ABSTRACT
Osteoarthritis (OA) is the most prevalent arthritis worldwide and is characterized by chronic pain and impaired physical function. We hypothesized that heightened pain in hand OA could be reduced with duloxetine or pregabalin. In this prospective, randomized clinical study, we recruited 65 participants, aged 40-75 years, with a Numerical Rating Scale (NRS) for pain of at least 5. Participants were randomized to one of the following three groups: duloxetine, pregabalin, and placebo. The primary endpoint was the NRS pain score, and the secondary endpoints included the Australian and Canadian Hand Osteoarthritis Index (AUSCAN) pain, stiffness, and function scores and quantitative sensory testing by pain pressure algometry. After 13 weeks, compared to placebo, ANOVA found significant differences between the three groups (P=0.0078). In the intention-to-treat analysis, the pregabalin group showed improvement for NRS pain (P=0.023), AUSCAN pain (P=0.008), and AUSCAN function (P=0.009), but no difference between duloxetine and placebo (P>0.05) was observed. In the per protocol analysis, NRS pain was reduced for pregabalin (P<0.0001) and duloxetine (P=0.029) compared to placebo. We conclude that centrally acting analgesics improve pain outcomes in people with hand arthritis, offering new treatment paradigms for OA pain.
ABSTRACT
Cerebral small vessel disease (SVD) is the major cause of vascular cognitive impairment, resulting in significant disability and reduced quality of life. Cognitive tests have been shown to be insensitive to change in longitudinal studies and, therefore, sensitive surrogate markers are needed to monitor disease progression and assess treatment effects in clinical trials. Diffusion tensor imaging (DTI) is thought to offer great potential in this regard. Sensitivity of the various parameters that can be derived from DTI is however unknown. We aimed to evaluate the differential sensitivity of DTI markers to detect SVD progression, and to estimate sample sizes required to assess therapeutic interventions aimed at halting decline based on DTI data. We investigated 99 patients with symptomatic SVD, defined as clinical lacunar syndrome with MRI confirmation of a corresponding infarct as well as confluent white matter hyperintensities over a 3 year follow-up period. We evaluated change in DTI histogram parameters using linear mixed effect models and calculated sample size estimates. Over a three-year follow-up period we observed a decline in fractional anisotropy and increase in diffusivity in white matter tissue and most parameters changed significantly. Mean diffusivity peak height was the most sensitive marker for SVD progression as it had the smallest sample size estimate. This suggests disease progression can be monitored sensitively using DTI histogram analysis and confirms DTI's potential as surrogate marker for SVD.
Subject(s)
Cerebral Small Vessel Diseases/pathology , Diffusion Tensor Imaging , Aged , Female , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Male , Middle Aged , Quality of LifeABSTRACT
PURPOSE: To determine which MR technique was the most sensitive to age-related white matter damage. We compared both diffusion tensor imaging (DTI) and magnetization transfer (MT) maps to determine which technique correlated most strongly with cognitive function in a middle-aged and elderly community population. MATERIALS AND METHODS: In all, 64 healthy subjects (aged 50-90) underwent MRI and neuropsychology. Histograms were generated for white matter mean diffusivity (MD), fractional anisotropy (FA), and MT ratio (MTR). White matter hyperintensity volume (WMH) and brain volume were also determined. Composite neuropsychological scores were derived for 4 cognitive domains (executive function, working memory, episodic memory, and information processing speed). RESULTS: All MRI parameters correlated with age (FA r = 0.726, P < 0.001; MD r = -0.619 P < 0.001, MTR r = -0.566, P < 0.001, WMH r = 0.511, P < 0.001). All MRI parameters correlated with cognition, but DTI, and particularly FA, correlated most strongly. Adding DTI parameters explained more variance in cognition than WMH alone; the increase was greatest with FA, which alone explained 45%, 33%, and 25% of the variance in cognition for information processing speed, episodic memory, and executive function, respectively. CONCLUSION: DTI appears the most sensitive imaging parameter to determine age-related white matter damage. The stronger relationship with FA suggests that axonal damage is important in age-related cognitive decline.
