Subject Retention in Prehospital Stroke Research Using a Telephone-Based Physician-Investigator Driven Enrollment Method.

Background and purposeSubject retention into clinical trials is vital, and prehospital enrollment may be associated with higher rates of subject withdrawal than more traditional methods of enrollment. We describe rates of subject retention in a prehospital trial of acute stroke therapy.MethodsAll subjects were enrolled into the NIH Field Administration of Stroke Therapy-Magnesium (FAST-MAG) phase 3 clinical trial. Paramedics screened eligible subjects and contacted the physician-investigator using a dedicated in-ambulance cellular phone. Physician-investigators obtained explicit informed consent from the subject or on-scene legally authorized representative (LAR) who reviewed and signed a consent form. Exception from informed consent (EFIC) was utilized in later stages of the study.ResultsThere were 1,700 subjects enrolled; 1,017 provided consent (60%), 662 were enrolled via LAR (39%), and 21 were enrolled via EFIC (1%). Of the 1,700 patients, 1,413 (83%) completed the 90-day visit, 265 (16%) died prior to the 90-day visit, and 22 (1.3%) withdrew from the study before completion. There were no differences in rates of withdrawal by method of study enrolment, i.e., self-consent (n = 14), 1.4%; LAR (n = 8), 1.2%; EFIC (n = 0) 0%.ConclusionThere was a high rate of retention when subjects were enrolled into prehospital stroke research using a phone-based method to obtain explicit consent

Imaging Biomarker Validation and Qualification Report: 6th OARSI Workshop on Imaging in Osteoarthritis Combined with 3rd OA Biomarkers Workshop.

Summary The sixth Osteoarthritis Research Society International (OARSI) Workshop on Imaging in Osteoarthritis combined with the third osteoarthritis (OA) Biomarkers Workshop is the first to bring together the imaging and molecular biomarker communities to focus on clinical validation and qualification of OA biomarkers. The workshop was held in Hilton Head, SC, USA, from June 12–14, 2012; 138 attendees participated, including representatives from academia, pharmaceutical and magnetic resonance imaging (MRI) industries, Food and Drug Administration (FDA), and National Institutes of Health (NIH). Presentations and discussions raised awareness, consolidated knowledge, and identified strategies to overcome challenges for the development and application of imaging and biochemical biomarkers in OA research studies and clinical trials. Conclusion The OA research communities need to work alongside regulatory agencies across the world, to qualify and validate new chemical and imaging biomarkers for future research and clinical trials

Imaging of Osteoarthritis

Osteoarthritis (OA) is the most prevalent joint disorder in the elderly, and there is no effective treatment. Imaging is essential for evaluating the synovial joint structures (including cartilage, meniscus, subchondral bone marrow and synovium) for diagnosis, prognosis, and follow-up. This article describes the roles and limitations of both conventional radiography and magnetic resonance (MR) imaging, and considers the use of other modalities (eg, ultrasonography, nuclear medicine, computed tomography [CT], and CT/MR arthrography) in clinical practice and OA research. The emphasis throughout is on OA of the knee. This article emphasizes research developments and literature evidence published since 2008

In-situ strain tuning of the Dirac surface states in Bi2Se3 films

Elastic strain has the potential for a controlled manipulation of the band gap and spin-polarized Dirac states of topological materials, which can lead to pseudo-magnetic-field effects, helical flat bands and topological phase transitions. However, practical realization of these exotic phenomena is challenging and yet to be achieved. Here, we show that the Dirac surface states of the topological insulator Bi2Se3 can be reversibly tuned by an externally applied elastic strain. Performing in-situ x-ray diffraction and in-situ angle-resolved photoemission spectroscopy measurements during tensile testing of epitaxial Bi2Se3 films bonded onto a flexible substrate, we demonstrate elastic strains of up to 2.1% and quantify the resulting reversible changes in the topological surface state. Our study establishes the functional relationship between the lattice and electronic structures of Bi2Se3 and, more generally, demonstrates a new route toward momentum-resolved mapping of strain-induced band structure changes

Side Differences of Thigh Muscle Cross-Sectional Areas and Maximal Isometric Muscle Force in Bilateral Knees with the Same Radiographic Disease Stage, but Unilateral Frequent Pain – Data from the Osteoarthritis Initiative

Objective To determine whether anatomical thigh muscle cross-sectional areas (MCSAs) and strength differ between osteoarthritis (OA) knees with frequent pain compared with contra-lateral knees without pain, and to examine the correlation between MCSAs and strength in painful vs painless knees. Methods Forty-eight subjects (31 women; 17 men; age 45–78 years) were drawn from 4,796 Osteoarthritis Initiative (OAI) participants, in whom both knees displayed the same radiographic stage (KLG2 or 3), one with frequent pain (most days of the month within the past 12 months) and the contra-lateral one without pain. Axial MR images were used to determine MCSAs of extensors, flexors and adductors at 35% femoral length (distal to proximal) and in two adjacent 5 mm images. Maximal isometric extensor and flexor forces were used as provided from the OAI database. Results Painful knees showed 5.2% lower extensor MCSAs (P = 0.00003; paired t-test), and 7.8% lower maximal extensor muscle forces (P = 0.003) than contra-lateral painless knees. There were no significant differences in flexor forces, or flexor and adductor MCSAs (P > 0.39). Correlations between force and MCSAs were similar in painful and painless OA knees (0.44 < r < 0.66). Conclusions Knees with frequent pain demonstrate lower MCSAs and force of the quadriceps (but not of other thigh muscles) compared with contra-lateral knees without knee pain with the same radiographic stage. Frequent pain does not appear to affect the correlations between MCSAs and strength in OA knees. The findings suggest that quadriceps strengthening exercise may be useful in treating symptomatic knee OA

Moderate physical activity may prevent cartilage loss in women with knee osteoarthritis : data from the Osteoarthritis Initiative

All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/coi_disclosure.pdf and declare: data acquisition in this study was funded by the Osteoarthritis Initiative, a public–private partnership comprised of five contracts (N01-AR-2-2258; N01-AR-2-2259;N01-AR-2-2260; N01-AR-2-2261; N01-AR-2-2262) funded by the National Institutes of Health, a branch of the Department of Health and Human Services, and conducted by the Osteoarthritis Initiative study Investigators. Private funding partners of the OAI include Merck Research Laboratories, Novartis Pharmaceuticals Corporation, GlaxoSmithKline, and Pfizer, Inc. Private sector funding for the Osteoarthritis Initiative is managed by the Foundation for the National Institutes of Health. The image analysis in this study was partly funded by the FNIH OA Biomarkers Consortium, with grants, direct and in -kind contributions, provided by: AbbVie; Amgen Inc.; Arthritis Foundation; Bioiberica S.A.; DePuy Mitek, Inc.; Flexion Therapeutics, Inc.; GlaxoSmithKline; Merck KGaA; Rottapharm | Madaus; Sanofi; and Stryker. Other parts of funding were provided by a direct grant from Merck KGaA, by a contract with the University of Pittsburgh (Pivotal OAI MRI Analyses [POMA]: NIH/NHLBI Contract No. HHSN2682010000 21C), by a vendor contract from the OAI coordinating center at University of California, San Francisco (N01-AR-2-2258), and by an ancillary study to the OAI held by the Division of Rheumatology, Feinberg School of Medicine, Northwestern University (R01 AR52918). This research has also received funding from the European Union Seventh Framework Programme (FP7-PEOPLE-2013-ITN; KNEEMO) under grant agreement number 607510. AGC is supported by a National Health and Medical Research Council (NHMRC) of Australia Early Career Fellowship (Neil Hamilton Fairley Clinical Fellowship No.1121173). The sponsors were not involved in the design and conduct of this particular study, in the analysis and interpretation of the data, and in the preparation, review, or approval of the manuscript.Peer reviewedPostprin

Tibial coverage, meniscus position, size and damage in knees discordant for joint space narrowing - data from the Osteoarthritis Initiative.

INTRODUCTION: Meniscal extrusion is thought to be associated with less meniscus coverage of the tibial surface, but the association of radiographic disease stage with quantitative measures of tibial plateau coverage is unknown. We therefore compared quantitative and semi-quantitative measures of meniscus position and morphology in individuals with bilateral painful knees discordant on medial joint space narrowing (mJSN). METHODS: A sample of 60 participants from the first half (2,678 cases) of the Osteoarthritis Initiative cohort fulfilled the inclusion criteria: bilateral frequent pain, Osteoarthritis Research Society International (OARSI) mJSN grades 1-3 in one, no-JSN in the contra-lateral (CL), and no lateral JSN in either knee (43 unilateral mJSN1; 17 mJSN2/3; 22 men, 38 women, body mass index (BMI) 31.3 + 3.9 kg/m(2)). Segmentation and three-dimensional quantitative analysis of the tibial plateau and meniscus, and semi-quantitative evaluation of meniscus damage (magnetic resonance imaging (MRI) osteoarthritis knee score = MOAKS) was performed using coronal 3T MR images (MPR DESSwe and intermediate-weighted turbo spin echo (IW-TSE) images). CL knees were compared using paired t-tests (between-knee, within-person design). RESULTS: Medial tibial plateau coverage was 36 + 9% in mJSN1 vs 45 + 8% in CL no-JSN knees, and was 31 + 9% in mJSN2/3 vs 46 + 6% in no-JSN knees (both P < 0.001). mJSN knees showed greater meniscus extrusion and damage (MOAKS), but no significant difference in meniscus volume. No significant differences in lateral tibial coverage, lateral meniscus morphology or position were observed. CONCLUSIONS: Knees with medial JSN showed substantially less medial tibial plateau coverage by the meniscus. We suggest that the less meniscal coverage, i.e., less mechanical protection may be a reason for greater rates of cartilage loss observed in JSN knees. Copyright 2012 Osteoarthritis Research Society International. All rights reserved

Impact of Diet and/or Exercise Intervention on Infrapatellar Fat Pad Morphology: Secondary Analysis from the Intensive Diet and Exercise for Arthritis (IDEA) Trial

The infrapatellar fat pad (IPFP) represents intra-articular adipose tissue that may contribute to intra-articular inflammation and pain by secretion of pro-inflammatory cytokines. Here we examined the impact of weight loss by diet and/or exercise interventions on IPFP volume

EFFECTS OF INTENSIVE DIET AND EXERCISE ON KNEE JOINT LOADS, INFLAMMATION, AND CLINICAL OUTCOMES AMONG OVERWEIGHT AND OBESE ADULTS WITH KNEE OSTEOARTHRITIS

Importance Knee osteoarthritis (OA), a common cause of chronic pain and disability, has biomechanical and inflammatory origins and is exacerbated by obesity. Objective To determine whether a ≥10% reduction in body weight induced by diet, with or without exercise, would improve mechanistic and clinical outcomes more than exercise alone. Design, Setting, and Participants Single-blind, 18-month, randomized clinical trial at Wake Forest University between July 2006 and April 2011. The diet and exercise interventions were center-based with options for the exercise groups to transition to a home-based program. Participants were 454 overweight and obese older community-dwelling adults (age ≥55 years with body mass index of 27-41) with pain and radiographic knee OA. Interventions Intensive diet-induced weight loss plus exercise, intensive diet-induced weight loss, or exercise. Main Outcomes and Measures Mechanistic primary outcomes: knee joint compressive force and plasma IL-6 levels; secondary clinical outcomes: self-reported pain (range, 0-20), function (range, 0-68), mobility, and health-related quality of life (range, 0-100). Results Three hundred ninety-nine participants (88%) completed the study. Mean weight loss for diet + exercise participants was 10.6 kg (11.4%); for the diet group, 8.9 kg (9.5%); and for the exercise group, 1.8 kg (2.0%). After 18 months, knee compressive forces were lower in diet participants (mean, 2487 N; 95% CI, 2393 to 2581) compared with exercise participants (2687 N; 95% CI, 2590 to 2784, pairwise difference [Δ]exercise vs diet = 200 N; 95% CI, 55 to 345; P = .007). Concentrations of IL-6 were lower in diet + exercise (2.7 pg/mL; 95% CI, 2.5 to 3.0) and diet participants (2.7 pg/mL; 95% CI, 2.4 to 3.0) compared with exercise participants (3.1 pg/mL; 95% CI, 2.9 to 3.4; Δexercise vs diet + exercise = 0.39 pg/mL; 95% CI, −0.03 to 0.81; P = .007; Δexercise vs diet = 0.43 pg/mL; 95% CI, 0.01 to 0.85, P = .006). The diet + exercise group had less pain (3.6; 95% CI, 3.2 to 4.1) and better function (14.1; 95% CI, 12.6 to 15.6) than both the diet group (4.8; 95% CI, 4.3 to 5.2) and exercise group (4.7; 95% CI, 4.2 to 5.1, Δexercise vs diet + exercise = 1.02; 95% CI, 0.33 to 1.71; Ppain = .004; 18.4; 95% CI, 16.9 to 19.9; Δexercise vs diet + exercise, 4.29; 95% CI, 2.07 to 6.50; Pfunction < .001). The diet + exercise group (44.7; 95% CI, 43.4 to 46.0) also had better physical health-related quality of life scores than the exercise group (41.9; 95% CI, 40.5 to 43.2; Δexercise vs diet + exercise = −2.81; 95% CI, −4.76 to −0.86; P = .005). Conclusions and Relevance Among overweight and obese adults with knee OA, after 18 months, participants in the diet + exercise and diet groups had more weight loss and greater reductions in IL-6 levels than those in the exercise group; those in the diet group had greater reductions in knee compressive force than those in the exercise group

Subchondral Bone Trabecular Integrity Predicts and Changes Concurrently with Radiographic and MRI Determined Knee Osteoarthritis Progression

OBJECTIVE: To evaluate subchondral bone trabecular integrity (BTI) on radiographs as a predictor of knee osteoarthritis (OA) progression. METHODS: Longitudinal (baseline, 12-month, and 24-month) knee radiographs were available for 60 female subjects with knee OA. OA progression was defined by 12- and 24-month changes in radiographic medial compartment minimal joint space width (JSW) and medial joint space area (JSA), and by medial tibial and femoral cartilage volume on magnetic resonance imaging. BTI of the medial tibial plateau was analyzed by fractal signature analysis using commercially available software. Receiver operating characteristic (ROC) curves for BTI were used to predict a 5% change in OA progression parameters. RESULTS: Individual terms (linear and quadratic) of baseline BTI of vertical trabeculae predicted knee OA progression based on 12- and 24-month changes in JSA (P < 0.01 for 24 months), 24-month change in tibial (P < 0.05), but not femoral, cartilage volume, and 24-month change in JSW (P = 0.05). ROC curves using both terms of baseline BTI predicted a 5% change in the following OA progression parameters over 24 months with high accuracy, as reflected by the area under the curve measures: JSW 81%, JSA 85%, tibial cartilage volume 75%, and femoral cartilage volume 85%. Change in BTI was also significantly associated (P < 0.05) with concurrent change in JSA over 12 and 24 months and with change in tibial cartilage volume over 24 months. CONCLUSION: BTI predicts structural OA progression as determined by radiographic and MRI outcomes. BTI may therefore be worthy of study as an outcome measure for OA studies and clinical trials. Copyright 2013 by the American College of Rheumatology