Inference under unequal probability sampling with the Bayesian exponentially tilted empirical likelihood.

Fully Bayesian inference in the presence of unequal probability sampling requires stronger structural assumptions on the data-generating distribution than frequentist semiparametric methods, but offers the potential for improved small-sample inference and convenient evidence synthesis. We demonstrate that the Bayesian exponentially tilted empirical likelihood can be used to combine the practical benefits of Bayesian inference with the robustness and attractive large-sample properties of frequentist approaches. Estimators defined as the solutions to unbiased estimating equations can be used to define a semiparametric model through the set of corresponding moment constraints. We prove Bernstein-von Mises theorems which show that the posterior constructed from the resulting exponentially tilted empirical likelihood becomes approximately normal, centred at the chosen estimator with matching asymptotic variance; thus, the posterior has properties analogous to those of the estimator, such as double robustness, and the frequentist coverage of any credible set will be approximately equal to its credibility. The proposed method can be used to obtain modified versions of existing estimators with improved properties, such as guarantees that the estimator lies within the parameter space. Unlike existing Bayesian proposals, our method does not prescribe a particular choice of prior or require posterior variance correction, and simulations suggest that it provides superior performance in terms of frequentist criteria.

Two-Part and Related Regression Models for Longitudinal Data.

Statistical models that involve a two-part mixture distribution are applicable in a variety of situations. Frequently, the two parts are a model for the binary response variable and a model for the outcome variable that is conditioned on the binary response. Two common examples are zero-inflated or hurdle models for count data and two-part models for semicontinuous data. Recently, there has been particular interest in the use of these models for the analysis of repeated measures of an outcome variable over time. The aim of this review is to consider motivations for the use of such models in this context and to highlight the central issues that arise with their use. We examine two-part models for semicontinuous and zero-heavy count data, and we also consider models for count data with a two-part random effects distribution.

Changes in severity of 2009 pandemic A/H1N1 influenza in England: a Bayesian evidence synthesis.

OBJECTIVE: To assess the impact of the 2009 A/H1N1 influenza pandemic in England during the two waves of activity up to end of February 2010 by estimating the probabilities of cases leading to severe events and the proportion of the population infected. DESIGN: A Bayesian evidence synthesis of all available relevant surveillance data in England to estimate severity of the pandemic. DATA SOURCES: All available surveillance systems relevant to the pandemic 2009 A/H1N1 influenza outbreak in England from June 2009 to February 2010. Pre-existing influenza surveillance systems, including estimated numbers of symptomatic cases based on consultations to the health service for influenza-like illness and cross sectional population serological surveys, as well as systems set up in response to the pandemic, including follow-up of laboratory confirmed cases up to end of June 2009 (FF100 and Fluzone databases), retrospective and prospective follow-up of confirmed hospitalised cases, and reported deaths associated with pandemic 2009 A/H1N1 influenza. Main outcome measures Age specific and wave specific probabilities of infection and symptomatic infection resulting in hospitalisation, intensive care admission, and death, as well as infection attack rates (both symptomatic and total). The probabilities of intensive care admission and death given hospitalisation over time are also estimated to evaluate potential changes in severity across waves. RESULTS: In the summer wave of A/H1N1 influenza, 0.54% (95% credible interval 0.33% to 0.82%) of the estimated 606,100 (419,300 to 886,300) symptomatic cases were hospitalised, 0.05% (0.03% to 0.08%) entered intensive care, and 0.015% (0.010% to 0.022%) died. These correspond to 3200 (2300 to 4700) hospital admissions, 310 (200 to 480) intensive care admissions, and 90 (80 to 110) deaths in the summer wave. In the second wave, 0.55% (0.28% to 0.89%) of the 1,352,000 (829,900 to 2,806,000) estimated symptomatic cases were hospitalised, 0.10% (0.05% to 0.16%) were admitted to intensive care, and 0.025% (0.013% to 0.040%) died. These correspond to 7500 (5900 to 9700) hospitalisations, 1340 (1030 to 1790) admissions to intensive care, and 240 (310 to 380) deaths. Just over a third (35% (26% to 45%)) of infections were estimated to be symptomatic. The estimated probabilities of infections resulting in severe events were therefore 0.19% (0.12% to 0.29%), 0.02% (0.01% to 0.03%), and 0.005% (0.004% to 0.008%) in the summer wave for hospitalisation, intensive care admission, and death respectively. The corresponding second wave probabilities are 0.19% (0.10% to 0.32%), 0.03% (0.02% to 0.06%), and 0.009% (0.004% to 0.014%). An estimated 30% (20% to 43%) of hospitalisations were detected in surveillance systems in the summer, compared with 20% (15% to 25%) in the second wave. Across the two waves, a mid-estimate of 11.2% (7.4% to 18.9%) of the population of England were infected, rising to 29.5% (16.9% to 64.1%) in 5-14 year olds. Sensitivity analyses to the evidence included suggest this infection attack rate could be as low as 5.9% (4.2% to 8.7%) or as high as 28.4% (26.0% to 30.8%). In terms of the probability that an infection leads to death in the second wave, these correspond, respectively, to a high estimate of 0.017% (0.011% to 0.024%) and a low estimate of 0.0027% (0.0024% to 0.0031%). CONCLUSIONS: This study suggests a mild pandemic, characterised by case and infection severity ratios increasing between waves. Results suggest low ascertainment rates, highlighting the importance of systems enabling early robust estimation of severity, to inform optimal public health responses, particularly in light of the apparent resurgence of the 2009 A/H1N1 strain in the 2010-11 influenza season.

Estimating time to onset of swine influenza symptoms after initial novel A(H1N1v) viral infection.

Characterization of the incubation time from infection to onset is important for understanding the natural history of infectious diseases. Attempts to estimate the incubation time distribution for novel A(H1N1v) have been, up to now, based on limited data or peculiar samples. We characterized this distribution for a generic group of symptomatic cases using laboratory-confirmed swine influenza case-information. Estimates of the incubation distribution for the pandemic influenza were derived through parametric time-to-event analyses of data on onset of symptoms and exposure dates, accounting for interval censoring. We estimated a mean of about 1·6-1·7 days with a standard deviation of 2 days for the incubation time distribution in those who became symptomatic after infection with the A(H1N1v) virus strain. Separate analyses for the <15 years and ≥ 15 years age groups showed a significant (P<0·02) difference with a longer mean incubation time in the older age group.

Development and initial validation of a screening questionnaire for psoriatic arthritis: the Toronto Psoriatic Arthritis Screen (ToPAS).

OBJECTIVE: To develop and validate a psoriatic arthritis (PsA) screening questionnaire: the Toronto Psoriatic Arthritis Screen (ToPAS). METHODS: The ToPAS was developed through review of items seen in patients with PsA and evaluation by patients with PsA and patients with other rheumatological conditions, and was administered to consecutive consenting patients attending five clinics: PsA, psoriasis, general dermatology, general rheumatology (excluding PsA patients) and family medicine. All patients were assessed by a rheumatologist according to a standard protocol. A three-step analysis strategy was adopted: a stepwise logistic regression to identify the questions most important in discriminating between those with and without PsA; a logistic model was fitted to three clinically relevant domains for PsA: skin, joints and nails; and a simpler weighting of each of the domains used in step 2. Receiver operating characteristic (ROC) curves were obtained based on these various models. RESULTS: In all, there were 134 patients from the PsA clinic, 123 with psoriasis, 118 from dermatology, 135 from rheumatology and 178 from family medicine. A simplified discriminatory score based on the skin, joint and nail domains gave results comparable to other methods with an observed overall sensitivity and specificity, based on a single cut point, of 86.8% and 93.1%. When the patients with PsA were compared with each of the other four patient groups individually, the sensitivity and specificity of the ToPAS were: psoriasis 89.1%, 86.3%; dermatology 91.9%, 95.2%; rheumatology 92.6%, 85.7%; and family medicine 90.4%, 100%. CONCLUSION: Our simplified index is very good at classifying those who are not diagnosed with PsA and those who are diagnosed with PsA.

Cardiovascular morbidity in psoriatic arthritis.

BACKGROUND: Increasing evidence for cardiovascular mortality among patients with psoriasis and psoriatic arthritis (PsA) has accumulated, together with evidence for increased prevalence of risk factors for cardiovascular disease (CVD). OBJECTIVES: To describe cardiovascular morbidity in PsA, determine its prevalence and identify risk factors for its development. METHODS: At the University of Toronto, patients were followed up prospectively according to a standard protocol, including disease-related features and comorbidities. Patients with CVD, including myocardial infarction (MI), angina, hypertension and cerebrovascular accident (CVA), were identified. The prevalence of CVD morbidities in these patients was compared with data from the Canadian Community Health Survey through standardised prevalence ratios (SPRs). Cox relative risk regression analysis was used to analyse risk factors. RESULTS: At the time of analysis, 648 patients were registered in the database. After clinic entry, 122 developed hypertension, 38 had an MI and 5, 21 and 11 had CVA, angina and congestive heart failure (CHF), respectively. 155 patients had at least one of these conditions. The SPRs for MI (2.57; 95% CI 1.73 to 3.80), angina (1.97; 95% CI 1.24 to 3.12) and hypertension (1.90; 95% CI 1.59 to 2.27) were statistically significant, whereas the SPRs for CHF (1.19; 95% CI 0.50 to 2.86) and CVA (0.91; 95% CI 0.34 to 2.43) were not. Factors associated with CVD included diabetes, hyperlipidaemia and high Psoriasis Area and Severity Index scores. CONCLUSION: Patients with PsA are at increased risk of cardiovascular morbidities compared with the general population. In addition to known risk factors for CVD, severe psoriasis is an important predictor in patients with PsA.

Occurrence and correlates of fatigue in psoriatic arthritis.

OBJECTIVE: To determine the relationship between fatigue and disease-related and psychosocial variables in psoriatic arthritis (PsA). METHOD: 499 patients attending the University of Toronto PsA Clinic were administered the modified fatigue severity scale (mFSS). At the time of mFSS administration, clinical and laboratory measures of disease activity and damage were recorded. Linear regression models were used to examine the cross-sectional relationship between disease-related and psychosocial variables and mFSS scores. RESULTS: At least moderate fatigue occurred in 49.5% of patients and severe fatigue in 28.7%. Univariately the vast majority of variables were significantly associated with mFSS scores. The final multivariate model was composed of female sex, the medical outcome survey short form 36 (SF-36) pain and mental health scales, the number of fibromyalgia tender points, the health assessment questionnaire (HAQ) and "ever used" methotrexate, and explained 54.5% of the variation in mFSS scores. The SF-36 mental health scale played the largest role in the multivariate model, uniquely accounting for 6.6% of the variation in the fatigue severity scale. The disease-related factors significant at the univariate level did not achieve statistical significance in the context of HAQ and pain measures. CONCLUSION: Fatigue is a common symptom in PsA, and is associated, in a multivariate model, with pain, female sex, physical functional disability, medication status and psychological distress. Fatigue appears to provide some information that does not overlap with the core set of outcome domains in PsA.

Mapping the platelet profile for functional genomic studies and demonstration of the effect size of the GP6 locus.

BACKGROUND: Evidence suggests the wide variation in platelet response within the population is genetically controlled. Unraveling the complex relationship between sequence variation and platelet phenotype requires accurate and reproducible measurement of platelet response. OBJECTIVE: To develop a methodology suitable for measuring signaling pathway-specific platelet phenotype, to use this to measure platelet response in a large cohort, and to demonstrate the effect size of sequence variation in a relevant model gene. METHODS: Three established platelet assays were evaluated: mobilization of [Ca(2+)](i), aggregometry and flow cytometry, each in response to adenosine 5'-diphosphate (ADP) or the glycoprotein (GP) VI-specific crosslinked collagen-related peptide (CRP). Flow cytometric measurement of fibrinogen binding and P-selectin expression in response to a single, intermediate dose of each agonist gave the best combination of reproducibility and inter-individual variability and was used to measure the platelet response in 506 healthy volunteers. Pathway specificity was ensured by blocking the main subsidiary signaling pathways. RESULTS: Individuals were identified who were hypo- or hyper-responders for both pathways, or who had differential responses to the two agonists, or between outcomes. 89 individuals, retested three months later using the same methodology, showed high concordance between the two visits in all four assays (r(2) = 0.872, 0.868, 0.766 and 0.549); all subjects retaining their phenotype at recall. The effect of sequence variation at the GP6 locus accounted for approximately 35% of the variation in the CRP-XL response. CONCLUSION: Genotyping-phenotype association studies in a well-characterized, large cohort provides a powerful strategy to measure the effect of sequence variation in genes regulating the platelet response.

Contrast-enhanced MR angiography for carotid disease: diagnostic and potential clinical impact.

OBJECTIVE: To compare contrast-enhanced MR angiography (CEMRA) with intra-arterial digital subtraction angiography (DSA) for evaluating carotid stenosis. METHODS: A total of 167 consecutive symptomatic patients, scheduled for DSA following screening duplex ultrasound (DUS), were prospectively recruited to have CEMRA. Three independent readers reported on each examination in a blinded and random manner. Agreement was assessed using the Bland-Altman method. Diagnostic and potential clinical impact of CEMRA was evaluated, singly and in combination with DUS. RESULTS: CEMRA tended to overestimate stenosis by a mean bias ranging from 2.4 to 3.8%. A significant part of the disagreement between CEMRA and DSA was directly caused by interobserver variability. For detection of severe stenosis, CEMRA alone had a sensitivity of 93.0% and specificity of 80.6%, with a diagnostic misclassification rate of 15.0% (n = 30). More importantly, clinical decision-making would, however, have been potentially altered only in 6.0% of cases (n = 12). The combination of concordant DUS and CEMRA reduced diagnostic misclassification rate to 10.1% (n = 19) at the expense of 47 (24.9%) discordant cases needing to proceed to DSA. An intermediate approach of selective DUS review resulted in a marginally worse diagnostic misclassification rate of 11.6% (n = 22) but with only 6.8% of discordant cases (n = 13). CONCLUSIONS: DSA remains the gold standard for carotid imaging. The clinical misclassification rate with CEMRA, however, is acceptably low to support its safe use instead of DSA. The appropriateness of combination strategies depends on institutional choice and cost-effectiveness issues.

Common mental disorder symptom counts in populations: are there distinct case groups above epidemiological cut-offs?

BACKGROUND: At the lower end of IQ distributions in general populations, there is a clear excess of cases, representing the distinct pathology of severe learning disability. This study aimed to establish whether such a subpopulation exists in distributions of common mental disorder and depression symptom scores, above epidemiological 'case' cut-offs. METHOD: Data from 9556 non-psychotic respondents to the 1993 OPCS (Office of Population Censuses and Surveys) National Household Psychiatric Morbidity Survey were analysed. The distribution of total neurotic symptom and depression scores from the revised Clinical Interview Schedule were examined. Automated least squares methods were used to fit the best single statistical distribution to the data. RESULTS: A single exponential curve provided the best fit for the whole population, but floor effects produced deviations at symptom counts of 0-3. After truncation, exponential distributions fitted excellently. Proportions of the population above conventional cut-offs of > or = 12 symptoms differed by < 12% from expected for a range of low and high prevalence groups. The single exponential model also fitted the depression score. CONCLUSIONS: Symptom counts for the common mental disorders fall within single population distributions, with little apparent numerical excess in the case range. High and low prevalences of these disorders appear to be population characteristics, with shifts in exponential means predicting proportions above case cut-offs.

Natural head posture--considerations of reproducibility.

This three-part study investigated the reproducibility of natural head posture (NHP) using radiographs and photographs. In part 1, reproducibility of cephalograms 1 year after the introduction of NHP was investigated and found to be less favourable (Dahlberg coefficient of 2.99 degrees) than most other previous investigations. In order to minimize radiation exposure of patients, reproducibility of photographs and method agreement between photographs and cephalograms were investigated in part 2. Reproducibility of the two photographs was poor (2.71 degrees). However, method agreement between cephalograms and the photographs taken at the same time was good (1.39 degrees). Replacement of the radiographic method with the photographic method for assessing NHP reproducibility appeared justified. Changing the protocol for achieving NHP in part 3 of the study improved reproducibility substantially (1.41 degrees). Various statistical methods were used to assess reproducibility and method agreement. Bland and Altman's graphical representation was found to be the most appropriate for method agreement. The Dahlberg coefficient, commonly used to assess NHP repeatability/reproducibility, does not provide an extreme enough interval to allow a sufficient clinical assessment of a method to be undertaken, compared with the reproducibility coefficient. That is, the latter provides a 95 per cent range, compared with 52 per cent with Dahlberg.

Pulsatile ocular blood flow: the effect of the Valsalva manoeuvre in open angle and normal tension glaucoma: a case report and prospective study.

AIM: A case of severe normal tension glaucoma is reported in a trumpet player, along with a study investigating the association between glaucoma and raised intrathoracic pressure, using measurements of pulsatile ocular blood flow (POBF). METHODS: Three patient groups were studied; normals (n = 34), untreated primary open angle glaucoma (POAG) (n = 20), and untreated normal tension glaucoma (NTG) (n = 22), with a total of 76 patients who underwent measurements of POBF using the OBF pneumotonometer at rest and while forcibly exhaling through a mouthpiece connected to a mercury manometer (30 mm Hg) (Valsalva manoeuvre). RESULTS: POBF fell during Valsalva in all groups with the greatest predictor being the resting value of POBF. There was no evidence of significant differences in the mean change in POBF occurring during the Valsalva manoeuvre for the three groups studied before or after adjusting for the sex, the resting POBF, and the resting IOP of the patients (p = 0.294 and p = 0.542, respectively). However, statistically significant associations were found between the change in POBF and sex (p = 0.049), resting POBF (p<0.0001) and resting IOP (p = 0.032). Males had a greater drop, on average, in POBF during Valsalva manoeuvre than females after adjusting for the other factors. Additionally, there was a significant difference in the mean change in IOP during Valsalva for the three groups (p = 0.002), with the difference occurring between the normal and POAG groups (p<0.005). The POAG group had, on average, a drop in IOP during Valsalva, while the other two groups had an increase in IOP. Also noted was a significant difference in the distributions of the risk factors among the three groups (p = 0.002). CONCLUSIONS: This study demonstrates no difference between groups with respect to resting or Valsalva POBF, but does demonstrate a possible trend with respect to IOP, with a drop in IOP occurring during Valsalva in the POAG group. There is, however, much variability in the data left unexplained by our models. Thus, unfortunately, we cannot advise our trumpet player whether his NTG is directly related to his trumpet playing.

Hyperuricemia, gout, and renal function after liver transplantation.

BACKGROUND: Hyperuricemia is a recognized complication of renal and cardiac transplantation, but the development of hyperuricemia and gout following liver transplantation have received less attention. We have retrospectively assessed the prevalence of hyperuricemia in 134 consecutive liver transplant recipients. RESULTS: Forty-seven percent of the liver transplant recipients studied had hyperuricemia. Serum creatinine was higher in hyperuricemic than in nonhyperuricemic patients. Peak uric acid correlated significantly with corresponding serum creatinine (rs=0.694). Only 6% developed gout. All the patients with gout and 10 hyperuricemic patients with renal impairment but without gout were treated with allopurinol. Over a median period of 3 months, mean serum creatinine fell from 177 micromol/l to 160 micromol/l (P=0.01), without change in type or dose of immuno-suppression. CONCLUSIONS: There is an important association between liver transplantation and hyperuricemia. Treatment with allopurinol results in a significant reduction in serum creatinine in patients with gout and in those with hyperuricemia and renal impairment.

MR imaging of the wrist: effect on clinical diagnosis and patient care.

PURPOSE: To evaluate the effect of magnetic resonance (MR) imaging of the wrist on clinicians' diagnoses, diagnostic certainty, and patient care. MATERIALS AND METHODS: A controlled observational study was performed. Referring clinicians completed questionnaires about diagnosis and intended management before and after wrist MR imaging. One hundred eighteen consecutive patients referred for MR imaging of the wrist were recruited from the MR imaging units at a regional teaching hospital and a large district general hospital. The main measures were changes in the clinicians' leading and subsidiary diagnoses after MR imaging, their certainty in these diagnoses, and changes in intended patient care. RESULTS: Questionnaires were incorrectly completed for five patients, questionnaires were not returned for three, appointments were canceled for 10, and two could not tolerate the MR examination. Complete follow-up data were available for 98 patients. The clinical diagnosis changed in 55 of 98 patients; in the remaining 43 patients, diagnostic certainty increased in 23. Clinicians reported that MR imaging had substantially improved their understanding of the disease in 67 of 98 patients. The care plan changed in 45 of 98 patients, with a shift away from surgical treatment. Twenty-eight patients were discharged without further investigation. MR imaging was similarly effective in the regional teaching center and the district general hospital. CONCLUSION: MR imaging of the wrist influences clinicians' diagnoses and management plans.

Prognostic variables in canine multicentric lymphosarcoma.

This paper presents the results of a prospective study to investigate the prognostic value of clinical staging, histological grading, immunophenotype, mitotic count and average numbers of argyrophilic nucleolar organiser region counts in dogs with multicentric lymphosarcoma treated with a standard chemotherapy protocol comprising vincristine, cyclophosphamide and prednisolone. Forty-nine dogs were treated according to the study protocol. Univariate and multivariate analysis with regression modelling was used to evaluate the prognostic importance of patient and tumour variables upon tumour response and relapse-free survival. Thirty-seven dogs (76 per cent) achieved a complete remission, seven (14 per cent) a partial remission and five (10 per cent) failed to respond to treatment. None of the variables examined had a statistically significant effect upon tumour response. Tumour immunophenotype was the only parameter found to have a significant influence on patient survival, the hazard ratio for T-cell versus B-cell immunophenotype was 3.99 with 95 per cent confidence interval from 1.399 to 11.372, P = 0.035.

Magnetic resonance imaging of the wrist: diagnostic performance statistics.

AIM: To review the published diagnostic performance statistics for magnetic resonance imaging (MRI) of the wrist for tears of the triangular fibrocartilage complex, the intrinsic carpal ligaments, and for osteonecrosis of the carpal bones. MATERIALS AND METHODS: We used Medline and Embase to search the English language literature. Studies evaluating the diagnostic performance of MRI of the wrist in living patients with surgical confirmation of MR findings were identified. RESULTS: We identified 11 studies reporting the diagnostic performance of MRI for tears of the triangular fibrocartilage complex for a total of 410 patients, six studies for the scapho-lunate ligament (159 patients), six studies for the luno-triquetral ligament (142 patients) and four studies (56 patients) for osteonecrosis of the carpal bones. CONCLUSIONS: Magnetic resonance imaging is an accurate means of diagnosing tears of the triangular fibrocartilage and carpal osteonecrosis. Although MRI is highly specific for tears of the intrinsic carpal ligaments, its sensitivity is low. The diagnostic performance of MRI in the wrist is improved by using high-resolution T2* weighted 3D gradient echo sequences. Using current imaging techniques without intra-articular contrast medium, magnetic resonance imaging cannot reliably exclude tears of the intrinsic carpal ligaments. Hobby, J. L. (2001). Clinical Radiology, 56, 50-57.

Changes in tumorigenesis- and angiogenesis-related gene transcript abundance profiles in ovarian cancer detected by tailored high density cDNA arrays.

BACKGROUND: Complementary DNA array analysis of gene expression has a potential application for clinical diagnosis of disease processes. However, accessibility, affordability, reproducibility of results, and management of the data generated remain issues of concern. Use of cDNA arrays tailored for studies of specific pathways, tissues, or disease states may render a cost- and time-effective method to define potential hallmark genotype alterations. MATERIALS AND METHODS: We produced a 332-membered human cDNA array on nylon membranes tailored for studies of angiogenesis and tumorigenesis in reproductive disease. We tested the system for reproducibility using a novel statistical approach for analysis of array data and employed the arrays to investigate gene expression alterations in ovarian cancer. RESULTS: Intra-assay analysis and removal of agreement outliers was shown to be a critical step prior to interpretation of cDNA array data. The system revealed highly reproducible results, with intermembrane coefficient of reproducibility of +/- 0.98. Comparison of placental and ovarian sample data confirmed expected differences in angiogenic profiles and tissue-specific markers, such as human placental lactogen (hPL). Analysis of expression profiles of five normal ovary and four poorly differentiated serous papillary ovarian adenocarcinoma samples revealed an overall increase in angiogenesis-related markers, including vascular endothelial growth factor (VEGF) and angiopoietin-1 in the diseased tissue. These were accompanied by increases in immune response mediators (e.g. HLA-DR, Ron), apoptotic and neoplastic markers (e.g. BAD protein, b-myb), and novel potential markers of ovarian cancer, such as cofilin, moesin, and neuron-restrictive silencer factor (REST) protein. CONCLUSIONS: In-house production of tailored cDNA arrays, coupled to comprehensive analysis of resulting hybridization profiles, provides an accessible, reliable, and highly effective method of applying array technology to study disease processes. In the ovary, abundance of specific tumor markers, increased macrophage recruitment mediators, a late-stage angiogenesis profile, and the presence of chemoresistance-related markers distinguished normal and advanced ovarian cancer tissue samples. Detection of such parallel changes in pathway- and tissue-specific markers may prove a hallmark ready for application in reproductive disease diagnostic and therapeutic developments.

Communication of doubt and certainty in radiological reports.

We have investigated the reliability of communication of uncertainty in radiological reports. The 18 most commonly used verbal expressions of probability were identified from a series of radiological reports. 11 clinicians (three radiologists, three rheumatologists and five orthopaedic surgeons) recorded the probability that they ascribed to each of the 18 expressions using visual analogue scales. Each subject was re-tested on four occasions at least 1 week apart. The results were analysed to assess reproducibility within and between individuals. We found considerable variation in the probabilities assigned to many commonly used expressions between subjects, and between repeated testing of the same subject. Some expressions were rated much more consistently than others. "Absent", "excludes", "unlikely", "probable", "certain" and "definite" were the most consistently rated expressions. We have identified a potential source of misunderstanding in radiological reports owing to differences in interpretation of expressions used by radiologists and referring clinicians.

Who should manage primary retinal detachments?

PURPOSE: To determine whether the outcome of primary retinal reattachment surgery in a subregion is improved by surgery being performed in a specialist vitreoretinal unit (VRU). METHODS: A subregional, population-based, retrospective audit cycle of primary retinal reattachment surgery was conducted by independent investigators. The subregion was defined as the catchment area of a teaching hospital (TH) with a specialist VRU and three neighbouring district general hospitals (DGHs). During the initial audit period (January 1989 to December 1990), 142 cases were treated at all four hospitals: TH/VRU (83), DGH-A (15), DGH-B (13), and DGH-C (31). Policy changes after the initial audit led to primary retinal reattachment surgery being predominantly performed by the VRU. During the re-audit period (September 1995 to August 1997), 160 cases were treated at two hospitals: VRU (148) and DGH-C (12). The outcome measure employed was complete retinal reattachment after a single procedure with a minimum follow-up of 12 months. RESULTS: The success rate for primary retinal reattachment surgery in the subregion improved from 76.1% to 88.8% (p = 0.006) following the policy changes. The success rate of the vitreoretinal specialists in the VRU (90%) was greater than the general ophthalmologists in the DGHs (ranging from 47% to 77%), despite case selection by the general ophthalmologists. The number of cases treated by the VRU increased by 156% in the 6.5 year interval between the two audits due to a widespread change in the model of care for primary retinal detachments (both within and outside the subregion). During the re-audit period, the VRU treated 348 primary retinal detachments (including referrals from outside the subregion), achieving a success rate of 86.8% with a single procedure and 97.4% with further surgery. This primary success rate included 35 cases (10%) treated by vitrectomy with silicone oil tamponade who did not undergo silicone oil removal. CONCLUSIONS: The outcome of primary retinal reattachment surgery can be improved if surgery is performed by a specialist VRU. It is suggested that the current standard for retinal reattachment with a single procedure should be set in the region of 85% to 90%. Changing the model of care so that primary retinal reattachment surgery is predominantly performed by a specialist VRU has important resource implications.