An audit of the implementation of the international consensus group's guidelines on reporting of blood films.

AIMS: This study was carried out as part of the Pathology Benchmarking Review and it audits the implementation of the guidelines for the reporting of blood films published by the International Consensus Group for Haematology Review. METHODS: Each laboratory completed a questionnaire about the number of blood counts and blood films performed. Information was collected on the criteria that were used for preparing a blood film and whether they had followed the guidelines of the International Consensus Group. RESULTS: 74 National Health Service organisations (151 laboratory sites) participated in the study. 24 laboratories had implemented the guideline, 21 with local modification, and 3 without modification. The reasons that prevented the full implementation of the guideline included the inability of laboratory information systems to be modified to include the guideline rules, the laboratory not agreeing with the guideline criteria, and the staff time required to implement the guide to justify the perceived local benefits of implementation. CONCLUSION: This is the first study that has assessed the implementation of the International Consensus Guidelines at a national level. Many laboratories had experienced difficulty in implementing the consensus guideline partly due to the complexity of the guideline. As a result 21 of the 24 laboratories that had attempted to implement the guideline had made local modification to the guideline. Since it was not possible to estimate the impact that local modification of the guideline would have on the percentage of blood films it was not possible to establish a benchmark of practice following implementation of the guideline.

A tabletop exercise to assess a hospital emergency blood management contingency plan in a simulated acute blood shortage.

The objective was to assess both our local plan and the assumptions made in the national guidelines on how laboratories should prepare for an acute shortage of red cells. The Chief Medical Officer's National Blood Transfusion Committee for England and North Wales has issued guidance on how hospitals should prepare contingency plans to deal with a shortage of red cells for transfusion. This study has therefore assessed the practicalities of these proposals together with assessing how well local policies would deal with this situation. A tabletop exercise was carried out in which all requests over a 21-day period were assessed. The restrictions as suggested by the national blood transfusion committee were applied and the impact on the blood stocks during an acute blood shortage was assessed. The results show that application of the national guidelines on the restriction of the use of red cells during an acute blood shortage resulted in all transfusion requests for red cells being met. We also appear to have shown that the assumptions made by the national transfusion team are realistic. Carrying out a tabletop exercise is a useful method to assess local procedures for dealing with an acute reduction in the supply of red cells.

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.

The addition of oral idarubicin to a chlorambucil/dexamethasone combination has a significant impact on time to treatment failure but none on overall survival in patients with low grade non-Hodgkin's lymphoma: Results of the Scotland and Newcastle Lymphoma Group randomized NHL VIII trial.

Two hundred untreated patients with low grade NHL (KIEL), including 155 follicular NHL, were randomized to six courses of treatment with chlorambucil 20 mg m-2 for 3 days and dexamethasone 4 mg bd for 5 days (CD) vs the same regimen plus oral idarubicin 10 mg m-2 for 3 days (CID). Responding patients could be randomized to no further treatment or maintenance treatment for up to 36 months with alpha interferon. Complete remissions/CRu were more frequent in the CID arm (35% vs 24%) but the overall response rate was similar; 87/91 (96%) vs 86/92 (93%). Overall survival (OS) did not differ between the two arms. Time to treatment failure (TTTF) was prolonged in the CID arm, p = 0.03; median time 28 vs 19 months. TTTF for the B-cell follicular group alone was for CID (77 patients) 33 months vs 18 months for CD (78 patients). Interferon conferred no apparent benefit. The Follicular Lymphoma International Prognostic Index (FLIPI) is confirmed as a good predictor of risk groups including a group of 23% with shorter survival. The addition of the oral anthracycline, idarubicin, led to a significant improvement in TTTF with low toxicity. The use of radiotherapy in this sub-group may have contributed to this result. CID is a potential for combination with antibody therapy particularly in older patient groups.

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 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.

An audit of the indications for the reporting of blood films: results from the National Pathology Benchmarking Study.

BACKGROUND: The National Pathology Benchmarking Review has completed seven years of analysis of the workload of haematology laboratories in the United Kingdom. OBJECTIVE: To audit criteria that laboratories use for preparing blood films against guidelines published by the International Consensus Group for Haematology Review. METHODS: Each laboratory completed a standard questionnaire about the number of blood counts and blood films done each year. Information was collected on the criteria that were used for preparing a blood film and the manufacturer of the equipment used to carry out the full blood count. RESULTS: 46 NHS trusts (93 laboratory sites) participated in the study. There was wide variation in the criteria used for preparing blood films when compared with the consensus guidelines. The variation in practice appeared to be irrespective of the type of hospital or the manufacturer of the equipment used for the blood count. CONCLUSIONS: There is a wide range in laboratory practice in preparing blood films. The publication of the consensus guidelines should help to standardise practice in this area. The next step in the study is to determine what the film review rate should be if these guidelines are implemented. This will then provide a benchmark of good practice which laboratories can use to assess their performance.

An audit of thrombophilia screens: results from the National Pathology Alliance benchmarking review.

AIMS: The National Pathology Alliance benchmarking review has completed six years of data collection and analysis of the workload and organisation of haematology laboratories in the UK. This study audits national practice of routine thrombophilia screening against the current standards, as set out in the British committee for standards in haematology (BCSH) guidelines on investigation of heritable thrombophilia. METHODS: Each laboratory completed a standard data collection questionnaire about the number of routine thrombophilia assays performed each year. Information was collected on which thrombophilia tests were performed as part of a routine thrombophilia screen. These results were then compared against the BCSH guidelines on investigation of heritable thrombophilia. RESULTS: Of the 57 National Health Service trusts that submitted data for review in 2002/2003, 47 performed a routine thrombophilia screen. Ten laboratories complied with the guidelines but 37 laboratories did not. CONCLUSION: There was variation in practice in the tests used in routine thrombophilia screens. There is evidence that some laboratories deviate from what may be regarded as "evidence based practice". The lack of compliance with the guidelines was in general associated with the performance of additional tests not recommended in the guideline. In a minority of laboratories, a clinically significant diagnosis would be missed by the failure to include one or more tests in a thrombophilia screen.

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.

Fatal radiation myelopathy after high-dose busulfan and melphalan chemotherapy and radiotherapy for Ewing's sarcoma: a review of the literature and implications for practice.

Radiation myelopathy is a rare, devastating, late effect of radiotherapy to the spinal cord. Spinal cord tolerance is currently accepted as about 50 Gy in 1.8-2 Gy fractions. However, the effect of chemotherapy on cord tolerance is unclear. This issue is important, given the increasing use of chemotherapy in combination with radiotherapy. We describe the case of a 17-year-old boy with a right apical paraspinal Ewing's tumour in the neck treated with induction chemotherapy, high-dose chemotherapy (busulfan and melphalan) with peripheral stem-cell rescue and, 4 months later, radiotherapy to the primary tumour site (cervical cord received 50 Gy in 30 fractions). After a latent period of 4 months, he developed a progressive, severe and ultimately fatal radiation myelopathy, which we suggest was due to a synergistic interaction between the high-dose chemotherapy and the radiotherapy. The use of such chemotherapy regimens in Ewing's tumours should be carefully considered, particularly when radiotherapy encompassing the spinal cord is an essential component of management.

ALK positive inflammatory myofibroblastic tumour of the pineal region.

Inflammatory myofibroblastic tumours (IMTs) are an uncommon spindle cell neoplasm with a dense inflammatory infiltrate, usually encountered in children. IMTs of the central nervous system are extremely rare. This report describes the case of an IMT in a 61 year old man, in the pineal region. The tumour was completely excised, and immunohistochemistry demonstrated anaplastic lymphoma kinase 1 expression. There was no tumour recurrence during 18 months of follow-up. Our case extends both the age range and sites of occurrence of this rare tumour.

Best Practice No 177: Best practice guideline: writing a business case for service development in pathology.

This guideline reviews the introduction and development of business planning in the National Health Service. A guideline for writing a business case for service development that would form part of a pathology business plan has been developed. This guideline outlines six steps that are required in the preparation of a business case. The format of the guideline has been developed largely from other national guidelines that have been published for the development of capital projects. In view of the publication of these guidelines, the scope of this guideline excludes business cases for information, management, and technology projects and large capital projects.

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.

High dose ifosfamide in combination with etoposide and epirubicin followed by autologous stem cell transplantation in the treatment of relapsed/refractory Hodgkin's disease: a report on toxicity and efficacy.

Patients with Hodgkin's disease (HD) refractory to first line chemotherapy and those who have rapid or multiple relapses have a very poor prognosis. With the increasing use of hybrid chemotherapy these patients will have been exposed to many of the drugs active in HD so it is important to develop salvage regimens that are novel and demonstrate activity in this group of patients. We report the use of a continuous high dose infusion of ïfosfamide at a dose of 9g/m(2) over 3 days in combination with etoposide and epirubicin followed by autologous stem cell transplant with either BEAM or Melphalan/VP16 conditioning in this difficult group. Forty six patients (28M:18F) with a median age of 28 years (range 13-45) were treated. Overall 39 out of 46 (85%) patients responded to treatment, with 17 achieving complete remission and 11 a good partial remission; 28 proceeded to autologous bone marrow/stem cell transplantation. In total, 23 patients are alive and in continuous remission with a follow up of between 12 and 61 months. Median overall survival for the whole group is 36 months. Haematological toxicity, particularly neutropenia (WHO grade IV), was observed in all cases but improved over the 3 courses of treatment in all patients. Non-haematological toxicity was not a major problem; no significant cardiac, hepatic, renal, pulmonary or neuro toxicity was observed and there were no deaths on treatment. This regime shows promise in patients with difficult Hodgkin's disease and warrants further study.

An audit of delays in diagnosis and treatment of lymphoma in district hospitals in the northern region of the United Kingdom.

Prompt diagnosis and treatment of malignant disorders is generally regarded as improving outcomes. There is good evidence for this in the most common solid tumours, bronchus, breast and large bowel. It might be expected that delays in diagnosis of lymphoma could affect the outcome of treatment, as well as causing dissatisfaction among patients and relatives. However it would be difficult to obtain definite evidence for this as a randomised trial of delay is an unethical proposition. The recently introduced National Priorities Guidance (NPG) Cancer Targets require that all new patients with suspected cancer should see a specialist within two weeks of referral by their General Practitioner (GP). There is no good evidence to support this requirement in lymphoma, but we decided to audit delays at different stages of the process of diagnosis and initial treatment of lymphoma as a base line to assess current performance, identify possible shortcomings and set achievable standards amenable to further audit.

Acquired haemophilia complicating the remission of a patient with high grade non-Hodgkin's lymphoma treated by fludarabine.

We report the development of a high titre antibody to factor VIII in a patient with previous high grade B cell non-Hodgkin's lymphoma treated with fludarabine. Unlike previous reports of factor VIII inhibitors and lymphoproliferative disease this patient's lymphoma was in remission. We speculate that the occurrence of the inhibitor is another manifestation of the increasingly recognized autoimmune side-effects of fludarabine.

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.

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.

Primary treatment of low-grade non-Hodgkin's lymphoma using an all oral anthracycline-containing regimen, chlorambucil, idarubicin, dexamethasone (CID)--a phase II study.

PURPOSE: The majority of patients with low-grade non-Hodgkin's lymphoma (LGNHL) are in the older age groups and are thus less able to tolerate aggressive treatment. Chlorambucil, alone and in combination, has been widely accepted as the initial treatment of choice for many years. The availability of an anthracycline which could be given orally in combination with chlorambucil and steroid led us to investigate the efficacy and toxicity of this novel regimen. METHODS: Patients (age less than 70 years) with a histologically confirmed diagnosis of LGNHL (Kiel classification) were eligible for the study if they had no previous chemotherapy. Treatment consisted of chlorambucil 20 mg/ m2 daily for 3 days given on each day in three divided doses, idarubicin 10 mg/m2 for 3 days before breakfast, and dexamethasone 4 mg twice daily for 5 days. All drugs were given orally. Treatment was repeated every 21 days for a maximum of six courses. The regimen was assessed for toxicity and response. RESULTS: A total of 72 patients were registered, and 64 were eligible (median age 52 years). Toxicity was assessed for all cycles given (347). The predominant toxicity was haematological, but in only one course did grade 4 neutropenia (less than 0.5 x 10(9)) occur. Alopecia was not a problem. Full doses of the treatment were administered to 40% of the patients, with no delays or dose reductions. The overall response rate was 83%. Six patients had static disease and two progressed on treatment. Lactate dehydrogenase (LDH) was found to be a good predictor of response to treatment. Of 12 patients documented to have raised LDH, 5 failed to respond to treatment, compared to 1 of 32 patients who had a normal LDH (chi2 10.65, P < 0.002). With a minimum follow-up of 4 years for all patients actuarial 5-year event-free survival was 22% and overall survival was 65%. However, in patients with best and intermediate risk LGNHL (by the SNLG Prognostic Index for Low Grade Disease) overall survival are 88% and 64%, respectively. CONCLUSIONS: This novel regimen was effective and well tolerated.