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1.
Euro Surveill ; 24(13)2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30940316

RESUMO

BACKGROUND: In 2015, Bristol (South West England) experienced a large increase in cases of meticillin-resistant Staphylococcus aureus (MRSA) infection in people who inject drugs (PWID). AIM: We aimed to characterise and estimate the prevalence of MRSA colonisation among PWID in Bristol and test evidence of a clonal outbreak. METHODS: PWID recruited through an unlinked-anonymous community survey during 2016 completed behavioural questionnaires and were screened for MRSA. Univariable logistic regression examined associations with MRSA colonisation. Whole-genome sequencing used lineage-matched MRSA isolates, comparing PWID (screening and retrospective bacteraemia samples from 2012-2017) with non-PWID (Bristol screening) in Bristol and national reference laboratory database samples. RESULTS: The MRSA colonisation prevalence was 8.7% (13/149) and was associated with frequently injecting in public places (odds ratio (OR): 5.5; 95% confidence interval (CI):1.34-22.70), recent healthcare contact (OR: 4.3; 95% CI: 1.34-13.80) and injecting in groups of three or more (OR: 15.8; 95% CI: 2.51-99.28). People reporting any one of: injecting in public places, injection site skin and soft tissue infection or hospital contact accounted for 12/13 MRSA positive cases (sensitivity 92.3%; specificity 51.5%). Phylogenetic analysis identified a dominant clade associated with infection and colonisation among PWID in Bristol belonging to ST5-SCCmecIVg. CONCLUSIONS: MRSA colonisation in Bristol PWID is substantially elevated compared with general population estimates and there is evidence of clonal expansion, community-based transmission and increased infection risk related to the colonising strain. Targeted interventions, including community screening and suppression therapy, education and basic infection control are needed to reduce MRSA infections in PWID.


Assuntos
Bacteriemia/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/epidemiologia , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/transmissão , Estudos Transversais , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Epidemiologia Molecular , Tipagem Molecular , Filogenia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Abuso de Substâncias por Via Intravenosa/epidemiologia , Inquéritos e Questionários , Reino Unido/epidemiologia , Sequenciamento Completo do Genoma
2.
AAPS PharmSciTech ; 18(4): 1158-1176, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27422651

RESUMO

Accelerated stability coupled with modeling to predict the stability of compounds, blends, and products at long-term storage conditions provides significant benefits in science-based decision-making throughout drug substance and drug product development. The study can often be completed, including data analysis in the space of three working weeks, and the information gathered and learning made in this time period can rival years of traditional analysis. The speed of the studies allows an earlier assessment of risk to quality enabling appropriate risk mitigation strategies to be implemented in a timely manner. The scientific foundation is based upon Arrhenius kinetic equations that can be linear or nonlinear in time, and can be based upon water vapor pressure or liquid water activity (relative humidity). A variety of kinetic models are evaluated, and the best model is chosen based upon both Bayesian information criteria and an automated assessment of kinetic model parameters fitting within acceptable ranges. Confidence intervals are estimated based upon a bootstrapping approach. Moisture vapor transmission rate models are applied on top of the resulting kinetic models in order to simulate different packaging types and the use of desiccant. The kinetic models are integrated with the prediction of packaging humidity over time to create a long-term prediction of impurities and other phenomena. The resulting models have been shown to be useful for not only the prediction of drug product impurities in long-term storage but other physical phenomena as well such as hydrate development and solvate loss.


Assuntos
Estabilidade de Medicamentos , Armazenamento de Medicamentos/métodos , Embalagem de Medicamentos/métodos , Cinética , Modelos Químicos
3.
Pharm Stat ; 15(1): 90-2, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26559516

RESUMO

Many scientists believe that small experiments, guided by scientific intuition, are simpler and more efficient than design of experiments. This belief is strong and persists even in the face of data demonstrating that it is clearly wrong. In this paper, we present two powerful teaching examples illustrating the dangers of small experiments guided by scientific intuition. We describe two, simple, two-dimensional spaces. These two spaces give rise to, and at the same time appear to generate supporting data for, scientific intuitions that are deeply flawed or wholly incorrect. We find these spaces useful in unfreezing scientific thinking and challenging the misplaced confidence in scientific intuition.


Assuntos
Projetos de Pesquisa/estatística & dados numéricos , Regressão Espacial , Ensino , Humanos
4.
Vet Surg ; 45(6): 726-35, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27381167

RESUMO

OBJECTIVE: To report the long-term radiographic and clinical outcome of the BioMedtrix TATE elbow arthroplasty system in dogs. Assessment was via radiographs, a surgeon-based questionnaire, and owner assessment of outcome using the Liverpool osteoarthritis in dogs (LOAD) and canine brief pain inventory (CBPI) questionnaires. STUDY DESIGN: Retrospective multicenter, case series. ANIMALS: Client-owned dogs undergoing TATE elbow arthroplasty. METHODS: Questionnaires were distributed to surgeons in the United Kingdom performing TATE elbow arthroplasty and to the owners of the dogs operated on. Owners completed the LOAD and CBPI questionnaires. All completed questionnaires from surgeons and owners, and radiographs of the dogs were collated and analyzed. RESULTS: Surgeon questionnaires and radiographs were obtained for 33 elbows from 32 dogs, with owner questionnaires obtained for 19 dogs. Perioperative, short-term, and mid-term complication rates were 60%, 15%, and 15%, respectively. Radiographic assessment of component alignment showed 62% of cartridges were valgus or varus malaligned and 56% of cartridges were either translated medially or laterally relative to the long axis of the ulnar. There was no significant association between component alignment and final clinical outcome. Surgeon assessment reported 24% of dogs to have full, 52% acceptable, and 24% unacceptable outcome. Owner assessment showed significant decreases in pain severity and pain interference from preoperative to final status but no change in mobility scores. CONCLUSIONS: A high complication rate and variability in component placement was recorded with TATE athroplasty. However, component malalignment did not negatively impact clinical outcome. Final clinical outcome was favorable for most cases with significant reductions in pain severity and interference scores despite no changes in mobility scores.


Assuntos
Artroplastia/veterinária , Doenças do Cão/cirurgia , Prótese de Cotovelo/veterinária , Osteoartrite/veterinária , Animais , Cães , Feminino , Membro Anterior/cirurgia , Masculino , Osteoartrite/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
5.
Vet Surg ; 44(1): 70-7, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24708556

RESUMO

OBJECTIVE: To describe and compare a large population of dogs that had pancarpal arthrodesis (PCA) using either a hybrid dynamic compression plate (HDCP) or a CastLess Plate (CLP). STUDY DESIGN: Multicenter, retrospective, cohort study. ANIMALS: Dogs (n = 240; 261 PCA). METHODS: Medical records (2000-2012) from 12 UK orthopedic centers were reviewed for dogs that had PCA to document signalment, diagnosis, arthrodesis method, and complication rates. Follow-up data were used to compare outcome (lameness evaluation and radiographic healing) after use of HDCP and CLP plates. RESULTS: PCA was performed with HDCP in 125 cases, CLP in 105, and by other techniques in 31. Carpal hyperextension injury was the most common diagnosis in HDCP and CLP groups. Surgical site infection (18.3%) was the most common postoperative complication. There was no difference in intra- (11% HDCP, 21% CLP) or postoperative (34% HDCP, 41% CLP) complication rates. Use of external coaptation did not affect postoperative complication rates or outcome. External coaptation related complications occurred in 32% HDCP and 18% CLP (P = .02). At median follow-up, most dogs were classified as having no or mild lameness (73% HDCP, 83% CLP) and there was radiographic healing in 40% HDCP and 46% CLP (P = .8) cases. CONCLUSIONS: CLP and HDCP may both be used successfully to achieve pancarpal arthrodesis. Adjunctive external coaptation does not appear to have a measurable clinical benefit but is associated with morbidity.


Assuntos
Artrodese/veterinária , Placas Ósseas/veterinária , Carpo Animal/cirurgia , Animais , Estudos de Coortes , Cães , Inglaterra , Feminino , Marcha , Masculino , Período Pós-Operatório , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/veterinária , Inquéritos e Questionários , Cicatrização
6.
Linacre Q ; 80(1): 17-23, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24845657

RESUMO

INTRODUCTION: Confirmation of ovulation can be difficult in clinical practice, as gold standard methods including serial transvaginal ultrasonography, serum luteinizing hormone (LH) measurements, or laparoscopic follicular observation are impractical. Numerous surrogate markers have been proposed and evaluated in relation to these gold standards that have more practical clinical applications. PURPOSE: To review the evidence on physiological signs of ovulation timing and fertility in order to determine valid markers that can be easily identified by women. METHODS: A literature review of primary resources in Ovid Medline was undertaken to identify studies examining physiological signs as they relate to gold standard assessment of ovulation. Studies examining the efficacy/effectiveness of different types of natural family planning were excluded. RESULTS: The most commonly encountered physiological signs were urine LH, cervical mucus, and basal body temperature (BBT). Urine LH as assessed by home monitoring systems indicated ovulation 91 percent of the time during the 2 days of peak fertility on the monitor and 97 percent during the 2 peak days plus 1. Cervical mucus peak characteristics were identified 78 percent of the time ±1 day, and 91 percent of the time ±2 days of LH surge indicating ovulation. Further research supports the importance of cervical mucus in overall fertility, as conception rates were more closely related to mucus quality than to timing of intercourse related to ovulation. As a lone indicator of ovulation, BBT is at best a retrospective marker, and functions best in conjunction with other signs of ovulation. Additionally, salivary ferning, salivary and vaginal fluid electrical potential, finger-finger electrical potential, and differential skin temperature were postulated as possible indicators, but were not found to be temporally related to ovulation. The research on differential skin temperature is promising, but minimal thus far in number, and has not been evaluated as an adjunct to BBT as yet. CONCLUSION: Home urinary LH monitors are becoming more widely available and less expensive giving women the potential to assess the ovulatory status of their cycle in real time. Cervical mucus observation is an effective and cost-efficient method, but requires some teaching to increase the confidence of users. In conjunction, LH monitors and cervical mucus can give the best indication of fertility and ovulation timing.

7.
Vet Surg ; 41(4): 471-81, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22530927

RESUMO

OBJECTIVE: To evaluate, using inverse dynamic analysis, the biomechanical outcome from tibial tuberosity advancement (TTA) surgery in dogs affected by unilateral cranial cruciate ligament failure (CCLF). STUDY DESIGN: Retrospective case series. ANIMALS: Dogs (n = 13) 11-20 months after surgery. METHODS: Kinematic and force data were collected from 13 dogs 11-20 months after TTA and inverse dynamics analysis of the dogs' pelvic limb mechanical function performed. Angle, moment, and power were calculated for each joint. Total support moment (TSM) was calculated. RESULTS: Six dogs were affected on the right side (Raff) and 7 on the left (Laff). Peak stifle flexor moment was significantly larger for the right stifle compared with the left in Laff dogs, but similar in Raff dogs. Peak stifle extensor moment was significantly larger for the left stifle compared with the right in Raff dogs, and was also larger for the left stifle compared with the right in Laff dogs. Stifle power in early stance was larger on the left in Raff dogs and significantly larger on the right in Laff dogs. TSM was larger on the right in Raff dogs and significantly larger on the right in Laff dogs. CONCLUSIONS: Affected limbs had a reduction in power of the stifle flexors. Irrespective of the side of CCLF, TSM was larger on the right side and the stifle extensor moment in late stance was larger on the left, perhaps indicating a mechanical limb dominance effect.


Assuntos
Lesões do Ligamento Cruzado Anterior , Ligamento Cruzado Anterior/cirurgia , Doenças do Cão/cirurgia , Cães/lesões , Joelho de Quadrúpedes/fisiologia , Animais , Fenômenos Biomecânicos , Doenças do Cão/fisiopatologia , Feminino , Marcha/fisiologia , Articulação do Quadril/fisiologia , Masculino , Estudos Retrospectivos , Joelho de Quadrúpedes/cirurgia , Articulações Tarsianas/fisiologia , Resultado do Tratamento
8.
Vet Surg ; 41(5): 545-50, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22731937

RESUMO

OBJECTIVE: To assess the variables associated with the complications of total hip replacement (THR) and report owner-assessed outcomes, through surgeon-based registration of cases via an online database, informed owner consent, and prospective outcomes assessment using a client-administered clinical metrology instrument. STUDY DESIGN: Prospective case series ANIMALS: Dogs (n = 170) METHODS: Entries into the British Veterinary Orthopaedic Association-Canine Hip Registry (BVOA-CHR) between January 2010 and August 2011 were reviewed. Variables evaluated included dog age, body weight, breed, and indication for THR and prosthesis. Associations between each variable and the incidence of complications were assessed using logistic regression. Additionally, an on-line, owner-administered outcomes assessment questionnaire (modified from the Liverpool Osteoarthritis in Dogs (LOAD) questionnaire) was used to collect data from owners. RESULTS: One hundred and seventy cases met the inclusion criteria. Surgical indications included hip dysplasia and coxofemoral osteoarthritis (n = 150), Legg-Calves-Perthes disease (7), coxofemoral luxation (6), fracture (4), slipped capital physis (2), and femoral head and neck ostectomy revision (1). Surgical implants were from 4 systems. The incidence of surgeon-reported complication was 9.4%. No significant association was identified between weight, age, sex, breed, indication for THR, surgical technique and prosthesis, and the incidence of complications. In 82% of the cases, owners described their satisfaction with the outcome of THR as "very good" and a total of 20% complication rate was reported. There was a statistically significant improvement in owner-assessed questionnaire score before and after THR (P < .001). CONCLUSIONS: The BVOA-CHR offers a novel framework for the prospective studies on THR and on a national/international scale. Initial complication rates from the BVOA-CHR are similar to previous studies.


Assuntos
Artroplastia de Quadril/veterinária , Doenças do Cão/cirurgia , Internet , Animais , Artroplastia de Quadril/efeitos adversos , Cães , Feminino , Displasia Pélvica Canina/cirurgia , Prótese de Quadril/efeitos adversos , Prótese de Quadril/veterinária , Humanos , Masculino , Osteoartrite do Quadril/cirurgia , Osteoartrite do Quadril/veterinária , Resultado do Tratamento
9.
Chemistry ; 17(47): 13230-9, 2011 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-21990071

RESUMO

The prevalence of the biaryl structural motif in biologically interesting and synthetically important molecules has inspired considerable interest in the development of methods for aryl-aryl bond formation. Herein we describe a novel strategy for this process involving the fluoride-free, palladium-catalysed cross-coupling of readily accessible aryldisiloxanes and aryl bromides. Using a statistical-based optimisation process, preparatively useful reaction conditions were formulated to allow the cross-coupling of a wide range of different substrates. This methodology represents an attractive, cost-efficient, flexible and robust alternative to the traditional transition-metal-catalysed routes typically used to generate molecules containing the privileged biaryl scaffold.


Assuntos
Reagentes de Ligações Cruzadas/química , Fluoretos/química , Hidrocarbonetos Bromados/química , Paládio/química , Siloxanas/química , Catálise , Estrutura Molecular
10.
Vet Surg ; 40(8): 972-80, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22091562

RESUMO

OBJECTIVE: To investigate, using objective gait analysis, the long-term outcome of dogs with medial coronoid process disease (MCPD) treated with conservative management (CM) versus arthroscopic treatment (AT). STUDY DESIGN: Prospective clinical trial. ANIMALS: Dogs (n = 20) with unilaterally confirmed MCPD. METHODS: Eleven dogs were treated arthroscopically with removal of coronoid fragments and burring of any associated chondromalacic cartridge and 9 dogs were managed conservatively. All dogs were administered a 6-week course of oral tepoxalin on enrollment. Inverse dynamics gait analysis was performed at initial presentation and at 4, 8, 26, and 52 weeks. The gait variables analyzed were elbow moment (EM), elbow power (EP), total support moment (TSM), and total support moment ratio (TSMR) as a measure of forelimb asymmetry. RESULTS: Affected peak EM increased from 0.58 to 0.76 Nm/kg in the AT dogs, and from 0.66 to 0.81 Nm/kg in the CM dogs and there was no significant difference between groups. Affected peak EP increased marginally in the AT dogs, but was unchanged in the CM dogs and there was no significant difference between groups. TSM increased from 1.49 to 1.92 Nm/kg in the AT dogs and from 1.52 to 2.06 Nm/kg in the CM dogs and there was no significant difference between groups. TSMR was statistically different between treatment groups at 1 (P = .003) and 2 months (P = .048) with the AT group more asymmetric and hence more lame. TSMR at 12 months was 0.83 (AT) and 0.86 (CM) implying a failure of return to soundness by either group. CONCLUSIONS: AT dogs had increased mechanical asymmetry at 4 and 8 weeks compared to the CM group revealing surgery worsened limb function. There was no significant difference in mechanical symmetry between groups at 26 and 52 weeks.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Artroscopia/veterinária , Doenças do Cão/terapia , Terapia por Exercício/veterinária , Marcha , Artropatias/veterinária , Coxeadura Animal/terapia , Animais , Cães , Feminino , Membro Anterior/cirurgia , Artropatias/terapia , Masculino , Modelos Estatísticos , Estudos Prospectivos , Resultado do Tratamento
11.
Vet Surg ; 40(6): 728-33, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21699552

RESUMO

OBJECTIVE: To describe incidence and type of postoperative complications in the surgical management of incomplete ossification of the humeral condyle (IOHC) and identify any risk factors associated with development of these complications. STUDY DESIGN: Case series. METHODS: Clinical records of dogs (n=57) that had prophylactic transcondylar screw insertion for treatment of IOHC (79 elbows) at 6 UK referral centers were reviewed. Signalment, presentation, surgical management, postoperative care, and complications were recorded. Postoperative complications were divided into seroma, surgical site infections (SSI) and implant complications. RESULTS: Spaniel breeds and entire males were overrepresented. The overall complication rate was 59.5%. Seroma (n=25) and SSI (24) were the most commonly encountered complications. Implant failure occurred in 2 dogs. Labrador retrievers were at greater risk of developing a postoperative complication than other breeds (P=.03). Increasing bodyweight was a significant risk factor for development of a SSI (P=.03). Placement of the transcondylar screw in lag fashion rather than as a positional screw reduced the incidence of postoperative SSI (P=.007). CONCLUSIONS: Surgical management of IOHC is associated with a high rate of postoperative complications. Placement of the transcondylar screw in lag fashion may limit postoperative complications and warrants further consideration.


Assuntos
Doenças do Desenvolvimento Ósseo/veterinária , Doenças do Cão/cirurgia , Complicações Pós-Operatórias/veterinária , Animais , Doenças do Desenvolvimento Ósseo/cirurgia , Cães , Feminino , Membro Anterior/patologia , Membro Anterior/cirurgia , Coxeadura Animal , Masculino , Razão de Chances , Fatores de Risco
12.
Am J Vet Res ; 71(1): 41-6, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20043779

RESUMO

OBJECTIVE: To quantify bone mineral density (BMD) in the medial coronoid process (MCP) of dogs with and without fragmented medial coronoid processes (FMCPs) by use of dualenergy x-ray absorptiometry. SAMPLE POPULATION: 50 osteochondral samples from 31 dogs that underwent subtotal coronoid ostectomy for unilateral or bilateral FMCP and 10 control osteochondral samples of the MCP collected from forelimbs of 5 cadaveric Greyhounds. PROCEDURES: Each sample was mounted in proximodistal and mediolateral orientations for BMD determinations via dual-energy x-ray absorptiometry, and area-of-interest data (0.03-cm(2) increments) were obtained. Values of BMD were compared between left and right limb control samples, between control and FMCP samples, and between axial and abaxial regions of the control or FMCP samples. RESULTS: The BMD in control and FMCP samples in both proximodistal and mediolateral orientations differed significantly. Mean BMD throughout the MCP was decreased in FMCP samples, compared with control sample findings. In both control and FMCP samples, BMD of the abaxial half of the MCP was 50% higher than that of the axial portion. CONCLUSIONS AND CLINICAL RELEVANCE: The similar pattern of BMD in osteochondral samples of the MCP in dogs with and without FMCP indicated that the MCP was eccentrically loaded during weight bearing. Topographic variation in BMD in the MCP, and hence tolerance to compressive loading, suggested that the abaxial portion of the MCP in dogs was more resistant to compressive load than was the axial edge. This difference may predispose the coronoid process to microcrack formation and fragmentation at that juxtaposition.


Assuntos
Densidade Óssea , Doenças do Cão/patologia , Artropatias/veterinária , Animais , Doenças do Cão/metabolismo , Cães , Membro Anterior/patologia , Artropatias/metabolismo , Artropatias/patologia
13.
Vet Comp Orthop Traumatol ; 22(3): 225-8, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19448870

RESUMO

A fracture of the proximal 1/3 of the ulna, with concurrent fractures of the proximal radial physis and the distal 1/3 of the diaphysis of the radius occurred in a three-month-old, male, neutered, Domestic Shorthaired cat. The ulnar fracture was stabilised with an intramedullary pin. The proximal radial physeal fracture was reduced and stabilised with two crossed Kirschner wires. The proximal radius was secured to the ulna with an additional Kirschner wire. The distal radial diaphyseal fracture was stabilised with a five-hole, 2.0 mm dynamic compression plate (DCP). Six weeks postoperatively the cat was using the limb comfortably and demonstrated a full range of motion of the elbow joint. There were radiographic signs of fracture union and the radioulnar pin had migrated. The Kirschner wires were removed. Follow-up at 18 months postoperatively revealed that the cat was using the limb normally without any lameness. A full, pain-free range of motion was present in the joints of the left thoracic limb.


Assuntos
Doenças do Gato/patologia , Fratura de Monteggia/patologia , Fratura de Monteggia/veterinária , Fraturas do Rádio/patologia , Fraturas do Rádio/veterinária , Rádio (Anatomia)/patologia , Animais , Gatos , Masculino , Fratura de Monteggia/diagnóstico por imagem , Prognóstico , Radiografia , Fraturas do Rádio/diagnóstico por imagem , Resultado do Tratamento , Fraturas da Ulna/diagnóstico por imagem , Fraturas da Ulna/patologia , Fraturas da Ulna/veterinária
14.
Pharmaceutics ; 11(4)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939803

RESUMO

The aim of the present study was to develop an alternative process to spray granulation in order to prepare high loaded spherical nicotinamide (NAM) pellets by wet extrusion and spheronisation. Therefore, a quality by design approach was implemented to model the effect of the process parameters of the extrusion-spheronisation process on the roundness, roughness and useable yield of the obtained pellets. The obtained results were compared to spray granulated NAM particles regarding their characteristics and their release profile in vitro after the application of an ileocolon targeted shellac coating. The wet extrusion-spheronisation process was able to form highly loaded NAM pellets (80%) with a spherical shape and a high useable yield of about 90%. However, the water content range was rather narrow between 24.7% and 21.3%. The design of experiments (DoE), showed that the spheronisation conditions speed, time and load had a greater impact on the quality attributes of the pellets than the extrusion conditions screw design, screw speed and solid feed rate (hopper speed). The best results were obtained using a low load (15 g) combined with a high rotation speed (900 m/min) and a low time (3⁻3.5 min). In comparison to spray granulated NAM pellets, the extruded NAM pellets resulted in a higher roughness and a higher useable yield (63% vs. 92%). Finally, the coating and dissolution test showed that the extruded and spheronised pellets are also suitable for a protective coating with an ileocolonic release profile. Due to its lower specific surface area, the required shellac concentration could be reduced while maintaining the release profile.

15.
Pharmaceutics ; 10(4)2018 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-30249025

RESUMO

This paper displays the potential of an in-line PAT system for early phase product development during pharmaceutical continuous manufacturing following a Quality by Design (QbD) framework. Hot melt extrusion (HME) is used as continuous manufacturing process and UV⁻Vis spectroscopy as an in-line monitoring system. A sequential design of experiments (DoE) (screening, optimisation and verification) was used to gain process understanding for the manufacture of piroxicam (PRX)/Kollidon® VA64 amorphous solid dispersions. The influence of die temperature, screw speed, solid feed rate and PRX concentration on the critical quality attributes (CQAs) absorbance and lightness of color (L*) of the extrudates was investigated using multivariate tools. Statistical analysis results show interaction effects between concentration and temperature on absorbance and L* values. Solid feed rate has a significant effect on absorbance only and screw speed showed least impact on both responses for the screening design. The optimum HME process conditions were confirmed by 4 independent studies to be 20% w/w of PRX, temperature 140 °C, screw speed 200 rpm and feed rate 6 g/min. The in-line UV-Vis system was used to assess the solubility of PRX in Kollidon® VA64 by measuring absorbance and L* values from 230 to 700 nm. Oversaturation was observed for PRX concentrations higher than 20% w/w. Oversaturation can be readily identified as it causes scattering in the visible range. This is observed by a shift of the baseline in the visible part of the spectrum. Extrudate samples were analyzed for degradation using off-line High-Performance Liquid Chromatography (HPLC) standard methods. Results from off-line experiments using differential scanning calorimetry (DSC), and X-ray diffraction (XRD) are also presented.

16.
J Biomech ; 40(16): 3732-7, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17675043

RESUMO

OBJECTIVE: To determine the load bearing areas of the canine acetabulum. MATERIALS AND METHODS: A kinematic study of four healthy dogs was used to determine the orientation of the femur to the pelvis at mid-stance. Femora and pelves from 10 canine cadavers were loaded with the physiological canine hip reaction force and angle being replicated. Impression material placed within the acetabulum was extruded from areas of load bearing. Digital images before and after loading were used to assess if six different regions of the acetabulum were fully, partially or non-load bearing. RESULTS: All areas of the acetabulum were partially or fully load bearing. The cranial and caudal thirds of the acetabulum were 7.9 and 13.1 times more likely to be fully load bearing than the central third, respectively. There was a significant difference in load bearing between the axial, middle and abaxial thirds of the acetabulum in all tests, with the middle and abaxial thirds 72.4 and 351 times more likely to be fully load bearing than the axial third, respectively. CONCLUSION: The cranial and caudal thirds and the middle and abaxial thirds of the canine acetabulum are fully load bearing. CLINICAL RELEVANCE: The caudal third of the canine acetabulum is loaded and therefore recommendations that fractures in this area be managed conservatively need to be reconsidered.


Assuntos
Acetábulo/fisiologia , Cabeça do Fêmur/fisiologia , Modelos Biológicos , Suporte de Carga/fisiologia , Animais , Cães , Estresse Mecânico
17.
Vet Comp Orthop Traumatol ; 30(3): 178-183, 2017 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-28331933

RESUMO

OBJECTIVES: To investigate the conformation of the proximal tibia in small breed dogs with and without cranial cruciate ligament disease (CCLD) and to identify morphologic abnormalities that may predispose to development of CCLD. METHODS: Mediolateral radiographs of the entire tibia of dogs <15 kg with surgically confirmed CCLD were retrospectively evaluated. Proximal tibial width (PTW), tibial plateau length (TPL), tibial plateau angle as described by Slocum and Slocum (sTPA), proximal tibial tuberosity angle (PTTA), tibial plateau angle as described by Inauen and colleagues (nTPA), and diaphyseal tibial width (DTW) were measured. The same variables were obtained from mediolateral radiographs of the entire tibia of dogs <15 kg without CCLD. In addition, a quotient nTPA/PTW, relative tibial tuberosity width (rTTW), and relative body weight (rBW) were calculated for each dog. Independent two-sample t-test (p = 0.05) was used to compare mean ± SD of all measured variables between the two groups. RESULTS: Gender, age, and weight mean ± SD were not significantly different between the two groups of dogs (p <0.05). Dogs with CCLD had significantly greater sTPA (p = 0.015) and rBW (p = 0.016). CLINICAL SIGNIFICANCE: In dogs of small breeds, a combination of an excessively steep tibial plateau and an increased relative body weight may predispose to early CCLD development. The slope of the tibial plateau was found to be caused by an abnormal caudal angulation of the proximal tibia, a phenomenon previously associated with CCLD development in small breed dogs in individual cases.


Assuntos
Doenças do Cão/patologia , Cães/lesões , Joelho de Quadrúpedes/anatomia & histologia , Tíbia/anatomia & histologia , Animais , Ligamento Cruzado Anterior , Fenômenos Biomecânicos , Cruzamento , Estudos Retrospectivos
18.
Vet Comp Orthop Traumatol ; 30(1): 69-74, 2017 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-27849110

RESUMO

OBJECTIVES: To assess the effect of intra-operative radiology on the quality of lag screw insertion for the management of sacroiliac joint luxations in cats. METHODS: In this retrospective single-centre study, the surgical, anaesthetic and imaging records of 40 screws (32 cats) placed with lag effect for management of sacroiliac luxation were reviewed. Postoperative radiographs were assessed for sacroiliac joint reduction, screw position, and sacral width purchased by each screw. Cases were divided into two groups according to the use of (IOR) or the absence of intra-operative radiology (NIOR). RESULTS: A total of 23 lag screws were placed with the aid of intra-operative radiology and 17 without. Three of the 23 screws placed in the IOR group exited the sacrum as opposed to eight of 17 screws in the NIOR group (p = 0.03). Mean sacral width purchased by the screws in the IOR group (70.8%) was also significantly higher (p = 0.002) than in the NIOR group (54.6%). Mean general anaesthetic times for unilateral and bilateral screw placement for the IOR group and NIOR group were not significantly different. CLINICAL SIGNIFICANCE: The use of intra-operative radiology can significantly improve the quality of lag screw insertion for the stabilization of sacroiliac luxations in cats, which should lead to a reduced incidence of postoperative screw loosening.


Assuntos
Parafusos Ósseos/veterinária , Gatos/lesões , Gatos/cirurgia , Luxações Articulares/veterinária , Radiografia/veterinária , Articulação Sacroilíaca/cirurgia , Animais , Feminino , Cuidados Intraoperatórios/veterinária , Luxações Articulares/diagnóstico por imagem , Masculino
19.
Vet Rec ; 181(1): 18, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28386028

RESUMO

The objective of this study was to assess the variables associated with complications of total hip replacement (THR) and report owner-assessed outcomes. Entries into the British Veterinary Orthopaedic Association-Canine Hip Registry (BVOA-CHR) between September 2011 and December 2012 were reviewed separately and in conjunction with previous data (January 2010-August 2011). An outcomes assessment questionnaire was used to collect data from owners. Incidences of surgeon-reported and owner-reported complications were 8.2 per cent and 4.3 per cent, respectively. THR using the BioMedtrix BFX cup/stem prosthesis had a greater incidence of complications compared with THR using the BioMedtrix CFX cup/stem prosthesis (P=0.002); complications were 4.48 times more likely when using the BioMedtrix BFX cup/stem prosthesis versus the BioMedtrix CFX cup/stem prosthesis. THR using the BioMedtrix BFX cup/stem prosthesis had a higher incidence of complications compared with THR using a hybrid prosthesis (BioMedtrix BFX cup/CFX stem, BioMedtrix CFX cup/BFX stem) (P=0.046); complications were 2.85 times more likely when using the BioMedtrix BFX cup/stem prosthesis versus a hybrid prosthesis. In 95 per cent of cases, owner satisfaction with the outcome of THR was 'very good' or 'good'. Complication rates from the BVOA-CHR are similar to previous studies. The data suggest that prosthesis type is associated with complication rate, with BioMedtrix BFX (circa 2012) having a high short-term complication rate.


Assuntos
Artroplastia de Quadril/veterinária , Doenças do Cão/cirurgia , Animais , Artroplastia de Quadril/efeitos adversos , Cães , Feminino , Prótese de Quadril/efeitos adversos , Prótese de Quadril/veterinária , Humanos , Masculino , Sistema de Registros , Resultado do Tratamento , Reino Unido
20.
Am J Vet Res ; 66(9): 1563-71, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16261830

RESUMO

OBJECTIVE: To quantify angular excursions; net joint moments; and powers across the stifle, tarsal, and metatarsophalangeal (MTP) joints in Labrador Retrievers and Greyhounds and investigate differences in joint mechanics between these 2 breeds of dogs. ANIMALS: 12 clinically normal dogs (6 Greyhounds and 6 Labrador Retrievers) with no history of hind limb lameness. PROCEDURE: Small retroreflective markers were applied to the skin over the pelvic limb joints, and a 4-camera kinematic system captured data at 200 Hz in tandem with force platform data while the dogs trotted on a runway. Breed-specific morphometric data were combined with kinematic and force data in an inverse-dynamics solution for stance-phase net joint moments and powers at the stifle, tarsal, and MTP joints. RESULTS: There were gross differences in kinematic patterns between Greyhounds and Labradors. At the stifle and tarsal joints, moment and power patterns were similar in shape, but amplitudes were larger for the Greyhounds. The MTP joint was a net absorber of energy, and this was greater in the Greyhounds. Greyhounds had a positive phase across the stifle, tarsal, and MTP joints at the end of stance for an active push-off, whereas for the Labrador Retrievers, the only positive phase was across the tarsus, and this was small, compared with values for the Greyhounds. CONCLUSIONS AND CLINICAL RELEVANCE: Gross differences in pelvic limb mechanics are evident between Greyhounds and Labrador Retrievers. Joint kinetics in specific dogs should be compared against breed-specific patterns.


Assuntos
Cães/fisiologia , Marcha/fisiologia , Membro Posterior/fisiologia , Articulações/fisiologia , Animais , Fenômenos Biomecânicos , Pesos e Medidas Corporais , Cães/anatomia & histologia
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