Abstract Background We aimed to determine if composite structural measures of knee osteoarthritis (KOA) progression on magnetic resonance (MR) imaging can predict the radiographic onset of accelerated knee osteoarthritis. Methods We used data from a nested case-control study among participants from the Osteoarthritis Initiative without radiographic KOA at baseline. Participants were separated into three groups based on radiographic disease progression over 4 years: 1) accelerated (Kellgren-Lawrence grades [KL] 0/1 to 3/4), 2) typical (increase in KL, excluding accelerated osteoarthritis), or 3) no KOA (no change in KL). We assessed tibiofemoral cartilage damage (four regions: medial/lateral tibia/femur), bone marrow lesion (BML) volume (four regions: medial/lateral tibia/femur), and whole knee effusion-synovitis volume on 3 T MR images with semi-automated programs. We calculated two MR-based composite scores. Cumulative damage was the sum of standardized cartilage damage. Disease activity was the sum of standardized volumes of effusion-synovitis and BMLs. We focused on annual images from 2 years before to 2 years after radiographic onset (or a matched time for those without knee osteoarthritis). To determine between group differences in the composite metrics at all time points, we used generalized linear mixed models with group (3 levels) and time (up to 5 levels). For our prognostic analysis, we used multinomial logistic regression models to determine if one-year worsening in each composite metric change associated with future accelerated knee osteoarthritis (odds ratios [OR] based on units of 1 standard deviation of change). Results Prior to disease onset, the accelerated KOA group had greater average disease activity compared to the typical and no KOA groups and this persisted up to 2 years after disease onset. During a pre-radiographic disease period, the odds of developing accelerated KOA were greater in people with worsening disease activity [versus typical KOA OR (95% confidence interval [CI]): 1.58 (1.08 to 2.33); versus no KOA: 2.39 (1.55 to 3.71)] or cumulative damage [versus typical KOA: 1.69 (1.14 to 2.51); versus no KOA: 2.11 (1.41 to 3.16)]. Conclusions MR-based disease activity and cumulative damage metrics may be prognostic markers to help identify people at risk for accelerated onset and progression of knee osteoarthritis.
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Biclustering reveals potential knee OA phenotypes in exploratory analyses: Data from the Osteoarthritis Initiative
Objective To apply biclustering, a methodology originally developed for analysis of gene expression data, to simultaneously cluster observations and clinical features to explore candidate phenotypes of knee osteoarthritis (KOA) for the first time. Methods Data from the baseline Osteoarthritis Initiative (OAI) visit were cleaned, transformed, and standardized as indicated (leaving 6461 knees with 86 features). Biclustering produced submatrices of the overall data matrix, representing similar observations across a subset of variables. Statistical validation was determined using the novel SigClust procedure. After identifying biclusters, relationships with key outcome measures were assessed, including progression of radiographic KOA, total knee arthroplasty, loss of joint space width, and worsening Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, over 96 months of follow-up. Results The final analytic set included 6461 knees from 3330 individuals (mean age 61 years, mean body mass index 28 kg/m 2 , 57% women and 86% White). We identified 6 mutually exclusive biclusters characterized by different feature profiles at baseline, particularly related to symptoms and function. Biclusters represented overall better (#1), similar (#2, 3, 6), and poorer (#4, 5) prognosis compared to the overall cohort of knees, respectively. In general, knees in biclusters #4 and 5 had more structural progression (based on Kellgren-Lawrence grade, total knee arthroplasty, and loss of joint space width) but tended to have an improvement in WOMAC pain scores over time. In contrast, knees in bicluster #1 had less incident and progressive KOA, fewer total knee arthroplasties, less loss of joint space width, and stable pain scores compared with the overall cohort. Significance We identified six biclusters within the baseline OAI dataset which have varying relationships with key outcomes in KOA. Such biclusters represent potential phenotypes within the larger cohort and may suggest subgroups at greater or lesser risk of progression over time.
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- Award ID(s):
- 2113404
- NSF-PAR ID:
- 10329771
- Editor(s):
- Shaharudin, Shazlin
- Date Published:
- Journal Name:
- PLOS ONE
- Volume:
- 17
- Issue:
- 5
- ISSN:
- 1932-6203
- Page Range / eLocation ID:
- e0266964
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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null (Ed.)Background Older adults who experience pain are more likely to reduce their community and life-space mobility (ie, the usual range of places in an environment in which a person engages). However, there is significant day-to-day variability in pain experiences that offer unique insights into the consequences on life-space mobility, which are not well understood. This variability is complex and cannot be captured with traditional recall-based pain surveys. As a solution, ecological momentary assessments record repeated pain experiences throughout the day in the natural environment. Objective The aim of this study was to examine the temporal association between ecological momentary assessments of pain and GPS metrics in older adults with symptomatic knee osteoarthritis by using a smartwatch platform called Real-time Online Assessment and Mobility Monitor. Methods Participants (n=19, mean 73.1 years, SD 4.8; female: 13/19, 68%; male: 6/19, 32%) wore a smartwatch for a mean period of 13.16 days (SD 2.94). Participants were prompted in their natural environment about their pain intensity (range 0-10) at random time windows in the morning, afternoon, and evening. GPS coordinates were collected at 15-minute intervals and aggregated each day into excursion, ellipsoid, clustering, and trip frequency features. Pain intensity ratings were averaged across time windows for each day. A random effects model was used to investigate the within and between-person effects. Results The daily mean pain intensities reported by participants ranged between 0 and 8 with 40% reporting intensities ≥2. The within-person associations between pain intensity and GPS features were more likely to be statistically significant than those observed between persons. Within-person pain intensity was significantly associated with excursion size, and others (excursion span, total distance, and ellipse major axis) showed a statistical trend (excursion span: P=.08; total distance: P=.07; ellipse major axis: P=.07). Each point increase in the mean pain intensity was associated with a 3.06 km decrease in excursion size, 2.89 km decrease in excursion span, 5.71 km decrease total distance travelled per day, 31.4 km2 decrease in ellipse area, 0.47 km decrease ellipse minor axis, and 3.64 km decrease in ellipse major axis. While not statistically significant, the point estimates for number of clusters (P=.73), frequency of trips (P=.81), and homestay (P=.15) were positively associated with pain intensity, and entropy (P=.99) was negatively associated with pain intensity. Conclusions In this demonstration study, higher intensity knee pain in older adults was associated with lower life-space mobility. Results demonstrate that a custom-designed smartwatch platform is effective at simultaneously collecting rich information about ecological pain and life-space mobility. Such smart tools are expected to be important for remote health interventions that harness the variability in pain symptoms while understanding their impact on life-space mobility.more » « less
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Background: Graft placement is a modifiable and often discussed surgical factor in anterior cruciate ligament (ACL) reconstruction (ACLR). However, the sensitivity of functional knee mechanics to variability in graft placement is not well understood.
Purpose: To (1) investigate the relationship of ACL graft tunnel location and graft angle with tibiofemoral kinematics in patients with ACLR, (2) compare experimentally measured relationships with those observed with a computational model to assess the predictive capabilities of the model, and (3) use the computational model to determine the effect of varying ACL graft tunnel placement on tibiofemoral joint mechanics during walking.
Study Design: Controlled laboratory study.
Methods: Eighteen participants who had undergone ACLR were tested. Bilateral ACL footprint location and graft angle were assessed using magnetic resonance imaging (MRI). Bilateral knee laxity was assessed at the completion of rehabilitation. Dynamic MRI was used to measure tibiofemoral kinematics and cartilage contact during active knee flexion-extension. Additionally, a total of 500 virtual ACLR models were created from a nominal computational knee model by varying ACL footprint locations, graft stiffness, and initial tension. Laxity tests, active knee extension, and walking were simulated with each virtual ACLR model. Linear regressions were performed between internal knee mechanics and ACL graft tunnel locations and angles for the patients with ACLR and the virtual ACLR models.
Results: Static and dynamic MRI revealed that a more vertical graft in the sagittal plane was significantly related ( P < .05) to a greater laxity compliance index ( R2= 0.40) and greater anterior tibial translation and internal tibial rotation during active knee extension ( R2= 0.22 and 0.23, respectively). Similarly, knee extension simulations with the virtual ACLR models revealed that a more vertical graft led to greater laxity compliance index, anterior translation, and internal rotation ( R2= 0.56, 0.26, and 0.13). These effects extended to simulations of walking, with a more vertical ACL graft inducing greater anterior tibial translation, ACL loading, and posterior migration of contact on the tibial plateaus.
Conclusion: This study provides clinical evidence from patients who underwent ACLR and from complementary modeling that functional postoperative knee mechanics are sensitive to graft tunnel locations and graft angle. Of the factors studied, the sagittal angle of the ACL was particularly influential on knee mechanics.
Clinical Relevance: Early-onset osteoarthritis from altered cartilage loading after ACLR is common. This study shows that postoperative cartilage loading is sensitive to graft angle. Therefore, variability in graft tunnel placement resulting in small deviations from the anatomic ACL angle might contribute to the elevated risk of osteoarthritis after ACLR.
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Importance Screening with low-dose computed tomography (CT) has been shown to reduce mortality from lung cancer in randomized clinical trials in which the rate of adherence to follow-up recommendations was over 90%; however, adherence to Lung Computed Tomography Screening Reporting & Data System (Lung-RADS) recommendations has been low in practice. Identifying patients who are at risk of being nonadherent to screening recommendations may enable personalized outreach to improve overall screening adherence.
Objective To identify factors associated with patient nonadherence to Lung-RADS recommendations across multiple screening time points.
Design, Setting, and Participants This cohort study was conducted at a single US academic medical center across 10 geographically distributed sites where lung cancer screening is offered. The study enrolled individuals who underwent low-dose CT screening for lung cancer between July 31, 2013, and November 30, 2021.
Exposures Low-dose CT screening for lung cancer.
Main Outcomes and Measures The main outcome was nonadherence to follow-up recommendations for lung cancer screening, defined as failing to complete a recommended or more invasive follow-up examination (ie, diagnostic dose CT, positron emission tomography–CT, or tissue sampling vs low-dose CT) within 15 months (Lung-RADS score, 1 or 2), 9 months (Lung-RADS score, 3), 5 months (Lung-RADS score, 4A), or 3 months (Lung-RADS score, 4B/X). Multivariable logistic regression was used to identify factors associated with patient nonadherence to baseline Lung-RADS recommendations. A generalized estimating equations model was used to assess whether the pattern of longitudinal Lung-RADS scores was associated with patient nonadherence over time.
Results Among 1979 included patients, 1111 (56.1%) were aged 65 years or older at baseline screening (mean [SD] age, 65.3 [6.6] years), and 1176 (59.4%) were male. The odds of being nonadherent were lower among patients with a baseline Lung-RADS score of 1 or 2 vs 3 (adjusted odds ratio [AOR], 0.35; 95% CI, 0.25-0.50), 4A (AOR, 0.21; 95% CI, 0.13-0.33), or 4B/X, (AOR, 0.10; 95% CI, 0.05-0.19); with a postgraduate vs college degree (AOR, 0.70; 95% CI, 0.53-0.92); with a family history of lung cancer vs no family history (AOR, 0.74; 95% CI, 0.59-0.93); with a high age-adjusted Charlson Comorbidity Index score (≥4) vs a low score (0 or 1) (AOR, 0.67; 95% CI, 0.46-0.98); in the high vs low income category (AOR, 0.79; 95% CI, 0.65-0.98); and referred by physicians from pulmonary or thoracic-related departments vs another department (AOR, 0.56; 95% CI, 0.44-0.73). Among 830 eligible patients who had completed at least 2 screening examinations, the adjusted odds of being nonadherent to Lung-RADS recommendations at the following screening were increased in patients with consecutive Lung-RADS scores of 1 to 2 (AOR, 1.38; 95% CI, 1.12-1.69).
Conclusions and Relevance In this retrospective cohort study, patients with consecutive negative lung cancer screening results were more likely to be nonadherent with follow-up recommendations. These individuals are potential candidates for tailored outreach to improve adherence to recommended annual lung cancer screening.
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Background Mucus cytokines have been linked to baseline metrics of quality of life and olfactory function in patients with chronic rhinosinusitis (CRS). However, their potential utility in predicting postoperative outcomes has not been assessed. Therefore, in this study we evaluated the role of mucus cytokines in predicting 22‐item Sino‐Nasal Outcomes Test (SNOT‐22) scores after endoscopic sinus surgery (ESS) in a prospective cohort of CRS patients.
Methods One hundred forty‐seven patients with CRS electing surgical therapy were enrolled in a longitudinal cohort study. Mucus was collected intraoperatively from the middle meatus and tested for interleukin (IL)‐1β, IL‐2, ‐4, ‐5, ‐6, ‐7,‐ 8, ‐9, ‐10, ‐12, ‐13, ‐17A, and ‐21; tumor necrosis factor (TNF)‐α; interferon‐γ; eotaxin; and RANTES (regulated‐on‐activation, normal T‐cell expressed and secreted) expression using a multiplex flow‐cytometric bead assay. Sixty‐two patients were followed postoperatively (average, 10.2 months) with baseline and follow‐up SNOT‐22 surveys. Stepwise multivariate linear regression was used to model relationships between baseline cytokines, phenotype, and average postoperative SNOT‐22 total and domain scores. A machine learning approach using a random forest algorithm was also used to investigate potential nonlinear relationships.
Results IL‐5 was an independent predictor of postoperative total SNOT‐22 improvement (β = −8.8,
p < 0.0001), whereas IL‐2 levels predicted postoperative worsening (β = 6.97,p = 0.0015). Similar relationships were also seen for postoperative SNOT‐22 domain scores. The overall model was also noted to be significant fit for the data (adjustedR 2= 0.398,p < 0.0001). The random forest model similarly identified IL‐5, TNF‐α, IL‐13, and IL‐2 as major predictors of postoperative SNOT‐22 scores.Conclusion Mucus cytokine profiles may help identify CRS patients who are likely to obtain postoperative improvement after ESS.
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1371/journal.pone.0266964
