A Socio-Psychological Study of a Community in the North of Scotland

Abstract Not Provided

The diagnostic accuracy of a single CEA blood test in detecting colorectal cancer recurrence: Results from the FACS trial

Objective: To evaluate the diagnostic accuracy of a single CEA (carcinoembryonic antigen) blood test in detecting colorectal cancer recurrence. Background: Patients who have undergone curative resection for primary colorectal cancer are typically followed up with scheduled CEA testing for 5 years. Decisions to investigate further (usually by CT imaging) are based on single test results, reflecting international guidelines. Methods: A secondary analysis was undertaken of data from the FACS trial (two arms included CEA testing). The composite reference standard applied included CT-CAP imaging, clinical assessment and colonoscopy. Accuracy in detecting recurrence was evaluated in terms of sensitivity, specificity, likelihood ratios, predictive values, time-dependent area under the ROC curves, and operational performance when used prospectively in clinical practice are reported. Results: Of 582 patients, 104 (17.9%) developed recurrence during the 5 year follow-up period. Applying the recommended threshold of 5µg/L achieves at best 50.0% sensitivity (95% CI: 40.1-59.9%); in prospective use in clinical practice it would lead to 56 missed recurrences (53.8%; 95% CI: 44.2-64.4%) and 89 false alarms (56.7% of 157 patients referred for investigation). Applying a lower threshold of 2.5µg/L would reduce the number of missed recurrences to 36.5% (95% CI: 26.5-46.5%) but would increase the false alarms to 84.2% (924/1097 referred). Some patients are more prone to false alarms than others – at the 5µg/L threshold, the 89 episodes of unnecessary investigation were clustered in 29 individuals. Conclusion: Our results demonstrated very low sensitivity for CEA, bringing to question whether it could ever be used as an independent triage test. It is not feasible to improve the diagnostic performance of a single test result by reducing the recommended action threshold because of the workload and false alarms generated. Current national and international guidelines merit re-evaluation and options to improve performance, such as making clinical decisions on the basis of CEA trend, should be further assessed

Extended scope of nursing practice: a multicentre randomised controlled trial of appropriately trained nurses and pre-registration house officers in pre-operative assessment in elective general surgery

Aim/ Principal Research Question:1) To determine whether pre-operative assessment carried out by an appropriately trained nurse (ATN) is equivalent in quality to that carried out by a pre-registration house officer (PRHO).2) To assess whether pre-assessments carried out by ATNs and PRHOs are equivalent in terms of cost.3) To determine whether assessments carried out by ATNs are acceptable to patients.4) To investigate the quality of communication between senior medical staff and ATNs.Factors of Interest:The extended role of appropriately trained nurses and pre-registration house officers in pre-operative assessment in elective general surgery.Methods:The study design was principally a prospective randomised equivalence trial but was accompanied by additional qualitative assessment of patient and staff perceptions, and an economic evaluation.The intervention consisted of a pre-operative assessment carried out by either an ATN or a PRHO. Of the patients who completed the study with a full evaluation, 926 patients were randomised to the PRHO arm of the trial and 948 to the ATN arm. Three ATNs took part in the study, one from each centre, together with a total of 87 PRHOs.Immediately following the initial assessment of a patient by a PRHO or an ATN, one of a number of clinical research fellows, all specialist registrars in anaesthetics, repeated the assessment and recorded it on a study form, together with a list of investigations required. The clinical research fellow then evaluated the competency of the initial assessor by comparing the quality of their assessment with their own. Any deficiencies in ordering of investigations and referral to other specialities were met in order to maximise patient care.Sample groups:All patients attending at one site for assessment prior to general anaesthetic for elective general, vascular, urological or breast surgery were potentially included in the study. Of 1907 patients who were randomised, 1874 completed the study with a full evaluation.The study was carried out at four NHS hospitals, three of which were teaching hospitals, in three NHS Trusts in Southampton, Sheffield and Doncaster.Outcome measures:Three areas of ATN and PRHO performance were judged separately, history taking, examination and ordering of tests, and each was graded into one of four categories, the most important of which was under-assessment, which would possibly have affected peri-operative management. In the case of ordering of tests, it was possible to have both over- and under-assessed a patient on different tests.Findings:The pre-operative assessments carried out by the ATNs were essentially equivalent to those performed by the PRHOs in terms of under-assessment that might possibly have affected peri-operative management, although there was variation between the ATNs in terms of the quality of history taking. This may be related to the low number of patients seen at one study site.PRHOs ordered significantly more unnecessary tests than the ATNs. The substitution of ATNs for PRHOs was calculated to be cost neutral.The results of the qualitative assessment showed that the use of ATNs for pre-operative assessment was acceptable to patients; however, there was no evidence that communication between senior medical staff and those carrying out pre-operative assessments was improved by their introduction.Conclusions:This study demonstrated no reason to inhibit the development of fully nurse-led pre-operative assessment, provided that the nurses are appropriately trained and maintain sufficient workload to retain skills.Implications for Further Research:Further research is needed in the following areas:1) the extent and type of training needed for nurses undertaking the pre-operative assessment role2) the use, costs and benefits of routine pre-operative testing.<br/

Recognition of skin malignancy by general practitioners: observational study using data from a population-based randomised controlled trial

Skin malignancy is an important cause of mortality in the United Kingdom and is rising in incidence every year. Most skin cancer presents in primary care, and an important determinant of outcome is initial recognition and management of the lesion. Here we present an observational study of interobserver agreement using data from a population-based randomised controlled trial of minor surgery. Trial participants comprised patients presenting in primary care and needing minor surgery in whom recruiting doctors felt to be able to offer treatment themselves or to be able to refer to a colleague in primary care. They are thus relatively unselected. The skin procedures undertaken in the randomised controlled trial generated 491 lesions with a traceable histology report: 36 lesions (7%) from 33 individuals were malignant or pre-malignant. Chance-corrected agreement (κ) between general practitioner (GP) diagnosis of malignancy and histology was 0.45 (0.36–0.54) for lesions and 0.41 (0.32–0.51) for individuals affected with malignancy. Sensitivity of GPs for the detection of malignant lesions was 66.7% (95% confidence interval (CI), 50.3–79.8) for lesions and 63.6% (95% CI, 46.7–77.8) for individuals affected with malignancy. The safety of patients is of paramount importance and it is unsafe to leave the diagnosis and treatment of potential skin malignancy in the hands of doctors who have limited training and experience. However, the capacity to undertake all of the minor surgical demand works demanded in hospitals does not exist. If the capacity to undertake it is present in primary care, then the increased costs associated with enhanced training for general medical practitioners (GPs) must be borne

Protein dynamics with off-lattice Monte Carlo moves

A Monte Carlo method for dynamics simulation of all-atom protein models is introduced, to reach long times not accessible to conventional molecular dynamics. The considered degrees of freedom are the dihedrals at C$_\alpha$-atoms. Two Monte Carlo moves are used: single rotations about torsion axes, and cooperative rotations in windows of amide planes, changing the conformation globally and locally, respectively. For local moves Jacobians are used to obtain an unbiased distribution of dihedrals. A molecular dynamics energy function adapted to the protein model is employed. A polypeptide is folded into native-like structures by local but not by global moves.Comment: 10 pages, 4 Postscript figures, uses epsf.sty and a4.sty; scheduled tentatively for Phys.Rev.E issue of 1 March 199

Interpreting declines in HIV test positivity:an analysis of routine data from Zimbabwe's national sex work programme, 2009–2019

Introduction: Early diagnosis of HIV is critical for epidemic control. To achieve this, successful testing programmes are essential and test positivity is often used as a marker of their performance. The aim of this study was to analyse trends and predictors of HIV test positivity over time and explore how an understanding of seroconversion rates could build on our interpretation of this indicator among female sex workers in Zimbabwe. Methods: We analysed HIV test data from Zimbabwe's nationally scaled sex work programme between 2009 and 2019. We defined test positivity as the proportion of all tests that were HIV positive and measured new diagnoses by estimating seroconversion rates among women with repeat tests, defined as an HIV-positive test after at least one HIV-negative test in the programme. We used logistic regression to analyse test positivity over three time-periods: 2009–2013, 2014–2017 and 2018–2019, adjusting for potential confounding by demographic factors and the mediating effects of time since last HIV test. We calculated the seroconversion rates for the same time-periods. Results: During the 10-year study period, 54,503 tests were recorded in 39,462 women. Between 2009 and 2013, 18% of tests were among women who reported testing in the previous 6 months. By 2018–2019, this had increased to 57%. Between 2018 and 2019, test positivity was 9.6%, compared to 47.9% for 2009–2013 (aOR 6.08 95% CI 5.52–6.70) and 18.8% for 2014–2017 (aOR 2.17 95% CI 2.06–2.28). Adjusting for time since last test reduced effect estimates for 2009–2013 (aOR 4.03 95% CI 3.64–4.45) and 2014–2017 (aOR 1.97 95% CI 1.86–2.09) compared to 2018–2019. Among 7573 women with an initial HIV-negative test in the programme and at least one subsequent test, 464 tested HIV positive at a rate of 3.9 per 100 pyar (95% CI 3.5–4.2).Conclusions: Test positivity decreased among women testing through the programme over time, while seroconversion rates remained high. These declines were partly driven by changes in individual testing history, reflecting comprehensive coverage of testing services and greater knowledge of HIV status, but not necessarily declining rates of seroconversion. Understanding testing history and monitoring new HIV infections from repeat tests could strengthen the interpretation of test positivity and provide a better understanding of programme performance.</p

Interpreting declines in HIV test positivity:an analysis of routine data from Zimbabwe's national sex work programme, 2009–2019

Introduction: Early diagnosis of HIV is critical for epidemic control. To achieve this, successful testing programmes are essential and test positivity is often used as a marker of their performance. The aim of this study was to analyse trends and predictors of HIV test positivity over time and explore how an understanding of seroconversion rates could build on our interpretation of this indicator among female sex workers in Zimbabwe. Methods: We analysed HIV test data from Zimbabwe's nationally scaled sex work programme between 2009 and 2019. We defined test positivity as the proportion of all tests that were HIV positive and measured new diagnoses by estimating seroconversion rates among women with repeat tests, defined as an HIV-positive test after at least one HIV-negative test in the programme. We used logistic regression to analyse test positivity over three time-periods: 2009–2013, 2014–2017 and 2018–2019, adjusting for potential confounding by demographic factors and the mediating effects of time since last HIV test. We calculated the seroconversion rates for the same time-periods. Results: During the 10-year study period, 54,503 tests were recorded in 39,462 women. Between 2009 and 2013, 18% of tests were among women who reported testing in the previous 6 months. By 2018–2019, this had increased to 57%. Between 2018 and 2019, test positivity was 9.6%, compared to 47.9% for 2009–2013 (aOR 6.08 95% CI 5.52–6.70) and 18.8% for 2014–2017 (aOR 2.17 95% CI 2.06–2.28). Adjusting for time since last test reduced effect estimates for 2009–2013 (aOR 4.03 95% CI 3.64–4.45) and 2014–2017 (aOR 1.97 95% CI 1.86–2.09) compared to 2018–2019. Among 7573 women with an initial HIV-negative test in the programme and at least one subsequent test, 464 tested HIV positive at a rate of 3.9 per 100 pyar (95% CI 3.5–4.2).Conclusions: Test positivity decreased among women testing through the programme over time, while seroconversion rates remained high. These declines were partly driven by changes in individual testing history, reflecting comprehensive coverage of testing services and greater knowledge of HIV status, but not necessarily declining rates of seroconversion. Understanding testing history and monitoring new HIV infections from repeat tests could strengthen the interpretation of test positivity and provide a better understanding of programme performance.</p