[Interest of the use of the "MYDEFI" smartphone application to help reduce alcohol consumption in the involvement of pharmacists in the prevention of at-risk consumption: Results of a survey in the Hauts-de-France]. / Intérêt de l'utilisation de l'application smartphone « MYDEFI ¼ d'aide à la réduction de la consommation d'alcool dans l'implication des pharmaciens dans la prévention de la consommation à risque : résultats d'une enquête dans les Hauts-de-France.

OBJECTIVES: Evaluate the interest in the MyDéfi application as a tool to help pharmacists identify and manage excessive alcohol consumption, as well as their perception and knowledge of alcohol and their possible role in its management. METHODS: Prospective mixed qualitative and quantitative study, based on face-to-face semi-directive interviews. RESULTS: The 101 pharmacists interviewed in Hauts-de-France region considered that the detection of alcohol consumption was part of their mission, even if it is a difficult subject, and that they had received specific training in alcohology during their university training. Only 12% were aware of early screening and brief intervention on alcohol. Several obstacles were mentioned, such as the lack of training and confidentiality, and difficulties related to patient specificities. Forty-one percent said that the pharmacy was not suitable and almost 72% said that the MyDéfi application could be useful for screening and 91% would recommend the application as one of the best supports, easy to advise with a personalised follow-up. For 32%, the application is accessible to patients (40% think that the main drawback of the application is inaccessibility and 27% its cost). CONCLUSION: Pharmacists consider that excessive alcohol use is a major problem that should mobilise them but many do not feel ready to offer brief interventions. After seeing how the MyDéfi application worked, the majority considered that it could help them in their prevention mission.

Comparison of the different supports used in veterinary medicine for pressure sore prevention.

OBJECTIVES: To compare the pressure-relieving capacity of different supports used in veterinary medicine and to find the more common pressure sore locations in laterally recumbent dogs, so as to recommend protocols for decubitus ulcer prevention. MATERIALS AND METHODS: We compared the support properties of: (1) blankets on the floor, (2) a standard mattress, (3) a veterinary memory foam mattress and (4) a human medicine memory foam mattress. Three cadaver dogs with different body condition scores but similar sizes were positioned on the different supports in lateral recumbency. Pressures were measured in each dog and at each support contact point over a 4-hour period using a TexiSense pressure mat. RESULTS: Regardless of the body condition score and the support used, the skin overlying the scapula-humeral articulation, the greater trochanter and the thirteenth rib were the recurrent risk zones. In these risk zones, pressure-relieving mats led to lower pressures than did the standard mats or the blanket placed on the floor. The contact pressures appeared to depend on body condition score, with maximal pressures observed in thin dogs. CLINICAL SIGNIFICANCE: It is important to use a pressure-relieving mat to reduce the risk of pressure sores, but static pressure-relieving mats are generally insufficient to maintain safe pressures in risk zones (<60 mmHg), particularly in thin patients, and so frequent changes in position are recommended.

Efficacy of Prolonged- and Immediate-release Tacrolimus in Kidney Transplantation: A Pooled Analysis of Two Large, Randomized, Controlled Trials.

BACKGROUND: Two large, prospective studies (12-03; OSAKA) compared the efficacy and tolerability of prolonged-release versus immediate-release tacrolimus in kidney transplant patients also receiving mycophenolate mofetil and low-dose corticosteroids (without induction therapy). METHODS: Data were combined into one database to compare results over 24 weeks using 3 alternative endpoints: biopsy-confirmed acute rejection (BCAR); the Food and Drug Administration composite endpoint (graft loss, BCAR, and loss to follow-up), and the European Medicines Agency composite endpoint (graft loss, BCAR, and graft dysfunction). The 95% confidence intervals were calculated (10% noninferiority margin). RESULTS: Overall, 633 patients received prolonged-release tacrolimus (12-03, n = 331; OSAKA, n = 302) and 645 received immediate-release tacrolimus (n = 336; n = 309). Baseline characteristics were comparable. Proportionately more patients receiving prolonged-release tacrolimus had trough levels of 5-15 ng/mL on day 1 (60.8%) and 2 (56.6%) versus immediate-release tacrolimus (42.5% and 43.9%, respectively, both P < .001). Efficacy of prolonged-release and immediate-release tacrolimus were similar as assessed by BCAR (13.9% vs 14.1%, respectively), European Medicines Agency composite endpoint (40.3% vs 38.3%) and US Food and Drug Administration composite endpoint (21.5% vs 19.8%). CONCLUSIONS: Novel efficacy endpoints as required by the European Medicines Agency and US Food and Drug Administration demonstrate noninferiority of prolonged-release versus immediate-release tacrolimus. Significantly more patients treated with prolonged-release tacrolimus versus immediate-release tacrolimus achieved trough levels of 5 to 15 ng/mL early after transplantation. ClinicalTrials.govNCT00189839; NCT00717470.

Assessment of a polyelectrolyte multilayer film coating loaded with BMP-2 on titanium and PEEK implants in the rabbit femoral condyle.

UNLABELLED: The aim of this study was to evaluate the osseointegration of titanium implants (Ti-6Al-4V, noted here TA6V) and poly(etheretherketone) PEEK implants induced by a BMP-2-delivering surface coating made of polyelectrolyte multilayer films. The in vitro bioactivity of the polyelectrolyte film-coated implants was assessed using the alkaline phosphatase assay. BMP-2-coated TA6V and PEEK implants with a total dose of 9.3µg of BMP-2 were inserted into the femoral condyles of New Zealand white rabbits and compared to uncoated implants. Rabbits were sacrificed 4 and 8weeks after implantation. Histomorphometric analyses on TA6V and PEEK implants and microcomputed tomography on PEEK implants revealed that the bone-to-implant contact and bone area around the implants were significantly lower for the BMP-2-coated implants than for the bare implants. This was confirmed by scanning electron microscopy imaging. This difference was more pronounced at 4weeks in comparison to the 8-week time point. However, bone growth inside the hexagonal upper hollow cavity of the screws was higher in the case of the BMP-2 coated implants. Overall, this study shows that a high dose of BMP-2 leads to localized and temporary bone impairment, and that the dose of BMP-2 delivered at the surface of an implant needs to be carefully optimized. STATEMENT OF SIGNIFICANCE: The presentation of growth factors from material surfaces currently presents significant challenges in academia, clinics and industry. Applying osteoinductive factors to different types of implants, made of metals or polymers, may improve bone repair in difficult situations. Here, we show the effects of an osteoinductive coating made of polyelectrolyte multilayer films on two widely used materials, titanium TA6V alloys and PEEK implants, which were implanted in the rabbit femoral condyle. We show that a too high dose of BMP-2 delivered from the screw surface has a negative short-term effect on bone regeneration in close vicinity of the screw surface. In contrast, bone formation was increased at early times in the empty spaces around the screw. These results highlight the need for future dose-dependence studies on bone formation in response to osteoinductive coatings.

Thoracic bite trauma in dogs and cats: a retrospective study of 65 cases.

OBJECTIVES: To report a case series of thoracic bite trauma in dogs and cats and to evaluate risk factors for mortality. METHODS: A retrospective study concerning thoracic bite wounds in dogs and cats was performed. Lesions were categorized by depth of penetration: no wound, superficial, deep or penetrating. Thoracic radiographic reports were reviewed. Lesion management was classified as non-surgical, wound exploration, or explorative thoracotomy. RESULTS: Sixty-five cases were collected. Twenty-two percent of patients with normal respiratory patterns showed thoracic radiographic lesions. Respiratory distress was not correlated with mortality. Twenty-eight patients were presented with superficial wounds and 13 with deep wounds. Eight patients exhibited penetrating wounds. Radiographic lesions were observed in 77% of dogs and 100% of cats. Explorative thoracotomy was performed in 28% of patients, and surgical wound exploration in 17.2%. With the exception of skin wounds, thoracic wall discontinuity was the most frequent lesion. Thoracotomy was associated with increased length of hospitalisation but was not correlated with mortality. The mortality rate was 15.4%. No studied factor correlated with mortality, and the long-term outcomes were excellent. CLINICAL SIGNIFICANCE: A penetrating injury, more than three radiographic lesions, or both together seemed to be indicative of the need for a thoracotomy. In the absence of these criteria, systematic bite wound explorative surgery is recommended, with extension to thoracotomy if thoracic body wall disruption is observed.

Meniscal biomechanical alterations in an ACLT rabbit model of early osteoarthritis.

OBJECTIVE: The purpose of this study was to analyze the early biomechanical alterations of menisci during the early stage of osteoarthritis (OA) development and to correlate them with the chemical composition and matrix alteration. A particular focus was paid to pathological changes in glycosaminoglycan (GAG) content and collagen fiber architecture. DESIGN: Menisci (n = 24) were removed from rabbits' knee joints 6 weeks following surgical anterior cruciate ligament transection (ACLT). Both the anterior and posterior regions of medial and lateral menisci were characterized using indentation tests, Raman microspectroscopy (RM), biphotonic confocal microscopy (BCM) and histology. RESULTS: Mechanical and matrix alterations occurred in both regions of medial and lateral menisci. A significant decrease in the mechanical properties was observed in OA menisci, with a mean reduced modulus from 2.3 to 1.1 MPa. Microstructural observations revealed less organized and less compact collagen bundles in operated menisci than in contralateral menisci, as well as a loss of fiber tension. GAG content was increased in OA menisci, especially in the damaged areas. Neither changes in the secondary structure of collagen nor mineralization were detected through RM at this stage of OA. CONCLUSION: ACLT led to a disorganization of the collagen framework at the early stage of OA development, which decreases the mechanical resistance of the menisci. GAG content increases in response to this degradation. All of these results demonstrate the strong correlation between matrix and mechanical alterations.

A novel biocompatible hyaluronic acid-chitosan hybrid hydrogel for osteoarthrosis therapy.

A conventional therapy for the treatment of osteoarthrosis is intra-articular injection of hyaluronic acid, which requires repeated, frequent injections. To extend the viscosupplementation effect of hyaluronic acid, we propose to associate it with another biopolymer in the form of a hybrid hydrogel. Chitosan was chosen because of its structural similarity to synovial glycosaminoglycans, its anti-inflammatory effects and its ability to promote cartilage growth. To avoid polyelectrolyte aggregation and obtain transparent, homogeneous gels, chitosan was reacetylated to a 50% degree, and different salts and formulation buffers were investigated. The biocompatibility of the hybrid gels was tested in vitro on human arthrosic synoviocytes, and in vivo assessments were made 1 week after subcutaneous injection in rats and 1 month after intra-articular injection in rabbits. Hyaluronic acid-chitosan polyelectrolyte complexes were prevented by cationic complexation of the negative charges of hyaluronic acid. The different salts tested were found to alter the viscosity and thermal degradation of the gels. Good biocompatibility was observed in rats, although the calcium-containing formulation induced calcium deposits after 1 week. The sodium chloride formulation was further tested in rabbits and did not show acute clinical signs of pain or inflammation. Hybrid HA-Cs hydrogels may be a valuable alternative viscosupplementation agent.

Chitosan solutions as injectable systems for dermal filler applications: Rheological characterization and biological evidence.

A new generation of dermal filler for wrinkle filler based on chitosan was compared to current hyaluronic acid-based dermal fillers by using a new rheological performance criterion based on viscosity during injection related to Newtonian viscosity. In addition an in vivo evaluation was performed for preclinical evidence of chitosan use as dermal filler. In this way, biocompatibility and dermis reconstruction was evaluated on a pig model.

A novel oxido-viscosifying Hyaluronic Acid-antioxidant conjugate for osteoarthritis therapy: biocompatibility assessments.

To overcome the problem of fast degradation of Hyaluronic Acid (HA) in the treatment of osteoarthritis (OA), HA was protected against the oxidative stress generated by the pathology. Antioxidant conjugated HAs were synthesized and tested in vitro for their resistance in an oxidative environment mimicking OA. HA-4-aminoresorcinol (HA-4AR) displayed the interesting property of increasing in viscosity under oxidative conditions because of crosslinking induced by electron transfer. The novel HA polymer conjugate was shown to be biocompatible in vitro on fibroblast-like synoviocytes extracted from an arthritic patient. This HA conjugate was also assessed in vivo by intra-articular injection in healthy rabbits and was found to be comparable to the native polymer in terms of biocompatibility. This study suggests that HA-4AR is a promising candidate for a next generation viscosupplementation formulation.

Intra-articular administration of xenogeneic neonatal Mesenchymal Stromal Cells early after meniscal injury down-regulates metalloproteinase gene expression in synovium and prevents cartilage degradation in a rabbit model of osteoarthritis.

OBJECTIVE: The anti-inflammatory and anti-catabolic effects of neonatal Mesenchymal Stromal Cell (MSC) were investigated in a xenogeneic model of mild osteoarthritis (OA). The paracrine properties of MSC on synoviocytes were further investigated in vitro. STUDY DESIGN: OA was induced by medial meniscal release (MMR) in 30 rabbit knees. A single early (day 3) or delayed (day 15) intra-articular (IA) injection of MSC isolated from equine Umbilical Cord Wharton's jelly (UC-MSC) was performed. Rabbits were euthanized on days 15 or 56. OA grading was performed and gene expression of inflammatory cytokines and metalloproteinases was measured in synovial tissue. Paracrine effects of UC-MSC were investigated using UC-conditioned vs control medium on rabbit primary synoviocytes stimulated with interleukin 1 beta in vitro. RESULTS: No adverse local or systemic responses were observed clinically after xenogeneic UC-MSC injection. At study end point, cartilage fibrillation was lower in early treatment than in delayed treatment group. Cellular infiltrate was observed in the synovium of both UC-MSC groups. OA synovium exhibited a reduced expression of metalloproteinases-1, -3, -13 in the early cell-treated group at d56. In vitro, UC-conditioned medium exerted anti-inflammatory and anti-catabolic effects on synoviocytes exposed to pro-inflammatory stimulus. CONCLUSIONS: Early IA injection of equine UC-MSC was effective in preventing OA signs in rabbit knees following MMR. UC-MSC target the synovium and modulate the gene expression pattern of synoviocytes to promote an anti-catabolic environment. This confirms the synovium is a major target and mediator of MSC therapy, modulating the expression of matrix-degrading enzymes.

Coil optimization for low-field MRI: a dedicated process for small animal preclinical studies.

We demonstrate a method for the fast in vivo quantification of small volumes, down to 25 µL, using low-field magnetic resonance imaging (MRI) coils. The coils were designed so as to maximize the signal-to-noise ratio (SNR) in the images. For this we developed an analytical model for describing the variations of the SNR with coil design and with size/shape suited to the object under observation. Based on the conclusions drawn from the model, the coil parameters were chosen in order to reach an SNR close to the maximum. For the validation of the model, coils were finally characterized in terms of quality factor using saline phantoms. The coil design procedure is illustrated here with two examples: first, the quantification of about 200 µL of intradermal injected gel on rabbits with a single loop surface coil and second, the imaging of the intervertebral disks in rat tails using a small volume coil to detect possible lesions. Such studies would not have been feasible for the clinical low-field MRI system at our disposal using any of the commercially available medium-sized manufactured coils. As a result of this simple optimization procedure, a wide range of applications is accessible even at low magnetic fields, leading to new opportunities for low-cost, though efficient, preclinical studies.

Comparison of radiographic measurements of the patellar tendon-tibial plateau angle with anatomical measurements in dogs. Validity of the common tangent and tibial plateau methods.

OBJECTIVE: To evaluate the validity of the common tangent and conventional tibial plateau angle methods for measuring the patellar tendon angle (PTA) in dogs. METHODS: Radiographs of cadaveric stifles (n = 20) placed at 135° in true lateral position were obtained to measure the PTA with both methods. A Kirschner wire was inserted perpendicularly to the patellar tendon at its insertion on the tibia and the stifle was dissected. Two Kirschner wires were then used to identify the anatomical landmarks of the tibial plateau. A digital image was obtained of the proximal tibia in true lateral position. Six blinded observers measured each PTA digitally while the anatomical PTA was determined by an independent blinded observer from the angle between the line representing the tibial plateau and the Kirschner wire representing the perpendicular to the patellar tendon. The agreement between the methods was determined statistically from an intraclass correlation coefficient (ICC). RESULTS: The global ICC for the common tangent method (0.44) and for the conventional method (0.4) indicated that their overall validity is poor. The measurements obtained by common tangentmethod and conventional method were respectively below and above the anatomical measurements. The reproducibility of the PTA measurements based on images of the dissected stifles was very good. CLINICAL SIGNIFICANCE: Both the common tangent and conventional methods show poor concordance with the anatomical measurement of PTA. Further studies are needed to determine if errors in measurements affect the clinical outcome.

Computed tomographic measurements with and without myelography to characterise thoracolumbar extruded disc herniation.

OBJECTIVE: To determine association between computed tomography measurements of spinal cord compression and postoperative outcome. METHODS: A retrospective review of medical records of dogs presenting with intervertebral disease. Data were collected with a minimum of 2 years follow-up period. Computed tomography morphometric indices, particularly the ratio of spinal cord or herniated disc to vertebral canal dimensions, were obtained from survey and myelogram computed tomographic images. The pattern of disc disease was scored as single or continuous (multiple herniated discs), and was compared to postoperative outcome. RESULTS: Fifty-two dogs were included. There was no significant correlation between the degree of spinal cord compression and postoperative outcome. However, postoperative outcome differed significantly between dogs with single or continuous patterns of disc disease (P=0·001). Of those with single patterns, 75% had a postoperative outcome score greater than 75% while 75% of continuous pattern cases had scores lower than 83%. CLINICAL SIGNIFICANCE: Simple observation of the pattern of disc disease as revealed by computed tomography could be used as a prognostic indicator. The outcome tends to be better for single patterns of disc disease, whereas the outcome was poor for most cases with continuous patterns.