positive results. M-PCR median turnaround times were 4 days in swab-only samples and 5 days with NPA. Antibiotics were prescribed in 50 episodes, at rates similar for RSV and rhinovirus. Pretest probability estimates of a viral cause were lower in episodes caused by rhinovirus than in episodes caused by RSV. The hospitals continued to use M-PCR for NPA-containing samples found to be RSV negative by DFA. Test implementation is more likely with higher diagnostic yield and a protocol that reflects day-to-day clinical and laboratory operations.

Rectal cancer: local staging and assessment of lymph node involvement with endoluminal US, CT, and MR imaging--a meta-analysis.

PURPOSE: To perform a meta-analysis to compare endoluminal ultrasonography (US), computed tomography (CT), and magnetic resonance (MR) imaging in rectal cancer staging. MATERIALS AND METHODS: Relevant articles published between 1985 and 2002 were included if more than 20 patients were studied, histopathologic findings were the reference standard, and data were presented for 2 x 2 tables; articles were excluded if data were reported elsewhere in more detail. Two reviewers independently extracted data on study characteristics and results. Bivariate random-effects approach was used to obtain summary estimates of sensitivity and specificity for invasion of muscularis propria, perirectal tissue, and adjacent organs and for lymph node involvement. Summary receiver operating characteristic (ROC) curves were fitted for perirectal tissue invasion and lymph node involvement. RESULTS: Ninety articles fulfilled all inclusion criteria. For muscularis propria invasion, US and MR imaging had similar sensitivities; specificity of US (86% [95% confidence interval [CI]: 80, 90]) was significantly higher than that of MR imaging (69% [95% CI: 52, 82]) (P =.02). For perirectal tissue invasion, sensitivity of US (90% [95% CI: 88, 92]) was significantly higher than that of CT (79% [95% CI: 74, 84]) (P <.001) and MR imaging (82% [95% CI: 74, 87]) (P =.003); specificities were comparable. For adjacent organ invasion and lymph node involvement, estimates for US, CT, and MR imaging were comparable. Summary ROC curve for US of perirectal tissue invasion showed better diagnostic accuracy than that of CT and MR imaging. Summary ROC curves for lymph node involvement showed no differences in accuracy. CONCLUSION: For local invasion, endoluminal US was most accurate and can be helpful in screening patients for available therapeutic strategies.

Tumor markers in the diagnosis of primary bladder cancer. A systematic review.

PURPOSE: We systematically reviewed the available evidence, and obtained and compared summary estimates of the sensitivity and specificity of cytology and the urine based markers bladder tumor antigen, BTA stat (Polymedco, Redmond, Washington), BTA TRAK (Polymedco), NMP22 (Matritech, Cambridge, Massachusetts), telomerase and fibrin degradation product in detecting primary bladder cancer. MATERIALS AND METHODS: Studies on the diagnosis of primary bladder cancer published from 1990 through November 2001 in English and German were retrieved from MEDLINE and EMBASE data bases. In our research we included studies that evaluated 1 or more of the markers, used cystoscopy as the reference standard and allowed the construction of a 2 x 2 contingency table for a per patient analysis. The data plus items on study and clinical characteristics were extracted by 2 observers. Sensitivity and specificity for each marker were estimated using a bivariate random effect meta-analysis. A multivariable analysis was performed to explain study variation. RESULTS: A total of 42 studies were included in our review. Only 2 studies were available on fibrin degradation product, hence a meta-analysis was not possible. Cytology had the best specificity at 94% (95% CI: 90% to 96%). This figure was significantly better than that of the other markers except for telomerase (specificity 86% [71% to 94%]). Telomerase had the best sensitivity (75% [71% to 79%]) but it was not significantly better than that of BTA stat (70% [66% to 74%]). Case control designs yielded lower values for sensitivity for the tumor markers cytology, bladder tumor antigen and BTA stat. CONCLUSIONS: Cytology has the best specificity and telomerase the best sensitivity. However, none of the markers studied here is sensitive enough to be recommended for daily routine.

Computed tomography and magnetic resonance imaging in staging of uterine cervical carcinoma: a systematic review.

OBJECTIVE: The goal of this article is to systematically review the available evidence on the diagnostic performance of computed tomography (CT) and magnetic resonance imaging (MRI) in staging of cervical carcinoma. METHODS: A comprehensive computer literature search was performed in MEDLINE and EMBASE databases from January 1985 to May 2002. Two reviewers independently scored methodological quality of included studies and extracted relevant data for data analysis. A bivariate random effect approach was used to summarize estimates of sensitivity and specificity values. Covariates were added to this model to study the influence of sample size, publication year, methodological criteria, and MRI techniques on summary estimates. RESULTS: Fifty-seven articles were included. In 49 articles one imaging modality was evaluated (MRI, 38; CT, 11), and in 8 articles, both. Inclusion criteria were: minimum of 10 patients included, histopathology as reference standard, sufficient data presented to construct 2(x) 2 tables. The exclusion criterion was: data reported elsewhere in more detail. Sensitivity estimates for parametrial invasion were 74% (95% C: 68-79%) for MRI and 55% (95% CI: 44-66%) for CT, and for lymph node involvement, 60% (95% CI 52%-68%) and 43% (95% CI: 37-57%), respectively. MRI and CT had comparable specificities for parametrial invasion and lymph node involvement. For bladder invasion and rectum invasion the sensitivities for MRI were respectively 75% (95% CI: 66-83%) and 71% (95% CI: 53-83%), higher compared with CT. The specificity in evaluating bladder invasion for MRI was significantly higher compared with CT: 91% (95% CI: 83-95%) for MRI and 73% (95% CI: 52-87%) for CT. The specificities for rectum invasion were comparable. Differences in patient sample size, publication year, methodological criteria, and MRI techniques had no effect on the summary estimates. CONCLUSIONS: For overall staging of cervical carcinoma, MRI is more accurate than CT.

Radiography in acute ankle injuries: the Ottawa Ankle Rules versus local diagnostic decision rules.

STUDY OBJECTIVE: We validate the Ottawa Ankle Rules and 2 Dutch ankle rules in distinguishing clinically significant fractures from insignificant fractures and other injuries in patients with a painful ankle presenting to the emergency department. METHODS: This prospective comparison of 3 ankle rules was conducted in the ED of a 580-bed community teaching hospital in Amsterdam from January 1998 to April 1999. Participants included 647 consecutive patients aged 18 years or older presenting with a painful ankle after trauma. All physicians received extensive and pictorial training on how to correctly score the respective items of the rules. The physician on call recorded these items derived from history and physical examination on a standardized data sheet. All patients subsequently underwent standard radiographic assessment. A radiologist and a trauma surgeon evaluated the radiographs blinded from the results of the data sheet form and the treatment given. The diagnostic performance of the 3 rules was measured in terms of sensitivity, specificity, and the reduction of radiographs. Receiver operating characteristic (ROC) curves were constructed, and the area under the ROC curves was calculated and compared. RESULTS: Seventy-four fractures were seen, of which 41 were clinically significant. The Ottawa Ankle Rules had a sensitivity of 98% for identifying clinically significant fractures; the local rules scored 88% and 59%, respectively. The potential savings in radiographs for the 3 decision rules were 24%, 54%, and 82%, respectively. The area under the ROC curve was better for both the local rules (0.84 and 0.83) compared with the Ottawa Ankle Rules (0.76). CONCLUSION: Because the identification of all relevant fractures is more important than a reduction in radiographs, the higher sensitivity of the Ottawa Ankle Rules makes these most suitable for implementation in The Netherlands.

Three-dimensional display modes for CT colonography: conventional 3D virtual colonoscopy versus unfolded cube projection.

The authors compared a conventional two-directional three-dimensional (3D) display for computed tomography (CT) colonography with an alternative method they developed on the basis of time efficiency and surface visibility. With the conventional technique, 3D ante- and retrograde cine loops were obtained (hereafter, conventional 3D). With the alternative method, six projections were obtained at 90 degrees viewing angles (unfolded cube display). Mean evaluation time per patient with the conventional 3D display was significantly longer than that with the unfolded cube display. With the conventional 3D method, 93.8% of the colon surface came into view; with the unfolded cube method, 99.5% of the colon surface came into view. Sensitivity and specificity were not significantly different between the two methods. Agreements between observers were kappa = 0.605 for conventional 3D display and kappa = 0.692 for unfolded cube display. Consequently, the latter method enhances the 3D endoluminal display with improved time efficiency and higher surface visibility.

Comparison of diagnostic decision rules and structured data collection in assessment of acute ankle injury.

BACKGROUND: Ankle decision rules help to determine which patients with ankle injuries should undergo radiography. However, these rules are limited by imperfect generalizability and sensitivity. The judgement of physicians, aided by structured data collection, is a potential alternative. We compared the diagnostic performance of 2 decision rules with the performance of physicians, aided by structured data collection, in ruling out fracture in patients with acute ankle injury. METHODS: Consecutive patients with acute ankle injury who visited the emergency department of a teaching community hospital in Amsterdam were included in the study. After taking the patient's history and performing a physical examination, the surgical resident in each case completed a specially developed structured data form incorporating all of the variables in the Ottawa and Leiden ankle rules, as well as some additional variables. The form then asked whether the resident thought radiography was necessary. Each patient then underwent ankle and midfoot radiography. The films were independently interpreted by a radiologist and a trauma surgeon, who were both blinded to the information on the data form. Sensitivity, specificity and the percentage of patients for whom radiography was recommended were the main outcome measures. RESULTS: Of 690 consecutive patients, 647 met the inclusion criteria. Fractures were observed in 74 (11%) of these patients. Sensitivity was 89% (95% confidence interval [CI] 80% to 95%) for the Ottawa ankle rules, 80% (95% CI 69% to 88%) for the Leiden ankle rule and 82% (95% CI 72% to 90%) for physicians' judgement. Specificity was 26% (95% CI 23% to 30%), 59% (95% CI 55% to 63%) and 68% (95% CI 64% to 71%) respectively. Radiography was recommended in 76% (95% CI 72% to 79%), 46% (95% CI 42% to 50%) and 38% (95% CI 34% to 42%) of cases respectively. The Ottawa rules missed 8 fractures, of which 1 was clinically significant, the Leiden rule missed 15 fractures, of which 5 were clinically significant, and the residents missed 13 fractures, of which 1 was clinically significant. INTERPRETATION: Physicians' judgement, aided by structured data collection, was similar to existing international and local decision rules in terms of sensitivity in identifying cases requiring radiography and may outperform these prediction rules in terms of minimizing radiographic examinations for patients with ankle trauma.

CT colonography: feasibility of substantial dose reduction--comparison of medium to very low doses in identical patients.

In a feasibility study, the authors compared polyp detection and interobserver variability at computed tomographic (CT) colonography in 15 patients with doses ranging from medium to very low (12.00-0.05 mSv). At levels down to 2% of the medium dose, the mean detection of polyps 5 mm or larger remained at least 74%, while the number of false-positive results decreased and the interobserver agreement remained constant. Initial observations indicate that it is feasible to reduce the radiation dose required for CT colonography. Further studies are needed, however, to investigate the clinical value of very low-dose CT colonography.

CT colonography at different radiation dose levels: feasibility of dose reduction.

PURPOSE: To investigate the sensitivity and specificity of polyp detection and the image quality of computed tomographic (CT) colonography at different radiation dose levels and to study effective doses reported in literature on CT colonography. MATERIALS AND METHODS: CT colonography and colonoscopy were performed with 100 mAs in 50 consecutive patients at high risk for colorectal cancer; 50- and 30-mAs CT colonographic examinations were simulated with controlled addition of noise to raw transmission measurements. One radiologist randomly evaluated all original and simulated images for the presence of polyps and scored image quality. Differences in image quality were assessed with the Wilcoxon rank test. Scan protocols from the literature and recent (unpublished) updates were collected. RESULTS: In nine of 10 patients with polyps 5 mm in diameter or larger (sensitivity, 90%) and in seven of 17 patients with polyps smaller than 5 mm, polyps were correctly identified with CT colonography at all dose levels. Specificity for patients without polyps 5 mm or larger was 53%-60% at all dose levels and for patients without any polyps was 26% (at 100 and 50 mAs) and 48% (at 30 mAs). Image quality decreased significantly as the dose level decreased. The median effective doses (supine and prone positions) calculated from protocols reported in the literature and updates were 7.8 and 8.8 mSv, respectively. CONCLUSION: Although image quality decreases significantly at 30 mAs (3.6 mSv), polyp detection remains unimpaired. The median dose for CT colonography at institutions that perform CT colonographic research is currently 8.8 mSv.