The association of biomarkers with pain and function in acute and subacute low back pain: a secondary analysis of an RCT.

BACKGROUND: Low back pain (LBP) is a common musculoskeletal condition and a major cause of disability worldwide. Previous studies have found associations of biomarkers with pain and pain-related disability in LBP patients. This study aimed to explore the association between serum biomarkers and pain and disability in patients with acute or subacute axial LBP. METHODS: This study was ancillary to a parent randomized controlled trial. Enrolled participants were randomized into three intervention groups: one of two types of spinal manipulation or medical care. In the parent study, 107 adults who experienced a new episode of LBP within 3 months prior to enrollment were recruited. For this study, 90 of these 107 participants consented to have blood samples obtained, which were drawn immediately before the beginning of treatment. Seven biomarkers were chosen based on previous literature and analyzed. Clinical outcomes were pain and Oswestry Disability Index (ODI) evaluated at baseline and 4 weeks. Spearman's |r| was used to study the association of initial levels of each biomarker with pain and ODI scores at baseline and with changes in outcome scores from baseline to 4 weeks (end of treatment) within each intervention group. RESULTS: At baseline, 4 of 7 biomarkers had an association with pain that was |r| ≥ .20: neuropeptide Y (NPY) (r = 0.23, p = .028), E-Selectin (r = 0.22, p = .043), vitamin D ((r = - 0.32, p = .002), and c-reactive protein (CRP) (r = 0.37, p = .001). No baseline biomarker had an association with disability that was |r| ≥ 0.20. For the correlations of baseline biomarkers with 4-week change in outcomes, vitamin D showed a correlation with change in disability and/or pain (|r| ≥ 0.20, p > .05) in manipulation-related groups, while CRP, NPY, and E-selectin along with TNFα, Substance P and RANTES showed at least one correlation with change in pain or disability (|r| ≥ 0.20, p > .05) in at least one of the treatment groups. CONCLUSIONS: In 90 LBP patients, the analyzed biomarkers, especially vitamin D, represent a small set of potential candidates for further research aimed at individualizing patient care. Overall, the associations investigated in the current study are an initial step in identifying the direct mechanisms of LBP and predicting outcomes of manipulation-related treatments or medical care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01211613, Date of Registration: September 29, 2010, https://clinicaltrials.gov/ct2/show/NCT01211613?term=schneider&cond=Low+Back+Pain&cntry=US&state=US%3APA&draw=2&rank=1.

Measuring nonspecific factors in treatment: item banks that assess the healthcare experience and attitudes from the patient's perspective.

PURPOSE: Nonspecific factors that accompany healthcare treatments, such as patients' attitudes and expectations, are important parts of the experience of care and can influence outcomes. However, no precise, concise, and generalizable instruments to measure these factors exist. We report on the development and calibration of new item banks, titled the Healing Encounters and Attitudes Lists (HEAL), that assess nonspecific factors across a broad range of treatments and conditions. METHODS: The instrument development methodology of the Patient-Reported Outcomes Measurement Information System (PROMIS(®)) was used. Patient focus groups and clinician interviews informed our HEAL conceptual model. Literature searches of eight databases yielded over 500 instruments and resulted in an initial item pool of several thousand items. After qualitative item analysis, including cognitive interviewing, 296 items were included in field testing. The calibration sample included 1657 respondents, 1400 obtained through an Internet panel and 257 from conventional and integrative medicine clinics. Following exploratory and confirmatory factor analyses, the HEAL item banks were calibrated using item response theory. RESULTS: The final HEAL item banks were Patient-Provider Connection (57 items), Healthcare Environment (25 items), Treatment Expectancy (27 items), Positive Outlook (27 items), and Spirituality (26 items). Short forms were also developed from each item bank. A six-item short form, Attitudes toward Complementary and Alternative Medicine (CAM), was also created. CONCLUSIONS: HEAL item banks provided substantial information across a broad range of each construct. HEAL item banks showed initial evidence of predictive and concurrent validity, suggesting that they are suitable for measuring nonspecific factors in treatment.

Assessment of vaccine testing at three laboratories using the guinea pig model of tuberculosis.

The guinea pig model of tuberculosis is used extensively in different locations to assess the efficacy of novel tuberculosis vaccines during pre-clinical development. Two key assays are used to measure protection against virulent challenge: a 30 day post-infection assessment of mycobacterial burden and long-term post-infection survival and pathology analysis. To determine the consistency and robustness of the guinea pig model for testing vaccines, a comparative assessment between three sites that are currently involved in testing tuberculosis vaccines from external providers was performed. Each site was asked to test two "subunit" type vaccines in their routine animal model as if testing vaccines from a provider. All sites performed a 30 day study, and one site also performed a long-term survival/pathology study. Despite some differences in experimental approach between the sites, such as the origin of the Mycobacterium tuberculosis strain and the type of aerosol exposure device used to infect the animals and the source of the guinea pigs, the data obtained between sites were consistent in regard to the ability of each "vaccine" tested to reduce the mycobacterial burden. The observations also showed that there was good concurrence between the results of short-term and long-term studies. This validation exercise means that efficacy data can be compared between sites.

Dietary polyunsaturated fatty acids modulate resistance to Mycobacterium tuberculosis in guinea pigs.

It is well established that the nutritional status of the host affects resistance to disease. The impact of dietary lipids on experimental pulmonary infection with mycobacteria has not been investigated. Therefore, the purpose of this study was to determine the role of dietary (n-3) and (n-6) fatty acids on immunity and resistance to aerosol infection with virulent Mycobacterium tuberculosis in guinea pigs. Weanling guinea pigs were fed purified, isocaloric diets differing only in lipid source, and the effects of diet on specific immune cell functions were evaluated after 3 or 6 wk. Dietary (n-3) fatty acid consumption reduced in vivo skin test and in vitro lympho-proliferative responses (P < 0.05) relative to (n-6) fatty acid consumption. The effect of diet on resistance to mycobacterial infection was assessed by enumerating viable mycobacteria in the lungs and spleens of guinea pigs infected with virulent M. tuberculosis by the aerosol route. (n-3) Fatty acid-fed guinea pigs had more bacteria in the lungs compared with (n-6) fatty acid-fed guinea pigs at 3 (P < 0.05) and 6 wk postinfection (P < 0.01). These data document the immunomodulatory effects of (n-3) fatty acid consumption in the context of tuberculosis resistance. The loss of antigen-specific T-cell functions in addition to impaired resistance to mycobacterial disease suggests a susceptible phenotype in (n-3) fatty acid-fed guinea pigs.