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Biomedical subjects

M Dawes

Publications and source records attributed to M Dawes.

At least 19 recordsLinked to original sources

Systematic reviews of clinical decision tools for acute abdominal pain.

OBJECTIVES: To review for acute abdominal pain (AAP), the diagnostic accuracies of combining decision tools (DTs) and doctors aided by DTs compared with those of unaided doctors. Also to evaluate the impact of providing doctors with an AAP DT on patient outcomes, clinical decisions and actions, what factors are likely to determine the usage rates and usability of a DT and the associated costs and likely cost-effectiveness of these DTs in routine use in the UK. DESIGN: Electronic databases were searched up to 1 July 2003. REVIEW METHODS: Data from each eligible study were extracted. Potential sources of heterogeneity were extracted for both questions. For the accuracy review, meta-analysis was conducted. Among studies comparing diagnostic accuracies of DTs with unaided doctors, error rate ratios provided estimates of the differences between the false-negative and false-positive rates of the DT and unaided doctors' performance. Pooled error rate ratios and 95% confidence intervals (CIs) for false-negative rates and false-positive rates were computed. Metaregression was used to explore heterogeneity. RESULTS: Thirty-two studies from 27 articles, all based in secondary care, were eligible for the review of DT accuracies, while two were eligible for the review of the accuracy of hospital doctors aided by DTs. Sensitivities and specificities for DTs ranged from 53 to 99% and from 30 to 99%, respectively. Those for unaided doctors ranged from 64 to 93% and from 39 to 91%, respectively. Thirteen studies reported false-positive and false-negative rates for both DTs and unaided doctors, enabling a direct comparison of their performance. In random effects meta-analyses, DTs had significantly lower false-positive rates (error rate ratio 0.62, 95% CI 0.46 to 0.83) than unaided doctors. DTs may have higher false-negative rates than unaided doctors (error rate ratio 1.34, 95% CI 0.93 to 1.93). Significant heterogeneity was present. Two studies compared the diagnostic accuracies of doctors aided by DTs to unaided doctors. In a multiarm cluster randomised controlled trial (n = 5193), the diagnostic accuracy of doctors not given access to DTs was not significantly worse (sensitivity 28.4% and specificity 96.0%) than that of three groups of aided doctors (sensitivities of 42.4-47.9%, and specificities of 95.5-96.5%, respectively). In an uncontrolled before-and-after study (n = 1484), the sensitivities and specificities of aided and unaided doctors were 95.5% and 91.5% (p = 0.24) and 78.1% and 86.4% (p < 0.001), respectively. The metaregression of DTs showed that prospective test-set validation at the site of the tool's development was associated with considerably higher diagnostic accuracy than prospective test-set validation at an independent centre [relative diagnostic odds ratio (RDOR) 8.2; 95% CI 3.1 to 14.7]. It also showed that the earlier in the year the study was performed the higher the performance (RDOR 0.88, 0.83 to 0.92), that when developers evaluated their own DT there was better performance than when independent evaluators carried out the study (RDOR = 3.0, 1.3 to 6.8), and that there was no evidence of association between other quality indicators and DT accuracy. The one eligible study of the impact study review, a four-arm cluster randomised trial (n = 5193), showed that hospital admission rates of patients by doctors not allocated to a DT (42.8%) were significantly higher than those by doctors allocated to three combinations of decision support (34.2-38.5%) (p < 0.001). There was no evidence of a difference between perforation rates (p = 0.19) and negative laparotomy rates in the four trial arms (p = 0.46). Usage rates of DTs by doctors in accident and emergency departments ranged from 10 to 77% in the six studies that reported them. Possible determinants of usability include the reasoning method used, the number of items used and the output format. A deterministic cost-effectiveness comparison demonstrated that a paper checklist is likely to be 100-900 times more cost-effective than a computer-based DT, under stated assumptions. CONCLUSIONS: With their significantly greater specificity and lower false-positive rates than doctors, DTs are potentially useful in confirming a diagnosis of acute appendicitis, but not in ruling it out. The clinical use of well-designed, condition-specific paper or computer-based structured checklists is promising as a way to improve impact on patient outcomes, subject to further research.

Abdominal Pain↗

Global perspectives of contemporary epidemiological trends of cutaneous malignant melanoma.

During the past several decades, there has been a substantial increase in the incidence of cutaneous melanoma among all caucasian populations. The number of deaths due to cutaneous malignant melanoma has also increased in most fair-skinned populations throughout the world in the past few decades. Trends in melanoma incidence worldwide are examined. The most recent data on the mortality from cutaneous melanoma are reported. The role of different environmental, genetic and host factors in the aetiology of melanoma is discussed.

Female↗

Tumour thickness as a predictor of occult lymph node metastases in patients with stage I and II melanoma undergoing sentinel lymph node biopsy.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a minimally invasive procedure used accurately to stage nodal basins at risk of occult metastases. There are no data as yet to show a survival benefit from SLNB and its use remains controversial. If Breslow thickness of the tumour correlates well with positive SLNB, it could be used to select patients for SLNB. METHODS: A quantitative systematic review of published studies on SLNB in patients with melanoma available by September 2001 was performed. RESULTS: Twelve studies containing 4218 patients with stage I and II melanoma were identified; 17.8 (95 per cent confidence interval 16.7 to 19.0) per cent of patients had nodal micrometastases detected by SLNB. The incidence of micrometastasis in sentinel nodes correlated directly with Breslow tumour thickness; it was 1.0 per cent for lesions of less than or equal to 0.75 mm, 8.3 per cent for 0.76-1.50 mm, 22.7 per cent for 1.51-4.0 mm and 35.5 per cent for more than 4.0 mm. CONCLUSION: The Breslow thickness of primary melanoma predicts the presence of a sentinel node metastasis. The published data are not sufficient to demonstrate a correlation between other known prognostic indicators and a positive SLNB.

Humans↗

Management of regional lymph nodes in patients with malignant melanoma: questionnaire survey of UK current practice.

In 2001, a short postal questionnaire regarding the management of regional lymph nodes in patients with cutaneous malignant melanoma was sent to 69 NHS departments of plastic and reconstructive surgery in the UK. Questionnaires were returned by 53 units, giving a response rate of 76.8%. Of these 53 units, 49 reported that they treat patients with primary malignant melanoma. There was considerable variation in the number of melanoma patients managed by each unit. This survey confirmed that elective lymph-node dissection is not routinely practiced in the UK; observation and therapeutic lymph-node dissection for patients who develop regional metastasis is the preferred pattern of care. The majority of centres in the UK do not use sentinel lymph node mapping: only 15 of the 49 units do so (30.6%). The number of sentinel lymph node biopsies performed in each unit varied significantly. There was considerable variation in the materials used and the process of care for sentinel lymph node biopsy. On the basis of this current practice, we recommend the setting up of a prospective clinical melanoma register to record the surgical treatment of melanoma patients.

Humans↗

Quantitative aspects of the inhibition by N(G)-monomethyl-L-arginine of responses to endothelium-dependent vasodilators in human forearm vasculature.

1. N(G)-monomethyl-L-arginine (L-NMMA) constricts human forearm resistance vasculature and selectively attenuates vasodilator responses to endothelium-dependent vasodilators. Incomplete inhibition of such responses could be due to an inadequate dose of L-NMMA or to NO-independent vasodilator mechanisms. 2. This study sought to determine doses of L-NMMA that are maximally effective in reducing basal and stimulated forearm blood flow. Drugs were infused via the brachial artery in 32 healthy men. Acetylcholine (11 - 330 nmol min(-1)) was compared with albuterol (0.33 - 10 nmol min(-1)), and nitroprusside (1.7 - 20 nmol min(-1)). 3. The effect of L-NMMA on basal flow approached maximum (53+/-2% reduction) at a dose of 16 micromol min(-1). L-NMMA (16 micromol min(-1)) did not significantly influence responses to nitroprusside, but antagonized acetylcholine and albuterol (each P<0.001, by repeated measures analysis of variance). 4. Inhibition of acetylcholine by L-NMMA (16 micromol min(-1)) was strongly influenced by acetylcholine dose (73+/-7% inhibition at 11 nmol min(-1), P<0.01; 4+/-11% inhibition at 330 nmol min(-1), P=NS, Student's paired t-test). Significant inhibition of albuterol was observed at all doses. 5. A higher dose of L-NMMA (64 micromol min(-1)) did not significantly inhibit the response to acetylcholine (330 nmol min(-1)). Responses to this dose of acetylcholine were unaffected by a cyclo-oxygenase (COX) inhibitor (indometacin) alone but combined COX and NO inhibition attenuated acetylcholine responses by 42+/-19%, implying that there is a compensatory increase in the contribution of prostaglandins or NO to acetylcholine-induced dilatation when one or other pathway is inhibited.

Acetylcholine↗

Drugs in pregnancy. Pharmacokinetics in pregnancy.

Pharmacokinetics describes the handling of a drug by the body - how the drug is absorbed, distributed and eliminated and how these processes determine plasma concentrations of the drug. Changes in maternal physiology during pregnancy influence pharmacokinetics, and this may have important sequelae for drug dosing, especially for drugs for which adverse effects occur at concentrations within, or just above, the therapeutic range. For many drugs absorption is decreased and elimination increased, thus tending to reduce plasma concentrations. There are, however, relatively few specific data on pharmacokinetics in pregnancy, compared to the non-gravid state, because of the obvious ethical issues surrounding studies during pregnancy. Most therapeutic guidelines are thus based on observational studies and basic principles.

Biological Availability↗

Presentation, management and course of angina and suspected angina in primary care.

Previous surveys may have underestimated both prevalence and incidence of ischemic heart disease in general practice. Case identification is difficult, as many patients presenting with chest pain turn out not to have ischemic heart disease, although their outcome is unclear otherwise. In this work we aimed to: (1) estimate prevalence and incidence of angina in one Oxford general practice; (2) describe the processes of assessment, investigation, and management of suspected angina; and (3) describe the 2-year symptomatic and functional outcome of angina patients, compared with patients whose provisional diagnosis of suspected ischemic heart disease (IHD) was not subsequently sustained (NCCP). A retrospective survey of patients was undertaken (aged 45-74 years) by hand searching paper and electronic medical records to find, as of 1 January 1992, all patients in the practice with continuing treatment of angina diagnosed before 1989, or those having a new diagnosis of angina being assessed (suspected angina) in the 3 year 1989-1991. Two years later, a postal questionnaire survey compared the symptomatic and functional outcome of confirmed IHD and NCCP. On 1 January 1992, the diagnosis of angina was recorded in the notes of 11.1% of patients aged 45-74 years, and the diagnosis was considered correct in 7.4%. Over a 3-year period, 129 people was suspected of suffering from angina, but in 71 (55%) the diagnosis was not confirmed; 76 (59%) were either referred to a specialist out-patient clinic or had an emergency admission. A 2-year follow-up found that similar proportions of patients with angina and noncardiac chest pain had a poor outcome in terms of symptoms, mental state, quality of everyday life, and continuing consultation. The clinical burden of ischemic heart disease in general practice has been underestimated by earlier methodological approaches using less complete ascertainment strategies. The adequacy of current diagnostic and management arrangements for patients with suspected angina merits review, at both the primary and secondary care levels.

Aged↗