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Article

Changes in Inflammatory and Bone Turnover Markers After Periodontal Disease Treatment in Patients With Diabetes

by Kenneth E. Izuora; Echezona E. Ezeanolue; Michael F. Neubauer; Civon L. Gewelber; Gayle L. Allenback; Guogen Shan; Guillermo Umpierrez

2016

Subjects
  • Health Sciences, General
  • File Download
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Abstract:Close

Background: The underlying mechanisms for increased osteopenia and fracture rates in patients with diabetes are not well understood, but may relate to chronic systemic inflammation. We assessed the effect of treating periodontal disease (POD), a cause of chronic inflammation, on inflammatory and bone turnover markers in patients with diabetes. Materials and Methods: Using an investigator-administered questionnaire, we screened a cross-section of patients presenting for routine outpatient diabetes care. We recruited 22 subjects with POD. Inflammatory and bone turnover markers were measured at baseline and 3 months following POD treatment (scaling, root planing and subantimicrobial dose doxycycline). Results: There were nonsignificant reductions in high-sensitivity C-reactive protein (6.34–5.52 mg/L, P = 0.626) and tumor necrosis factor-alpha (10.37–10.01 pg/mL, P = 0.617). There were nonsignificant increases in urinary C-terminal telopeptide (85.50–90.23 pg/mL, P = 0.684) and bone-specific alkaline phosphatase (7.45–8.79 pg/mL, P = 0.074). Patients with >90% adherence with doxycycline were 6.4 times more likely to experience reduction in tumor necrosis factor-alpha (P = 0.021) and 2.8 times more likely to experience reductions in high-sensitivity C-reactive protein (P = 0.133). Conclusions: Treatment of POD in patients with diabetes resulted in nonsignificant lowering of inflammatory markers and nonsignificant increase in bone turnover markers. However, adherence to doxycycline therapy resulted in better treatment effects.

Article

Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus

by J G Hanly; M B Urowitz; L Su; S-C Bae; C Gordon; A Clarke; S Bernatsky; A Vasudevan; D Isenberg; A Rahman; D J Wallace; P R Fortin; D Gladman; J Romero-Diaz; J Sanchez-Guerrero; M A Dooley; I Bruce; K Steinsson; M Khamashta; S Manzi; R Ramsey-Goldman; G Sturfelt; O Nived; R van Vollenhoven; M Ramos-Casals; C Aranow; M Mackay; K Kalunian; G S Alarcón; B J Fessler; G Ruiz-Irastorza; M Petri; Sung Lim; D Kamen; C Peschken; V Farewell; K Thompson; C Theriault; J T Merrill

2011

Subjects
  • Health Sciences, General
  • Health Sciences, Epidemiology
  • Health Sciences, Medicine and Surgery
  • File Download
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Abstract:Close

Objective: Neuropsychiatric events occur unpredictably in systemic lupus erythematosus (SLE) and most biomarker associations remain to be prospectively validated. This study examined a disease inception cohort of 1047 SLE patients to determine which autoantibodies at enrolment predicted subsequent neuropsychiatric events. Methods: Patients with a recent SLE diagnosis were assessed prospectively for up to 10 years for neuropsychiatric events using the American College of Rheumatology case definitions. Decision rules of graded stringency determined whether neuropsychiatric events were attributable to SLE. Associations between the first neuropsychiatric event and baseline autoantibodies (lupus anticoagulant (LA), anticardiolipin, anti- β2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor) were tested by Cox proportional hazards regression. Results: Disease duration at enrolment was 5.4±4.2 months, follow-up was 3.6±2.6 years. Patients were 89.1% female with mean (±SD) age 35.2±13.7 years. 495/1047 (47.3%) developed one or more neuropsychiatric event (total 917 events). Neuropsychiatric events attributed to SLE were 15.4% (model A) and 28.2% (model B). At enrolment 21.9% of patients had LA, 13.4% anticardiolipin, 15.1% anti-β2 glycoprotein-I, 9.2% anti-ribosomal P and 13.7% anti-NR2 antibodies. LA at baseline was associated with subsequent intracranial thrombosis (total n=22) attributed to SLE (model B) (HR 2.54, 95% CI 1.08 to 5.94). Anti-ribosomal P antibody was associated with subsequent psychosis (total n=14) attributed to SLE (model B) (HR 3.92, 95% CI 1.23 to 12.5, p=0.02). Other autoantibodies did not predict neuropsychiatric events. Conclusion: In a prospective study of 1047 recently diagnosed SLE patients, LA and anti-ribosomal P antibodies are associated with an increased future risk of intracranial thrombosis and lupus psychosis, respectively.

Article

Context-Dependent Neural Activation: Internally and Externally Guided Rhythmic Lower Limb Movement in Individuals With and Without Neurodegenerative Disease

by Madeleine Hackney; Ho Lim Lee; Jessica Battisto; Bruce Crosson; Keith McGregor

2015

Subjects
  • Biology, Neuroscience
  • Health Sciences, Rehabilitation and Therapy
  • Health Sciences, General
  • File Download
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Abstract:Close

Parkinson's disease is a neurodegenerative disorder that has received considerable attention in allopathic medicine over the past decades. However, it is clear that, to date, pharmacological and surgical interventions do not fully address symptoms of PD and patients' quality of life. As both an alternative therapy and as an adjuvant to conventional approaches, several types of rhythmic movement (e.g., movement strategies, dance, tandem biking, and Tai Chi) have shown improvements to motor symptoms, lower limb control, and postural stability in people with PD (1-6). However, while these programs are increasing in number, still little is known about the neural mechanisms underlying motor improvements attained with such interventions. Studying limb motor control under task-specific contexts can help determine the mechanisms of rehabilitation effectiveness. Both internally guided (IG) and externally guided (EG) movement strategies have evidence to support their use in rehabilitative programs. However, there appears to be a degree of differentiation in the neural substrates involved in IG vs. EG designs. Because of the potential task-specific benefits of rhythmic training within a rehabilitative context, this report will consider the use of IG and EG movement strategies, and observations produced by functional magnetic resonance imaging and other imaging techniques. This review will present findings from lower limb imaging studies, under IG and EG conditions for populations with and without movement disorders. We will discuss how these studies might inform movement disorders rehabilitation (in the form of rhythmic, music-based movement training) and highlight research gaps. We believe better understanding of lower limb neural activity with respect to PD impairment during rhythmic IG and EG movement will facilitate the development of novel and effective therapeutic approaches to mobility limitations and postural instability.

Article

Simulating clinical trial visits yields patient insights into study design and recruitment

by S Sam Lim; Alan J Kivitz; Doug McKinnell; M Edward Pierson; Faye S O'Brien

2017

Subjects
  • Health Sciences, General
  • Health Sciences, Health Care Management
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Purpose: We elicited patient experiences from clinical trial simulations to aid in future trial development and to improve patient recruitment and retention. Patients and methods: Two simulations of draft Phase II and Phase III anifrolumab studies for systemic lupus erythematosus (SLE)/lupus nephritis (LN) were performed involving African-American patients from Grady Hospital, an indigent care hospital in Atlanta, GA, USA, and white patients from Altoona Arthritis and Osteoporosis Center in Altoona, PA, USA. The clinical trial simulation included an informed consent procedure, a mock screening visit, a mock dosing visit, and a debriefing period for patients and staff. Patients and staff were interviewed to obtain sentiments and perceptions related to the simulated visits. Results: The Atlanta study involved 6 African-American patients (5 female) aged 27–60 years with moderate to severe SLE/LN. The Altoona study involved 12 white females aged 32–75 years with mild to moderate SLE/LN. Patient experiences had an impact on four patient-centric care domains: 1) information, communication, and education; 2) responsiveness to needs; 3) access to care; and 4) coordination of care; and continuity and transition. Patients in both studies desired background material, knowledgeable staff, family and friend support, personal results, comfortable settings, shorter wait times, and greater scheduling flexibility. Compared with the Altoona study patients, Atlanta study patients reported greater preferences for information from the Internet, need for strong community and online support, difficulties in discussing SLE, emphasis on transportation and child care help during the visits, and concerns related to financial matters; and they placed greater importance on time commitment, understanding of potential personal benefit, trust, and confidentiality of patient data as factors for participation. Using these results, we present recommendations to improve study procedures to increase retention, recruitment, and compliance for clinical trials. Conclusion: Insights from these two studies can be applied to the development and implementation of future clinical trials to improve patient recruitment, retention, compliance, and advocacy.

Article

Coronary revascularization vs. medical therapy following coronary-computed tomographic angiography in patients with low-,intermediate- and high-risk coronary artery disease: results from the CONFIRM long-termregistry

by Joshua Schulman-Marcus; Fay Y. Lin; Heidi Gransar; Daniel Berman; Tracy Callister; Augustin DeLago; Martin Hadamitzky; Joerg Hausleiter; Mouaz Al-Mallah; Matthew Budoff; Philipp Kaufmann; Stephan Achenbach; Gilbert Raff; Kavitha Chinnaiyan; Filippo Cademartiri; Erica Maffei; Todd Villines; Yong-Jin Kim; Jonathon Leipsic; Gudrun Feuchtner; Ronen Rubinshtein; Gianluca Pontone; Daniele Andreini; Hugo Marques; Hyuk-Jae Chang; Benjamin J.W. Chow; Ricardo C. Cury; Allison Dunning; Leslee J Shaw; James K. Min

2017

Subjects
  • Health Sciences, Medicine and Surgery
  • Health Sciences, General
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Aims To identify the effect of early revascularization on 5-year survival in patients with CAD diagnosed by coronarycomputed tomographic angiography (CCTA). Methods and results We examined 5544 stable patients with suspected CAD undergoing CCTA who were followed a median of 5.5 years in a large international registry. Patients were categorized as having low-, intermediate-, or high-risk CAD based on CCTA findings. Two treatment groups were defined: early revascularization within 90 days of CCTA (n = 1171) and medical therapy (n = 4373). To account for the non-randomized referral to revascularization, we developed a propensity score by logistic regression. This score was incorporated into Cox proportional hazard models to calculate the effect of revascularization on all-cause mortality. Death occurred in 363 (6.6%) patients and was more frequent in medical therapy. In multivariable models, when compared with medical therapy, the mortality benefit of revascularization varied significantly over time and by CAD risk (P for interaction 0.04). In high-risk CAD, revascularization was significantly associated with lower mortality at 1 year (hazard ratio [HR] 0.22, 95% confidence interval [CI] 0.11-0.47) and 5 years (HR 0.31, 95% CI 0.18-0.54). For intermediate-risk CAD, revascularization was associated with reduced mortality at 1 year (HR 0.45, 95% CI 0.22-0.93) but not 5 years (HR 0.63, 95% CI 0.33-1.20). For low-risk CAD, there was no survival benefit at either time point. Conclusions Early revascularization was associated with reduced 1-year mortality in intermediate-and high-risk CAD detected by CCTA, but this association only persisted for 5-year mortality in high-risk CAD.

Article

Potency Analysis of Mesenchymal Stromal Cells Using a Combinatorial Assay Matrix Approach

by Raghavan Chinnadurai; Devi Rajan; Muna Qayed; Dalia Arafat; Marco Garcia; Yifei Liu; Subra Kugathasan; Larry J Anderson; Greg Gibson; Jacques Galipeau

2018

Subjects
  • Health Sciences, Medicine and Surgery
  • Biology, Cell
  • Health Sciences, General
  • File Download
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Assays that can characterize MSC immune potency need to be identified for use in advanced clinical trials. MSCs possess a number of putative regenerative and immunomodulatory properties, and an assay matrix approach may best capture involved effector pathways. We have tested two assay systems to measure the potency of MSCs derived from human subjects: MSC secretome analysis and a quantitative RNA-based array for genes specific to immunomodulatory and homing properties of MSCs. Secretome analysis identified a unique cytokine signature that is upregulated by MSCs or downregulated in responder PBMCs and correlated with T cell suppression. Use of interferon-γ as a surrogate for the action of activated PBMCs on MSCs served as an alternative for the use of human PBMCs as responder cells in a potency assay. Our approach and results define and simplify the multifunctional or matrix responses of MSCs and may serve as a platform for robust potency analysis. Assays that inform on mesenchymal stromal cell (MSC) immune potency need to be defined in advanced clinical trials. Chinnadurai et al. tested an in vitro assay matrix approach combining molecular genetic and secretome analysis, elements of which could be deployed to define MSC immune modulatory potency.
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