Person:

Collins, Jamie

Introduction: Biomarkers to identify osteoarthritis (OA) patients at risk for disease progression are needed. As part of a proteomic analysis of knee synovial fluid from normal and OA patients, differentially expressed proteins were identified that could represent potential biomarkers for OA. This study aimed to use mass spectrometry assays to identify representative peptides from several proteins in synovial fluid and peripheral blood, and assess their levels as biomarkers of OA progression. Methods: Multiplexed high throughput selected reaction monitoring (SRM) assays were developed to measure tryptic peptides representative of 23 proteins in matched serum and synovial fluid samples from late OA subjects at the time of joint replacement. Subsequently plasma samples from the baseline visit of 173 subjects in an observational OA cohort were tested by SRM for peptides from nine of these proteins: afamin, clusterin, cartilage oligomeric matrix protein, hepatocyte growth factor, kallistatin, insulin-like growth factor binding protein, acid labile subunit, lubricin, lumican, and pigment epithelium-derived factor. Linear regression was used to determine the association between the peptide biomarker level at baseline and change in joint space width (ΔJSW) from baseline to 30 months, adjusting for age and sex. Results: In the matched cohort, 17 proteins could be identified in synovial fluid and 16 proteins were detected in serum. For the progression cohort, the average age was 62 and average ΔJSW over 30 months was 0.68 mm. A high correlation between different peptides from individual proteins was observed, indicating our assays correctly measured their target proteins. Peptides representative of clusterin, lumican and lubricin showed statistically significant associations with joint space narrowing after adjustment for age and sex. Partial R2 values showed clusterin FMETVAEK and lubricin LVEVNPK peptide biomarkers explains about 2 to 3% of the variability of ΔJSW, similar to that explained by age. A biomarker score combining normalized data for both lubricin and clusterin peptides increased the model R2 to 0.079. Conclusions: Our results suggest that when combined, levels of peptides representative of clusterin and lubricin in plasma are as predictive of OA progression as age. Replication of these findings in other prospective OA cohorts is planned. Electronic supplementary material The online version of this article (doi:10.1186/s13075-014-0456-6) contains supplementary material, which is available to authorized users.

Background: To address both the growing burden of joint disease and the gaps in medical access in developing nations, medical relief organizations have begun to launch programs to perform total joint replacement (TJR) on resident populations in developing countries. One outcome of TJR of particular interest is physical activity (PA) since it is strongly linked to general health. This study evaluates the amount of postoperative participation in PA in low-income patients who received total joint replacement in the Dominican Republic and identifies preoperative predictors of postoperative PA level. Methods: We used the Yale Physical Activity Survey (YPAS) to assess participation in postoperative PA 1–4 years following total knee or hip replacement. We compared the amount of aerobic PA reported by postoperative TJR patients with the levels of PA recommended by the CDC and WHO. We also analyzed preoperative determinants of postoperative participation in aerobic PA in bivariate and multivariate analyses. Results: 64 patients out of 170 eligible subjects (52/128 TKR and 14/42 THR) who received TJR between 2009–2012 returned for an annual follow-up visit in 2013, with a mean treatment-to-follow-up time of 2.1 years. 43.3% of respondents met CDC/WHO criteria for sufficient participation in aerobic PA. Multivariate analyses including data from 56 individuals identified that patients who were both younger than 65 and at least two years postoperative had an adjusted mean activity dimensions summary index (ADSI) 22.9 points higher than patients who were 65 or older and one year postoperative. Patients who lived with friends or family had adjusted mean ADSI 17.2 points higher than patients living alone. Patients who had the most optimistic preoperative expectations of outcome had adjusted mean ADSI scores that were 19.8 points higher than those who were less optimistic. Conclusion: The TJR patients in the Dominican cohort participate in less PA than recommended by the CDC/WHO. Additionally, several associations were identified that potentially affect PA in this population; specifically, participants who are older than 65, recently postoperative, less optimistic about postoperative outcomes and who live alone participate in less PA.

Background: Valid measures of physical activity are critical research tools. The objective of this study was to develop a Spanish translation of the Yale Physical Activity Survey, and to provide preliminary evidence of its validity in a population of Dominican patients with lower extremity arthritis. Methods: A Dominican bilingual health care professional translated the Yale Physical Activity Survey (YPAS) from English to Spanish. Several Dominican adults reviewed the translation to ensure it was linguistically and culturally appropriate. The questionnaire was back-translated to English by a North American researcher who is fluent in Spanish. Discrepancies between the original and back-translated versions were resolved by the translator and back-translator. The Spanish translation was administered to 108 Dominican subjects with advanced hip or knee arthritis prior to (N = 44) or one to four years following (N = 64) total joint replacement. We assessed construct validity by examining the association of YPAS scores and measures of functional status and pain (WOMAC), quality of life (EQ-5D) and the number of painful lower extremity joints. Results: A higher YPAS Part II Activity Dimensions Summary Index score had weak to modest correlations with worse function and quality of life as measured with the WOMAC function scale (r = 0.21, p = 0.03), SF-36 Physical Activity Scale (r = 0.29, p = 0.004) and EQ-5D (r = 0.34, p = 0.0007). Total minutes of vigorous activity and walking had weak to modest correlation with these measures (WOMAC Function Scale (r = 0.15, p = 0.15), SF-36 Physical Activity Scale (r = 0.21, p = 0.04) and EQ-5D utility (r = 0.24, p = 0.02)). Correlations between the YPAS Part I energy expenditure score and these measures were lower (WOMAC Function Scale (r = 0.07, p = 0.49), SF-36 Physical Activity Scale (r = 0.03, p = 0.74) and EQ-5D utility (r = 0.18, p = 0.07)). Conclusions: We have developed a new Spanish translation of the Yale Physical Activity Survey and provided evidence of convergent validity in a sample of Dominican patients prior to or 1–4 years following total joint replacement.

Background: The incidence of knee osteoarthritis (OA) is rising. While several risk factors have been associated with the development of knee OA, this information is not readily accessible to those at risk for osteoarthritis. Risk calculators have been developed for several prevalent chronic conditions but not for OA. Using published evidence on established risk factors, we developed an interactive, personalized knee OA risk calculator (OA Risk C) and conducted a pilot study to evaluate its acceptability and feasibility. Methods: We used the Osteoarthritis Policy (OAPol) Model, a validated, state-transition simulation of the natural history and management of OA, to generate data for OA Risk C. Risk estimates for calculator users were based on a set of demographic and clinical factors (age, sex, race/ethnicity, obesity) and select risk factors (family history of knee OA, occupational exposure, and history of knee injury). OA Risk C presents personalized risk of knee OA in several ways to maximize understanding among a wide range of users. We conducted a study of 45 subjects in a primary care setting to establish the feasibility and acceptability of the OA risk calculator. Pilot study participants were asked several questions regarding ease of use, clarity of presentation, and clarity of the graphical representation of their risk. These questions used a five-level agreement scale ranging from strongly disagree to strongly agree. Results: OA Risk C depicts information about users’ risk of symptomatic knee OA in 5 year intervals. Study participants estimated their lifetime risk at 38 %, while their actual lifetime risk, as estimated by OA Risk C, was 25 %. Eighty-four percent of pilot study participants reported that OA Risk C was easy to understand, and 89 % agreed that the graphs depicting their risk were clear and comprehensible. Conclusions: We have developed a personalized, computer-based OA risk calculator that is easy to use. OA Risk C may be utilized to estimate individuals’ knee OA risk and to deliver educational and behavioral interventions focused on osteoarthritis risk reduction.

Introduction: Varicella zoster virus (VZV) causes varicella (chicken pox) and herpes zoster (shingles). Worldwide, these diseases are associated with significant morbidity. Most of the epidemiological data on VZV come from high income countries. There are few data on VZV in Africa, where tropical climates and high HIV/AIDS prevalence rates are expected to impact the epidemiology of VZV. Safe and effective vaccinations for both varicella and herpes zoster exist, but are not routinely used in Africa. There are very few data available on VZV disease burden in Africa to guide the introduction of these vaccines on the continent. Our aim is to conduct a systematic review of the VZV-associated morbidity and mortality in Africa, which will provide critical information that could be used to develop vaccination policies against these diseases in Africa. Methods and analysis Electronic databases will be searched and all studies published after 1974 that meet predefined criteria will be assessed. The primary outcomes for the study are VZV incidence/prevalence, hospitalisation rates and total death rates. The secondary outcome for this study is the proportion of VZV hospitalisations and/or deaths associated with HIV/AIDS. Two reviewers will screen the titles and abstracts, and then independently review the full texts, to determine if studies are eligible for inclusion. A risk of bias and quality assessment tool will be used to score all included studies. Following standardised data extraction, a trend analysis using R-programming software will be conducted to investigate the trend of VZV. Depending on the characteristics of included studies, subgroup analyses will be performed. This review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Ethics and dissemination As this is a protocol for a systematic review, which will use already published data, no ethics approval is required. Findings will be disseminated in peer-reviewed journals. Trial registration number CRD42015026144.

Background: To describe the scoring methodology and MRI assessments used to evaluate the cross-sectional features observed in cases and controls, to define change over time for different MRI features, and to report the extent of changes over a 24-month period in the Foundation for National Institutes of Health Osteoarthritis Biomarkers Consortium study nested within the larger Osteoarthritis Initiative (OAI) Study. Methods: We conducted a nested case–control study. Cases (n = 406) were knees having both radiographic and pain progression. Controls (n = 194) were knee osteoarthritis subjects who did not meet the case definition. Groups were matched for Kellgren-Lawrence grade and body mass index. MRIs were acquired using 3 T MRI systems and assessed using the semi-quantitative MOAKS system. MRIs were read at baseline and 24 months for cartilage damage, bone marrow lesions (BML), osteophytes, meniscal damage and extrusion, and Hoffa- and effusion-synovitis. We provide the definition and distribution of change in these biomarkers over time. Results: Seventy-three percent of the cases had subregions with BML worsening (vs. 66 % in controls) (p = 0.102). Little change in osteophytes was seen over 24 months. Twenty-eight percent of cases and 10 % of controls had worsening in meniscal scores in at least one subregion (p < 0.001). Seventy-three percent of cases and 53 % of controls had at least one area with worsening in cartilage surface area (p < 0.001). More cases experienced worsening in Hoffa- and effusion synovitis than controls (17 % vs. 6 % (p < 0.001); 41 % vs. 18 % (p < 0.001), respectively). Conclusions: A wide range of MRI-detected structural pathologies was present in the FNIH cohort. More severe changes, especially for BMLs, cartilage and meniscal damage, were detected primarily among the case group suggesting that early changes in multiple structural domains are associated with radiographic worsening and symptomatic progression.

Background: We designed and implemented the Brigham and Women’s Wellness Initiative (B-Well), a single-arm study to examine the feasibility of a workplace program that used individual and team-based financial incentives to increase physical activity among sedentary hospital employees. Methods: We enrolled sedentary, non-clinician employees of a tertiary medical center who self-reported low physical activity. Eligible participants formed or joined teams of three members and wore Fitbit Flex activity monitors for two pre-intervention weeks followed by 24 weeks during which they could earn monetary rewards. Participants were rewarded for increasing their moderate-to-vigorous physical activity (MVPA) by 10% from the previous week or for meeting the Centers for Disease Control and Prevention (CDC) physical activity guidelines (150 min of MVPA per week). Our primary outcome was the proportion of participants meeting weekly MVPA goals and CDC physical activity guidelines. Secondary outcomes included Fitbit-wear adherence and factors associated with meeting CDC guidelines more consistently. Results: B-Well included 292 hospital employees. Participants had a mean age of 38 years (SD 11), 83% were female, 38% were obese, and 62% were non-Hispanic White. Sixty-three percent of participants wore the Fitbit ≥4 days per week for ≥20 weeks. Two-thirds were satisfied with the B-Well program, with 79% indicating that they would participate again. Eighty-six percent met either their personal weekly goal or CDC physical activity guidelines for at least 6 out of 24 weeks, and 52% met their goals or CDC physical activity guidelines for at least 12 weeks. African Americans, non-obese subjects, and those with lower impulsivity scores reached CDC guidelines more consistently. Conclusions: Our data suggest that a financial incentives-based workplace wellness program can increase MVPA among sedentary employees. These results should be reproduced in a randomized controlled trial. Trial registration Clinicaltrials.gov, NCT02850094. Registered July 27, 2016 [retrospectively registered].

Background: There are limited data on the incidence of concussion and concussion symptom nondisclosure among collegiate women’s ice hockey athletes. Purpose: To determine the incidence of sports-related concussion (SRC) in National Collegiate Athletic Association (NCAA) women’s ice hockey athletes. Study Design: Descriptive epidemiology study. Methods: An anonymous online survey was completed by 459 NCAA women’s ice hockey athletes. Players reported diagnosed concussions as well as incidents where they experienced an impact or blow to the head followed by symptoms associated with a concussion; reports spanned the duration of the 2014-2015 season and throughout players’ organized hockey career. Results: About half (n = 219, 47.7%) of respondents reported at least 1 diagnosed concussion over the duration of their entire organized ice hockey career. A total of 13.3% (n = 61) of respondents reported a diagnosed concussion during the 2014-2015 season. The incidence rate was 1.18 (95% CI, 0.92-1.51) per 1000 athlete-exposures to a game or practice and 0.58 (95% CI, 0.45-0.74) per 1000 hours of ice time. One-third (34.2%, n = 157) of players reported at least 1 impact where they experienced concussion-like symptoms during the 2014-2015 season; 82.8% of these players reported that they continued to play after at least 1 of these impacts, and 66.8% of players reported at least 1 impact where they never disclosed any symptoms. Conclusion: There is a high incidence of SRC in collegiate women’s ice hockey and a concerning level of symptom nondisclosure. Additional research is needed to understand the causes of concussion and reasons for the lack of symptom disclosure, including factors specific to female athletes and contextual issues specific to women’s collegiate ice hockey.

Background: Low enrollment rates are a threat to the external validity of clinical trials. The purpose of this study was to identify factors associated with lower enrollment rates in randomized controlled trials (RCTs) involving orthopedic procedures. Methods: We performed a search in PubMed/MEDLINE for RCTs that involved any orthopedic surgical procedure, compared different intraoperative interventions, were published in English in a peer-reviewed journal between 2003 and 2014, and reported the numbers of both enrolled and eligible subjects. The primary outcome was the enrollment rate, defined as the number of enrolled subjects divided by the number of eligible subjects. We used a meta-regression to identify factors associated with lower enrollment rates. Results: The combined estimate of enrollment rate across all 393 studies meeting inclusion criteria was 90% (95% CI: 89–92%). Trials in North America had significantly lower enrollment rates compared to trials in the rest of the world (80% vs. 92%, p < 0.0001). Trials comparing operative and non-operative treatments had significantly lower enrollment rates than trials comparing two different operative interventions (80% vs. 91%, p < 0.0001). Among trials comparing operative and non-operative interventions, there was a marked difference in enrollment rate by region: 49% in North America and 86% elsewhere (p < 0.0001). Conclusions: RCTs investigating orthopedic procedures have variable enrollment rates depending on their location and the difference between the interventions being studied. North American trials that compare operative and non-operative interventions have the lowest enrollment rates. Investigators planning RCTs would be well advised to consider these data in planning recruitment efforts.

Background: Varicella zoster virus (VZV) causes varicella and herpes zoster. These vaccine preventable diseases are common globally. Most available data on VZV epidemiology are from industrialised temperate countries and cannot be used to guide decisions on the immunization policy against VZV in Africa. This systematic review aims to review the published data on VZV morbidity and mortality in Africa. Methods: All published studies conducted in Africa from 1974 to 2015 were eligible. Eligible studies must have reported any VZV epidemiological measure (incidence, prevalence, hospitalization rate and mortality rate). For inclusion in the review, studies must have used a defined VZV case definition, be it clinical or laboratory-based. Results: Twenty articles from 13 African countries were included in the review. Most included studies were cross-sectional, conducted on hospitalized patients, and half of the studies used varying serological methods for diagnosis. VZV seroprevalence was very high among adults. Limited data on VZV seroprevalence in children showed very low seropositivity to anti-VZV antibodies. Co-morbidity with VZV was common. Conclusion: There is lack of quality data that could be used to develop VZV control programmes, including vaccination, in Africa. Trial registration PROSPERO 2015: CRD42015026144. Electronic supplementary material The online version of this article (10.1186/s12879-017-2815-9) contains supplementary material, which is available to authorized users.