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New in the non-rheumatology journals: Another skeletal procedure, spinal augmentation, proves no better than conservative therapy when bias is removed from analysis. Also: Why disabling musculoskeletal conditions don't get the support they deserve, and a more complicated future for inflammatory disease research.
Last week's articles on rheumatology topics in the major nonspecialty journals
Vertebral FractureEditor's Note: Spinal Augmentation for Vertebral Fracture JAMA Intern Med. Published online July 8, 2013
Original Investigation: Less is More. Major Medical Outcomes With Spinal Augmentation vs Conservative TherapyJAMA Intern Med. Published online July 8, 2013
Invited Commentary: Vertebral Augmentation vs Nonsurgical Therapy: Improved Symptoms, Improved Survival, or Neither?JAMA Intern Med. Published online July 8, 2013
Spinal augmentation (vertebroplasty or kyphoplasty) for vertebral fracture in osteoporosis was no more effective than conservative therapy in reducing the rate of major complications or mortality, according to a retrospective cohort analysis of Medicare claims. Augmentation resulted in higher rates of hospitalization and admission to the intensive care unit and to skilled nursing facilities. Previous studies, including randomized, controlled trials, have reached conflicting results. This study first compared 10,541 patients treated with augmentation to 115,851 patients treated conservatively. Using traditional covariate adjustments, mortality was significantly lower in the augmented group. The investigators then tried to account for selection bias First, 3,023 patients (29%) did not have augmentation during the first 30 days. Those patients had significantly lower rates of major medical complications than the controls – which suggested that the augmentation group was healthier. Second, the investigators used propensity score matching to identify 9,085 matched pairs of augmented and control patients. In those 9,085 matched pairs, the benefits of augmentation disappeared. The results highlight “how analyses of claims-based data that do not adequately account for unrecognized confounding can arrive at misleading conclusions,” said the investigators.
Musculoskeletal DisabilityThe State of US Health, 1990-2010: Burden of Diseases, Injuries, and Risk FactorsJAMA, July 10, 2013
Editorial: The State of Health in the United StatesJAMA, July 10, 2013
The Global Burden of Disease framework determines which diseases, injuries and risk factors cause the greatest losses of health, measured by years of life lost to premature mortality (YLL), years lived with disability (YLD), and disability-adjusted life-years (DALY). Other international studies compare life expectancy or mortality; this study is unique in comparing disability and morbidity, which makes musculoskeletal disease more significant. Morbidity and chronic disability, driven by an aging population, now account for nearly half the U.S. health burden. The diseases with the largest number of YLDs were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders. Osteoarthritis ranked further down, and rheumatoid arthritis much further down. The leading risk factors for DALY were dietary, tobacco, body mass index, high blood pressure, high fasting plasma glucose, physical activity, and alcohol use.
In an editorial, Harvey V. Feinberg says, “the main sources of diminished function and quality of life (such as musculoskeletal conditions and mental illness) differ from the most prominent causes of death (such as heart disease and cancer) and may receive less attention in policy and research than they warrant.”
Chronic Inflammatory DisordersHow Cytokine Networks Fuel Inflammation: Interleukin-17 and a tale of two autoimmune diseasesNature Medicine, July 8, 2013
How Cytokine Networks Fuel Inflammation: Toward a cytokine-based disease taxonomyNature Medicine, July 8, 2013
Rather than being highly redundant, “chronic inflammatory diseases depend on fragile communication networks of cytokines, which collapse upon neutralization of functionally vulnerable nodes” such as tumor necrosis factor-α (TNF-α). What other vulnerable nodes are there? Most chronic inflammatory diseases respond to TNF-α inhibition but differ in their response to interleukin-17 (IL-17), IL-6, IL-1, and IL-23 inhibition. The interleukin inhibitors will have to be tailored to the cytokine pathways of specific diseases, and will be more complicated than TNF-α inhibition. For example, T helper type 17 (TH17) cells produce IL-17A as their signature cytokine, a key mediator of chronic tissue inflammation first identified in rheumatoid arthritis. However, TH17 cells produce other cytokines. The pathogenic role of TH17 cells depends on other TH17-derived cytokines, and the tissue context of the inflammation. Early studies show that IL-17 blockade, for example with secukinumab, may be effective in psoriasis, multiple sclerosis and ankylosing spondylitis.
Contaminated injectionsBill Calls for Tighter Regulation of Drug CompoundersJAMA, July 10, 2013
The Case for Clarifying FDA Authority: Large-Scale Drug Compounding and the Ongoing Risk to Public Health.Committee Staff Report. United States Senate, Health, Education, Labor, and Pensions Committee, May 22, 2013
The Senate, Health, Education, Labor, and Pensions Committee approved the Pharmaceutical Compounding Quality and Accountability Act (S959), which would give the Food and Drug Administration oversight over large compounding companies that sell sterile drugs across state lines in advance of a prescription. At least 48 compounding pharmacies have been selling contaminated or unsafe drugs.