Comparison of the Efficacy of a Diabetes Education Programme for Type 1 Diabetes (PRIMAS) in a Randomised Controlled Trial Setting and the Effectiveness in a Routine Care Setting: Results of a Comparative Effectiveness Study

Background

The effectiveness of an intervention in clinical practice is often reduced compared to the efficacy demonstrated in a randomised controlled trial (RCT). In this comparative effectiveness study, the RCT-proven efficacy of a diabetes education programme for type 1 diabetic patients (PRIMAS) was compared to the effectiveness observed in an implementation trial (IT) under routine care conditions.

Methods

75 patients with type 1 diabetes received PRIMAS through an RCT, whereas 179 patients were observed in an implementation trial. Baseline characteristics and treatment outcomes at the 6-month follow-up (improvement of HbA1c, hypoglycaemia problems, and diabetes-related distress) were compared.

Results

At baseline, the type 1 diabetic patients in the RCT had a significant longer diabetes duration (18.7±12.3 vs. 13.8±12.7 yrs., p = .005), lower self-efficacy scores (21.9±4.7 vs. 23.7±6.1, p = .02) and a greater number of diabetes complications (0.8±1.3 vs. 0.4±0.9, p = .02). After 6 months, PRIMAS achieved comparable effects under RCT and implementation trial conditions, as demonstrated by improvement in HbA1c (-0.36%±1.1 vs. -0.37±1.2; Δ -0.01, 95% CI -0.33 to 0.31) and hypoglycaemia unawareness (-0.5±1.4 vs. -0.3±1.4; Δ 0.18, 95% CI -0.21 to 0.57). The likelihood of clinical improvement did not depend on the trial setting (RCT vs. IT: OR 1.18, 95% CI 0.60 to 2.33). The participants with worse glycaemic control (OR 1.40, 95% CI 1.02 to 1.92), hypoglycaemia problems (OR 2.13, 95% CI 1.53 to 2.97) or elevated diabetes distress (OR 1.40, 95% CI 1.03 to 1.89) had a better chance of clinical improvement.

Conclusions

The effectiveness of PRIMAS under routine care conditions was comparable to the efficacy demonstrated in the RCT. Clinical improvement was independent of the setting in which PRIMAS was evaluated. The PRIMAS education programme for type 1 diabetes can be delivered under conditions of routine care without a loss of effectiveness, compared to its original evaluation in an RCT.     

A Spanish founder mutation in the chloride channel gene, CLCNKB, as a cause of atypical Bartter syndrome in adult age

BACKGROUND: Mutations in the chloride channel gene, CLCNKB, usually cause classic Bartter syndrome (cBS) or a mixed Bartter-Gitelman phenotype in the first years of life. METHODS: We report an adult woman with atypical BS caused by a homozygous missense mutation, A204T, in the CLCNKB gene, which has previously been described as the apparently unique cause of cBS in Spain. RESULTS: The evaluation of this patient revealed an overlap of phenotypic features ranging from severe biochemical and systemic disturbances typical of cBS to scarce symptoms and diagnosis in the adult age typical of Gitelman syndrome. The tubular disease caused a dramatic effect on mental, growth and puberal development leading to low IQ, final short stature and abnormal ovarian function. Furthermore, low serum PTH concentrations with concomitant nephrocalcinosis and normocalcaemia were observed. Both ovarian function and serum PTH levels were normalized after treatment with cyclooxygenase inhibitors. CONCLUSIONS: The present report confirms a weak genotype-phenotype correlation in patients with CLCNKB mutations and supports the founder effect of the A204T mutation in Spain. In our country, the genetic diagnosis of adult patients with hereditary hypokalaemic tubulopathies should include a screening of A204T mutation in the CLCNKB gene.     

Regulation of Autophosphorylation Controls PLK4 Self-Destruction and Centriole Number

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Synthesis and biological activity of new series of N-modified analogues of the N/OFQ(1–13)NH2 with aminophosphonate moiety

New series of N-modified analogues of the N/OFQ(1-13)NH(2) with aminophosphonate moiety have been synthesized and investigated for biological activity. These peptides were prepared by solid-phase peptide synthesis-Fmoc-strategy. The N/OFQ(1-13)NH(2) analogues were tested for agonistic activity in vitro on electrically stimulated rat vas deferens smooth-muscle preparations isolated from Wistar albino rats. Our study has shown that the selectivity of the peptides containing 1-[(methoxyphosphono)methylamino]cycloalkanecarboxylic acids to the N-side of Phe is not changed-they remain selective agonists of NOP receptors. The derivative with the largest ring (NOC-6) demonstrated efficacy similar to that of N/OFQ(1-13)NH(2), but in a 10-fold higher concentration. The agonistic activity of newly synthesized N-modified analogues of N/OFQ(1-13)NH(2) with aminophosphonate moiety was investigated for the first time.     

Antropological measurement of the sacroiliac joint

This study was done on 65 isolated pelvic bones, These cadavers belonged to adult people of mature and old age, and they had no pathological changes. These measurements were performed on osteological collection of Department of Anatomy Drago Perovi?. Many geometrical parameters of facies auricularis were measured, which we considered important for further studies, simulations of joint's action, transfer calculations of the forces from spine to hip joint. We used paper, which partially adapted to the surface of facies auricularis, so the values are closer to real ones than projection values. The results have shown that the average surface of facies auricularis is 13.46 cm(2). There was no statistical significance found between left and right cadavers. For easier orientation we divided surface of facies auricularis into two parts: vertical and horizontal. Height of the vertical part was 3.99 cm, while the width was 2.05 cm. Height of horizontal part was 2.07 cm and the width 3.62 cm.     

Gene expression patterns in an onychophoran reveal that regionalization predates limb segmentation in pan‐arthropods

SUMMARY In arthropods, such as Drosophila melanogaster, the leg gap genes homothorax (hth), extradenticle (exd), dachshund (dac), and Distal‐less (Dll) regionalize the legs in order to facilitate the subsequent segmentation of the legs. We have isolated homologs of all four leg gap genes from the onychophoran Euperipatoides kanangrensis and have studied their expression. We show that leg regionalization takes place in the legs of onychophorans even though they represent simple and nonsegmented appendages. This implies that leg regionalization evolved for a different function and was only later co‐opted for a role in leg segmentation. We also show that the leg gap gene patterns in onychophorans (especially of hth and exd) are similar to the patterns in crustaceans and insects, suggesting that this is the plesiomorphic state in arthropods. The reversed hth and exd patterns in chelicerates and myriapods are therefore an apomorphy for this group, the Myriochelata, lending support to the Myriochelata and Tetraconata clades in arthropod phylogeny.     

Different regulation of N-cadherin and cadherin-11 in rat hippocampus

Cadherin-mediated specific cell adhesion is an important process in brain development as well as in synaptic plasticity in the adult brain. In this study the authors quantified mRNA levels of N-cadherin and cadherin-11 in different brain regions for the first time. In hippocampus N-cadherin mRNA levels were very high at embryonic stages and decreased during further development, whereas cadherin-11 mRNA levels were highest at postnatal stages. However, N-cadherin protein level was not altered during hippocampal development and cadherin-11 protein was low at embryonic but high at postnatal and adult stages. In cultured hippocampal neurons both cadherins became colocalized and recruited to synaptic sites during ongoing differentiation, with especially high accumulation of cadherin-11 at synapses. These data hint at a critical role of N-cadherin at early embryonic stages and early synaptogenesis, whereas cadherin-11 might be more important for further stabilization of synapses in the postnatal period and adulthood.     

Blood peptidome-degradome profile of breast cancer

Background

Cancer invasion and metastasis are closely associated with activities within the degradome; however, little is known about whether these activities can be detected in the blood of cancer patients.

Methodology and Principal Findings

The peptidome-degradome profiles of pooled blood plasma sampled from 15 breast cancer patients (BCP) and age, race, and menopausal status matched control healthy persons (HP) were globally characterized using advanced comprehensive separations combined with tandem Fourier transform mass spectrometry and new data analysis approaches that facilitated top-down peptidomic analysis. The BCP pool displayed 71 degradome protein substrates that encompassed 839 distinct peptidome peptides. In contrast, the HP 50 degradome substrates found encompassed 425 peptides. We find that the ratios of the peptidome peptide relative abundances can vary as much as >4000 fold between BCP and HP. The experimental results also show differential degradation of substrates in the BCP sample in their functional domains, including the proteolytic and inhibitory sites of the plasmin-antiplasmin and thrombin-antithrombin systems, the main chains of the extracellular matrix protection proteins, the excessive degradation of innate immune system key convertases and membrane attack complex components, as well as several other cancer suppressor proteins.

Conclusions

Degradomics-peptidomics profiling of blood plasma is highly sensitive to changes not evidenced by conventional bottom-up proteomics and potentially provides unique signatures of possible diagnostic utility.