Objective The impact of increasing utilization of total knee arthroplasty (TKA) on lifetime costs in persons with knee OA is under-studied. Methods We used the Osteoarthritis Policy Model to estimate total lifetime costs and TKA utilization under a range of TKA eligibility criteria among US persons with symptomatic knee OA. Current TKA utilization was estimated from the Multicenter Osteoarthritis Study and calibrated to Health Care Utilization Project (HCUP) data. OA treatment efficacy and toxicity were drawn from published literature. Costs in 2013 USD were derived from Medicare reimbursement schedules and Red Book Online®. Time costs were derived from published literature and the US Bureau of Labor Statistics. Results Estimated average discounted (3%/year) lifetime costs for persons diagnosed with knee OA were $140,300. Direct medical costs were $129,600, with $12,400 (10%) attributable to knee OA over 28 years. OA patients spent, on average, 13 (SD 10) years waiting for TKA after failing non-surgical regimens. Under current TKA eligibility criteria, 54% of knee OA patients underwent TKA over their lifetimes. Estimated OA-related discounted lifetime direct medical costs ranged from $12,400 (54% TKA uptake) when TKA eligibility was limited to K-L 3 or 4 to $16,000 (70% TKA uptake) when eligibility was expanded to include symptomatic OA with a lesser degree of structural damage. Conclusion Due to low efficacy of non-surgical regimens, knee OA treatment-attributable costs are low, representing a small portion of all costs for OA patients. Expanding TKA eligibility increases OA-related costs substantially for a population, underscoring the need for more effective non-operative therapies.

Objective To estimate incidence and lifetime risk of diagnosed symptomatic knee OA and age of diagnosis of knee OA based on self-reports in the US population. Methods We estimated incidence of diagnosed symptomatic knee OA in the US by combining data on age-, sex-, and obesity-specific prevalence from the 2007–2008 National Health Interview Survey (NHIS) with disease duration estimates derived from the Osteoarthritis Policy (OAPol) Model, a validated computer simulation model of knee OA. We used the OAPol Model to estimate the mean and median ages of diagnosis and lifetime risk. Results The estimated incidence of diagnosed symptomatic knee OA was highest among adults aged 55 to 64, ranging from 0.37% per year for non-obese males to 1.02% per year for obese females. The estimated median age of knee OA diagnosis was 55 years. The estimated lifetime risk was 13.83%, ranging from 9.60% for non-obese males to 23.87% in obese females. About 9.29% of the US population is diagnosed with symptomatic knee OA by age 60. Conclusion The diagnosis of symptomatic knee OA occurs relatively early in life suggesting that prevention programs should be offered relatively early in the life course. Further research is needed to understand the future burden of healthcare utilization resulting from earlier diagnosis of knee OA.

IMPORTANCE Visual dysfunction and poor cognition are highly prevalent among older adults; however, the relationship is not well defined.OBJECTIVE To evaluate the association of measured and self-reported visual impairment (VI) with cognition in older US adults.

Among the hallmark phenotypes reported in individuals with fragile X syndrome (FXS) are deficits in attentional function, inhibitory control, and cognitive flexibility, a set of cognitive skills thought to be associated with the prefrontal cortex (PFC). However, despite substantial clinical research into these core deficits, the PFC has received surprisingly little attention in preclinical research, particularly in animal models of FXS. In this study, we sought to investigate the molecular, cellular, and behavioral consequences of the loss of the fragile X mental retardation protein in the PFC of Fmr1 KO mice, a mouse model of FXS. We identify a robust cognitive impairment in these mice that may be related to the deficits in cognitive flexibility observed in individuals with FXS. In addition, we report that levels of proteins involved in synaptic function, including the NMDA receptor subunits NR1, NR2A, and NR2B; the scaffolding proteins PSD-95 and SAPAP3; and the plasticity-related gene Arc, are decreased in the prefrontal cortex of Fmr1 KO mice and are partly correlated with behavioral performance. Finally, we report that expression of c-Fos, a marker of neuronal activity, is decreased in the PFC of Fmr1 KO mice. Together, these data suggest that Fmr1 KO mice may represent a valuable animal model for the PFC-associated molecular, cellular, and behavioral abnormalities in FXS and that this model may be useful for testing the efficacy of therapeutic strategies aimed at treating the cognitive impairments in FXS.is the most common form of inherited mental retardation and a leading known cause of autism (1). It is caused by loss of the Fmr1 gene product fragile X mental retardation protein (FMRP), an mRNA-binding protein involved in translational regulation (2, 3). FMRP is thought to repress the synthesis of proteins required for protein synthesisdependent synaptic plasticity (4, 5). In FXS, the absence of FMRP is hypothesized to result in unrestricted synthesis of plasticity-related proteins (6, 7), impairing the ability of synapses to appropriately undergo plasticity in an activity-dependent and stimulus-specific manner. In support of this hypothesis, mice with a deletion in the Fmr1 gene (Fmr1 KO mice) display aberrant forms of plasticity (4) and an increase in immature dendritic spines that presumably reflects an abnormal synaptic connectivity (8). Together, these synaptic alterations are thought to underlie the cognitive and behavioral phenotypes that are the hallmark features of FXS.Among the most common symptoms reported in FXS are deficits in attentional function, inhibitory control, and cognitive flexibility (9), cognitive skills that have all been linked to the prefrontal cortex (PFC) and associated fronto-striatal networks (10, 11). Anatomical and imaging studies of individuals with FXS have identified structural alterations in PFC, and numerous fMRI studies have shown aberrant patterns of neural activity in fronto-striatal pathways during cognitive tasks (12). Together, all of these results suggest that...