The value of fast-acting insulin aspart compared with insulin aspart for patients with diabetes mellitus treated with bolus insulin from a UK health care system perspective.

Background: Fast-acting insulin aspart is a new formulation of the rapid-acting insulin analogue insulin aspart and represents an advancement over current rapid-acting insulin analogues in terms of onset of action and postprandial glucose control. The objective of the current analysis was to demonstrate the cost impact of prescribing fast-acting insulin aspart instead of insulin aspart, to highlight the value of fast-acting insulin aspart for the treatment of people with diabetes requiring mealtime insulin.

Methods: A cost-impact analysis was conducted from the perspective of the UK National Health Service (NHS).

Hypoglycemia Event Rates: A Comparison Between Real-World Data and Randomized Controlled Trial Populations in Insulin-Treated Diabetes.

Introduction: Hypoglycemia is the most common adverse effect of diabetes therapy, particularly insulin treatment. Hypoglycemia is associated with considerable clinical and economic burden, and may be under-reported. The aim of this study was to com pare the frequency of hypoglycemic events reported in real-world settings with those reported in clinical trials.

Cost effectiveness of tenofovir disoproxil fumarate for the treatment of chronic hepatitis B from a Canadian public payer perspective.

Introduction: Previous research has demonstrated that tenofovir disoproxil fumarate (DF) is the most cost-effective nucleos(t)ide treatment for chronic hepatitis B (CHB) in the UK, Spain, Italy and France. However, to our knowledge, no published studies have yet evaluated the cost effectiveness of any treatments for CHB in a Canadian setting, where relative prices and management of CHB differ from those in Europe.

Aim: Our objective was to determine the cost effectiveness of tenofovir DF compared with other nucleos(t)ide therapies licensed for CHB in Canada from the perspective of publicly funded healthcare payers.

Hypoglycemia: an overview of fear of hypoglycemia, quality-of-life, and impact on costs.

Background: The clinical goal in the treatment of diabetes is to achieve good glycemic control. Tight glycemic control achieved with intensive glucose lowering treatment reduces the risk of long-term micro- and macro-vascular complications of diabetes, resulting in an improvement in quality-of-life for the patient and decreased healthcare costs. The positive impact of good glycemic control is, however, counterbalanced by the negative impact of an increased incidence of hypoglycemia.

Mixed treatment comparison meta-analysis evaluating the relative efficacy of nucleos(t)ides for treatment of nucleos(t)ide-naive patients with chronic hepatitis B.

Background/aims: Five nucleoside/nucleotide treatments are now available for chronic hepatitis B (CHB). This meta-analysis aimed to assess the relative efficacy of adefovir, entecavir, lamivudine, telbivudine, tenofovir disoproxil fumarate (TDF), and nucleos(t)ide combinations in the treatment of CHB.

Methods: A systematic review of MEDLINE and the Cochrane library was conducted to identify all studies evaluating these nucleos(t)ides in adults with CHB.

Enoxaparin is a cost-effective adjunct to fibrinolytic therapy for ST-elevation myocardial infarction in contemporary practice.

Introduction: In patients receiving fibrinolytic therapy for ST-elevation myocardial infarction (STEMI), adjunct treatment with enoxaparin has been shown to provide superior net clinical benefit compared with unfractionated heparin (UFH) in the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment - Thrombolysis in Myocardial Infarction (ExTRACT-TIMI) 25 study. The objective of this study was to compare the cost effectiveness of enoxaparin and UFH strategies.

Methods: A cost-utility analysis was conducted using a two-stage model: (1) A 30-day decision tree analytical model for the acute treatment phase, and (2) a lifetime Markov model (from 30 days post-STEMI until death) populated using patient survival data.

The cost-effectiveness of somatropin treatment for short children born small for gestational age (SGA) and children with growth hormone deficiency (GHD) in Sweden.

Objective: Reduction in health-related quality of life is common in children born small for gestational age (SGA) or children with growth hormone deficiency (GHD). Growth hormone treatment with somatropin in these children leads to normalisation of height. The aim of this study was to determine whether somatropin is a cost-effective treatment option for short children born SGA and GHD children in Sweden.

Genome-wide analysis of copy number changes and loss of heterozygosity in myelodysplastic syndrome with del(5q) using high-density single nucleotide polymorphism arrays.

Background: We undertook a genome wide single nucleotide polymorphism analysis of a spectrum of patients with myelodysplastic syndrome del(5q) in order to investigate whether additional genomic abnormalities occur. Single nucleotide polymorphism array analysis has been shown to detect not only gene deletions but also regions of uniparental disomy that can pinpoint particular regions for mutation analysis.

Design And Methods: We studied 42 cases of myelodysplastic syndrome with del(5q), comprising 21 patients with 5q- syndrome and 21 with del(5q) (not 5q- syndrome), and 45 healthy controls by genome wide single nucleotide polymorphism analysis with the 50K Affymetrix single nucleotide polymorphism arrays.

Haploinsufficiency of RPS14 in 5q- syndrome is associated with deregulation of ribosomal- and translation-related genes.

We have previously demonstrated haploinsufficiency of the ribosomal gene RPS14, which is required for the maturation of 40S ribosomal subunits and maps to the commonly deleted region, in the 5q- syndrome. Patients with Diamond-Blackfan anaemia (DBA) show haploinsufficiency of the closely related ribosomal protein RPS19, and show a consequent downregulation of multiple ribosomal- and translation-related genes. By analogy with DBA, we have investigated the expression profiles of a large group of ribosomal- and translation-related genes in the CD34(+) cells of 15 myelodysplastic syndrome (MDS) patients with 5q- syndrome, 18 MDS patients with refractory anaemia (RA) and a normal karyotype, and 17 healthy controls.

The role of the iron transporter ABCB7 in refractory anemia with ring sideroblasts.

Refractory Anemia with Ring Sideroblasts (RARS) is an acquired myelodysplastic syndrome (MDS) characterized by an excess iron accumulation in the mitochondria of erythroblasts. The pathogenesis of RARS and the cause of this unusual pattern of iron deposition remain unknown. We considered that the inherited X-linked sideroblastic anemia with ataxia (XLSA/A) might be informative for the acquired disorder, RARS.

Gene expression profiling of CD34+ cells in patients with the 5q- syndrome.

The transcriptome of the CD34+ cells was determined in a group of 10 patients with the 5q- syndrome using a comprehensive array platform, and was compared with the transcriptome of CD34+ cells from 16 healthy control subjects and 14 patients with refractory anaemia and a normal karyotype. The majority of the genes assigned to the commonly deleted region (CDR) of the 5q- syndrome at 5q31-q32 showed a reduction in expression levels in patients with the 5q- syndrome, consistent with the loss of one allele. Candidate genes showing haploinsufficiency in the 5q- syndrome included the tumour suppressor gene SPARC and RPS14, a component of the 40S ribosomal subunit.

Gene expression profiles of CD34+ cells in myelodysplastic syndromes: involvement of interferon-stimulated genes and correlation to FAB subtype and karyotype.

To gain insight into the poorly understood pathophysiology of the myelodysplastic syndromes (MDSs), we have determined the gene expression profiles of the CD34+ cells of 55 patients with MDS by using a comprehensive array platform. These profiles showed many similarities to reported interferon-gamma-induced gene expression in normal CD34+ cells; indeed the 2 most up-regulated genes, IFIT1 and IFITM1, are interferon-stimulated genes (ISGs). Alterations in the expression of ISGs may play a role in the hematologic features of MDS, such as peripheral blood cytopenias.

Gene expression profiling in the myelodysplastic syndromes.

The myelodysplastic syndromes (MDS) are a heterogeneous group of haematopoietic malignancies, characterized by blood cytopenias, ineffective hematopoiesis and hypercellular bone marrow. Several genetic alterations have been reported in MDS but these are not MDS-specific and the underlying molecular causes of the disease remain poorly understood. Gene expression microarray technology allows the simultaneous parallel analysis of many thousands of genes and has already provided novel insights into cancer pathogenesis.

Low expression of the putative tumour suppressor gene gravin in chronic myeloid leukaemia, myelodysplastic syndromes and acute myeloid leukaemia.

The putative tumour suppressor gene gravin is down-regulated in several solid tumours and is implicated in tumorigenesis. We have evaluated the expression levels of the gravin gene in the CD34(+)/blast cells of a range of myeloid malignancies as compared with controls using real-time quantitative polymerase chain reaction (PCR). Gravin was markedly down-regulated in 41 of 41 patients with acute myeloid leukaemia (AML), nine of 10 patients with myelodysplastic syndromes (MDS) and 33 of 33 patients with chronic myeloid leukaemia (CML), of whom 24 were in blast crisis (BC).

NRAS, FLT3 and TP53 mutations in patients with myelodysplastic syndrome and a del(5q).

Mutations of the NRAS and TP53 genes and internal tandem duplication (ITD) of the FLT3 gene are among the most frequently observed molecular abnormalities in the myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We sought to determine the incidence of these abnormalities in patients with MDS and a 5q deletion. NRAS and FLT3 mutations are uncommon in MDS patients with a 5q deletion and TP53 mutation is associated with the more advanced MDS subtypes.

Gene expression profiling in the myelodysplastic syndromes using cDNA microarray technology.

The myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal disorders of the haematopoietic stem cell and primarily involve cells of the myeloid lineage. Using cDNA microarrays comprising 6000 human genes, we studied the gene expression profiles in the neutrophils of 21 MDS patients, seven of which had the 5q- syndrome, and two acute myeloid leukaemia (AML) patients when compared with the neutrophils from pooled healthy controls. Data analysis showed a high level of heterogeneity of gene expression between MDS patients, most probably reflecting the underlying karyotypic and genetic heterogeneity.

Novel translocations that disrupt the platelet-derived growth factor receptor beta (PDGFRB) gene in BCR-ABL-negative chronic myeloproliferative disorders.

The BCR-ABL-negative chronic myeloproliferative disorders (CMPD) and myelodysplastic/myeloproliferative diseases (MDS/MPD) are a spectrum of related conditions for which the molecular pathogenesis is poorly understood. Translocations that disrupt and constitutively activate the platelet-derived growth factor receptor beta(PDGFRB) gene at chromosome band 5q33 have been described in some patients, the most common being the t(5;12)(q33;p13). An accurate molecular diagnosis of PDGFRB-rearranged patients has become increasingly important since recent data have indicated that they respond very well to imatinib mesylate therapy.

Narrowing and genomic annotation of the commonly deleted region of the 5q- syndrome.

The 5q- syndrome is the most distinct of the myelodysplastic syndromes, and the molecular basis for this disorder remains unknown. We describe the narrowing of the common deleted region (CDR) of the 5q- syndrome to the approximately 1.5-megabases interval at 5q32 flanked by D5S413 and the GLRA1 gene.