Institute of Chartered Accountants of Nigeria

About: Institute of Chartered Accountants of Nigeria is a based out in . It is known for research contribution in the topics: Population & Adipose tissue. The organization has 528 authors who have published 579 publications receiving 18688 citations.

Direct Medical Costs of Type 2 Diabetes in France: An Insurance Claims Database Analysis.

Abstract: Our objects was to estimate the direct healthcare costs of type 2 diabetes mellitus (T2DM) in France in 2013. Data were drawn from a random sample of ≈600,000 patients registered in the French national health insurances database, which covers 90% of the French population. An algorithm was used to select patients with T2DM. Direct healthcare costs from a collective perspective were derived from the database and compared with those from a control group to estimate the cost of diabetes and related comorbidities. Overall direct costs were also compared according to the diabetes therapies used throughout the year 2013. Cost analysis was available for a sample of 25,987 patients with T2DM (mean age 67.5 ± standard deviation 12.5; 53.9% male) matched with a control group of 76,406 individuals without diabetes. Overall per patient per year medical expenditures were €6506 ± 10,106 in the T2DM group as compared with €3668 ± 6954 in the control group. The cost difference between the two groups was €2838 per patient per year, mainly due to hospitalizations, medication and nursing care costs. Total per capita annual costs were lowest for patients receiving metformin monotherapy (€4153 ± 6170) and highest for those receiving insulin (€12,890). However, apart from patients receiving insulin, costs did not differ markedly across the different oral treatment patterns. Extrapolating these results to the whole T2DM population in France, total direct costs of diagnosed T2DM in 2013 was estimated at over €8.5 billion. This estimate highlights the substantial economic burden of this condition on society.

Comparison of different methods for the estimation of aortic pulse wave velocity from 4D flow cardiovascular magnetic resonance

Abstract: Arterial pulse wave velocity (PWV) is associated with increased mortality in aging and disease. Several studies have shown the accuracy of applanation tonometry carotid-femoral PWV (Cf-PWV) and the relevance of evaluating central aorta stiffness using 2D cardiovascular magnetic resonance (CMR) to estimate PWV, and aortic distensibility-derived PWV through the theoretical Bramwell-Hill model (BH-PWV). Our aim was to compare various methods of aortic PWV (aoPWV) estimation from 4D flow CMR, in terms of associations with age, Cf-PWV, BH-PWV and left ventricular (LV) mass-to-volume ratio while evaluating inter-observer reproducibility and robustness to temporal resolution. We studied 47 healthy subjects (49.5 ± 18 years) who underwent Cf-PWV and CMR including aortic 4D flow CMR as well as 2D cine SSFP for BH-PWV and LV mass-to-volume ratio estimation. The aorta was semi-automatically segmented from 4D flow data, and mean velocity waveforms were estimated in 25 planes perpendicular to the aortic centerline. 4D flow CMR aoPWV was calculated: using velocity curves at two locations, namely ascending aorta (AAo) and distal descending aorta (DAo) aorta (S1, 2D-like strategy), or using all velocity curves along the entire aortic centreline (3D-like strategies) with iterative transit time (TT) estimates (S2) or a plane fitting of velocity curves systolic upslope (S3). For S1 and S2, TT was calculated using three approaches: cross-correlation (TTc), wavelets (TTw) and Fourier transforms (TTf). Intra-class correlation coefficients (ICC) and Bland-Altman biases (BA) were used to evaluate inter-observer reproducibility and effect of lower temporal resolution. 4D flow CMR aoPWV estimates were significantly (p < 0.05) correlated to the CMR-independent Cf-PWV, BH-PWV, age and LV mass-to-volume ratio, with the strongest correlations for the 3D-like strategy using wavelets TT (S2-TTw) (R = 0.62, 0.65, 0.77 and 0.52, respectively, all p < 0.001). S2-TTw was also highly reproducible (ICC = 0.99, BA = 0.09 m/s) and robust to lower temporal resolution (ICC = 0.97, BA = 0.15 m/s). Reproducible 4D flow CMR aoPWV estimates can be obtained using full 3D aortic coverage. Such 4D flow CMR stiffness measures were significantly associated with Cf-PWV, BH-PWV, age and LV mass-to-volume ratio, with a slight superiority of the 3D strategy using wavelets transit time (S2-TTw).

What the Genetics of Lipodystrophy Can Teach Us About Insulin Resistance and Diabetes

Abstract: Genetic lipodystrophic syndromes are rare diseases characterized by generalized or partial fat atrophy (lipoatrophy) associated with severe metabolic complications such as insulin resistance (IR), diabetes, dyslipidemia, nonalcoholic fatty liver disease, and ovarian hyperandrogenism. During the last 15 years, mutations in several genes have been shown to be responsible for monogenic forms of lipodystrophic syndromes, of autosomal dominant or recessive transmission. Although the molecular basis of lipodystrophies is heterogeneous, most mutated genes lead to impaired adipogenesis, adipocyte lipid storage, and/or formation or maintenance of the adipocyte lipid droplet (LD), showing that primary alterations of adipose tissue (AT) can result in severe systemic metabolic and endocrine consequences. The reduced expandability of AT alters its ability to buffer excess caloric intake, leading to ectopic lipid storage that impairs insulin signaling and other cellular functions (“lipotoxicity”). Genetic studies have also pointed out the close relationships between ageing, inflammatory processes, lipodystrophy, and IR.

RUNX1 mutations in blast-phase chronic myeloid leukemia associate with distinct phenotypes, transcriptional profiles, and drug responses.

Abstract: Blast-phase chronic myeloid leukemia (BP-CML) is associated with additional chromosomal aberrations, RUNX1 mutations being one of the most common. Tyrosine kinase inhibitor therapy has only limited efficacy in BP-CML, and characterization of more defined molecular subtypes is warranted in order to design better treatment modalities for this poor prognosis patient group. Using whole-exome and RNA sequencing we demonstrate that PHF6 and BCORL1 mutations, IKZF1 deletions, and AID/RAG-mediated rearrangements are enriched in RUNX1mut BP-CML leading to typical mutational signature. On transcriptional level interferon and TNF signaling were deregulated in primary RUNX1mut CML cells and stem cell and B-lymphoid factors upregulated giving a rise to distinct phenotype. This was accompanied with the sensitivity of RUNX1mut blasts to CD19-CAR T cells in ex vivo assays. High-throughput drug sensitivity and resistance testing revealed leukemia cells from RUNX1mut patients to be highly responsive for mTOR-, BCL2-, and VEGFR inhibitors and glucocorticoids. These findings were further investigated and confirmed in CRISPR/Cas9-edited homozygous RUNX1-/- and heterozygous RUNX1-/mut BCR-ABL positive cell lines. Overall, our study provides insights into the pathogenic role of RUNX1 mutations and highlights personalized targeted therapy and CAR T-cell immunotherapy as potentially promising strategies for treating RUNX1mut BP-CML patients.