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Biomedical subjects

C Sherlaw-Johnson

Publications and source records attributed to C Sherlaw-Johnson.

18 recordsLinked to original sources

Estimating the long-term impact of a prophylactic human papillomavirus 16/18 vaccine on the burden of cervical cancer in the UK.

To predict the public health impact on cervical disease by introducing human papillomavirus (HPV) vaccination in the United Kingdom, we developed a mathematical model that can be used to reflect the impact of vaccination in different countries with existing screening programmes. Its use is discussed in the context of the United Kingdom. The model was calibrated with published data. The impact of vaccination on cervical cancer and deaths, precancerous lesions and screening outcomes were estimated for a vaccinated cohort of 12-year-old girls, among which it is estimated that there would be a reduction of 66% in the prevalence of high-grade precancerous lesions and a 76% reduction in cervical cancer deaths. Estimates for various other measures of the population effects of vaccination are also presented. We concluded that it is feasible to forecast the potential effects of HPV vaccination in the context of an existing national screening programme. Results suggest a sizable reduction in the incidence of cervical cancer and related deaths. Areas for future research include investigation of the beneficial effects of HPV vaccination on infection transmission and epidemic dynamics, as well as HPV-related neoplasms in other sites.

Calibration↗

Reduction in wound infection rates by wound surveillance with postdischarge follow-up and feedback.

BACKGROUND: Surgical wound surveillance with postdischarge follow-up is rarely done in the UK as it is seen as expensive. The aim of this study was to determine whether employing a dedicated team was effective and reduced costs. METHODS: Infection data were collected prospectively with postdischarge follow-up at 2-3 months, and fed back to surgeons. Wound infection was defined using both ASEPSIS wound scoring and criteria of the US Centers for Disease Control (CDC) definitions. RESULTS: Over 4 years, 15 548 patient episodes were included. Postdischarge surveillance data were available for 79.9 per cent of the 15 154 records of patients who survived. There was a significant reduction in the rate of wound infection between the first and fourth years by ASEPSIS and CDC definitions: odds ratio 0.77 (95 per cent confidence interval (c.i.) 0.64 to 0.92) and 0.69 (95 per cent c.i. 0.57 to 0.83), respectively. The proportion of infections fell significantly in orthopaedic, cardiac and thoracic surgery. The annual budget for wound surveillance was pound 91,600. Changes in infection rates contributed pound 347,491 to the reduction in cost among the patients surveyed. CONCLUSION: Wound surveillance was associated with a reduction in rates of wound infection within 4 years. The cost reduction as a result of fewer infections exceeded the cost of surveillance after 2 years.

Cost-Benefit Analysis↗

An evaluation of liquid-based cytology and human papillomavirus testing within the UK cervical cancer screening programme.

The aim of this study is to evaluate different options for introducing liquid-based cytology (LBC) and human papillomavirus (HPV) testing into the UK cervical cancer screening programme. These include options that incorporate HPV testing either as a triage for mild and borderline smear abnormalities or as a primary screening test. Outcomes include the predicted impact on resource use, total cost, life years and cost-effectiveness. Extensive sensitivity analysis has been carried out to explore the importance of the uncertainty associated with disease natural history and the impact of screening. Under baseline assumptions, the cost-effectiveness of different options for introducing LBC appears favourable, and these results are consistent under a range of assumptions for its impact on the diagnostic effectiveness of cytology. However, if we assume a higher marginal cost of LBC in comparison to conventional methods, primary smear testing options are predicted to be more cost-effective without LBC. Combined LBC primary smear and HPV testing with a 5-year interval is similar in both cost and effectiveness to the other 3-yearly options of primary smear testing or primary HPV testing alone. However, both primary HPV testing and combined options would give rise to a far greater risk of inappropriate colposcopy throughout a woman's lifetime. British Journal of Cancer (2004) 91, 84-91. doi:10.1038/sj.bjc.6601884 www.bjcancer.com Published online 25 May 2004

Adult↗

Computer tools to assist the monitoring of outcomes in surgery.

OBJECTIVE: In recent years, there has been increasing use of analytical and graphical methods to assist the monitoring of outcomes in adult cardiac surgery. In this paper, we present extensions to the basic VLAD methodology that add flexibility and assist in its interpretation. METHODS: Using techniques from probability theory, we have devised graphical tools whereby deviations from expected outcomes can be monitored to see how likely they are to have occurred by chance. The methods are based upon pre-operative assessments of risk and use exact analytical techniques. RESULTS: These tools allow deviations from expected outcomes to be readily assessed and compared with the distribution of chance outcomes. Appropriate colour coding allows interpretation in terms of a temperature gradient. CONCLUSIONS: Exact analysis methods based on the use of pre-operative risk assessment provide a useful means for assisting the interpretation of VLAD charts. Such analysis has the advantage that it is applicable even for relatively short series of operations. Also, it takes specific account of the heterogeneity of case mix when quantifying the variability that is expected. By displaying the overall history of outcomes in a visually intuitive manner, it complements the more formal tools for detecting isolated good and bad runs that are available.

Cardiovascular Surgical Procedures↗

The planning of cervical cancer screening programmes in eastern Europe: is viral testing a suitable alternative to smear testing?

Cervical cancer screening with human papillomavirus (HPV) DNA testing has potential advantages over conventional, smear testing in that it can predict cases in which invasive cancers are more likely to develop, may be cheaper to implement and improve compliance. In areas of the world where little formalized cervical cancer screening takes place, or where health resources are limited, HPV testing has been suggested as a possible alternative for primary screening. In this paper we demonstrate the use of mathematical modelling to evaluate the effects of setting up screening programmes in Eastern Europe with HPV DNA testing as the primary screening tool and compare it with conventional smear testing. The impact of screening is measured in terms of the life years gained and the resulting resource usage and cost. We investigate several screening options with different screening intervals and age ranges for the target population.

Adult↗

Likely variations in perioperative mortality associated with cardiac surgery: when does high mortality reflect bad practice?

OBJECTIVE: Several methods exist for estimating the risk of perioperative mortality based on preoperative risk factors; graphical methods such as the variable life adjusted display (VLAD) can be used to examine how an individual surgeon's performance for a series of operations fares against what would be expected, given the case mix. This study aimed to devise a method for assessing the natural variation in outcome in order to assist with making judgements about individual performance, in particular whether seemingly poor performance could have occurred by chance. METHOD: The risk scoring system has been derived and validated locally for cardiac surgery. A method is described for calculating the probability that an observed number of deaths occurs within a sequence of operations if perioperative mortality is regarded as a chance event with an expected value derived from the risk score. To illustrate this method, nested prediction intervals are superimposed onto VLAD plots for a series of 393 isolated coronary artery bypass and isolated valve operations performed by a single surgeon. RESULTS: Using the locally derived risk score, the VLAD plot for the individual surgeon shows a net life gain of about 6 over the predicted number of survivors, which is observed to be within the 90% prediction interval. If the Parsonnet scoring system is used instead of the locally derived risk score, the net life gain is considerably overestimated. CONCLUSIONS: The nested prediction intervals are straightforward to generate and can be integrated into a visually informative display. As an indication of the inherent variability in outcome, they have a valuable role in the monitoring of surgical performance.

Clinical Competence↗

Withdrawing low risk women from cervical screening programmes: mathematical modelling study.

OBJECTIVE: To evaluate the impact of policies for removing women before the recommended age of 64 from screening programmes for cervical cancer in the United Kingdom. DESIGN: A mathematical model of the clinical course of precancerous lesions which accounts for the influence of infection with the human papillomavirus, the effects of screening on the progression of disease, and the accuracy of the testing procedures. Two policies are compared: one in which women are withdrawn from the programme if their current smear is negative and they have a recent history of regular, negative results and one in which women are withdrawn if their current smear test is negative and a simultaneous test is negative for exposure to high risk types of human papillomavirus. SETTING: United Kingdom cervical screening programme. MAIN OUTCOME MEASURES: The incidence of invasive cervical cancer and the use of resources. RESULTS: Early withdrawal of selected women from the programme is predicted to give rise to resource savings of up to 25% for smear tests and 18% for colposcopies when withdrawal occurs from age 50, the youngest age considered in the study. An increase in the incidence of invasive cervical cancer, by up to 2 cases/100 000 women each year is predicted. Testing for human papillomavirus infection to determine which women should be withdrawn from the programme makes little difference to outcome. CONCLUSIONS: This model systematically analyses the consequences of screening options using available data and the clinical course of precancerous lesions. If further audit studies confirm the model's forecasts, a policy of early withdrawal might be considered. This would be likely to release substantial resources which could be channelled into other aspects of health care or may be more effectively used within the cervical screening programme to counteract the possible increase in cancer incidence that early withdrawal might bring.

Adult↗

Monitoring the results of cardiac surgery by variable life-adjusted display.

BACKGROUND: Conventional assessment of the outcome of cardiac surgery usually takes the form of retrospective mortality figures and, at best, indicates an average performance over time. Summary tables conceal good and bad runs, and without risk adjustment they are difficult to interpret. We developed a refinement of the cumulative sum method that weights death and survival by each patient's risk status and provides a display of surgical performance over time. METHODS: The variable life-adjusted (VLAD) plot shows the difference between expected and actual cumulative mortality. VLAD shows whether a surgeon's performance is above or below what might be expected. This mortality-scoring system accumulates penalties for each death and rewards for every survivor, based on the inherent risk of perioperative death of each case concerned. FINDINGS: We illustrate the results of three performance reviews, displayed as VLADs. The first shows the results of an individual surgeon for 547 consecutive cardiac-surgical cases. The overall mortality was 36% less than that predicted by the Parsonnet scoring system. The second displays the results for 5000 consecutive patients who underwent cardiopulmonary bypass between 1992 and 1996, divided into six contemporaneous series. The predicted mortality was 9% compared with 6% actual mortality. The third is a plot for a trainee surgeon and clearly shows how a period of poor performance was identified and then substantially improved, which would not have been revealed by conventional tables of summary statistics. INTERPRETATION: VLAD provides a graphical display of risk-adjusted survival figures for individual surgeons or units over time and could be modified to monitor performance over a range of treatments and outcomes.

Cardiovascular Surgical Procedures↗

Evaluating cervical cancer screening programmes for developing countries.

This study evaluates cervical screening programmes for regions of the world where resources are scarce and little screening currently takes place. It investigates infrequent screening and programmes in which as many women as possible are screened just once in their lifetime. It also compares the effectiveness of cytology and human papillomavirus (HPV) testing for primary screening. Different programmes are evaluated by a stochastic model of the progression of pre-cancer, its relationship to papillomavirus infection and the diagnostic accuracy of alternative screening methods. These are compared in terms of the impact on the incidence of invasive cancer and resource use. Important factors that determine the suitability of different screening programmes are the available resources and the expected population coverage. Blanket screening for women aged 30-59 years, with the aim of covering all just once in their lifetime, could reduce the incidence of invasive cancer by up to 30%. A 10-year programme would require about 50% more routine screening tests to bring about the same reduction in incidence and a 5-year programme about 2.5-3 times as many. With either approach it would be more effective for resource use to concentrate on screening women aged 30-59 than a wider age group. Whether HPV testing would be more effective as a primary screening method than cytology depends on the underlying prevalence of HPV infection, the accuracy of cytology, the cost and the suitability of the testing procedure under field conditions.

Adult↗

Can papilloma virus testing be used to improve cervical cancer screening?

This report investigates different options for using human papillomavirus (HPV) testing in cervical cancer prevention. These options are evaluated by a stochastic model of the progression of pre-malignancy and its relationship to HPV infection. Three screening policies are compared: 2 based on cytological screening, with or without HPV testing, and 1 in which HPV testing is the primary screening method. A policy of HPV testing for women with mildly abnormal smears would have little effect on the overall incidence of invasive cancer when compared with a policy of repeat cytology, provided follow-up is efficient. Moreover, the potential value of HPV testing as a primary screening method is strongly dependent on the proportion of neoplasias that are HPV-negative. Important factors in assessing the future role of HPV testing would be cost-effectiveness and benefits from improved compliance.

Adult↗

Displaying the long-term progression of patients with coronary artery disease.

Cardiac clinicians are often faced with the problem of trying to assimilate details of a patient's long-term history. Case notes are often lengthy, making this process difficult if not impossible in the time available during an outpatient examination. A computer system has been developed to assist with this task. This generates a graphical summary of the principal features of a patient's long-term progression. It gives an overview of how the patient's anginal status has changed, his or her drug treatment and any surgical interventions. The system also allows the clinican to display summaries of diagnostic tests carried out. The system can be used to assist clinical management and speed up outpatient examination. It can also be used to facilitate case conference sessions and has potential for being used in medical education.

Coronary Disease↗

A randomized study of MOD versus VAD in the treatment of relapsed and resistant multiple myeloma.

67 patients with relapsed or resistant multiple myeloma were randomized to receive either VAD (vincristine, doxorubicin, dexamethasone) or MOD (mitozantrone, vincristine, dexamethasone). 12/30 (40%) patients receiving VAD and 15/37 (41%) patients receiving MOD achieved plateaux. The median duration of plateaux was significantly longer on VAD (15 months) than on MOD (8 months). No significant difference in overall survival was seen between the two treatment arms. The only toxicity which was severe in more than 5% of treatment cycles on either treatment arm was myelosuppression. No toxicity was significantly more severe on MOD than VAD. However, hair loss was significantly more severe on VAD than MOD. The frequencies of thrombocytopenia, haematuria and cutaneous toxicity were significantly greater on VAD than on MOD. Raised serum direct bilirubin levels were seen significantly more often on MOD than VAD. MOD and VAD have similar efficacy in relapsed/resistant multiple myeloma. MOD is the less toxic of the two regimens.

Aged↗

P-COMM-B induction chemotherapy in intermediate and high grade non-Hodgkin's lymphoma.

57 patients with newly diagnosed intermediate or high grade non-Hodgkin's lymphoma with stage II to IV disease were treated with P-COMM-B (prednisolone, cyclophosphamide, vincristine, mitozantrone, methotrexate and bleomycin). 46% patients achieved a complete remission and 26% achieved a partial remission. Projected disease-free survival in complete remission at 5 years is 56% and projected overall survival at 5 years is 37%. Neutropenia and proximal myopathy were the commonest severe toxicities encountered and two deaths were clearly related to treatment (3.5%). P-COMM-B is effective first-line chemotherapy in intermediate and high grade non-Hodgkin's lymphoma. The efficacy and toxicity of P-COMM-B appear to be comparable to those of the best contemporary regimen, CHOP.

Adolescent↗

Cytological screening and management of abnormalities in prevention of cervical cancer: an overview with stochastic modelling.

AIMS: To develop a mathematical model of the histological changes of precancer and the development of invasive cancer and how these are related to cytological findings. To use this to investigate the effects on incidence of cervical cancer, number of smear tests and colposcopies, of different schedules for cervical screening, and the clinical management policies for dyskaryosis. METHODS: A stochastic model was developed relating the available data on tissue progression to the cytological findings. Two strategies, A and B, were compared: under A, women with any abnormal smear receive immediate colposcopy and treatment; under B, women with mild or borderline dyskaryosis have repeated smears at six monthly intervals with colposcopy only for persistent abnormalities. RESULTS: The model predicted an incidence of invasive cervical cancer in an unscreened population of women aged over 18 years of 5.9 per 10,000 per year. With 70% coverage and three yearly screening under strategy A, the incidence fell to 2.00 and under B to 2.10. The number of smears required was similar but A required two to three times as many colposcopies as B. Raising the coverage to 90% reduced the incidence to around 1 per 10,000 per year but changing the screening interval, the specificity or sensitivity of cytology had much less effect. CONCLUSION: The model has been tested under a wide range of possible variations in natural history, specificity and sensitivity of cytology. For low grade smear abnormalities, open colposcopic referral is predicted to reduce invasive cancer only slightly more than repeat cytology, at the expense of much additional colposcopy. Improving cytological coverage is suggested as more effective in reducing invasive cancer than increased use of colposcopy or more frequent screening.

Colposcopy↗