Contact sensitisation in oral lichen planus: An Australian perspective.

BACKGROUND: The role of contact sensitisation in the pathogenesis of oral lichen planus (OLP) has not been clearly defined. OBJECTIVE: We aimed to evaluate relevant contact sensitisers in OLP. METHODS: A retrospective study was conducted on OLP patients who underwent patch testing from 1 January 2006 to 31 December 2020 at an Australian tertiary dermatology institution, compared to cheilitis patients patch tested over the same time period. RESULTS: Ninety-six OLP patients and 152 cheilitis patients were patch tested during the 15-year period. Seventy-one (73.9%) OLP patients and 100 (65.8%) cheilitis patients recorded one or more relevant reactions. Forty-three (44.8%), 22 (22.9%), 21 (21.9%) and 17 (17.7%) OLP patients had relevant reactions to mercury-related chemicals, amalgam, spearmint and carvone, respectively, compared to 6 (3.9%), 3 (2.0%), 4 (2.6%) and 0 (0%) cheilitis patients, respectively (p-value <0.001 each). Four (4.2%) OLP patients had relevant positive reactions to sodium metabisulfite, compared to none in the cheilitis group (p-value 0.021). CONCLUSION: While dental amalgam is used less frequently these days, we report that mercury (found in amalgam) and additionally spearmint and carvone are relevant sensitisers in OLP in Australia. Sodium metabisulfite may also be a relevant sensitiser in OLP, which has not previously been reported.

The effect of a novel, digital physical activity and emotional well-being intervention on health-related quality of life in people with chronic kidney disease: trial design and baseline data from a multicentre prospective, wait-list randomised controlled trial (kidney BEAM).

BACKGROUND: Physical activity and emotional self-management has the potential to enhance health-related quality of life (HRQoL), but few people with chronic kidney disease (CKD) have access to resources and support. The Kidney BEAM trial aims to evaluate whether an evidence-based physical activity and emotional wellbeing self-management programme (Kidney BEAM) leads to improvements in HRQoL in people with CKD. METHODS: This was a prospective, multicentre, randomised waitlist-controlled trial, with health economic analysis and nested qualitative studies. In total, three hundred and four adults with established CKD were recruited from 11 UK kidney units. Participants were randomly assigned to the intervention (Kidney BEAM) or a wait list control group (1:1). The primary outcome was the between-group difference in Kidney Disease Quality of Life (KDQoL) mental component summary score (MCS) at 12 weeks. Secondary outcomes included the KDQoL physical component summary score, kidney-specific scores, fatigue, life participation, depression and anxiety, physical function, clinical chemistry, healthcare utilisation and harms. All outcomes were measured at baseline and 12 weeks, with long-term HRQoL and adherence also collected at six months follow-up. A nested qualitative study explored experience and impact of using Kidney BEAM. RESULTS: 340 participants were randomised to Kidney BEAM (n = 173) and waiting list (n = 167) groups. There were 96 (55%) and 89 (53%) males in the intervention and waiting list groups respectively, and the mean (SD) age was 53 (14) years in both groups. Ethnicity, body mass, CKD stage, and history of diabetes and hypertension were comparable across groups. The mean (SD) of the MCS was similar in both groups, 44.7 (10.8) and 45.9 (10.6) in the intervention and waiting list groups respectively. CONCLUSION: Results from this trial will establish whether the Kidney BEAM self management programme is a cost-effective method of enhancing mental and physical wellbeing of people with CKD. TRIAL REGISTRATION: NCT04872933. Registered 5th May 2021.

The Limitations of Frailty Assessment Tools in ANCA-Associated Vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) can be associated with a high burden of morbidity and mortality in an ageing population. It is increasingly recognised that individualised management is needed. Few studies have looked specifically at frailty related outcomes in AAV and a gap remains in understanding the application of frailty assessment tools in these patients. We carried out a single centre, cohort study between 2017 to 2022. Forty-one patients who had newly diagnosed or relapsing AAV and aged ≥65 years were included. The Clinical Frailty Scale (CFS) score at presentation was assessed by health care practitioners and interval CFS scores were carried out a minimum of 6 weeks from diagnosis. The aim was to determine if patients living with frailty had worse outcomes or if their perceived frailty improved with immunosuppressive treatment. The median CFS at diagnosis was 4 (vulnerable) and this remained at follow up. There was no significant interval change in CFS (P=0.16) suggesting that the patients did not become frailer and instead there was a tendency towards improved frailty scores at re-assessment. There was no significant difference in end stage kidney disease between those with higher (>5) or lower (≤5) CFS (P=1.0), although crude mortality was higher among those with an initial CFS >5 (P=0.03). Overall, we demonstrated that CFS has limitations in determining patients that may be frail as a result of disease burden with the potential to improve with treatment and clinicians should be mindful of this when making decisions relating to management.

Symptom-burden in people living with frailty and chronic kidney disease.

BACKGROUND: Frailty is independently associated with worse health-related quality of life (HRQOL) in chronic kidney disease (CKD). However, the relationship between frailty and symptom experience is not well described in people living with CKD. This study's aim was to evaluate the relationship between frailty and symptom-burden in CKD. METHODS: This study is a secondary analysis of a cross-sectional observational study, the QCKD study (ISRCTN87066351), in which participants completed physical activity, cardiopulmonary fitness, symptom-burden and HRQOL questionnaires. A modified version of the Frailty Phenotype, comprising 3 self-report components, was created to assess frailty status. Multiple linear regression was performed to assess the association between symptom-burden/HRQOL and frailty. Logistic regression was performed to assess the association between experiencing symptoms frequently and frailty. Principal Component Analysis was used to assess the experienced symptom clusters. RESULTS: A total of 353 patients with CKD were recruited with 225 (64%) participants categorised as frail. Frail participants reported more symptoms, had higher symptom scores and worse HRQOL scores. Frailty was independently associated with higher total symptom score and lower HRQOL scores. Frailty was also independently associated with higher odds of frequently experiencing 9 out of 12 reported symptoms. Finally, frail participants experienced an additional symptom cluster that included loss of appetite, tiredness, feeling cold and poor concentration. CONCLUSIONS: Frailty is independently associated with high symptom-burden and poor HRQOL in CKD. Moreover, people living with frailty and CKD have a distinctive symptom experience. Proactive interventions are needed that can effectively identify and address problematic symptoms to mitigate their impact on HRQOL.

Pooled analysis of two randomized, double-blind trials comparing proposed biosimilar LA-EP2006 with reference pegfilgrastim in breast cancer.

BACKGROUND: Following the functional and physicochemical characterization of a proposed biosimilar, comparative clinical studies help to confirm biosimilarity by demonstrating similar safety and efficacy to the reference product in a sensitive patient population. PATIENTS AND METHODS: LA-EP2006 is a proposed biosimilar that has been developed for pegfilgrastim, a long-acting form of granulocyte colony-stimulating factor for the prevention of neutropenia. The current analysis reports data pooled from two independent, multinational, prospective, randomized, controlled, double-blind phase III studies of similar design comparing the safety and efficacy of reference pegfilgrastim with LA-EP2006 in patients with breast cancer receiving myelotoxic (neo)adjuvant TAC (docetaxel, doxorubicin, and cyclophosphamide) chemotherapy and requiring granulocyte colony-stimulating factor. RESULTS: A total of 624 patients were randomized in the PROTECT-1 and PROTECT-2 studies (NCT01735175; NCT01516736) (LA-EP2006: n = 314; reference: n = 310). Baseline characteristics of patients were well balanced across treatment groups. The primary end point, mean duration of severe neutropenia in the first chemotherapy cycle was similar in both the LA-EP2006 and reference groups (1.05 ± 1.055 days versus 1.01 ± 0.958 days), with a treatment difference of - 0.04 days [95% confidence interval (CI): -0.19 to 0.11] that met the equivalence criteria (the 95% CI were within the defined margin of ±1 day). Secondary end points, such as the nadir of absolute neutrophil count and the incidence of febrile neutropenia, were also similar between LA-EP2006 and reference pegfilgrastim. The safety and tolerability profile of LA-EP2006 was similar to that observed with reference pegfilgrastim, and there were no reports of neutralizing antibodies. CONCLUSIONS: This pooled analysis confirms, as a part of totality of evidence approach, that the proposed biosimilar pegfilgrastim LA-EP2006 has a comparable efficacy and safety profile to reference pegfilgrastim in patients with breast cancer receiving TAC chemotherapy. CLINICAL TRIAL NUMBERS: NCT01735175 and NCT01516736.

Lubricin/proteoglycan 4 increases in both experimental and naturally occurring equine osteoarthritis.

OBJECTIVE: The goals of this study were (1) to quantify proteoglycan 4 (PRG4) gene expression; (2) to assess lubricin immunostaining; and (3) to measure synovial fluid lubricin concentrations in clinical and experimental models of equine carpal osteoarthritis (OA). DESIGN: Lubricin synovial fluid concentrations and cartilage and synovial membrane PRG4 expression were analyzed in research horses undergoing experimental OA induction (n = 8) and in equine clinical patients with carpal OA (n = 58). Lubricin concentrations were measured using a custom sandwich enzyme-linked immunosorbent assay, and PRG4 expression was quantified using qRT-PCR. Lubricin immunostaining was assessed in synovial membrane and osteochondral sections in the experimental model. RESULTS: Lubricin concentrations increased in synovial fluid following induction of OA, peaking at 21 days post-operatively in OA joints vs sham-operated controls (331 ± 69 µg/mL vs 110 ± 19 µg/mL, P = 0.001). Lubricin concentrations also increased in horses with naturally occurring OA as compared to control joints (152 ± 32 µg/mL vs 68 ± 4 µg/mL, P = 0.003). Synovial membrane PRG4 expression increased nearly 2-fold in naturally occurring OA (P = 0.003), whereas cartilage PRG4 expression decreased 2.5-fold (P = 0.025). Lubricin immunostaining was more pronounced in synovial membrane from OA joints as compared to controls, with intense lubricin localization to sites of cartilage damage. CONCLUSIONS: Although PRG4 gene expression decreases in OA cartilage, synovial membrane PRG4 expression, synovial fluid lubricin concentrations and lubricin immunostaining all increase in an equine OA model. Lubricin may be elevated to protect joints from post-traumatic OA.

A radiologic and anatomic assessment of injectate spread following transmuscular quadratus lumborum block in cadavers.

We performed bilateral transmuscular quadratus lumborum blocks in six cadavers using iodinated contrast and methylene blue. Computed tomography imaging was performed in four cadavers and anatomical dissection was completed in five. This demonstrated spread to the lumbar paravertebral space in 63% of specimens, laterally to the transversus abdominis muscle in 50% and caudally to the anterior superior iliac spine in 63% of specimens. There was no radiographic evidence of spread to the thoracic paravertebral space. Anatomical dissection revealed dye staining of the upper branches of the lumbar plexus and the psoas major muscle in 70% of specimens. Further clinical studies are required to confirm if the quadratus lumborum block might be a suitable alternative to lumbar plexus block.

Efficacy of the nanoparticle-drug conjugate CRLX101 in combination with bevacizumab in metastatic renal cell carcinoma: results of an investigator-initiated phase I-IIa clinical trial.

BACKGROUND: Anti-angiogenic therapies are effective in metastatic renal cell carcinoma (mRCC), but resistance is inevitable. A dual-inhibition strategy focused on hypoxia-inducible factor (HIF) is hypothesized to be active in this refractory setting. CRLX101 is an investigational camptothecin-containing nanoparticle-drug conjugate (NDC), which durably inhibits HIF1α and HIF2α in preclinical models and in gastric cancer patients. Synergy was observed in the preclinical setting when combining this NDC and anti-angiogenic agents, including bevacizumab. PATIENTS AND METHODS: Patients with refractory mRCC were treated every 2 weeks with bevacizumab (10 mg/kg) and escalating doses of CRLX101 (12, 15 mg/m(2)) in a 3 + 3 phase I design. An expansion cohort of 10 patients was treated at the recommended phase II dose (RP2D). Patients were treated until progressive disease or prohibitive toxicity. Adverse events (AEs) were assessed using CTCAE v4.0 and clinical outcome using RECIST v1.1. RESULTS: Twenty-two patients were response-evaluable in an investigator-initiated trial at two academic medical centers. RCC histologies included clear cell (n = 12), papillary (n = 5), chromophobe (n = 2), and unclassified (n = 3). Patients received a median of two prior therapies, with at least one prior vascular endothelial tyrosine kinase inhibitor therapy (VEGF-TKI). No dose-limiting toxicities were observed. Grade ≥3 AEs related to CRLX101 included non-infectious cystitis (5 events), fatigue (3 events), anemia (2 events), diarrhea (2 events), dizziness (2 events), and 7 other individual events. Five of 22 patients (23%) achieved partial responses, including 3 of 12 patients with clear cell histology and 2 of 10 patients (20%) with non-clear cell histology. Twelve of 22 patients (55%) achieved progression-free survival (PFS) of >4 months. CONCLUSIONS: CRLX101 combined with bevacizumab is safe in mRCC. This combination fulfilled the protocol's predefined threshold for further examination with responses and prolonged PFS in a heavily pretreated population. A randomized phase II clinical trial in mRCC of this combination is ongoing.

DISEÑO DE UNA PLATAFORMA INTEROPERABLE PARA UN OBSERVATORIO DE HÁBITOS Y ESTILOS DE VIDA SALUDABLE / DESIGN OF A INTEROPERABLE OBSERVATORY PLATFORM FOR HABITS ANDHEALTHY LIFESTYLES / CONCEPÇÃO DE UMA PLATAFORMA INTEROPERÁVEL PARA UM OBSERVATÓRIO HÁBITOS E ESTILOS DE VIDA SAUDÁVEIS

Esta investigación muestra el diseño de una plataforma interoperable que hace uso del estándar HL7 (Health Level Seven) y permite el registro y análisis de datos relacionados con estilos de vida saludable y prácticas de actividad física en adultos y adultos mayores de las zonas rurales de Colombia. El proyecto se centra en la utilización de las TIC para generar un sistema interoperable que permita la consolidación de los datos, con el fin de facilitar cifras epidemiológicas, hacer diagnósticos que permitan generar estrategias de promoción de la salud y prevención de la enfermedad en las que se promueva la actividad física; y consolidar un marco de referencia para las entidades interesadas. Esta plataforma provee un servicio de integración que puede ser utilizado por entidades externas, compartiendo así información relacionada con hábitos y estilos de vida saludables. Dicha plataforma, utiliza tecnología web ASP.net, con un modelo arquitectural MVC (Modelo Vista Controlador), lenguaje C#, un motor de base de datos SQLServer y servicios web a nivel de integración que usa HL7 como estándar de intercambio de mensajes. Se generó una prueba de control realizada en el año 2014, en ocho municipios del departamento de Cundinamarca en los cuales se aplicaron 304 instrumentos, con los cuales se alimentó la plataforma.

This research shows the design of an interoperable platform that uses the HL7 standard (Health Level Seven) and allows the record and analysis of data related to healthy lifestyles and practices of physical activity in adults and older adults in rural areas of Colombia. The project focuses on the use of ICT to generate an interoperable system that allows the consolidation of data, in order to facilitate epidemiological records, make diagnoses that generate strategies for health promotion and disease prevention in which promote physical activity; and build a framework for stakeholders. This platform provides an integration service that can be used by external entities, to reporting information related to habits and healthy lifestyles. This platform uses web ASP.net technology with architectural model MVC (Model View Controller), C # language, a database SQLServer motor and web services to integration with HL7 standard for the exchange of information. Was performed a control test in to 2014, in eight municipalities of the department of Cundinamarca in which 304 instruments were applied to upload to the platform.

Esta pesquisa mostra o desenho de uma plataforma interoperável que usa o HL7 (Health Level Seven) padrão e permite a gravação e análise de dados relacionados com os estilos de vida saudáveis e prática de atividade física em adultos e idosos nas zonas rurais da Colômbia. O projecto centra-se na utilização das TIC para gerar um sistema de interoperabilidade que permite a consolidação de dados, a fim de facilitar números epidemiológicos, fazer diagnósticos que podem gerar estratégias para promover a saúde e prevenção de doença em que promoção da atividade física; e construir uma estrutura para as partes interessadas. Esta plataforma fornece um serviço de integração que pode ser usado por entidades externas, a partilha de informações relacionadas a hábitos e estilos de vida saudáveis. Esta plataforma, utilizando a tecnologia web ASP.net com um padrão de arquitetura MVC (Model View Controller), a linguagem C#, banco de dados SQLServer do motor e nível de integração de serviços web usando a troca de mensagens HL7 padrão. Um teste de controle realizado em 2014, em oito municípios de Cundinamarca em que foram aplicados 304 instrumentos, com os quais a plataforma foi alimentado foi gerado.

A chondrocyte infiltrated collagen type I/III membrane (MACI® implant) improves cartilage healing in the equine patellofemoral joint model.

UNLABELLED: Autologous chondrocyte implantation (ACI) has improved outcome in long-term studies of joint repair in man. However, ACI requires sutured periosteal flaps to secure the cells, which precludes minimally-invasive implantation, and introduces complications with arthrofibrosis and graft hypertrophy. This study evaluated ACI on a collagen type I/III scaffold (matrix-induced autologous chondrocyte implantation; MACI(®)) in critical sized defects in the equine model. METHODS: Chondrocytes were isolated from horses, expanded and seeded onto a collagen I/III membrane (ACI-Maix™) and implanted into one of two 15-mm defects in the femoral trochlear ridge of six horses. Control defects remained empty as ungrafted debrided defects. The animals were examined daily, scored by second look arthroscopy at 12 weeks, and necropsy examination 6 months after implantation. Reaction to the implant was determined by lameness, and synovial fluid constituents and synovial membrane histology. Cartilage healing was assessed by arthroscopic scores, gross assessment, repair tissue histology and immunohistochemistry, cartilage glycosaminoglycan (GAG) and DNA assay, and mechanical testing. RESULTS: MACI(®) implanted defects had improved arthroscopic second-look, gross healing, and composite histologic scores, compared to spontaneously healing empty defects. Cartilage GAG and DNA content in the defects repaired by MACI implant were significantly improved compared to controls. Mechanical properties were improved but remained inferior to normal cartilage. There was minimal evidence of reaction to the implant in the synovial fluid, synovial membrane, subchondral bone, or cartilage. CONCLUSIONS: The MACI(®) implant appeared to improve cartilage healing in a critical sized defect in the equine model evaluated over 6 months.

Osteoporosis Assessment Questionnaire-Physical Function (OPAQ-PF): a psychometrically validated osteoporosis-targeted patient reported outcome measure of daily activities of physical function.

UNLABELLED: The purpose of this study was to evaluate the measurement properties of the Osteoporosis Assessment Questionnaire-Physical Functioning (OPAQ-PF). Based on this study, the OPAQ-PF has confirmed unidimensionality and acceptable reliability, construct validity, and sensitivity to change in a recent fracture/no recent fracture osteoporosis sample. METHODS: Dimensionality was established through exploratory and confirmatory factor analysis. Patients completed three patient reported outcome (PRO) measures and four performance-based measures (PBMs) at baseline to enable an evaluation of construct validity. Patients without a recent fracture completed the OPAQ-PF 2 weeks after baseline to enable an evaluation of test-retest reliability. Ability to detect change and interpretation of change were investigated following completion of the OPAQ-PF 12 and 24 weeks postbaseline by patients with a recent fracture. RESULTS: A prospective psychometric validation study in 144 postmenopausal women, with moderate to severe osteoporosis, 37 of whom had experienced a recent fragility fracture (<6 weeks). Unidimensionality was established for the OPAQ-PF by factor analysis. The OPAQ-PF had good internal consistency (α = 0.974) and test-retest reliability (mean intraclass correlation coefficient (ICC) 0.993. The OPAQ-PF differentiated between patients with/without recent fracture, and by severity of osteoarthritis; it correlated strongly with hypothesized-related scales and PBMs (r > 0.3, p < 0.001). Ability to detect change was established with high correlations between changes in OPAQ-PF score and changes in global concept scores in recent fracture patients (r ≥ 0.6, 24-week change). Effect size of change on OPAQ-PF score increased by level of global change (p < 0.001). Anchor-based methods identified an OPAQ-PF change of 10 at an individual patient level and 20 at a group level as meaningful to patients. CONCLUSIONS: The OPAQ-PF has confirmed unidimensionality and acceptable reliability, construct validity, and sensitivity to change in a recent fracture/no recent fracture osteoporosis sample.

Antibody-directed coupling of endoglin and MMP-14 is a key mechanism for endoglin shedding and deregulation of TGF-ß signaling.

Endoglin is a transforming growth factor ß (TGF-ß) coreceptor that serves as a prognostic, diagnostic and therapeutic vascular target in human cancer. A number of endoglin ectodomain-targeting antibodies (Abs) can effectively suppress both normal and tumor-associated angiogenesis, but their molecular actions remain poorly characterized. Here we define a key mechanism for TRACON105 (TRC105), a humanized monoclonal Ab in clinical trials for treatment of advanced or metastatic tumors. TRC105, along with several other endoglin Abs tested, enhance endoglin shedding through direct coupling of endoglin and the membrane-type 1 matrix metalloproteinase (MMP)-14 at the cell surface to release the antiangiogenic factor, soluble endoglin (sEng). In addition to this coupling process, endoglin shedding is further amplified by increased MMP-14 expression that requires TRC105 concentration-dependent c-Jun N-terminal kinase (JNK) activation. There were also notable counterbalancing effects on canonical Smad signaling in which TRC105 abrogated both the steady-state and TGF-ß-induced Smad1/5/8 activation while augmenting Smad2/3 activation. Interestingly, TRC105-induced sEng and aberrant Smad signaling resulted in an excessive migratory response through enhanced stress fiber formation and disruption of endothelial cell-cell junctions. Collectively, our study defines endoglin shedding and deregulated TGF-ß signaling during migration as major mechanisms by which TRC105 inhibits angiogenesis.

Patient-reported fatigue and its impact on patients with systemic lupus erythematosus.

Fatigue is a hallmark symptom of systemic lupus erythematosus (SLE), often associated with flares, side effects of treatment, and extensive organ damage and may have a significant impact on health-related quality of life (HrQoL). To date, the experience of fatigue in patients with SLE is underexplored. This study explored the experience of fatigue in patients with SLE and its impact on their lives through qualitative interviews. This cross-sectional qualitative study was conducted with 22 adult patients with SLE, recruited from two clinical sites in the United States. In-person semi-structured interviews were conducted and thematic analysis was performed focusing on the experience of fatigue in SLE. Results indicated that 21 out of 22 patients experienced fatigue due to SLE. Patients reported that fatigue was variable in nature in terms of both severity and frequency. Fatigue was described as having an impact on multiple aspects of a patient's life: emotions, cognition, work, activities of daily living, leisure activities, social activities, and family activities. Understanding how patients with SLE describe the symptom of fatigue and how it impacts their lives is the key to better understanding how to measure fatigue in clinical studies evaluating new treatments for SLE.

Dynamic compression plate (DCP) fixation of propagating medial condylar fractures of the third metacarpal/metatarsal bone in 30 racehorses: retrospective analysis (1990-2005).

REASONS FOR PERFORMING STUDY: An in-depth review of dynamic compression plate (DCP) fixation of propagating medial condyle fractures of the third metacarpus or metatarsus has not been previously reported. OBJECTIVES: To describe the technique, evaluate short-term outcome and long-term race performance of racehorses that underwent DCP fixation for repair of propagating or spiralling medial condylar fractures of the third metacarpal (McIII) or metatarsal (MtIII) bone. STUDY DESIGN: Retrospective case series. METHODS: The surgical case records of 30 horses with propagating fractures of the medial condyle of McIII or MtIII were reviewed. Medical information included: age, breed, sex, presentation, how injury occurred (racing or training), surgical treatment and post operative complications. Racing information included: starts, top 3 placing and career earnings. RESULTS: Long propagating fractures of the medial condyle of Mc/tIII were identified in 23 Thoroughbred (TB) and 7 Standardbred (STB) racehorses. The fracture spiralled proximally in 22 of 30 cases (73%). Standardbreds had a higher propensity for hindlimb involvement (71%), whereas TBs tended to have more front limb involvement (61%). Twelve of 30 (40%) horses raced post surgery. Career earnings were significantly lower for TB horses with medial condylar fractures; $34,916 when compared with the national average of $60,841 (P≤0.03). Overall, horses having DCP fixation for medial condylar fractures had less starts post surgery (3.1 TBs and 5.8 STBs) compared with the national average (7 TBs and 17.3 STBs) and decreased lifetime starts 13.4 (TBs) compared with 17.3 nationally. CONCLUSIONS: Propagating medial condyle fractures can be repaired with plate fixation to potentially lessen the risk of catastrophic fracture destabilisation and return to racing can be expected in 40% of horses. Further prospective studies are warranted comparing lag screw fixation with DCP fixation for repair of severe medial condylar fractures of the metacarpus/metatarsus.

Development of the Osteoporosis Assessment Questionnaire--physical Function (OPAQ-PF): an osteoporosis-targeted, patient-reported outcomes (PRO) measure of physical function.

UNLABELLED: We have developed a short, patient-reported outcome questionnaire--the Osteoporosis Assessment Questionnaire--Physical Function (OPAQ-PF)--that assesses the impact of osteoporosis on physical function. OPAQ-PF contains 15 items in three domains (mobility, physical positions, and transfers) and has content validity in osteoporosis patients with and without a history of fracture. INTRODUCTION: This paper describes the development of the Osteoporosis Assessment Questionnaire--Physical Function (OPAQ-PF), a patient-reported outcome (PRO) questionnaire based on OPAQ v.2.0 (60 items, 14 domains) that assesses the impact of osteoporosis on physical function. METHODS: OPAQ v.2.0 was administered to patients with osteoporosis. Item response theory methodology and clinical judgment were used to retain/eliminate items. The resulting instrument was modified during two sets of concept elicitation and cognitive debriefing interviews with osteoporosis patients. RESULTS: Item response theory-based analysis of OPAQ v.2.0 (n = 1,478) coupled with clinician input resulted in the generation of a 21-item, six-domain instrument with a frequency response format. Interview data from 32 participants were used to modify this version and led to generation of the final instrument, OPAQ-PF. This final version has a severity response format and contains 15 items in three domains (mobility, physical positions, and transfers) that group together to provide an overall assessment of physical function in patients with osteoporosis. Twenty-two of the 32 interview participants (69 %) had previously sustained a fracture. Symptoms occurred primarily in these patients. CONCLUSIONS: OPAQ-PF represents a brief, focused, PRO instrument that assesses physical function in patients with osteoporosis, specifically related to mobility, physical positions, and transfers. This questionnaire has content validity in osteoporosis patients who have, and have not, sustained a prior fracture.

Review of health-related quality of life data in multiple myeloma patients treated with novel agents.

In multiple myeloma (MM), health-related quality of life (HRQoL) data is becoming increasingly important, owing to improved survival outcomes and the impact of treatment-related toxicity on HRQoL. Researchers are more frequently including HRQoL assessments in clinical trials, but analysis and reporting of this data has not been consistent. A systematic literature review assessed the effect of novel agents (thalidomide, bortezomib and lenalidomide) on HRQoL in MM patients, and evaluated the subsequent reporting of these HRQoL results. A relatively small body of literature addresses HRQoL data in MM patients treated with novel MM therapeutic agents: 9 manuscripts and 15 conference proceedings. The literature demonstrates the complementary value of HRQoL when assessing clinical response, progression, overall survival and toxicity. However, weaknesses and inconsistencies in analysis and presentation of HRQoL data were observed, often complicating interpretation of the impact of treatment on HRQoL in MM. Further evaluation of HRQoL in MM patients treated with novel agents is required in larger cohorts, and ideally in head-to-head comparative studies. Additionally, the development of standardised MM-specific best practice guidelines in HRQoL data collection and analysis is recommended. These would ensure that future data are more useful in guiding predictive models and clinical decisions.

Development of a conceptual model of health-related quality of life for systemic lupus erythematosus from the patient's perspective.

AIMS: The aim of this study was to evaluate the impact of systemic lupus erythematosus (SLE) on the lives of patients in order to inform the development of a conceptual model. METHODS: Twenty-two participants with SLE (defined as meeting four of the 11 ACR criteria) were recruited for this study. Semi-structured, in-person interviews were conducted with each participant, exploring the symptoms experienced and the impact on the patient's life. Thematic analysis of interview transcripts was conducted in ATLAS.ti software to identify areas of impact and explore the interrelationships between concepts to inform the development of a conceptual model. RESULTS: Almost all participants were female (95%); the sample was diverse in terms of age (mean age of 45.5 years; age range of 20-60 years), ethnicity (59% black/African American) and disease duration. Commonly reported symptoms were pain, fatigue/tiredness and skin problems. Qualitative analysis revealed seven themes relating to the impact of SLE symptoms on patient's Health Related Quality of Life (HRQL): emotions, social, family and leisure activities, daily activities, cognition, appearance, employment activities and independence. The interrelationships between symptoms, impacts and symptom triggers are illustrated in a conceptual model. CONCLUSIONS: The conceptual model illustrates the wide-reaching impact of SLE symptoms on a patient's HRQL, and the potential broad impact of a treatment that improves SLE symptoms.

A collagenase gel/physical defect model for controlled induction of superficial digital flexor tendonitis.

REASONS FOR PERFORMING STUDY: A consistent and clinically relevant model for the induction of core lesions confined to the mid-metacarpal superficial digital flexor tendon (SDFT) has not been previously reported. Injection of bacterial collagenase is commonly used but often results in large, irregular and inconsistent lesions that disrupt the superficial tendon layers and epitenon. OBJECTIVE: To develop and evaluate a new injection technique for collagenase induction of SDFT injury. METHODS: Collagenase gel was injected into a physical columnar defect created by longitudinally placing a curved 16 gauge 8.89 cm needle in the mid-metacarpal SDFT in a randomly selected forelimb of 10 horses. A placebo treatment injection was performed 1 week later. Serial ultrasound examinations were performed. Horses were subjected to euthanasia at 2 (n = 2), 4 (n = 2), 8 (n = 4) and 16 (n = 2) weeks post treatment injection. Post mortem magnetic resonance imaging and histological analysis were performed. Gene expression (18S, SCX, TNC, TNMD, COL1A1, COL3A1, COMP, DCN, MMP1, MMP3 and MMP13), total DNA, glycosaminoglycan and collagen content were determined for experimental tendons (n = 10) and unaffected tendons (n = 9). RESULTS: Mid-metacarpal SDFT core lesion induction was successful in all tendons with consistent lesion cross-sectional area and minimal epitenon disruption. Histology confirmed loss of normal tendon architecture after tendonitis induction and subsequent healing of the tendon core lesion. Compared with gene expression in unaffected tendons, several tested genes were significantly upregulated (COL1A1, COL3A1, TNMD, SCX, TNC, MMP13), while others showed significant downregulation (COMP, DCN, and MMP3). CONCLUSION: Compared with the previously used direct injection of collagenase, this injection technique was easily performed and induced more consistent lesions that were mid-metacarpal and did not disrupt the epitenon. POTENTIAL RELEVANCE: This model will allow for objective assessment of therapies for tendon regeneration in the mid-metacarpal SDFT prior to clinical trials and routine clinical application.

Treatment of subchondral cystic lesions of the medial femoral condyle of mature horses with growth factor enhanced chondrocyte grafts: a retrospective study of 49 cases.

REASONS FOR PERFORMING STUDY: To evaluate the long-term clinical outcome after allogeneic chondrocyte and insulin-like growth factor-I (IGF-I) grafting of subchondral cystic lesions (SCLs) of the femoral condyle in horses. OBJECTIVE: To test the hypothesis that chondrocyte and IGF-I grafts will improve the long-term clinical outcome in arthroscopically debrided SCLs. METHODS: Medical records of 49 horses with SCLs of the femoral condyle treated by debridement and implantation of chondrocytes and IGF-I were reviewed. Preoperative radiographs were obtained, and caudocranial radiographic projections were used to establish a ratio between cyst and femoral condyle size. Arthroscopic cyst debridement followed by filling of the bone void with autologous cancellous bone (45 horses) or tricalcium phosphate granules (4 horses) was performed. A paired syringe containing a fibrinogen and chondrocyte mixture in one syringe and calcium-activated bovine thrombin with IGF-I in the other was used to cover the surface. A successful outcome was defined as a horse that performed to its intended use without lameness. RESULTS: A successful outcome was achieved in 36 of 49 horses (74%). Preoperative radiography was performed in all horses, with 33 horses having unilateral SCLs of the medial femoral condyle, 15 horses having bilateral SCLs of the medial femoral condyle, and one horse having bilateral SCLs of the lateral femoral condyle. Median age of the horses was 3.3 years. Fifteen horses had preoperative radiographic and arthroscopic evidence of osteoarthritis (OA). A successful outcome was not influenced by age of horse, presence of pre-existing osteoarthritis or preoperative size of the subchondral cyst. Grafting resulted in success for 80% of horses >3 years old, and in 80% of horses with OA. CONCLUSIONS: Implantation of allogeneic chondrocytes supplemented with IGF-I is an effective treatment for horses with SCLs of the femoral condyle, and particularly for older horses and horses with pre-existing osteoarthritis. POTENTIAL RELEVANCE: Chondrocyte implantation may offer a greater chance of long-term success in older horses and horses with osteoarthritis than has been previously reported with cyst debridement alone.