Gender inequalities in the promptness of diagnosis of bladder and renal cancer after symptomatic presentation: evidence from secondary analysis of an English primary care audit survey

Objectives: To explore whether women experience greater delays in the diagnosis of bladder and renal cancer when first presenting to a general practitioner with symptoms caused by those cancers and potential reasons for such gender inequalities. Design: Prospective national audit survey of cancer diagnosis. Setting: English primary care (2009–2010). Participants: 920 patients with bladder and 398 patients with renal cancer (252 (27%) and 165 (42%), respectively, were women). Primary and secondary outcome measures: Proportion of patients with three or more pre-referral consultations; number of days from first presentation to referral; proportion of patients who presented with haematuria and proportion of patients investigated in primary care. Results: Women required three or more prereferral consultations more often than men (27% (95% CI 21% to 33%) vs 11% (9% to 14%) for bladder (p<0.001); and 30% (22% to 39%) vs 18% (13% to 25%) for renal cancer (p=0.025)) and had a greater number of days from presentation to referral. In multivariable analysis (adjusting for age, haematuria status and use of primary care-led investigations), being a woman was independently associated with higher odds of three or more pre-referral consultations (OR=3.29 (2.06 to 5.25, p<0.001) for bladder cancer; and OR=1.90 (1.06 to 3.42, p=0.031) for renal cancer). Although presentation with haematuria was associated with more timely diagnosis of bladder cancer, gender inequalities did not vary by haematuria status for either cancer (p=0.18 for bladder and p=0.27 for renal). Each year in the UK, approximately 700 women with either bladder or renal cancer experience a delayed diagnosis because of their gender, of whom more than a quarter (197, or 28%) present with haematuria. Conclusions: There are notable gender inequalities in the timeliness of diagnosis of urological cancers. There is a need to both reinforce existing guidelines on haematuria investigation and develop new diagnostic decision aids and tests for patients who present without haematuria

Measures of promptness of cancer diagnosis in primary care: Secondary analysis of national audit data on patients with 18 common and rarer cancers

Background: Evidence is needed about the promptness of cancer diagnosis and associations between its measures. Methods: We analysed data from the National Audit of Cancer Diagnosis in Primary Care 2009–10 exploring the association between the interval from first symptomatic presentation to specialist referral (the primary care interval, or ‘interval’ hereafter) and the number of pre-referral consultations. Results: Among 13 035 patients with any of 18 different cancers, most (82%) were referred after 1 (58%) or 2 (25%) consultations (median intervals 0 and 15 days, respectively) while 9%, 4% and 5% patients required 3, 4 or 5 þ consultations (median intervals 34, 47 and 97 days, respectively) (Spearman’s r ¼ 0.70). The association was at least moderate for any cancer (Spearman’s r range: 0.55 (prostate) 0.77 (brain)). Patients with cancers with a higher proportion of three or more pre-referral consultations typically also had longer median intervals (e.g., multiple myeloma) and vice versa (e.g., breast cancer). Conclusion: The number of pre-referral consultations has construct validity as a measure of the primary care interval. Developing interventions to reduce the number of pre-referral consultations can help improve the timeliness of cancer diagnosis, and constitutes a priority for early diagnosis initiatives and research

Comparison of cancer diagnostic intervals before and after implementation of NICE guidelines: analysis of data from the UK General Practice Research Database

Background: The primary aim was to use routine data to compare cancer diagnostic intervals before and after implementation of the 2005 NICE Referral Guidelines for Suspected Cancer. The secondary aim was to compare change in diagnostic intervals across different categories of presenting symptoms. Methods: Using data from the General Practice Research Database, we analysed patients with one of 15 cancers diagnosed in either 2001–2002 or 2007–2008. Putative symptom lists for each cancer were classified into whether or not they qualified for urgent referral under NICE guidelines. Diagnostic interval (duration from first presented symptom to date of diagnosis in primary care records) was compared between the two cohorts. Results: In total, 37 588 patients had a new diagnosis of cancer and of these 20 535 (54.6%) had a recorded symptom in the year prior to diagnosis and were included in the analysis. The overall mean diagnostic interval fell by 5.4 days (95% CI: 2.4–8.5; Po0.001) between 2001–2002 and 2007–2008. There was evidence of significant reductions for the following cancers: (mean, 95% confidence interval) kidney (20.4 days, 0.5 to 41.5; P ¼ 0.05), head and neck (21.2 days, 0.2–41.6; P ¼ 0.04), bladder (16.4 days, 6.6–26.5; Pp0.001), colorectal (9.0 days, 3.2–14.8; P ¼ 0.002), oesophageal (13.1 days, 3.0–24.1; P ¼ 0.006) and pancreatic (12.6 days, 0.2–24.6; P ¼ 0.04). Patients who presented with NICE-qualifying symptoms had shorter diagnostic intervals than those who did not (all cancers in both cohorts). For the 2007–2008 cohort, the cancers with the shortest median diagnostic intervals were breast (26 days) and testicular (44 days); the highest were myeloma (156 days) and lung (112 days). The values for the 90th centiles of the distributions remain very high for some cancers. Tests of interaction provided little evidence of differences in change in mean diagnostic intervals between those who did and did not present with symptoms specifically cited in the NICE Guideline as requiring urgent referral. Conclusion: We suggest that the implementation of the 2005 NICE Guidelines may have contributed to this reduction in diagnostic intervals between 2001–2002 and 2007–2008. There remains considerable scope to achieve more timely cancer diagnosis, with the ultimate aim of improving cancer outcomes

Evaluating a computer aid for assessing stomach symptoms (ECASS): study protocol for a randomised controlled trial

Background: For most cancers, only a minority of patients have symptoms meeting the National Institute for Health and Clinical Excellence guidance for urgent referral. For gastro-oesophageal cancers, the ‘alarm’ symptoms of dysphagia and weight loss are reported by only 32 and 8 % of patients, respectively, and their presence correlates with advanced-stage disease. Electronic clinical decision-support tools that integrate with clinical computer systems have been developed for general practice, although uncertainty remains concerning their effectiveness. The objectives of this trial are to optimise the intervention and establish the acceptability of both the intervention and randomisation, confirm the suitability and selection of outcome measures, finalise the design for the phase III definitive trial, and obtain preliminary estimates of the intervention effect. Methods/design: This is a two-arm, multi-centre, cluster-randomised, controlled phase II trial design, which will extend over a 16-month period, across 60 general practices within the North East and North Cumbria and the Eastern Local Clinical Research Network areas. Practices will be randomised to receive either the intervention (the electronic clinical decision-support tool) or to act as a control (usual care). From these practices, we will recruit 3000 adults who meet the trial eligibility criteria and present to their GP with symptoms suggestive of gastro-oesophageal cancer. The main measures are the process data, which include the practitioner outcomes, service outcomes, diagnostic intervals, health economic outcomes, and patient outcomes. One-on-one interviews in a sub-sample of 30 patient-GP dyads will be undertaken to understand the impact of the use or non-use of the electronic clinical decision-support tool in the consultation. A further 10–15 GPs will be interviewed to identify and gain an understanding of the facilitators and constraints influencing implementation of the electronic clinical decision-support tool in practice. Discussion: We aim to generate new knowledge on the process measures regarding the use of electronic clinical decision-support tools in primary care in general and to inform a subsequent definitive phase III trial. Preliminary data on the impact of the support tool on resource utilisation and health care costs will also be collected. Trial registration: ISRCTN Registry, ISRCTN12595588

HI in the Outskirts of Nearby Galaxies

The HI in disk galaxies frequently extends beyond the optical image, and can trace the dark matter there. I briefly highlight the history of high spatial resolution HI imaging, the contribution it made to the dark matter problem, and the current tension between several dynamical methods to break the disk-halo degeneracy. I then turn to the flaring problem, which could in principle probe the shape of the dark halo. Instead, however, a lot of attention is now devoted to understanding the role of gas accretion via galactic fountains. The current $\rm \Lambda$ cold dark matter theory has problems on galactic scales, such as the core-cusp problem, which can be addressed with HI observations of dwarf galaxies. For a similar range in rotation velocities, galaxies of type Sd have thin disks, while those of type Im are much thicker. After a few comments on modified Newtonian dynamics and on irregular galaxies, I close with statistics on the HI extent of galaxies.Comment: 38 pages, 17 figures, invited review, book chapter in "Outskirts of Galaxies", Eds. J. H. Knapen, J. C. Lee and A. Gil de Paz, Astrophysics and Space Science Library, Springer, in pres

On the fourth-order accurate compact ADI scheme for solving the unsteady Nonlinear Coupled Burgers' Equations

The two-dimensional unsteady coupled Burgers' equations with moderate to severe gradients, are solved numerically using higher-order accurate finite difference schemes; namely the fourth-order accurate compact ADI scheme, and the fourth-order accurate Du Fort Frankel scheme. The question of numerical stability and convergence are presented. Comparisons are made between the present schemes in terms of accuracy and computational efficiency for solving problems with severe internal and boundary gradients. The present study shows that the fourth-order compact ADI scheme is stable and efficient

A straw drift chamber spectrometer for studies of rare kaon decays

We describe the design, construction, readout, tests, and performance of planar drift chambers, based on 5 mm diameter copperized Mylar and Kapton straws, used in an experimental search for rare kaon decays. The experiment took place in the high-intensity neutral beam at the Alternating Gradient Synchrotron of Brookhaven National Laboratory, using a neutral beam stop, two analyzing dipoles, and redundant particle identification to remove backgrounds

Semiparametric theory and empirical processes in causal inference

In this paper we review important aspects of semiparametric theory and empirical processes that arise in causal inference problems. We begin with a brief introduction to the general problem of causal inference, and go on to discuss estimation and inference for causal effects under semiparametric models, which allow parts of the data-generating process to be unrestricted if they are not of particular interest (i.e., nuisance functions). These models are very useful in causal problems because the outcome process is often complex and difficult to model, and there may only be information available about the treatment process (at best). Semiparametric theory gives a framework for benchmarking efficiency and constructing estimators in such settings. In the second part of the paper we discuss empirical process theory, which provides powerful tools for understanding the asymptotic behavior of semiparametric estimators that depend on flexible nonparametric estimators of nuisance functions. These tools are crucial for incorporating machine learning and other modern methods into causal inference analyses. We conclude by examining related extensions and future directions for work in semiparametric causal inference

Fusion of secretory vesicles isolated from rat liver

Secretory vesicles isolated from rat liver were found to fuse after exposure to Ca2+. Vescle fusion is characterized by the occurrence of twinned vesicles with a continuous cleavage plane between two vesicles in freeze-fracture electron microscopy. The number of fused vesicles increases with increasing Ca2+-concentrations and is half maximal around 10–6 m. Other divalent cations (Ba2+, Sr2+, and Mg2+) were ineffective. Mg2+ inhibits Ca2+-induced fusion. Therefore, the fusion of secretory vesiclesin vitro is Ca2+ specific and exhibits properties similar to the exocytotic process of various secretory cells. Various substances affecting secretionin vivo (microtubular inhibitors, local anethetics, ionophores) were tested for their effect on membrane fusion in our system. The fusion of isolated secretory vesicles from liver was found to differ from that of pure phospholipid membranes in its temperature dependence, in its much lower requirement for Ca2+, and in its Ca2+-specificity. Chemical and enzymatic modifications of the vesicle membrane indicate that glycoproteins may account for these differences