Best practice in primary care pathology: review 9.

This ninth best-practice review examines two series of common primary care questions in laboratory medicine: (i) potassium abnormalities and (ii) venous leg ulcer microbiology. The review is presented in question-and-answer format, referenced for each question series. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by MEDLINE EMBASE searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus rather than evidence-based. They will be updated periodically to take account of new information.

Best practice in primary care pathology: review 8.

This eighth best practice review examines four series of common primary care questions in laboratory medicine: (i) sodium abnormalities; (ii) faecal occult blood testing; (iii) warfarin management; and (iv) sputum cytology in diagnosis of bronchopulmonary malignancy. The review is presented in question-answer format, referenced for each question series. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus rather than evidence-based. They will be updated periodically to take account of new information.

Best practice in primary care pathology: review 7.

This seventh best-practice review examines four series of common primary care questions in laboratory medicine: (1) blood count abnormalities 2; (2) cardiac troponins; (3) high-density lipoprotein cholesterol; and (4) viral diseases 2. The review is presented in a question-answer format, with authorship attributed for each question series. The recommendations are a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. The recommendations are not standards, but form a guide to be set in the clinical context. Most are consensus based rather than evidence based. They will be updated periodically to take account of new information.

Best practice in primary care pathology: review 6.

This sixth best practice review examines four series of common primary care questions in laboratory medicine: (1) laboratory monitoring in hypertension and heart failure abnormalities; (2) markers of inflammatory joint disease; (3) laboratory investigation of chronic diarrhoea; and (4) mumps and chickenpox. The review is presented in question-answer format, referenced for each question series. The recommendations represent a precis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus based rather than evidence based. They will be updated periodically to take account of new information.

Liquorice and soy sauce, a life-saving concoction in a patient with Addison's disease.

Addison's disease is a relatively common disorder to endocrinologists, but is rare and potentially fatal when presenting acutely. Treatment now involves replacement of glucocorticoids and mineralocorticoids with synthetic compounds, although historically patients took common salt and plant-based preparations. We describe the case of a 42-year-old woman who self-treated undiagnosed Addison's disease for several years with soy sauce and liquorice sticks. She presented with a four-week history of decreased energy, malaise and postural dizziness. Our patient described an unusual diet of liquorice sticks and soy sauce, consuming around 46 g of salt per week. There was a family history of Type 1 diabetes mellitus. Physical examination was unremarkable, although subsequent investigation confirmed Addison's disease. Liquorice provided glycyrrhizic acid and glycyrrhetinic acid, which act on 11-beta hydroxysteroid dehydrogenase enzymes. In this case, the net effect was potentiation of glucocorticoid action on renal mineralocorticoid receptors in the context of failing adrenocortical steroid production. The case highlights the importance of taking a dietary history to aid diagnosis.

Best practice in primary care pathology: review 5.

This fifth best practice review examines three series of common primary care questions in laboratory medicine: (1) minor liver function test abnormalities; (2) laboratory monitoring of patients receiving lithium; and (3) investigation of possible venous thromboembolism. The review is presented in question-answer format, referenced for each question series. The recommendations represent a precis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus-based rather than evidence-based. They will be updated periodically to take account of new information.

Best practice in primary care pathology: review 3.

This best practice review examines four series of common primary care questions in laboratory medicine: (i) "minor" blood platelet count and haemoglobin abnormalities; (ii) diagnosis and monitoring of anaemia caused by iron deficiency; (iii) secondary hyperlipidaemia and hypertriglyceridaemia; and (iv) glycated haemoglobin and microalbumin use in diabetes. The review is presented in question-answer format, referenced for each question series. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards, but form a guide to be set in the clinical context. Most of the recommendations are based on consensus rather than evidence. They will be updated periodically to take account of new information.

Best practice in primary care pathology: review 4.

This fourth best practice review examines four series of common primary care questions in laboratory medicine are examined in this review: (1) safety monitoring for three common drugs; (2) use of prostate-specific antigen; (3) investigation of vaginal discharge; and (4) investigation of subfertility. The review is presented in question-answer format, referenced for each question series. The recommendations represent a precis of the guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most of them are consensus based rather than evidence based. They will be updated periodically to take account of new information.

Best practice in primary care pathology: review 2.

This second best practice review examines five series of common primary care questions in laboratory medicine: (1) laboratory testing for allergy, (2) diagnosis and monitoring of menopause, (3) the use of urine cytology, (4) the usefulness of the erythrocyte sedimentation rate, and (5) the investigation of possible urinary tract infection. The review is presented in a question-answer format. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents, and evidence based medicine reviews, supplemented by MEDLINE EMBASE searches to identify relevant primary research documents. They are standards but form a guide to be set in the clinical context. Most are consensus rather than evidence based. They will be updated periodically to take account of new information.

Methodology for constructing guidance.

Although guidance exists for the use of many laboratory tests in a wide range of clinical situations, this guidance is spread among a range of literature sources, and is often directed at laboratory specialists rather than test users. Individual general practices display large variations in standardised test requesting, yet much of their testing activity involves a relatively small range of tests. This paper describes a methodological approach to review the available evidence and guidance and to extract relevant primary research work to examine a range of testing scenarios in general practice, with the aim of formulating guidance based on the best available evidence or consensus opinions.

Best practice in primary care pathology: review 1.

This first best practice review examines four series of common primary care questions in laboratory medicine, namely: (i) measurement and monitoring of cholesterol and of liver and muscle enzymes in patients in the context of lipid lowering drugs, (ii) diagnosis and monitoring of vitamin B12/folate deficiency, (iii) investigation and monitoring of paraprotein bands in blood, and (iv) management of Helicobacter pylori infection. The review is presented in a question-answer format, referenced for each question series. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents, and evidence based medicine reviews, supplemented by MEDLINE EMBASE searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus rather than evidence based. They will be updated periodically to take account of new information.

des-Asp-angiotensin I: its identification in rat blood and confirmation as a substrate for converting enzyme.

The observation that angiotensin III is present in the circulation of the rat in amounts similar to those of angiotensin II has led to the notion that it may, in part, be formed by the action of converting enzyme on des-Asp-angiotensin I without the prior formation of angiotensin II. This possibility was studied in conscious rats using a combination of RIA and chromatographic techniques which allowed the separate measurement of angiotensin I, des-Asp-angiotensin I, angiotensin II, and angiotensin III in rat blood. Infusion of des-Asp1-[Ile5]angiotensin I at 50, 150, and 450 ng/kg . min resulted in a progressive increase in the plasma concentration of angiotensin III up to 279 +/- 50 (SD) pg/ml compared to 9 +/- 9 (SD) pg/ml after dextrose infusion. Regardless of the infusion of des Asp-[Ile5]angiotensin I, plasma angiotensin III made up a constant 46 +/- 8% (+/- SD) of the total immunoactive material, the remainder being composed of smaller metabolic fragments, indicating a rapid rate of clearance of angiotensin III. Captopril completely inhibited the rise in angiotensin III after des-Asp1-[Ile5]angiotensin I infusion. A substance which chromatographed as des-Asp-[Ile5]angiotensin I was detected in rat blood and made up 19% of the angiotensin I immunoactive material, while angiotensin III made up 44% of the angiotensin II immunoactive material. These results confirm that des-Asp1-[Ile5]angiotensin I is a substrate for converting enzyme in the rat, and the presence of a chromatographically similar substance in the circulation suggests that at least part of the angiotensin III in rat blood may be formed by the action of converting enzyme on endogenous des-Asp-angiotensin I. (Endocrinology 108: 406, 1981)

Probucol reduces plasma lipid peroxides in man.

Although primarily used as a lipid lowering drug, probucol also possesses anti-oxidant activity and has been shown in animal models to inhibit or delay the progression of atherosclerosis. It has been suggested that this anti-atherosclerotic effect may occur through inhibition of free radical oxidation of low density lipoprotein. The aim of this study was to investigate the effects of probucol on free radical activity in hyperlipidaemic patients. Plasma lipid peroxides were measured before probucol treatment, at 4 and 12 weeks treatment and then 4 weeks after stopping probucol. Lipid peroxide concentrations were significantly reduced during and 4 weeks after stopping treatment with probucol, when compared with baseline values. There were no changes in plasma vitamin E concentrations. The results of this study indicate that probucol reduces lipid peroxidation in patients, an effect which may occur through a free radical scavenging action.

Method for assessment of laboratory turnaround times: comparison before, during, and after analysis.

AIMS: To establish a mechanism to examine the components of turnaround time in a representative cross-section of laboratory users; and to identify potential areas for improvement. METHODS: Information was collected manually from result reports received by eight laboratory users: three wards in the main hospital, four GP practices, and one local psychiatric hospital. This was combined with data from the departmental computer files to create a spreadsheet detailing different time points in the processing of a specimen, from venepuncture to receipt of result report. RESULTS: At the main hospital, 80% of samples arrived within two hours of venesection and 95% by four hours; 75% of samples were analysed within two hours; 85% of results arrived in the wards within six hours of printing, although 12% took more than 18 hours to arrive; median overall time six hours. At the satellite (psychiatric) hospital, all samples arrived within seven hours of venesection; 45% were analysed within two hours--the rest the following morning; there were highly variable post-analytical times, minimum 18 hours, maximum 122 hours; the median overall time was 69 hours. Twenty five per cent of samples from GPs took more than 20 hours to arrive; 75% were analysed within two hours, the rest took over 18 hours--waiting overnight; the post-analytical times were highly variable, minimum 22 hours, maximum 122 hours; the median overall time was 50 hours. CONCLUSIONS: The method is easily repeatable and demonstrates the need for local improvement in the post-analytical period. Although specific to the individual data handling system for one laboratory, this method may be used as a basis for other laboratories in pathology disciplines to undertake a representative assessment of turnaround times for different groups of laboratory users.

Benchmarking general practice use of pathology services: a model for monitoring change.

AIMS: To identify a model to assess general practitioner use of pathology services that could be applied to assess specific interventions designed to promote best practice. METHODS: A database containing standardised requesting data for 22 general practices was constructed. The database contained 28 tests covering 95% of general practitioner activity, distributed across pathology, and it was evaluated during two sequential six month periods. A comparison of ranks of requesting activity between different time periods was undertaken by calculating Pearson rank correlation coefficients. Requesting numbers were also adjusted for patients' age and sex distributions within the 22 practices for a sample of three high volume tests. The effects of distributing requesting guidelines and details of requesting activity were assessed during two sequential three month periods. RESULTS: Requesting activity was extremely stable during the two baseline periods for most test (r > 0.80 for 20 of the 28 tests). Several less discriminatory tests were identified. Age and sex adjustment had minimal impact on the ranks of requesting activity. Requesting activity during the two three month periods after distributing guidelines and comparative details of individual requesting activity showed little change (overall correlation coefficient, 0.844 between baseline and intervention periods). CONCLUSIONS: Ranking general practitioners requesting activity adjusted for practice list size provides a reproducible means of measuring requesting activity for most pathology tests performed in general practice. Activity was not influenced by age or sex of patients on the practice list. Distributing requesting guidelines and individual requesting activity on their own do not have any measurable impact on requesting activity. More innovative (possibly multiple) interventions might be required to influence general practitioner requesting practice.

Inequalities of primary care microbiology testing between hospital catchment areas.

AIMS: To compare differences in microbiology testing activity between general practices within and between five hospitals in two National Health Service (NHS) regions in England. METHODS: Retrospective capture of standardised microbiology testing activity from the laboratory computer databases. Six equivalent tests were identified and compared. Data were obtained for 174 general practices in eight primary care groups, served by two NHS hospital trusts and three public health laboratories. The total catchment population was 1,180,000 people. Comparative test activities were displayed graphically and differences in median test activity and the hospital activity distributions were examined by the Wilcoxon signed rank test. RESULTS: Median testing activity differed by 200% (urine) to 800% (wound swabs) between the trusts that performed the highest and the lowest number of tests, and from 300% to 1900% between the top and bottom 10% activity bands of general practices. Large and significant differences were found between the hospitals, irrespective of whether they belonged to the same trust, and irrespective of their geographical location. CONCLUSIONS: Large differences in microbiology testing exist within individual trust catchment areas in primary care, and there are also considerable differences between trusts. These inequalities may also introduce a selection bias into epidemiological and antibiotic resistance surveillance. This indicates a widespread need to examine and deal with the reasons responsible for these differences.

Is clinical practice variability the major reason for differences in pathology requesting patterns in general practice?

AIMS: To examine whether variations in pathology test requesting between different general practices can be accounted for by sociodemographic or other descriptive indicators of the practice. METHOD: This was a comparative analysis of requesting patterns across a range of pathology tests representing 95% of those requested in general practice, in 22 general practices in a single district, serving a population of 165 000. Spearman correlation coefficients were calculated and both the top and bottom fifths of activity were displayed graphically to detect trends at the extremes of the ranges. RESULTS: The proportion of women of childbearing age, median practice Townsend scores, or the existence of specialist miniclinics within the practice did not have a demonstrable impact on requesting patterns. A weak correlation was found between the proportion of elderly patients and creatinine/electrolyte testing but not for the other two tests examined for this patient group. CONCLUSIONS: The large differences observed in general practice pathology requesting probably result mostly from individual variation in clinical practice and are therefore potentially amenable to change.

Laboratory turnround time: closing the loop.

AIMS: To institute recommendations from a laboratory turnround time study; to evaluate audit methods; and to quantify improvements achieved. METHODS: Changes to result report distribution and specimen delivery were affected by posting results directly from the laboratory followed by the introduction of a twice daily courier service. Improvements were evaluated by repeating the turnround time audit described in an earlier report. Pre-, peri- and post-analytical turnround times were compared before and after changes had been instituted. RESULTS: Directly posting general practitioner (GP) results increased the percentage of reports which reached their destination within one and two days after they were generated from 13 to 29% and from 68 to 82%, respectively. Pre- and postanalytical times were superimposable before and after posting was started. Corresponding improvements to the satellite hospital service were from 25 to 78% and from 60 to 82%, respectively. The courier service shortened the median total turnround time from 50 to nine hours for GPs and from 69 to 18 hours for the satellite hospital. Fifty three per cent of GP reports and 21% of satellite hospital reports arrived on the same day as the sample was taken: 99% and 94%, respectively, had arrived by the next day. The number of analytically "old" samples which arrived the day after they had been taken, thus invalidating many results, fell from 25 to 3%. CONCLUSIONS: These audits of laboratory turnround time have been used to present a valid case for changes to laboratory transport and to quantify the improvements achieved. They produce consistent and repeatable results, which may also be used to monitor future performance, to assess further changes and to establish the cost-effectiveness of resources used.

Development of a competency based training programme to support multidisciplinary working in a combined biochemistry/haematology laboratory.

The aim of this study was to develop a competency based training programme to support multidisciplinary working in a combined biochemistry and haematology laboratory. The training programme was developed to document that staff were trained in the full range of laboratory tests that they were expected to perform. This programme subsequently formed the basis for the annual performance review of all staff. All staff successfully completed the first phase of the programme. This allowed laboratory staff to work unsupervised at night as part of a partial shift system. All staff are now working towards achieving a level of competence equivalent to the training level required for state registration by the Council for Professions Supplementary to Medicine. External evaluation of the training programme has included accreditation by the Council for Professions Supplementary to Medicine and reinspection by Clinical Pathology Accreditation (UK) Ltd. The development of a competency based training system has facilitated the introduction of multidisciplinary working in the laboratory. In addition, it enables the documentation of all staff to ensure that they are fully trained and are keeping up to date, because the continuing professional development programme in use in our laboratory has been linked to this training scheme. This approach to documentation of training facilitated a recent reinspection by Clinical Pathology Accreditation (UK) Ltd.

Effects of changes in acid base and calcium concentration on fasting serum insulin, proinsulin, and glucose concentrations.

AIMS: To test the hypothesis that alterations in acid base or calcium concentration may affect proinsulin processing or the insulin secretion mechanism. METHODS: Changes in proinsulin secretion or cleavage were assessed by measuring serum intact proinsulin and immunoreactive insulin concentrations in three models of acid base and calcium disturbance: (1) subacute changes in acid base status in six volunteers who received oral placebo, ammonium chloride, or sodium bicarbonate for three five day periods; (2) acute changes in calcium concentration in eight subjects who received 25 mmol oral calcium; (3) chronic changes in calcium concentration in seven patients with primary hyperparathyroidism and five with pseudohypoparathyroidism. RESULTS: Acid base changes were confirmed by rises in serum bicarbonate concentrations (p < 0.01). No changes in serum insulin, intact proinsulin, or the proinsulin:insulin molar ratio were found. Serum calcium concentrations increased (2.49 v 2.38 mmol/l; p < 0.05) and parathyroid hormone concentrations decreased (1.1 v 1.9 pmol/l; p < 0.01) two hours after acute calcium loading. There were no significant differences in serum glucose, insulin, or intact proinsulin concentrations. Fasting proinsulin concentrations were significantly lower in the hyperparathyroid group (1.1 v 2.1 pmol/l; p < 0.05) and increased significantly after parathyroidectomy (2.1 v 1.1 pmol/l; p < 0.05). CONCLUSIONS: The results indicate that subacute acid base changes do not affect proinsulin cleavage. Although acute calcium loading has no demonstrable effect, chronic hypercalcaemia may influence the mechanism of insulin secretion.