Freeman B.J.C.,Spinal Unit |
Freeman B.J.C.,University of Adelaide |
Ludbrook G.L.,Spinal Unit |
Ludbrook G.L.,University of Adelaide |
And 5 more authors.
Spine | Year: 2013
STUDY DESIGN.: Multicenter, randomized, double-blind, placebo-controlled trial. OBJECTIVE.: To examine the safety and efficacy of three different doses of the tumor necrosis factor alpha (TNF-α) inhibitor etanercept versus placebo for the treatment of symptomatic lumbar disc herniation (LDH). SUMMARY OF BACKGROUND DATA.: TNF-α is considered to be a major cause of radicular leg pain associated with symptomatic LDH. Systemic administration of TNF-α inhibitors for sciatica has indicated a trend toward efficacy. METHODS.: Forty-nine subjects aged between 18 and 70 years, with persistent lumbosacral radicular pain secondary to LDH, and an average leg pain intensity of 5/10 or more were randomized to 1 of 4 groups: 0.5-mg, 2.5-mg, 12.5-mg etanercept, or placebo. Subjects received 2 transforaminal epidural injections, 2 weeks apart, and were assessed for efficacy up to 26 weeks after the second injection. The primary outcome measure was the change in mean daily worst leg pain (WLP). Secondary outcomes included average leg pain, worst back pain, average back pain, in-clinic pain, Oswestry Disability Index, patient global impression of change, and tolerability. RESULTS:: Forty-three of the 49 randomized patients completed the study. Patients receiving 0.5-mg etanercept showed a clinically and statistically significant (P< 0.1) reduction in mean daily WLP compared with the placebo cohort from 2 to 26 weeks for both the per protocol population (-5.13 vs. -1.95; P= 0.066) and the intention-to-treat population (-4.40 vs. -1.84; P= 0.058). Fifty percent of these subjects reported a 100% reduction in WLP 4 weeks post-treatment compared with 0% of subjects in the placebo cohort. Improvements in all secondary outcomes were also observed in the 0.5-mg etanercept cohort. The overall incidence of adverse events was similar in placebo and all etanercept cohorts. CONCLUSION.: Two transforaminal injections of etanercept provided clinically significant reductions in mean daily WLP and worst back pain compared with placebo for subjects with symptomatic LDH. Epidural etanercept may offer patients with sciatica a safe and effective nonoperative treatment. © 2013, Lippincott Williams & Wilkins.
Davis G.A.,Cabrini Medical Center |
Davis G.A.,Florey Institute of Neuroscience and Mental Health |
Castellani R.J.,University of Maryland, Baltimore |
McCrory P.,Florey Institute of Neuroscience and Mental Health
Neurosurgery | Year: 2015
The recent interest in concussion in sport has resulted in significant media focus about chronic traumatic encephalopathy (CTE), although a direct causative link(s) between concussion and CTE is not established. Typically, sport-related CTE occurs in a retired athlete with or without a history of concussion(s) who presents with a constellation of cognitive, mood, and/or behavioral symptoms and who has postmortem findings of tau deposition within the brain. There are many confounding variables, however, that can account for brain tau deposition, including genetic mutations, drugs, normal aging, environmental factors, postmortem brain processing, and toxins. To understand the roles of such factors in neurodegenerative diseases that may occur in athletes, this article reviews some neurodegenerative diseases that may present with similar findings in nonathletes. The article also reviews pathological changes identified with normal aging, and reviews the pathological findings of CTE in light of all these factors. While many of these athletes have a history of exposure to head impacts as a part of contact sport, there is insufficient evidence to establish causation between sports concussion and CTE. It is likely that many of the cases with neuropathological findings represent the normal aging process, the effects of opiate abuse, or a variant of frontotemporal lobar degeneration. Whether particular genetic causes may place athletes at greater risk of neurodegenerative disease is yet to be determined.. Copyright © 2015 by the Congress of Neurological Surgeons.
Gross D.P.,University of Alberta |
Deshpande S.,University of Lethbridge |
Werner E.L.,University of Bergen |
Reneman M.F.,University of Groningen |
And 3 more authors.
Spine Journal | Year: 2012
Mass media campaigns designed to alter societal views and individual behaviors about back pain have been undertaken and evaluated in multiple countries. In contrast to the original Australian campaign, subsequent campaigns have been less successful, with improvements observed in beliefs without the corresponding changes in related behaviors. This article summarizes the results of a literature review, expert panel, and workshop held at the Melbourne International Forum XI: Primary Care Research on Low Back Pain in March 2011 on the role and interplay of various social behavior change strategies, including public education, law and legislation, healthy public policy, and social marketing in achieving a sustained reduction in the societal burden of back pain. Given the complexities inherent to health-related behaviors change, the Rothschild framework is applied in which behavior change strategies are viewed on a continuum from public education at one end through law and health policy at the other. Educational endeavors should likely be augmented with social marketing endeavors and supportive laws and health policy to foster sustained change in outcomes such as work disability and health utilization. Practical suggestions are provided for future interventions aimed at changing back pain-related behaviors. Evaluation of previous back pain mass media campaigns reveals that education alone is unlikely to foster positive and persisting behavioral change without concomitant strategies. © 2012 Elsevier Inc. All rights reserved.
Kremer J.,Albany Medical College |
Li Z.-G.,Peking University |
Hall S.,Cabrini Medical Center |
Fleischmann R.,Metroplex Clinical Research Center |
And 10 more authors.
Annals of Internal Medicine | Year: 2013
Background: Many patients with rheumatoid arthritis (RA) do not achieve adequate and safe responses with disease-modifying antirheumatic drugs (DMARDs). Tofacitinib is a novel, oral, Janus kinase inhibitor that treats RA. Objective: To evaluate the efficacy and safety of tofacitinib in combination with nonbiologic DMARDs. Design: 1-year, double-blind, randomized trial (ClinicalTrials.gov: NCT00856544). Setting: 114 centers in 19 countries. Patients: 792 patients with active RA despite nonbiologic DMARD therapy. Intervention: Patients were randomly assigned 4:4:1:1 to oral tofacitinib, 5 mg or 10 mg twice daily, or placebo advanced to tofacitinib, 5 mg or 10 mg twice daily. Measurements: Primary end points were 20% improvement in American College of Rheumatology (ACR20) criteria; Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less than 2.6; DAS28-4(ESR)- defined remission, change in Health Assessment Questionnaire Disability Index (HAQ-DI) score, and safety assessments. Results: Mean treatment differences for ACR20 response rates (month 6) for the 5-mg and 10-mg tofacitinib groups compared with the combined placebo groups were 21.2% (95% CI, 12.2% to 30.3%; P < 0.001) and 25.8% (CI, 16.8% to 34.8%; P < 0.001), respectively. The HAQ-DI scores (month 3) and DAS28- 4(ESR) less than 2.6 response rates (month 6) were also superior in the tofacitinib groups versus placebo. The incidence rates of serious adverse events for patients receiving 5-mg tofacitinib, 10-mg tofacitinib, or placebo were 6.9, 7.3, or 10.9 events per 100 patientyears of exposure, respectively. In the tofacitinib groups, 2 cases of tuberculosis, 2 cases of other opportunistic infections, 3 cardiovascular events, and 4 deaths occurred. Neutrophil counts decreased, hemoglobin and low- and high-density lipoprotein cholesterol levels increased, and serum creatinine levels had small increases in the tofacitinib groups. Limitations: Placebo groups were smaller and of shorter duration. Patients received primarily methotrexate. The ability to assess drug combinations other than tofacitinib plus methotrexate was limited. Conclusion: Tofacitinib improved disease control in patients with active RA despite treatment with nonbiologic DMARDs, primarily methotrexate. © 2013 American College of Physicians.
Makdissi M.,Florey Institute of Neuroscience and Mental Health |
Makdissi M.,University of Melbourne |
Davis G.,Florey Institute of Neuroscience and Mental Health |
Davis G.,Cabrini Medical Center |
And 6 more authors.
British Journal of Sports Medicine | Year: 2013
Background One of the key difficulties while managing concussion in sport is that there are few prognostic factors to reliably predict clinical outcome. The aims of the current paper are to review the evidence for concussion modifiers and to consider how the evaluation and management of concussion may differ in specific groups. Methods A qualitative review of the literature on concussion was conducted with a focus on prognostic factors and specific groups including children, female athletes and elite versus non-elite players. PubMed, MEDLINE and SportsDiscus databases were reviewed. Results The literature demonstrates that number and severity of symptoms and previous concussions are associated with prolonged recovery and/or increased risk of complications. Brief loss of consciousness (LOC) and/or impact seizures do not reliably predict outcomes following a concussion, although a cautious approach should be adopted in an athlete with prolonged LOC or impact seizures (ie, >1 min). Children generally take longer to recover from concussions and assessment batteries have yet to be validated in the younger age group. Currently, there are insufficient data on the influence of genetics and gender on outcomes following a concussion. Conclusions Several modifiers are associated with prolonged recovery or increased risk of complications following a concussion and have important implications for management. Children with concussion should be managed conservatively, with an emphasis on return to learn as well as return to sport. In cases of concussions managed with limited resources (eg, non-elite players), a conservative approach should also be taken. There should be an emphasis on concussion education in all sports and at all levels, particularly in junior and community-based competitions.