Specialist integrated haematological malignancy diagnostic services: an Activity Based Cost (ABC) analysis of a networked laboratory service model.

AIMS: Specialist Integrated Haematological Malignancy Diagnostic Services (SIHMDS) were introduced as a standard of care within the UK National Health Service to reduce diagnostic error and improve clinical outcomes. Two broad models of service delivery have become established: 'co-located' services operating from a single-site and 'networked' services, with geographically separated laboratories linked by common management and information systems. Detailed systematic cost analysis has never been published on any established SIHMDS model. METHODS: We used Activity Based Costing (ABC) to construct a cost model for our regional 'networked' SIHMDS covering a two-million population based on activity in 2011. RESULTS: Overall estimated annual running costs were £1 056 260 per annum (£733 400 excluding consultant costs), with individual running costs for diagnosis, staging, disease monitoring and end of treatment assessment components of £723 138, £55 302, £184 152 and £94 134 per annum, respectively. The cost distribution by department was 28.5% for haematology, 29.5% for histopathology and 42% for genetics laboratories. Costs of the diagnostic pathways varied considerably; pathways for myelodysplastic syndromes and lymphoma were the most expensive and the pathways for essential thrombocythaemia and polycythaemia vera being the least. CONCLUSIONS: ABC analysis enables estimation of running costs of a SIHMDS model comprised of 'networked' laboratories. Similar cost analyses for other SIHMDS models covering varying populations are warranted to optimise quality and cost-effectiveness in delivery of modern haemato-oncology diagnostic services in the UK as well as internationally.

Analysis of 16S rDNA sequences from pathogenic Leptospira serovars and use of single nucleotide polymorphisms for rapid speciation by D-HPLC.

Leptospira have a worldwide distribution and include important zoonotic pathogens yet diagnosis and differentiation still tend to rely on traditional bacteriological and serological approaches. In this study a 1.3 kb fragment of the rrs gene (16S rDNA) was sequenced from a panel of 22 control strains, representing serovars within the pathogenic species Leptospira interrogans, Leptospiraborgpetersenii, and Leptospirakirschneri, to identify single nucleotide polymorphisms (SNPs). These were identified in the 5' variable region of the 16S sequence and a 181 bp PCR fragment encompassing this region was used for speciation by Denaturing High Performance Liquid Chromatography (D-HPLC). This method was applied to eleven additional species, representing pathogenic, non-pathogenic and intermediate species and was demonstrated to rapidly differentiate all but 2 of the non-pathogenic Leptospira species. The method was applied successfully to infected tissues from field samples proving its value for diagnosing leptospiral infections found in animals in the UK.

The development of a real-time PCR to detect pathogenic Leptospira species in kidney tissue.

A LightCycler real-time PCR hybridization probe-based assay that detects a conserved region of the16S rRNA gene of pathogenic but not saprophytic Leptospira species was developed for the rapid detection of pathogenic leptospires directly from processed tissue samples. In addition, a differential PCR specific for saprophytic leptospires and a control PCR targeting the porcine beta-actin gene were developed. To assess the suitability of these PCR methods for diagnosis, a trial was performed on kidneys taken from adult pigs with evidence of leptospiral infection, primarily a history of reproductive disease and serological evidence of exposure to pathogenic leptospires (n=180) and aborted pig foetuses (n=24). Leptospire DNA was detected by the 'pathogenic' specific PCR in 25 tissues (14%) and the control beta-actin PCR was positive in all 204 samples confirming DNA was extracted from all samples. No leptospires were isolated from these samples by culture and no positives were detected with the 'saprophytic' PCR. In a subsidiary experiment, the 'pathogenic' PCR was used to analyse kidney samples from rodents (n=7) collected as part of vermin control in a zoo, with show animals with high microagglutination titres to Leptospira species, and five were positive. Fifteen PCR amplicons from 1 mouse, 2 rat and 14 pig kidney samples, were selected at random from positive PCRs (n=30) and sequenced. Sequence data indicated L. interrogans DNA in the pig and rat samples and L. inadai DNA, which is considered of intermediate pathogenicity, in the mouse sample. The only successful culture was from this mouse kidney and the isolate was confirmed to be L. inadai by classical serology. These data suggest this suite of PCRs is suitable for testing for the presence of pathogenic leptospires in pig herds where abortions and infertility occur and potentially in other animals such as rodents.

Hepatitis-associated aplastic anaemia treated successfully with antilymphocyte globulin.

Aplastic anaemia may occur following an acute attack of hepatitis. This is a rare condition, which if not recognized and promptly treated, may be fatal. Antilymphocyte globulin and allogeneic bone marrow transplantation have been used in the treatment of this condition. We report the case of a young man who developed severe aplastic anaemia following nonviral hepatitis.

Prevalence of leptospira species among farmed and domestic animals in Greece.

A total of 1527 serum samples from pigs, goats, sheep, cattle and dogs in Greece were examined by the microscopic agglutination test and 11-8 per cent of them had antibodies against one or more Leptospira serovars at titres of 1/100 or more. The predominant serovar affecting farm animal species was Bratislava, and Copenhageni was common among dogs and the second most important serovar when all animals were considered together. Another prevalent serovar was Australis, but antibodies to Pomona were detected only in goats and cattle.

Acute Myelogenous Leukaemia in Patients 60 Years and Older: A Retrospective Analysis from St Bartholomew's Hospital 1969-1999.

Between 1969 and 1999, 420 patients (age > 60 years) with newly diagnosed AML were managed at St Bartholomew's Hospital (SBH), London, UK. Sixty-nine percent of patients received therapy with curative intent Eighty-eight patients (31%) of the latter achieved complete remission (CR), representing an overall CR rate of 21%. Treatment failure due to early death (ED) and resistant disease (RD) occurred in 50 and 19%, respectively. With median follow up of 11 years, actuarial survivals at 1,3 and 5 years were 20, 7 and 4%, respectively, the median survival of the entire cohort was 2 months. For patients who achieved CR, median survival was significantly better than that of patients in whom treatment failed (14 vs. 6 months). Over the 30 years, CR rate and the relative incidence of RD both increased from 13 to 45%, and 3 to 27%, respectively, whilst ED rate reduced from 84 to 27%. Multivariate analysis showed that treatment era, hepatosplenomegaly and increasing age predicted for reduced CR rate and OS. Although elderly patients with AML are characterised by a poor response to intensive chemotherapy, significant improvements in supportive care and the delivery of intensive treatment have led to improved CR rates and OS. New therapeutic strategies and a greater awareness of prognostic factors may further improve clinical outcome in this important group of patients.