Level of participation in physical therapy or an internet-based exercise training program: associations with outcomes for patients with knee osteoarthritis.

BACKGROUND: To examine whether number of physical therapy (PT) visits or amount of use of an internet-based exercise training (IBET) program is associated with differential improvement in outcomes for participants with knee osteoarthritis (OA). METHODS: A secondary analysis was performed using data from participants in 2 arms of a randomized control trial for individuals with symptomatic knee OA: PT (N = 135) or IBET (N = 124). We examined associations of number of PT visits attended (up to 8) or number of days the IBET website was accessed during the initial 4-month study period with changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total, pain and function subscales, as well as a 2-min Step Test, at 4-month and 12-month follow-up. RESULTS: Participants with more PT visits experienced greater improvement in WOMAC total score (estimate per additional visit = - 1.18, CI 95% = - 1.91, 0.46, p <  0.001) and function subscore (estimate = - 0.80, CI 95% = - 1.33, - 0.28, p <  0.001) across follow-up periods. For WOMAC pain subscale, the association with number of PT visits varied significantly between 4- and 12-month follow-up, with a stronger relationship at 4-months. There was a non-significant trend for more PT visits to be associated with greater improvement in 2-min Step Test. More frequent use of the IBET website was not associated with greater improvement for any outcome, at either time point. CONCLUSION: Increased number of PT visits was associated with improved outcomes, and some of this benefit persisted 8 months after PT ended. This provides guidance for PT clinical practice and policies. TRIAL REGISTRATION: NCT02312713 , posted 9/25/2015.

Physical therapy vs. internet-based exercise training (PATH-IN) for patients with knee osteoarthritis: study protocol of a randomized controlled trial.

BACKGROUND: Physical activity improves pain and function among individuals with knee osteoarthritis (OA), but most people with this condition are inactive. Physical therapists play a key role in helping people with knee OA to increase appropriate physical activity. However, health care access issues, financial constraints, and other factors impede some patients from receiving physical therapy (PT) for knee OA. A need exists to develop and evaluate other methods to provide physical activity instruction and support to people with knee OA. This study is examining the effectiveness of an internet-based exercise training (IBET) program designed for knee OA, designed by physical therapists and other clinicians. METHODS/DESIGN: This is a randomized controlled trial of 350 participants with symptomatic knee OA, allocated to three groups: IBET, standard PT, and a wait list (WL) control group (in a 2:2:1 ratio, respectively). The study was funded by the Patient Centered Outcomes Research Institute, which conducted a peer review of the proposal. The IBET program provides patients with a tailored exercise program (based on functional level, symptoms, and current activity), video demonstrations of exercises, and guidance for appropriate exercise progression. The PT group receives up to 8 individual visits with a physical therapist, mirroring standard practice for knee OA and with an emphasis on a home exercise program. Outcomes are assessed at baseline, 4 months (primary time point) and 12 months (to assess maintenance of treatment effects). The primary outcome is the Western Ontario and McMaster Universities Osteoarthritis Index, and secondary outcomes include objective physical function, satisfaction with physical function, physical activity, depressive symptoms and global assessment of change. Linear mixed models will be used to compare both the IBET and standard PT groups to the WL control group, examine whether IBET is non-inferior to PT (a treatment that has an established evidence base for knee OA), and explore whether participant characteristics are associated with differential effects of IBET and/or standard PT. This research is in compliance with the Helsinki Declaration and was approved by the Institutional Review Board of the University of North Carolina at Chapel Hill. DISCUSSION: The IBET program could be disseminated widely at relatively low cost and could be an important resource for helping patients with knee OA to adopt and maintain appropriate physical activity. This trial will provide an important evaluation of the effectiveness of this IBET program for knee OA. TRIAL REGISTRATION: NCT02312713.

Fall Risk and Utilization of Balance Training for Adults With Symptomatic Knee Osteoarthritis: Secondary Analysis From a Randomized Clinical Trial.

BACKGROUND AND PURPOSE: Knee osteoarthritis (KOA) is a common disease that hinders activity participation in older adults. Associated symptoms and physiological changes can increase risk of falling in individuals with KOA. Balance training can decrease fall risks in older adults. Limited evidence exists regarding utilization of balance training in physical therapy (PT) for this population. This secondary data analysis investigated the proportion of participants at high risk for falling in the PhysicAl THerapy vs. INternet-based Exercise Training for Patients with Osteoarthritis (PATH-IN) study and the frequency with which balance training was utilized as an intervention in PT. METHODS: PATH-IN study participants (N = 344) performed the Four-Stage Balance Test and the Timed Up and Go (TUG) test during baseline assessment. Participants were randomly allocated to PT, an Internet-based exercise program, or a control group. Participants were classified as being at high risk for falling if they did not progress to the single-leg stance (SLS) during the Four-Stage Balance Test, were unable to maintain SLS for 5 seconds, or took longer than 13.5 seconds to complete the TUG test. The proportion of participants at high risk for falling was calculated for all participants and separately for those allocated to PT. In addition, PT notes were coded for balance training and the frequency of balance training utilization was calculated. RESULTS AND DISCUSSION: Upon enrollment, 35.5% (N = 122) of all participants and 36.2% (N = 50) of those allocated to PT were at high risk for falling. Of participants allocated to PT with documentation available for coding (N = 118), 35.5% (N = 42) were at high risk for falling. Balance training was provided to 62.7% (N = 74) during at least one PT session. Of those classified as being at high risk for falling, 33.3% (N = 14) did not receive balance training. CONCLUSIONS: The finding of high fall risks in more than one-third of all participants with KOA is consistent with previous reports of a higher risk of falling in this population. Many PT participants did receive some balance training; however, one-third of participants at high risk for falling did not. Balance training for individuals with KOA at high risk for falling may be underutilized.

Sociodemographic and Clinical Correlates of Physical Therapy Utilization in Adults With Symptomatic Knee Osteoarthritis.

Background: Physical therapy is essential for conservative management of symptomatic knee osteoarthritis (OA). However, physical therapy utilization data are limited for knee OA. Objective: The purpose of this study is to identify correlates of physical therapy utilization among adults with symptomatic knee OA. Design: The design consisted of secondary analysis using baseline data from a randomized controlled trial of 350 adults with physician-diagnosed symptomatic knee OA. Methods: Patients completed baseline surveys regarding demographics, pain, function, medical history, and prior physical therapy utilization for symptomatic knee OA. Multivariable logistic regression identified correlates of physical therapy utilization, with models adjusted for body mass index and age. Interactions of race and sex with all other characteristics were evaluated. Results: One hundred and eighty-one patients (52%) reported prior physical therapy utilization. Factors independently associated with increased odds of physical therapy utilization were female sex (odds ratio [OR] = 3.06, 95% CI = 1.58-5.93), bachelor degree or higher degree (OR = 2.44, 95% CI = 1.15-5.16), prior knee injury (OR = 1.86, 95% CI = 1.08-3.19), and duration of knee OA symptoms (OR = 2.16, 95% CI = 1.09-4.29 for >5-10 years; OR = 2.11, 95% CI = 1.10-4.04 for >10 years). Whites who had received a joint injection were >3 times as likely to have utilized physical therapy (OR = 3.69, 95% CI = 1.94-7.01); this relationship did not exist for non-whites who had received joint injections. Limitations: A sample enrolled in an exercise study may limit generalizability. Self-report of physical therapy may misclassify utilization. It cannot be determined whether lack of utilization resulted from lack of referral or from patients choosing not to attend physical therapy. Conclusion: Physical therapy is underutilized to manage symptomatic knee OA. Women and those with a bachelor degree or higher degree, prior knee injury, and longer duration of knee OA symptoms were more likely to have used therapy previously. Differences by race in the link between joint injection and physical therapy utilization may reflect a reduced likelihood of referral and decreased use of health interventions for symptomatic knee OA among non-whites, or both.

Fear of Movement and Associated Factors Among Adults With Symptomatic Knee Osteoarthritis.

OBJECTIVE: To examine the frequency of and factors associated with fear of movement (FOM) among patients with symptomatic knee osteoarthritis (KOA), using the new Brief Fear of Movement (BFOM) measure. METHODS: Participants (n = 350) enrolled in a clinical trial completed the BFOM scale prior to randomization. The relationships of BFOM with the following characteristics were examined: age, sex, race, education, pain and activities of daily living (ADL) subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS), knee symptom duration, depressive symptoms (8-item Patient Health Questionnaire [PHQ-8]), history of falls and knee injury, family history of knee problems, self-efficacy for exercise (SEE), and unilateral balance test. A proportional odds logistic regression model examined multivariable associations of participant characteristics with a 3-level BFOM variable (agreement with 0, 1-2, or ≥3 items). RESULTS: The majority of participants (77%) agreed with at least 1 item on the BFOM scale, and 36% endorsed 3+ items, suggesting a high degree of FOM. In the multivariable model, the following remained significant after backward selection: age (odds ratio [OR] 0.79 per 10-point increase, 95% confidence interval [95% CI] 0.66-0.95), KOOS ADL (OR 0.86 per 10-point increase, 95% CI 0.76-0.97), PHQ-8 (OR 1.15, 95% CI 1.08-1.22), and SEE (OR 0.87 per 10-point increase, 95% CI 0.78-0.96). CONCLUSION: FOM was common among patients with symptomatic KOA, and this could negatively impact physical activity. Psychological variables were significantly associated with FOM, suggesting behavioral and psychological interventions may decrease FOM and improve outcomes among individuals with symptomatic KOA.

Differential Diagnosis and Intervention of Proximal Median Nerve Entrapment: A Resident's Case Problem.

Study Design Resident's case problem. Background Entrapment neuropathies represent a diagnostic challenge and require a comprehensive understanding of the nerve's path and the anatomical structures that may cause compression of the nerve. This resident's case problem details the evaluation and differential diagnosis process for median nerve entrapment resulting from forceful and repetitive pronation/supination motions. Diagnosis Median nerve compression syndromes include pronator syndrome, anterior interosseous nerve syndrome, and carpal tunnel syndrome. A cluster of clinical special tests were performed to determine the anatomical site of median nerve entrapment. Based on the patient's history and clinical test results, a diagnosis of pronator syndrome was determined. Provocation testing specific to pronator syndrome assisted with further localizing the site of entrapment to the pronator teres muscle, which guided effective management strategies. Discussion This resident's case problem illustrates the importance of detailed anatomical knowledge and a differential diagnostic process when evaluating a patient with signs and symptoms of an entrapment neuropathy of the median nerve. Electrodiagnostic studies are useful in ruling out carpal tunnel and anterior interosseous nerve syndromes, but are often inconclusive in cases of pronator syndrome. Therefore, a diagnosis of pronator syndrome in this case problem was based on a detailed understanding of median nerve anatomy, potential sites of compression, and unique clinical features associated with this condition. Level of Evidence Differential diagnosis, level 4. J Orthop Sports Phys Ther 2016;46(9):800-808. Epub 5 Aug 2016. doi:10.2519/jospt.2016.6723.

Recommendations for the evaluation of specimen stability for flow cytometric testing during drug development.

The objective of this manuscript is to present an approach for evaluating specimen stability for flow cytometric methods used during drug development. While this approach specifically addresses stability assessment for assays to be used in clinical trials with centralized testing facilities, the concepts can be applied to any stability assessment for flow cytometric methods. The proposed approach is implemented during assay development and optimization, and includes suggestions for designing a stability assessment plan, data evaluation and acceptance criteria. Given that no single solution will be applicable in all scenarios, this manuscript offers the reader a roadmap for stability assessment and is intended to guide the investigator during both the method development phase and in the experimental design of the validation plan.

Structural basis for microtubule recognition by the human kinetochore Ska complex.

The ability of kinetochores (KTs) to maintain stable attachments to dynamic microtubule structures ('straight' during microtubule polymerization and 'curved' during microtubule depolymerization) is an essential requirement for accurate chromosome segregation. Here we show that the kinetochore-associated Ska complex interacts with tubulin monomers via the carboxy-terminal winged-helix domain of Ska1, providing the structural basis for the ability to bind both straight and curved microtubule structures. This contrasts with the Ndc80 complex, which binds straight microtubules by recognizing the dimeric interface of tubulin. The Ska1 microtubule-binding domain interacts with tubulins using multiple contact sites that allow the Ska complex to bind microtubules in multiple modes. Disrupting either the flexibility or the tubulin contact sites of the Ska1 microtubule-binding domain perturbs normal mitotic progression, explaining the critical role of the Ska complex in maintaining a firm grip on dynamic microtubules.

Development and validation of flow cytometry methods for pharmacodynamic clinical biomarkers.

Flow cytometry is a powerful analytical tool for the analysis of multiple biological parameters of individual cells or particles within heterogeneous cell populations. It has been widely used in biomedical research to perform immunophenotyping, cell counting and numerous cell function assessments, such as intracellular cytokine production, protein phosphorylation, cell proliferation and apoptosis. The implementation of standardized flow cytometry-based biomarker assays in clinical trials remains a challenge due to the limited stability of clinical specimens and the technical variations between instruments. To ensure data quality, it is crucial to develop robust assays for clinical applications. In this review, we summarize current practice in developing, validating and implementing flow cytometry assays to evaluate biomarkers in clinical research.