Age as the time dimension:
Article: Both Baseline and Change in Lower Limb Muscle Strength in Younger Women Are Independent Predictors of Balance in Middle-age: A 12-yr Population-based Prospective Study.
Article link: http://onlinelibrary.wiley.com/doi/10.1002/jbmr.3103/epdf
Research Question: To examine whether lower limb muscle strength (LMS) in young women and changes in LMS are independent predictors of balance in middle-age.
Significance: Among young women, greater LMS at baseline and slower decline over time are both associated with better balance in midlife. Analogous to the contributions of peak bone mass and bone loss to fracture risk in older adults, this suggests that both improvement of muscle strength in younger age and prevention of age-related loss of muscle strength could be potentially useful strategies to improve balance and reduce falls in later life.
Study sample: This was an observational 10-yr follow-up of 470 women aged 25-44 years at baseline who had previously participated in a 2-yr population-based randomized controlled trial of osteoporosis education interventions.
Longitudinal study design: Women aged 25-44 years were randomly selected from the 2000 Tasmanian Electoral Roll. Women were recruited if they were free of the following conditions: previous measurement of bone density, thyroid disease, renal failure, malignancy, or rheumatoid arthritis, a history of hysterectomy or hormone replacement therapies, pregnancy or planning pregnancy within 2 years of study entry, or lactating. At baseline, 470 women were randomly assigned to one of two osteoporosis educational interventions: group education using the Osteoporosis Prevention and Self-management course or an information leaflet.
Analysis approach: Bone mineral density was measured at the spine and hip at baseline and mean spine and hip T-score used to provide feedback of relative fracture risk as part of the education intervention (higher risk (mean T-score < 0) vs. normal risk (mean T-score ≥ 0)). Linear regression was used to examine the association between baseline LMS (by dynamometer) and change in LMS over 12 years with balance at 12 years (timed up and go test (TUG), step test (ST), functional reach test (FRT) and lateral reach test (LRT)).
Time since study enrollment as the time dimension:
Article: Association of Trabecular Bone Score (TBS) with Incident Clinical and Radiographic Vertebral Fractures Adjusted for Lumbar Spine BMD in Older Men: A Prospective Cohort Study.
Article link: http://onlinelibrary.wiley.com/doi/10.1002/jbmr.3130/epdf
Research question: To determine the associations of TBS with incident radiographic and clinical vertebral fractures in a cohort of community-dwelling older men. Among men in the Manitoba Bone Density Cohort, TBS was not associated with incident clinical vertebral fracture ascertained using administrative claims data, but the accuracy of claims data for incident vertebral fracture may be suboptimal. Additionally, among older men no prior study has examined the association of TBS with incident vertebral fractures identified on the basis of radiographs alone.
Significance: Trabecular Bone Score (TBS) is associated with incident hip and major osteoporotic fractures in older men, but its association with incident vertebral fracture is uncertain.
Study sample: From 2000 to 2002, 5994 community-dwelling men >65 years old were enrolled into the prospective MrOS study in six regions of the United States, described in previous publications.
Longitudinal study design: Participants have been followed since enrollment for incident fractures, falls, prostate cancers, and death.
Analysis approach: TBS was estimated from baseline spine DXA scans for 5,831 older men enrolled in the Osteoporotic Fractures in Men (MrOS) study. Cox proportional hazard models were used to determine the association of TBS (per 1 SD decrease) with incident clinical vertebral fractures. Logistic regression was used to determine the association between TBS (per 1 SD decrease) and incident radiographic vertebral fracture among the subset of 4,309 men with baseline and follow-up lateral spine radiographs. The authors also examined whether any associations varied by body mass index (BMI) category.
Another time dimension:
Article: Longitudinal assessment of urinary PCA3 for predicting prostate cancer grade reclassification in favorable-risk men during active surveillance.
Article link: https://www.nature.com/pcan/journal/vaop/ncurrent/full/pcan201716a.html
Research question: To assess the utility of urinary prostate cancer antigen 3 (PCA3) as both a one-time and longitudinal measure in men on active surveillance (AS).
Significance: Although methods of monitoring and triggers for curative intervention vary among Active Surveillance programs, the majority of protocols require serial prostate biopsy, a procedure associated with patient discomfort and risk of complications. As such, alternative methods of monitoring are needed. One potential option is prostate cancer antigen 3 (PCA3), a noncoding mRNA first described in 1999 that is highly overexpressed in PCa tissue. Since its introduction to clinical use, several studies have exhibited a significant association of PCA3 with PCa. To this point, however, evaluation of PCA3 in the AS population remains quite limited. Findings suggest potential utility of PCA3 in the AS setting but remained limited by small sample size and short-term follow-up. Furthermore, the utility of repeated PCA3 measures has yet to be demonstrated.
Study sample: Since 1995, the institutional review board-approved Johns Hopkins AS program has enrolled 1511 men with favorable-risk (low-risk or very-low-risk) PCa with informed consent.
Longitudinal study: Monitoring included semiannual PSA and digital rectal exam (DRE) as well as annual prostate biopsy and/or more recently prostate magnetic resonance imaging (MRI) for most men. Since 2007, urine samples were obtained at clinic visits after standard DRE. In order to assess for longitudinal changes in PCA3, the study cohort was limited to subjects with at least two urine samples obtained over greater than or equal to 3 years of follow-up (that is, at least 3 years apart) and a prostate biopsy within 6 months of each PCA3 assessment (n=294). Further, owing to variable effect of 5-alpha reductase inhibitor (5-ARI) medications on PCA3, 34 men who were on 5-ARI at the time of PCA3 assessment were excluded. The sample size is similar to a prior analysis of the AS cohort. The chosen outcome of interest was grade reclassification (GR) defined as any Gleason score >6 cancer detected on follow-up biopsy.
Analysis approach: Patient demographics as well as first (fPCA3) and subsequent (sPCA3) PCA3 scores were compared between men who did and did not undergo GR using t-test, Mann–Whitney test or chi-squared test, as appropriate. PCA3 scores were transformed into logarithmic scale to correct for skew and stabilize variance. A linear mixed-effects model with random effects was used to assess the longitudinal changes in PCA3 over time and also to evaluate its association with the outcome of interest. Additionally, the utility of a single PCA3 value for independently predicting high-grade disease was assessed using a multivariable logistic regression model adjusting for age, disease volume (very-low-risk or low-risk status) and PSAD. Model accuracy was assessed by measuring the area under the receiver operating characteristic curve (AUC), and the goodness-of-fit of the multivariable model was evaluated using Hosmer–Lemeshow goodness-of-fit test. One-sided tests were used for a priori hypotheses that were directional, and statistical significance was set at P<0.05.