User needs elicitation via analytic hierarchy process (AHP). A case study on a Computed Tomography (CT) scanner

Background: The rigorous elicitation of user needs is a crucial step for both medical device design and purchasing. However, user needs elicitation is often based on qualitative methods whose findings can be difficult to integrate into medical decision-making. This paper describes the application of AHP to elicit user needs for a new CT scanner for use in a public hospital. Methods: AHP was used to design a hierarchy of 12 needs for a new CT scanner, grouped into 4 homogenous categories, and to prepare a paper questionnaire to investigate the relative priorities of these. The questionnaire was completed by 5 senior clinicians working in a variety of clinical specialisations and departments in the same Italian public hospital. Results: Although safety and performance were considered the most important issues, user needs changed according to clinical scenario. For elective surgery, the five most important needs were: spatial resolution, processing software, radiation dose, patient monitoring, and contrast medium. For emergency, the top five most important needs were: patient monitoring, radiation dose, contrast medium control, speed run, spatial resolution. Conclusions: AHP effectively supported user need elicitation, helping to develop an analytic and intelligible framework of decision-making. User needs varied according to working scenario (elective versus emergency medicine) more than clinical specialization. This method should be considered by practitioners involved in decisions about new medical technology, whether that be during device design or before deciding whether to allocate budgets for new medical devices according to clinical functions or according to hospital department

The Genetic Effect of Copy Number Variations on the Risk of Type 2 Diabetes in a Korean Population

BACKGROUND: Unlike Caucasian populations, genetic factors contributing to the risk of type 2 diabetes mellitus (T2DM) are not well studied in Asian populations. In light of this, and the fact that copy number variation (CNV) is emerging as a new way to understand human genomic variation, the objective of this study was to identify type 2 diabetes-associated CNV in a Korean cohort. METHODOLOGY/PRINCIPAL FINDINGS: Using the Illumina HumanHap300 BeadChip (317,503 markers), genome-wide genotyping was performed to obtain signal and allelic intensities from 275 patients with type 2 diabetes mellitus (T2DM) and 496 nondiabetic subjects (Total n = 771). To increase the sensitivity of CNV identification, we incorporated multiple factors using PennCNV, a program that is based on the hidden Markov model (HMM). To assess the genetic effect of CNV on T2DM, a multivariate logistic regression model controlling for age and gender was used. We identified a total of 7,478 CNVs (average of 9.7 CNVs per individual) and 2,554 CNV regions (CNVRs; 164 common CNVRs for frequency>1%) in this study. Although we failed to demonstrate robust associations between CNVs and the risk of T2DM, our results revealed a putative association between several CNVRs including chr15:45994758-45999227 (P = 8.6E-04, P(corr) = 0.01) and the risk of T2DM. The identified CNVs in this study were validated using overlapping analysis with the Database of Genomic Variants (DGV; 71.7% overlap), and quantitative PCR (qPCR). The identified variations, which encompassed functional genes, were significantly enriched in the cellular part, in the membrane-bound organelle, in the development process, in cell communication, in signal transduction, and in biological regulation. CONCLUSION/SIGNIFICANCE: We expect that the methods and findings in this study will contribute in particular to genome studies of Asian populations

Therapeutic aims of drugs offering only progression-free survival are misunderstood by patients, and oncologists may be overly optimistic about likely benefits

PURPOSE: The use of novel and often expensive drugs offering limited survival benefit in advanced disease is controversial. Treatment recommendations are influenced by patient characteristics and trial data showing overall response rates (ORR), progression-free survival (PFS) and overall survival (OS). PFS is frequently the primary outcome in licencing studies. PATIENTS AND METHODS: As part of a longitudinal study Assessing the 'VALue' to patients of PROgression Free Survival (AVALPROFS), oncologists completed checklists at baseline following consultations with patients. Questions probed perceived clinical benefits of the drugs to populations in general. Patients completed study-specific interview schedules at baseline, 6 weeks into treatment, and at withdrawal due to toxicity or progression. Patients also completed tumour- and treatment-specific quality of life questionnaires monthly for their time in the study. Only baseline results are reported here. RESULTS: Thirty-two UK oncologists discussed management options with 90 patients with heterogeneous advanced cancers. Oncologists' estimates of medical benefit in general from treatment varied between 10 and 80 %. They expected 46/90 (51 %) of their patients to derive some clinical benefit from the prescribed treatment but were either unsure or expected none for 44/90 (49 %). Predictions of life expectancy were variable but 62 % (56/90) of patients were expected to survive longer with treatment. A majority of patients 51/90 (57 %) had 'no idea' or were 'unclear' what PFS meant and 45/90 (50 %) thought extension of life was the primary therapeutic aim of treatment. CONCLUSION: Discussions between doctors and patients with metastatic disease about future management plans and likely therapeutic gains are challenging. Factors influencing decisions about putative benefits of novel drugs are often applied inconsistently can be overly optimistic and may even contradict published data

Changes in treatment and mortality of acute myocardial infarction in Estonian tertiary and secondary care hospitals in 2001 and 2007

<p>Abstract</p> <p>Background</p> <p>High quality care for acute myocardial infarction (AMI) improves patient outcomes. Still, AMI patients are treated in hospitals with unequal access to percutaneous coronary intervention. The study compares changes in treatment and 30-day and 3-year mortality of AMI patients hospitalized into tertiary and secondary care hospitals in Estonia in 2001 and 2007.</p> <p>Results</p> <p>Final analysis included 423 cases in 2001 (210 from tertiary and 213 from secondary care hospitals) and 687 cases in 2007 (327 from tertiary and 360 from secondary care hospitals). The study sample in 2007 was older and had twice more often diabetes mellitus. The patients in the tertiary care hospitals underwent reperfusion for ST-elevation myocardial infarction, cardiac catheterization and revascularisation up to twice as often in 2007 as in 2001. In the secondary care, patient transfer for further invasive treatment into tertiary care hospitals increased (<it>P </it>< 0.001). Prescription rates of evidence-based medications for in-hospital and for outpatient use were higher in 2007 in both types of hospitals. However, better treatment did not improve significantly the short- and long-term mortality within a hospital type in crude and baseline-adjusted analysis. Still, in 2007 a mortality gap between the two hospital types was observed (<it>P </it>< 0.010).</p> <p>Conclusions</p> <p>AMI treatment improved in both types of hospitals, while the improvement was more pronounced in tertiary care. Still, better treatment did not result in a significantly lower mortality. Higher age and cardiovascular risk are posing a challenge for AMI treatment.</p

Cdx ParaHox genes acquired distinct developmental roles after gene duplication in vertebrate evolution

BACKGROUND: The functional consequences of whole genome duplications in vertebrate evolution are not fully understood. It remains unclear, for instance, why paralogues were retained in some gene families but extensively lost in others. Cdx homeobox genes encode conserved transcription factors controlling posterior development across diverse bilaterians. These genes are part of the ParaHox gene cluster. Multiple Cdx copies were retained after genome duplication, raising questions about how functional divergence, overlap, and redundancy respectively contributed to their retention and evolutionary fate. RESULTS: We examined the degree of regulatory and functional overlap between the three vertebrate Cdx genes using single and triple morpholino knock-down in Xenopus tropicalis followed by RNA-seq. We found that one paralogue, Cdx4, has a much stronger effect on gene expression than the others, including a strong regulatory effect on FGF and Wnt genes. Functional annotation revealed distinct and overlapping roles and subtly different temporal windows of action for each gene. The data also reveal a colinear-like effect of Cdx genes on Hox genes, with repression of Hox paralogy groups 1 and 2, and activation increasing from Hox group 5 to 11. We also highlight cases in which duplicated genes regulate distinct paralogous targets revealing pathway elaboration after whole genome duplication. CONCLUSIONS: Despite shared core pathways, Cdx paralogues have acquired distinct regulatory roles during development. This implies that the degree of functional overlap between paralogues is relatively low and that gene expression pattern alone should be used with caution when investigating the functional evolution of duplicated genes. We therefore suggest that developmental programmes were extensively rewired after whole genome duplication in the early evolution of vertebrates

Microarray identifies ADAM family members as key responders to TGF-β1 in alveolar epithelial cells

The molecular mechanisms of Idiopathic Pulmonary Fibrosis (IPF) remain elusive. Transforming Growth Factor beta 1(TGF-β1) is a key effector cytokine in the development of lung fibrosis. We used microarray and computational biology strategies to identify genes whose expression is significantly altered in alveolar epithelial cells (A549) in response to TGF-β1, IL-4 and IL-13 and Epstein Barr virus. A549 cells were exposed to 10 ng/ml TGF-β1, IL-4 and IL-13 at serial time points. Total RNA was used for hybridisation to Affymetrix Human Genome U133A microarrays. Each in vitro time-point was studied in duplicate and an average RMA value computed. Expression data for each time point was compared to control and a signal log ratio of 0.6 or greater taken to identify significant differential regulation. Using normalised RMA values and unsupervised Average Linkage Hierarchical Cluster Analysis, a list of 312 extracellular matrix (ECM) proteins or modulators of matrix turnover was curated via Onto-Compare and Gene-Ontology (GO) databases for baited cluster analysis of ECM associated genes. Interrogation of the dataset using ontological classification focused cluster analysis revealed coordinate differential expression of a large cohort of extracellular matrix associated genes. Of this grouping members of the ADAM (A disintegrin and Metalloproteinase domain containing) family of genes were differentially expressed. ADAM gene expression was also identified in EBV infected A549 cells as well as IL-13 and IL-4 stimulated cells. We probed pathologenomic activities (activation and functional activity) of ADAM19 and ADAMTS9 using siRNA and collagen assays. Knockdown of these genes resulted in diminished production of collagen in A549 cells exposed to TGF-β1, suggesting a potential role for these molecules in ECM accumulation in IPF

Hemangiopericytomas of the spine: case report and review of the literature

We describe a rare case of a primary intracranial meningeal hemangiopericytoma (HPC) with late metastasis to the cervical spine. A 36-year-old woman had a left occipital lesion that was histopathologically identified as HPC. Fourteen years after resection, the tumor recurred and was treated with radiotherapy. Three years later, CT imaging showed a large mass in the liver consistent with metastatic HPC, and MRI of the cervical spine showed an extensive lesion of the C3 vertebral body. The patient underwent C3 corpectomy with en-bloc tumor removal and follow-up radiation with no local recurrence or other spinal metastasis for the following 4 years. Regardless of the subtype of spinal HPC, complete surgical removal and radiotherapy appear to be treatment of choice

Pathological and Incidental Findings on Brain MRI in a Single-Center Study of 229 Consecutive Girls with Early or Precocious Puberty

Central precocious puberty may result from organic brain lesions, but is most frequently of idiopathic origin. Clinical or biochemical factors which could predict a pathological brain MRI in girls with CPP have been searched for. With the recent decline in age at pubertal onset among US and European girls, it has been suggested that only girls with CPP below 6 years of age should have brain MRI performed

Dystrophin Is Required for the Normal Function of the Cardio-Protective KATP Channel in Cardiomyocytes

Duchenne and Becker muscular dystrophy patients often develop a cardiomyopathy for which the pathogenesis is still unknown. We have employed the murine animal model of Duchenne muscular dystrophy (mdx), which develops a cardiomyopathy that includes some characteristics of the human disease, to study the molecular basis of this pathology. Here we show that the mdx mouse heart has defects consistent with alteration in compounds that regulate energy homeostasis including a marked decrease in creatine-phosphate (PC). In addition, the mdx heart is more susceptible to anoxia than controls. Since the cardio-protective ATP sensitive potassium channel (KATP) complex and PC have been shown to interact we investigated whether deficits in PC levels correlate with other molecular events including KATP ion channel complex presence, its functionality and interaction with dystrophin. We found that this channel complex is present in the dystrophic cardiac cell membrane but its ability to sense a drop in the intracellular ATP concentration and consequently open is compromised by the absence of dystrophin. We further demonstrate that the creatine kinase muscle isoform (CKm) is displaced from the plasma membrane of the mdx cardiac cells. Considering that CKm is a determinant of KATP channel complex function we hypothesize that dystrophin acts as a scaffolding protein organizing the KATP channel complex and the enzymes necessary for its correct functioning. Therefore, the lack of proper functioning of the cardio-protective KATP system in the mdx cardiomyocytes may be part of the mechanism contributing to development of cardiac disease in dystrophic patients