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Neurons expressing the calcium binding proteins (CaBPs) parvalbumin (PV) and calbindin (CB) have shown age-related density changes throughout the ascending auditory system of both rodents and macaque monkeys. In the cerebral cortex, neurons expressing these CaBPs express markers of γ-aminobutyric acidergic neurotransmission, such as GAD67, and have well-understood physiological response properties. Recent evidence suggests that, in the rodent auditory brainstem, CaBP-containing cells do not express GAD67. It is unknown whether PV- and CB-containing cells in subcortical auditory structures of macaques similarly do not express GAD67, and a better understanding of the neurotransmission of neurons expressing these proteins is necessary for understanding the age-related changes in their density throughout the macaque auditory system. This was investigated with immunofluorescent double-labeling techniques to coregister PV- and CB-expressing neurons with GAD67 in the superior olivary complex and the inferior colliculus of young and aged rhesus macaques. The proportions of GAD67-expressing PV- and CB-positive neurons were computed with unbiased sampling techniques. Our results indicate that between 42% and 62% of PV- and CB-positive neurons in the auditory brainstem and midbrain express GAD67, which is significantly less than in the cerebrum. In general, fewer PV(+) neurons and more CB(+) neurons expressed GAD67 as a function of age. These results demonstrate that the inhibitory molecular profile of PV- and CB-expressing neurons can change with age in subcortical auditory structures and that these neurons are distinct from the well-described inhibitory interneurons that express these proteins in the cerebral cortex.

We compared the cost-effectiveness of therapeutic laparoscopy and open laparotomy for treatment of laparoscopically diagnosed ectopic pregnancy. Clinical outcomes of ectopic pregnancy treatment were based on results of a randomised trial done between 1987 and 1989 at Sahlgrenska University Hospital (Göteborg, Sweden). We estimated costs for inpatient and follow-up care of ectopic pregnancy by the two methods. Observed resource use (eg, procedure duration) was multiplied by 1992 estimates of resource unit cost (eg, cost per minute of laparoscopy time), based on detailed internal cost accounting data from Huddinge University Hospital. By specified criteria, the initial procedure eliminated trophoblastic activity without major complications in 81% (95% CI: 68-90) of 52 laparoscopy patients, versus 95% (85-99) of 57 laparotomy patients. Residual trophoblast or complications were successfully treated in all remaining patients. Mean simulated costs (standard error) for the overall laparoscopy strategy were 28,058 (1780) Swedish kronor versus 32,699 (1080) kronor for laparotomy (p = 0.03). In the baseline simulation and most sensitivity analyses, laparoscopy produced final outcomes equivalent to those of laparotomy at lower costs. As laparoscopic outcomes improve, this newer approach should become increasingly preferable. [ABSTRACT FROM AUTHOR]

Locus coeruleus (LC) neurons send their noradrenergic axons across multiple brain regions, including neocortex, subcortical regions, and spinal cord. Many aspects of cognition are known to be dependent on the noradrenergic system, and it has been suggested that dysfunction in this system may play central roles in cognitive decline associated with both normative aging and neurodegenerative disease. While basic anatomical and biochemical features of the LC have been examined in many species, detailed characterizations of the structure and function of the LC across the lifespan are not currently available. This includes the rhesus macaque, which is an important model of human brain function because of their striking similarities in brain architecture and behavioral capacities. In the present study, we describe a method to combine structural MRI, Nissl, and immunofluorescent histology from individual monkeys to reconstruct, in 3 dimensions, the entire macaque LC nucleus. Using these combined methods, a standardized volume of the LC was determined, and high-resolution confocal images of tyrosine hydroxylase-positive neurons were mapped into this volume. This detailed representation of the LC allows definitions to be proposed for three distinct subnuclei, including a medial region and a lateral region (based on location with respect to the central gray, inside or outside, respectively), and a compact region (defined by densely packed neurons within the medial compartment). This enabled the volume to be estimated and cell density to be calculated independently in each LC subnucleus for the first time. This combination of methods should allow precise characterization of the LC and has the potential to do the same for other nuclei with distinct molecular features., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

One hallmark of normative brain aging is vast heterogeneity in whether older people succumb to or resist cognitive decline. Resilience describes a brain's capacity to maintain cognition in the face of aging and disease. One factor influencing resilience is brain reserve-the status of neurobiological resources available to support neuronal circuits as dysfunction accumulates. This study uses a cohort of behaviorally characterized adult, middle-aged, and aged rats to test whether neurobiological factors that protect inhibitory neurotransmission and synapse function represent key components of brain reserve. Histochemical analysis of extracellular matrix proteoglycans, which play critical roles in stabilizing synapses and modulating inhibitory neuron excitability, was conducted alongside analyses of lipofuscin-associated autofluorescence. The findings indicate that aging results in lower proteoglycan density and more lipofuscin in CA3. Aged rats with higher proteoglycan density exhibited better performance on the Morris watermaze, whereas lipofuscin abundance was not related to spatial memory. These data suggest that the local environment around neurons may protect against synapse dysfunction or hyperexcitability and could contribute to brain reserve mechanisms., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Synapse loss and altered plasticity are significant contributors to memory loss in aged individuals. Microglia, the innate immune cells of the brain, play critical roles in maintaining synapse function, including through a recently identified role in regulating the brain extracellular matrix. This study sought to determine the relationship between age, microglia, and extracellular matrix structure densities in the macaque retrosplenial cortex. Twenty-nine macaques ranging in age from young adult to aged were behaviorally characterized on 3 distinct memory tasks. Microglia, parvalbumin (PV)-expressing interneurons and extracellular matrix structures, known as perineuronal nets (PNNs), were immuno- and histochemically labeled. Our results indicate that microglia densities increase in the retrosplenial cortex of aged monkeys, while the proportion of PV neurons surrounded by PNNs decreases. Aged monkeys with more microglia had fewer PNN-associated PV neurons and displayed slower learning and poorer performance on an object recognition task. Stepwise regression models using age and the total density of aggrecan, a chondroitin sulfate proteoglycan of PNNs, better predicted memory performance than did age alone. Together, these findings indicate that elevated microglial activity in aged brains negatively impacts cognition in part through mechanisms that alter PNN assembly in memory-associated brain regions., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Hippocampal gamma and theta oscillations are associated with mnemonic and navigational processes and adapt to changes in the behavioral state of an animal to optimize spatial information processing. It has been shown that locomotor activity modulates gamma and theta frequencies in rats, although how age alters this modulation has not been well studied. Here, we examine gamma and theta local-field potential and place cell activity in the hippocampus CA1 region of young and old male rats as they performed a spatial eye-blink conditioning task across 31 d. Although mean gamma frequency was similar in both groups, gamma frequency increased with running speed at a slower rate in old animals. By contrast, theta frequencies scaled with speed similarly in both groups but were lower across speeds in old animals. Although these frequencies scaled equally well with deceleration and speed, acceleration was less correlated with gamma frequency in both age groups. Additionally, spike phase-locking to gamma, but not theta, was greater in older animals. Finally, aged rats had reduced within-field firing rates but greater spatial information per spike within the field. These data support a strong relationship between locomotor behavior and local-field potential activity and suggest that age significantly affects this relationship. Furthermore, observed changes in CA1 place cell firing rates and information content lend support to the hypothesis that age may result in more general and context-invariant hippocampal representations over more detailed information. These results may explain the observation that older adults tend to recall the gist of an experience rather than the details. SIGNIFICANCE STATEMENT Hippocampal oscillations and place cell activity are sensitive to sensorimotor input generated from active locomotion, yet studies of aged hippocampal function often do not account for this. By considering locomotion and spatial location, we identify novel age-associated differences in the scaling of oscillatory activity with speed, spike-field coherence, spatial information content, and within-field firing rates of CA1 place cells. These results indicate that age has an impact on the relationship between locomotion and hippocampal oscillatory activity, perhaps indicative of alterations to afferent input. These data also support the hypothesis that aged hippocampal place cells, compared with young, may more often represent more general spatial information. If true, these results may help explain why older humans tend to recall less specific and more gist-like information., (Copyright © 2022 the authors.)

During aging, microglia produce inflammatory factors, show reduced tissue surveillance, altered interactions with synapses, and prolonged responses to CNS insults, positioning these cells to have profound impact on the function of nearby neurons. We and others recently showed that microglial attributes differ significantly across brain regions in young adult mice. However, the degree to which microglial properties vary during aging is largely unexplored. Here, we analyze and manipulate microglial aging within the basal ganglia, brain circuits that exhibit prominent regional microglial heterogeneity and where neurons are vulnerable to functional decline and neurodegenerative disease. In male and female mice, we demonstrate that VTA and SNc microglia exhibit unique and premature responses to aging, compared with cortex and NAc microglia. This is associated with localized VTA/SNc neuroinflammation that may compromise synaptic function as early as middle age. Surprisingly, systemic inflammation, local neuron death, and astrocyte aging do not appear to underlie these early aging responses of VTA and SNc microglia. Instead, we found that microglial lysosome status was tightly linked to early aging of VTA microglia. Microglial ablation/repopulation normalized VTA microglial lysosome swelling and suppressed increases in VTA microglial density during aging. In contrast, CX3CR1 receptor KO exacerbated VTA microglial lysosome rearrangements and VTA microglial proliferation during aging. Our findings reveal a previously unappreciated regional variation in onset and magnitude of microglial proliferation and inflammatory factor production during aging and highlight critical links between microglial lysosome status and local microglial responses to aging. SIGNIFICANCE STATEMENT Microglia are CNS cells that are equipped to regulate neuronal health and function throughout the lifespan. We reveal that microglia in select brain regions begin to proliferate and produce inflammatory factors in late middle age, months before microglia in other brain regions. These findings demonstrate that CNS neuroinflammation during aging is not uniform. Moreover, they raise the possibility that local microglial responses to aging play a critical role in determining which populations of neurons are most vulnerable to functional decline and neurodegenerative disease., (Copyright © 2022 the authors.)

Highlighted Research Paper: AMPA Receptors Exist in Tunable Mobile and Immobile Synaptic Fractions In Vivo , by Haiwen Chen, Richard H. Roth, Elena Lopez-Ortega, Han L. Tan, and Richard L. Huganir., (Copyright © 2021 Gray and De Biase.)

Deficits in auditory and visual processing are commonly encountered by older individuals. In addition to the relatively well described age-associated pathologies that reduce sensory processing at the level of the cochlea and eye, multiple changes occur along the ascending auditory and visual pathways that further reduce sensory function in each domain. One fundamental question that remains to be directly addressed is whether the structure and function of the central auditory and visual systems follow similar trajectories across the lifespan or sustain the impacts of brain aging independently. The present study used diffusion magnetic resonance imaging and electrophysiological assessments of auditory and visual system function in adult and aged macaques to better understand how age-related changes in white matter connectivity at multiple levels of each sensory system might impact auditory and visual function. In particular, the fractional anisotropy (FA) of auditory and visual system thalamocortical and interhemispheric corticocortical connections was estimated using probabilistic tractography analyses. Sensory processing and sensory system FA were both reduced in older animals compared with younger adults. Corticocortical FA was significantly reduced only in white matter of the auditory system of aged monkeys, while thalamocortical FA was lower only in visual system white matter of the same animals. Importantly, these structural alterations were significantly associated with sensory function within each domain. Together, these results indicate that age-associated deficits in auditory and visual processing emerge in part from microstructural alterations to specific sensory white matter tracts, and not from general differences in white matter condition across the aging brain. SIGNIFICANCE STATEMENT Age-associated deficits in sensory processing arise from structural and functional alterations to both peripheral sensory organs and central brain regions. It remains unclear whether different sensory systems undergo similar or distinct trajectories in function across the lifespan. To provide novel insights into this question, this study combines electrophysiological assessments of auditory and visual function with diffusion MRI in aged macaques. The results suggest that age-related sensory processing deficits in part result from factors that impact the condition of specific white matter tracts, and not from general decreases in connectivity between sensory brain regions. Such anatomic specificity argues for a framework aimed at understanding vulnerabilities with relatively local influence and brain region specificity., (Copyright © 2020 the authors.)

Deficits in auditory function and cognition are hallmarks of normative aging. Recent evidence suggests that hearing-impaired individuals have greater risks of developing cognitive impairment and dementia compared to people with intact auditory function, although the neurobiological bases underlying these associations are poorly understood. Here, a colony of aging macaques completed a battery of behavioral tests designed to probe frontal and temporal lobe-dependent cognition. Auditory brainstem responses (ABRs) and visual evoked potentials were measured to assess auditory and visual system function. Structural and diffusion magnetic resonance imaging were then performed to evaluate the microstructural condition of multiple white matter tracts associated with cognition. Animals showing higher cognitive function had significantly better auditory processing capacities, and these associations were selectively observed with tasks that primarily depend on temporal lobe brain structures. Tractography analyses revealed that the fractional anisotropy (FA) of the fimbria-fornix and hippocampal commissure were associated with temporal lobe-dependent visual discrimination performance and auditory sensory function. Conversely, FA of frontal cortex-associated white matter was not associated with auditory processing. Visual sensory function was not associated with frontal or temporal lobe FA, nor with behavior. This study demonstrates significant and selective relationships between ABRs, white matter connectivity, and higher-order cognitive ability., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Hippocampal sharp-wave ripples are brief high-frequency (120-250 Hz) oscillatory events that support mnemonic processes during sleep and awake behavior. Although ripples occurring during sleep are believed to facilitate memory consolidation, waking ripples may also be involved in planning and memory retrieval. Recent work from our group determined that normal aging results in a significant reduction in the peak oscillatory frequency and rate-of-occurrence of ripples during sleep that may contribute to age-associated memory decline. It is unknown, however, how aging alters waking ripples. We investigated whether characteristics of waking ripples undergo age-dependent changes. Sharp-wave ripple events were recorded from the CA1 region of the hippocampus in old (n = 5) and young (n = 6) F344 male rats as they performed a place-dependent eyeblink conditioning task. Several novel observations emerged from this analysis. First, although aged rats expressed more waking ripples than young rats during track running and reward consumption, this effect was eliminated, and, in the case of track-running, reversed when time spent in each location was accounted for. Thus, aged rats emit more ripples, but young rats express a higher ripple rate. This likely results from reduced locomotor activity in aged animals. Furthermore, although ripple rates increased as young rats approached rewards, rates did not increase in aged rats, and rates in aged and young animals were not affected by eyeblink conditioning. Finally, although the oscillatory frequency of ripples was lower in aged animals during rest, frequencies in aged rats increased during behavior to levels indistinguishable from young rats. Given the involvement of waking ripples in memory retrieval, a possible consequence of slower movement speeds of aged animals is to provide more opportunity to replay task-relevant information and compensate for age-related declines in ripple rate during task performance., (© 2018 Wiley Periodicals, Inc.)

The use of animal models in brain aging research has led to numerous fundamental insights into the neurobiological processes that underlie changes in brain function associated with normative aging. Macaque monkeys have become the predominant nonhuman primate model system in brain aging research due to their striking similarities to humans in their behavioral capacities, sensory processing abilities, and brain architecture. Recent public concern about nonhuman primate research has made it imperative to attempt to clearly articulate the potential benefits to human health that this model enables. The present review will highlight how nonhuman primates provide a critical bridge between experiments conducted in rodents and development of therapeutics for humans. Several studies discussed here exemplify how nonhuman primate research has enriched our understanding of cognitive and sensory decline in the aging brain, as well as how this work has been important for translating mechanistic implications derived from experiments conducted in rodents to human brain aging research.

Brain tissue contains autofluorescing elements that potentially impede accurate identification of neurons when visualized with fluorescent microscopy. Age-related accumulation of molecules with autofluorescent properties, such as lipofuscin, can possess spectral profiles that invade the typical emission range of fluorophores commonly utilized in fluorescent microscopy. The traditional method for accounting for this native fluorescence is to apply lipophilic dyes that are able to sequester these unwanted signals. While effective, such dyes can present a range of problems including the obstruction of fluorescent probe emissions. The present study utilizes aged primate midbrain tissue stained for tyrosine hydroxylase and calbindin to investigate an image processing approach for removing autofluorescence utilizing spectral imaging and linear unmixing. This technique is then compared against the traditional, dye-based autofluorescence sequestration method using Sudan Black B (SBB). Spectral imaging and linear unmixing yielded significantly higher cell numbers than SBB treatment. This finding suggests that computational approaches for removing autofluorescence in neural tissue are both viable and preferential to dye-based approaches for estimation of cell body numbers.

Immediate-early genes (IEGs) are rapidly and transiently induced following excitatory neuronal activity including maximal electroconvulsive shock treatment (ECT). The rapid RNA response can be blocked by the sodium channel antagonist tetrodotoxin (TTX), without blocking seizures, indicating a role for electrical stimulation in electroconvulsive shock-induced mRNA responses. In behaving animals, Arc mRNA is selectively transcribed following patterned neuronal activity and rapidly trafficked to dendrites where it preferentially accumulates at active synapses for local translation. Here we examined whether there is a relationship between the current intensities that elicit seizures and the threshold for Arc mRNA transcription in the rat hippocampus and perirhinal cortex (PRC). Animals received ECT of varying current intensities (0, 20, 40 65, 77 and 85 mA) and were sacrificed 5 min later. While significantly more CA1, CA3 and perirhinal pyramidal cells expressed Arc at the lowest stimulus intensity compared to granule cells, there was an abrupt threshold transition that occurred in all four regions at 77 mA. This precise threshold for Arc expression in all temporal lobe neurons examined may involve regulation of the calcium-dependent mechanisms that are upstream to activity-dependent IEG transcription.

Background: The study of learning in populations of subjects can provide insights into the changes that occur in the brain with aging, drug intervention, and psychiatric disease., New Method: We introduce a separable two-dimensional (2D) random field (RF) model for analyzing binary response data acquired during the learning of object-reward associations across multiple days. The method can quantify the variability of performance within a day and across days, and can capture abrupt changes in learning., Results: We apply the method to data from young and aged macaque monkeys performing a reversal-learning task. The method provides an estimate of performance within a day for each age group, and a learning rate across days for each monkey. We find that, as a group, the older monkeys require more trials to learn the object discriminations than do the young monkeys, and that the cognitive flexibility of the younger group is higher. We also use the model estimates of performance as features for clustering the monkeys into two groups. The clustering results in two groups that, for the most part, coincide with those formed by the age groups. Simulation studies suggest that clustering captures inter-individual differences in performance levels., Comparison With Existing Method(s): In comparison with generalized linear models, this method is better able to capture the inherent two-dimensional nature of the data and find between group differences., Conclusions: Applied to binary response data from groups of individuals performing multi-day behavioral experiments, the model discriminates between-group differences and identifies subgroups., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Deficits in cognitive functions that rely on the integrity of the frontal and temporal lobes are characteristic of normative human aging. Due to similar aging phenotypes and homologous cortical organization between nonhuman primates and humans, several species of macaque monkeys are used as models to explore brain senescence. These macaque species are typically regarded as equivalent models of cognitive aging, yet no direct comparisons have been made to support this assumption. Here we used adult and aged rhesus and bonnet macaques (Macaca mulatta and Macaca radiata) to characterize the effect of age on acquisition and retention of information across delays in a battery of behavioral tasks that rely on prefrontal cortex and medial temporal lobe networks. The cognitive functions that were tested include visuospatial short-term memory, object recognition memory, and object-reward association memory. In general, bonnet macaques at all ages outperformed rhesus macaques on tasks thought to rely primarily on the prefrontal cortex, and were more resilient to age-related deficits in these behaviors. On the other hand, both species were comparably impaired by age on tasks thought to preferentially engage the medial temporal lobe. Together, these results suggest that rhesus and bonnet macaques are not equivalent models of cognitive aging and highlight the value of cross-species comparisons. These observations should enable improved design and interpretation of future experiments aimed at understanding changes in cognition across the lifespan., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim: Cognitive aging is known to alter reward-guided behaviors that require interactions between the orbitofrontal cortex (OFC) and amygdala. In macaques, OFC, but not amygdala volumes decline with age and correlate with performance on a reward devaluation (RD) task. The present study used diffusion magnetic resonance imaging (dMRI) methods to investigate whether the condition of the white matter associated with amygdala-OFC connectivity changes with age and relates to reward devaluation., Methods: Diffusion-, T1- and T2-weighted MRIs were acquired from adult and aged bonnet macaques. Using probabilistic tractography, fractional anisotropy (FA) estimates from two separate white matter tracts associated with amygdala-OFC connectivity, the uncinate fasciculus (UF) and amygdalofugal (AF) pathways, were obtained. Performance measures on RD and reversal learning (RL) tasks were also acquired and related to FA indices from each anatomical tract., Results: Aged monkeys were impaired on both the RD and RL tasks and had lower FA indices in the AF pathway. Higher FA indices from the right hemisphere UF pathway correlated with better performance on an object-based RD task, whereas higher FA indices from the right hemisphere AF were associated with better performance on an object-free version of the task. FA measures from neither tract correlated with RL performance., Conclusions: These results suggest that the condition of the white matter connecting the amygdala and OFC may impact reward devaluation behaviors. Furthermore, the observation that FA indices from the UF and AF differentially relate to reward devaluation suggests that the amygdala-OFC interactions that occur via these separate tracts are partially independent., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest.

Objectives: As sepsis hospitalizations have increased, in-hospital sepsis deaths have declined. However, reported rates may remain higher among racial/ethnic minorities. Most previous studies have adjusted primarily for age and sex. The effect of other patient and hospital characteristics on disparities in sepsis mortality is not yet well-known. Furthermore, coding practices in claims data may influence findings. The objective of this study was to use a broad method of capturing sepsis cases to estimate 2004-2013 trends in risk-adjusted in-hospital sepsis mortality rates by race/ethnicity to inform efforts to reduce disparities in sepsis deaths., Design: Retrospective, repeated cross-sectional study., Setting: Acute care hospitals in the Healthcare Cost and Utilization Project State Inpatient Databases for 18 states with consistent race/ethnicity reporting., Patients: Patients diagnosed with septicemia, sepsis, organ dysfunction plus infection, severe sepsis, or septic shock., Measurements and Main Results: In-hospital sepsis mortality rates adjusted for patient and hospital factors by race/ethnicity were calculated. From 2004 to 2013, sepsis hospitalizations for all racial/ethnic groups increased, and mortality rates decreased by 5-7% annually. Mortality rates adjusted for patient characteristics were higher for all minority groups than for white patients. After adjusting for hospital characteristics, sepsis mortality rates in 2013 were similar for white (92.0 per 1,000 sepsis hospitalizations), black (94.0), and Hispanic (93.5) patients but remained elevated for Asian/Pacific Islander (106.4) and "other" (104.7; p < 0.001) racial/ethnic patients., Conclusions: Our results indicate that hospital characteristics contribute to higher rates of sepsis mortality for blacks and Hispanics. These findings underscore the importance of ensuring that improved sepsis identification and management is implemented across all hospitals, especially those serving diverse populations.

One hallmark of the normal cognitive aging process involves alterations in executive function. Executive function can be divided into at least three separable components, including set shifting, attentional updating and monitoring, and inhibition of prepotent responses. The ability to study the neural basis of cognitive aging has been enriched by the use of animal models such as the macaque monkey. In aged macaques, changes in attentional updating and monitoring systems are poorly understood compared to changes in shifting and inhibition. A partial explanation for this is the fact that the tasks designed to study executive function in aged monkeys, to date, primarily have probed shifting and inhibition processes. Here we examine how aging impacts attentional updating and monitoring processes in monkeys using an interference task designed after a paradigm used to examine multi-tasking in older humans. Young and aged macaque monkeys were tested on this interference task as well as on an object reversal learning task to study these processes in the same animals. Relative to the young monkeys, aged animals were impaired on both tasks. Proactive and retroactive interference did not differ between age groups on an array of 40 object pairs presented each day in the object reversal learning task. The levels of performance on the interference task were not correlated with levels of performance in the object reversal task. These results suggest that attentional updating and monitoring and affective shifting are separable functions in the macaque, and that normal aging affects these mental operations independently., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Age-related deficits in episodic memory result, in part, from declines in the integrity of medial temporal lobe structures, such as the hippocampus, but are not thought to be due to widespread loss of principal neurons. Studies in rodents suggest, however, that inhibitory interneurons may be particularly vulnerable in advanced age. Optimal encoding and retrieval of information depend on a balance of excitatory and inhibitory transmission. It is not known whether a disruption of this balance is observed in aging non-human primates, and whether such changes affect network function and behavior. To examine this question, we combine large-scale electrophysiological recordings with cell-type-specific imaging in the medial temporal lobe of cognitively assessed, aged rhesus macaques. We found that neuron excitability in the hippocampal region CA3 is negatively correlated with the density of somatostatin-expressing inhibitory interneurons in the vicinity of the recording electrodes in the stratum oriens. By contrast, no hyperexcitability or interneuron loss was observed in the perirhinal cortex of these aged, memory-impaired monkeys. These data provide a link, for the first time, between selective increases in principal cell excitability and declines in a molecularly defined population of interneurons that regulate network inhibition., Competing Interests: The authors declare no competing financial interests.

Unlabelled: Spatial and episodic memory performance declines with age, and the neural basis for this decline is not well understood. Sharp-wave ripples are brief (∼70 ms) high-frequency oscillatory events generated in the hippocampus and are associated with the consolidation of spatial memories. Given the connection between ripple oscillations and memory consolidation, we investigated whether the structure of ripple oscillations and ripple-triggered patterns of single-unit activity are altered in aged rats. Local field and single-unit activity surrounding sharp-wave ripple events were examined in the CA1 region of the hippocampus of old (n = 5) and young (n = 6) F344 rats during periods of rest preceding and following performance on a place-dependent eyeblink-conditioning task. Neural responses in aged rats differed from responses in young rats in several ways. First, compared with young rats, the rate of ripple occurrence (ripple density) is reduced in aged rats during postbehavior rest. Second, mean ripple frequency during prebehavior and postbehavior rest is lower in aged animals (aged: 132 Hz; young: 146 Hz). Third, single neurons in aged animals responded more consistently from ripple to ripple. Fourth, variability in interspike intervals was greater in aged rats. Finally, neurons were tuned to a narrower range of phases of the ripple oscillation relative to young animals. Together, these results suggest that the CA1 network in aged animals has a reduced "vocabulary" of available representational states., Significance Statement: The hippocampus is a structure that is critical for the formation of episodic memories. Sharp-wave ripple events generated in the hippocampus have been implicated in memory consolidation processes critical to memory stabilization. We examine here whether these ripple oscillations are altered over the course of the life span, which could contribute to hippocampus-dependent memory deficits that occur during aging. This experiment used young and aged memory-impaired rats to examine age-related changes in ripple architecture, ripple-triggered spike variance, and spike-phase coherence. We found that there are, indeed, significant changes in characteristics of ripples in older animals that could impact consolidation processes and memory stabilization in the aged brain., (Copyright © 2016 the authors 0270-6474/16/365650-11$15.00/0.)

Hippocampal circuits are among the best described networks in the mammalian brain, particularly with regard to the alterations that arise during normal aging. Decades of research indicate multiple points of vulnerability in aging neural circuits, and it has been proposed that each of these changes make a contribution to observed age-related cognitive deficits. Another view has been relatively overlooked - namely that some of these changes arise in adaptive response to protect network function in aged animals. This possibility leads to a rather different view on the biological variation of function in the brain of older individuals. Using the hippocampus as a model neural circuit we discuss how, in normally aged animals, some age-related changes may arise through processes of neural plasticity that serve to enhance network function rather than to hinder it. Conceptually disentangling the initial age-related vulnerabilities from changes that result in adaptive response will be a major challenge for the future research on brain aging. We suggest that a reformulation of how normal aging could be understood from an adaptive perspective will lead to a deeper understanding of the secrets behind successful brain aging and our recent cultural successes in facilitating these processes., (Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Congenital heart defects (CHDs) occur in approximately 8 per 1000 live births. Improvements in detection and treatment have increased survival. Few national estimates of the healthcare costs for infants, children and adolescents with CHDs are available., Methods: We estimated hospital costs for hospitalizations using pediatric (0-20 years) hospital discharge data from the 2009 Healthcare Cost and Utilization Project Kids' Inpatient Database (KID) for hospitalizations with CHD diagnoses. Estimates were up-weighted to be nationally representative. Mean costs were compared by demographic factors and presence of critical CHDs (CCHDs)., Results: Up-weighting of the KID generated an estimated 4,461,615 pediatric hospitalizations nationwide, excluding normal newborn births. The 163,980 (3.7%) pediatric hospitalizations with CHDs accounted for approximately $5.6 billion in hospital costs, representing 15.1% of costs for all pediatric hospitalizations in 2009. Approximately 17% of CHD hospitalizations had a CCHD, but it varied by age: approximately 14% of hospitalizations of infants, 30% of hospitalizations of patients aged 1 to 10 years, and 25% of hospitalizations of patients aged 11 to 20 years. Mean costs of CHD hospitalizations were higher in infancy ($36,601) than at older ages and were higher for hospitalizations with a CCHD diagnosis ($52,899). Hospitalizations with CCHDs accounted for 26.7% of all costs for CHD hospitalizations, with hypoplastic left heart syndrome, coarctation of the aorta, and tetralogy of Fallot having the highest total costs., Conclusion: Hospitalizations for children with CHDs have disproportionately high hospital costs compared with other pediatric hospitalizations, and the 17% of hospitalizations with CCHD diagnoses accounted for 27% of CHD hospital costs., (© 2014 Wiley Periodicals, Inc.)

Neurochemical changes in the expression of various proteins within the central auditory system have been associated with natural aging. These changes may compensate in part for the loss of auditory sensitivity arising from two phenomena of the aging auditory system: cochlear histopathologies and increased excitability of central auditory neurons. Recent studies in the macaque monkey have revealed age-related changes in the density of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase (NADPHd) and parvalbumin (PV)-positive cells within the inferior colliculus and superior olivary complex. The cochlear nucleus (CN), which is the first central auditory nucleus, remains unstudied. Since the CN participates in the generation of the auditory brainstem response (ABR) and receives direct innervation from the cochlea, it serves as an ideal nucleus to compare the relationship between these neurochemical changes and the physiological and peripheral changes of the aging auditory system. We used stereological sampling to calculate the densities of NADPHd and PV reactive neurons within the three subdivisions of the CN in middle-aged and aged rhesus macaques. Regression analyses of these values with ABR properties and cochlear histopathologies revealed relationships between these cell types and the changing characteristics of the aging auditory system. Our results indicate that NADPHd expression does change with age in a specific subdivision of the CN, but PV does not. Conversely, PV expression correlated with ABR amplitudes and outer hair cell loss in the cochlea, but NADPHd did not. These results indicate that NADPHd and PV may take part in distinct compensatory efforts of the aging auditory system., (Copyright © 2013 Wiley Periodicals, Inc.)

Age-related hearing loss (ARHL) is marked by audiometric hearing deficits that propagate along the auditory pathway. Neurochemical changes as a function of aging have also been identified in neurons along the auditory pathway in both rodents and carnivores, however, very little is known about how these neurochemicals change in the non-human primate. To examine how these compensatory neurochemical changes relate to normal aging and audiometric sensitivity along the auditory pathway, we collected auditory brainstem responses (ABRs) and brain specimens from seven rhesus monkeys spanning in age from 15 to 35 years old, and examined the relationship between click evoked ABR thresholds and the ABR evoked pure tone average (PTA) and changes in the number of parvalbumin and NADPH-diaphorase positive cells in the auditory midbrain. We found that the number of parvalbumin positive cells in the central nucleus and the surrounding cortex regions of the inferior colliculus were strongly correlated with advancing age and ABR PTA. We also found that the numbers of NADPHd positive cells in these same regions were not associated with normal aging or changes in the ABR thresholds. These findings suggest that the auditory midbrain undergoes an up-regulation of parvalbumin expressing neurons with aging that is related to changes in the processing of frequencies across the audiometric range.

Background: Differences in quality of care may contribute to racial variation in outcomes of bladder cancer (BCa). Quality indicators in patients undergoing surgery for BCa include the use of high-volume surgeons and high-volume hospitals, and, when clinically indicated, receipt of pelvic lymphadenectomy, receipt of continent urinary diversion, and undergoing radical cystectomy instead of partial cystectomy. The authors compared these quality indicators as well as adverse perioperative outcomes in black patients and white patients with BCa., Methods: The Healthcare Cost and Utilization Project State Inpatient Databases for New York, Florida, and Maryland (1996-2009) were used, because they consistently included race, surgeon, and hospital identifiers. Quality indicators were compared across racial groups using regression models adjusting for age, sex, Elixhauser comorbidity sum, insurance, state, and year of surgery, accounting for clustering within hospital., Results: Black patients were treated more often by lower volume surgeons and hospitals, they had significantly lower receipt of pelvic lymphadenectomy and continent diversion, and they experienced higher rates of adverse outcomes compared with white patients. These associations remained significant for black patients who received treatment from surgeons and at hospitals in the top volume decile., Conclusions: Black patients with BCa had lower use of experienced providers and institutions for BCa surgery. In addition, the quality of care for black patients was lower than that for whites even if they received treatment in a high-volume setting. This gap in quality of care requires further investigation., (© 2013 American Cancer Society.)

Objective: Children and adolescents are known to experience poor health care quality; some groups of children have poorer health care than others. We sought to examine trends over time in health care quality and disparities by race, Hispanic ethnicity, income, insurance, gender, rurality, and special health care needs., Methods: Source data were extracted from the 2011 National Healthcare Quality Report (NHQR) and National Healthcare Disparities Report (NHDR) database, which contains aggregated data from many government and private sources for the years 2000 through 2009. The NHQR and NHDR approaches to calculating disparities and trends in quality and disparities were used. Within each quality measure with available data, results for demographic subgroups of children characterized by race/ethnicity, income, insurance, residence, special health care need, and gender were compared to those of a reference group to determine whether disparities existed and whether disparities had changed over time., Results: Of 68 measures with data for calculating potential disparities, 50 showed disparities in quality for at least 1 comparison subgroup in the most recent year of data available, while 18 measures showed no such disparities. Of the 50 measures with current disparities, 39 measures had sufficient data to calculate trends. Among the 137 comparisons made within these 39 measures, there was no change in disparities over time for 126 comparisons, 3 comparisons worsened, and 8 comparisons improved., Conclusions: There was some progress in health care quality and reducing disparities in children's health care quality from 2000 to 2009; opportunities for targeting improvement strategies remain., (Published by Elsevier Inc.)

Positive immunoreactivity to the calcium-binding protein parvalbumin (PV) and nitric oxide synthase NADPH diaphorase (NADPHd) is well documented within neurons of the central auditory system of both rodents and primates. These proteins are thought to play roles in the regulation of auditory processing. Studies examining the age-related changes in expression of these proteins have been conducted primarily in rodents but are sparse in primate models. In the brainstem, the superior olivary complex (SOC) is crucial for the computation of sound source localization in azimuth, and one hallmark of age-related hearing deficits is a reduced ability to localize sounds. To investigate how these histochemical markers change as a function of age and hearing loss, we studied eight rhesus macaques ranging in age from 12 to 35 years. Auditory brainstem responses (ABRs) were obtained in anesthetized animals for click and tone stimuli. The brainstems of the sesame animals were then stained for PV and NADPHd reactivity. Reactive neurons in the three nuclei of the SOC were counted, and the densities of each cell type were calculated. We found that PV and NADPHd expression increased with both age and ABR thresholds in the medial superior olive but not in either the medial nucleus of the trapezoid body or the lateral superior olive. Together these results suggest that the changes in protein expression employed by the SOC may compensate for the loss of efficacy of auditory sensitivity in the aged primate.

Subcortical auditory structures in the macaque auditory system increase their densities of neurons expressing the calcium binding protein parvalbumin (PV) with age. However, it is unknown whether these increases occur in the thalamic division of the auditory system, the medial geniculate nucleus (MGN). Furthermore, it is also unclear whether these age-related changes are specific to the macaque auditory system or are generalized to other sensory systems. To address these questions, the PV immunoreactivity of the medial and lateral geniculate nuclei (LGN) from seven rhesus macaques ranging in age from 15 to 35 was assessed. Densities of PV expressing neurons in the three subdivisions of the MGN and the six layers of the LGN were calculated separately using unbiased stereological sampling techniques. We found that the ventral and magnocellular subdivisions of the MGN and all six layers of the LGN increased their expressions of PV with age, although increases in the MGN were greater in magnitude than in the LGN. Together, these results suggest that the MGN shows age-related increases in PV expression as is seen throughout the macaque ascending auditory system, and that the analogous region of the visual system shows smaller increases. We conclude that, while there are some similarities between sensory systems, the age-related neurochemical changes seen throughout the macaque auditory system cannot be fully generalized to other sensory systems.

Purpose: Difference in the quality of care may contribute to the less optimal prostate cancer treatment outcomes among black men compared with white men. We determined whether a racial quality of care gap exists in surgical care for prostate cancer, as evidenced by racial variation in the use of high volume surgeons and facilities, and in the quality of certain outcome measures of care., Materials and Methods: We performed cross-sectional and cohort analyses of administrative data from the Healthcare Cost and Utilization Project all-payer State Inpatient Databases, encompassing all nonfederal hospitals in Florida, Maryland and New York State from 1996 to 2007. Included in analysis were men 18 years old or older with a diagnosis of prostate cancer who underwent radical prostatectomy. We compared the use of surgeons and/or hospitals in the top quartile of annual volume for this procedure, inpatient blood transfusion, complications, mortality and length of stay between black and white patients., Results: Of 105,972 patients 81,112 (76.5%) were white, 14,006 (13.2%) were black, 6,999 (6.6%) were Hispanic and 3,855 (3.6%) were all other. In mixed effects multivariate models, black men had markedly lower use of high volume hospitals (OR 0.73, 95% CI 0.70-0.76) and surgeons (OR 0.67, 95% CI 0.64-0.70) compared to white men. Black men also had higher odds of blood transfusion (OR 1.08, 95% CI 1.01-1.14), longer length of stay (OR 1.07, 95% CI 1.06-1.07) and inpatient mortality (OR 1.73, 95% CI 1.02-2.92)., Conclusions: Using an all-payer data set, we identified concerning potential quality of care gaps between black and white men undergoing radical prostatectomy for prostate cancer., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Study Design: Sequential cross-sectional analysis., Objective: To document vertebroplasty rates and costs., Summary of Background Data: Little is known about interstate variation in rates or about nation-wide costs associated with the growing use of percutaneous vertebroplasty., Methods: Using specific CPT-4 billing codes, we reviewed aggregate Medicare Part B fee-for-service claims data (cross-stratified by physician specialty and treatment setting) on thoracolumbar vertebroplasties performed from 2001-2005. Vertebroplasty rates for individual states were expressed per 100,000 Part B fee-for-service enrollees. Nation-wide facility and physician charges (combining expected contributions from all sources) allowed by Medicare for vertebroplasties and associated imaging guidance procedures were applied to observed vertebroplasty volumes. These charges (reflecting direct medical costs from an all-payer perspective) were expressed in 2005 dollars using the Producer Price Index., Results: Vertebroplasty rates for individual states rose but varied considerably, ranging from 0.0 to 515.6/100,000 Medicare Part B fee-for-service enrollees in 2001 (median state rate = 35.4), and from 9.8 to 849.5 in 2005 (median state rate = 75.0). On average, 1.3 vertebral levels were treated per procedure, varying by treatment site and physician specialty. Fluoroscopic rather than computed tomography guidance was used in 98.7% of cases. Total nation-wide inflation-adjusted charges rose from $76.0 million for 14,142 cases performed in 2001 to $152.3 million for 29,090 cases in 2005. While vertebroplasty was predominantly an outpatient procedure, inpatient cases generated most of the charges. Increasing volumes and costs were associated with cases performed in ambulatory surgery centers and physicians' offices., Conclusion: Nation-wide vertebroplasty volumes and inflation-adjusted charges doubled from 2001 to 2005 in this Medicare population. Procedure rates varied considerablyby state. Almost all cases involved fluoroscopic guidance; procedures treating multiple vertebral levels were not uncommon. Procedures performed in free-standing facilities are of growing importance. Given the issues surrounding appropriate vertebroplasty use, future practice patterns and outcomes should be closely tracked.

Study Design: Retrospective cohort study using a hospital discharge registry of all nonfederal acute care hospitals in Washington state., Objectives: To determine the cumulative incidence of reoperation following lumbar surgery for degenerative disease and, for specific diagnoses, to compare the frequency of reoperation following fusion with that following decompression alone., Summary of Background Data: Repeat lumbar spine operations are generally undesirable, implying persistent symptoms, progression of degenerative changes, or treatment complications. Compared to decompression alone, spine fusion is commonly viewed as a stabilizing treatment that may reduce the need for additional surgery. However, indications for fusion surgery in degenerative spine disorders remain controversial, and the effects of fusion on reoperation rates are unclear., Methods: Adults who underwent inpatient lumbar surgery for degenerative spine disorders in 1990-1993 (n = 24,882) were identified from International Classification of Diseases ninth Revision, Clinical Modification codes and then categorized as having either a lumbar decompression surgery or lumbar fusion surgery. We then compared the subsequent incidence of lumbar spine surgery between these groups., Results: Patients who had surgery in 1990-93 had a 19% cumulative incidence of reoperation during the subsequent 11 years. Patients with spondylolisthesis had a lower cumulative incidence of reoperation after fusion surgery than after decompression alone (17.1% vs. 28.0%, P = 0.002). For other diagnoses combined, the cumulative incidence of reoperation was higher following fusion than following decompression alone (21.5% vs. 18.8%, P = 0.008). After fusion surgery, 62.5% of reoperations were associated with a diagnosis suggesting device complication or pseudarthrosis., Conclusion: Patients should be informed that the likelihood of reoperation following a lumbar spine operation is substantial. For spondylolisthesis, reoperation is less likely following fusion than following decompression alone. For other degenerative spine conditions, the cumulative incidence of reoperation is higher or unimproved after a fusion procedure compared to decompression alone.

Study Design: Sequential cross-sectional study., Objectives: To quantify patterns of outpatient lumbar spine surgery., Summary of Background Data: Outpatient lumbar spine surgery patterns are undocumented., Methods: We used CPT-4 and ICD-9-CM diagnosis/procedure codes to identify lumbar spine operations in 20+ year olds. We combined sample volume estimates from the National Hospital Discharge Survey (NHDS), the National Survey of Ambulatory Surgery (NSAS), and the Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS) with complete case counts from HCUP's State Inpatient Databases (SIDs) and State Ambulatory Surgery Databases (SASDs) for four geographically diverse states. We excluded pregnant patients and those with vertebral fractures, cancer, trauma, or infection. We calculated age- and sex-adjusted rates., Results: Ambulatory cases comprised 4% to 13% of procedures performed from 1994 to 1996 (NHDS/NSAS data), versus 9% to 17% for 1997 to 2000 (SID/SASD data). Discectomies comprised 70% to 90% of outpatient cases. Conversely, proportions of discectomies performed on outpatients rose from 4% in 1994 to 26% in 2000. Outpatient fusions and laminectomies were uncommon. NIS data indicate that nationwide inpatient surgery rates were stable (159 cases/100,000 in 1994 vs. 162/100,000 in 2000). However, combined data from all sources suggest that inpatient and outpatient rates rose from 164 cases/100,000 in 1994 to 201/100,000 in 2000., Conclusions: While inpatient lumbar surgery rates remained relatively stable for 1994 to 2000, outpatient surgery increased over time.

Study Design: Retrospective cohort study using national sample administrative data., Objectives: To determine if lumbar fusion rates increased in the 1990s and to compare lumbar fusion rates with those of other major musculoskeletal procedures., Summary of Background Data: Previous studies found that lumbar fusion rates rose more rapidly during the 1980s than did other types of lumbar surgery., Methods: We used the Healthcare Cost and Utilization Project Nationwide Inpatient Sample from 1988 through 2001 to examine trends. U.S. Census data were used for calculating age and sex-adjusted population-based rates. We excluded patients with vertebral fractures, cancer, or infection., Results: In 2001, over 122,000 lumbar fusions were performed nationwide for degenerative conditions. This represented a 220% increase from 1990 in fusions per 100,000. The increase accelerated after 1996, when fusion cages were approved. From 1996 to 2001, the number of lumbar fusions increased 113%, compared with 13 to 15% for hip replacement and knee arthroplasty. Rates of lumbar fusion rose most rapidly among patients aged 60 and above. The proportion of lumbar operations involving a fusion increased for all diagnoses., Conclusions: Lumbar fusion rates rose even more rapidly in the 90s than in the 80s. The most rapid increases followed the approval of new surgical implants and were much greater than increases in other major orthopedic procedures. The most rapid increases in fusion rates were among adults aged 60 and above. These increases were not associated with reports of clarified indications or improved efficacy, suggesting a need for better data on the efficacy of various fusion techniques for various indications.

Salmonella enterica isolates (n = 182) were examined for mutations in the quinolone resistance-determining region of gyrA, gyrB, parC, and parE. The frequency, location, and type of GyrA substitution varied with the serovar. Mutations were found in parC that encoded Thr57-Ser, Thr66-Ile, and Ser80-Arg substitutions. Mutations in the gyrB quinolone resistance-determining region were located at codon Tyr420-Cys or Arg437-Leu. Novel mutations were also found in parE encoding Glu453-Gly, His461-Tyr, Ala498-Thr, Val512-Gly, and Ser518-Cys. Although it is counterintuitive, isolates with a mutation in both gyrA and parC were more susceptible to ciprofloxacin than were isolates with a mutation in gyrA alone.

Context: Faster magnetic resonance imaging (MRI) scanning has made MRI a potential cost-effective replacement for radiographs for patients with low back pain. However, whether rapid MRI scanning results in better patient outcomes than radiographic evaluation or a cost-effective alternative is unknown., Objective: To determine the clinical and economic consequences of replacing spine radiographs with rapid MRI for primary care patients., Design, Setting, and Patients: Randomized controlled trial of 380 patients aged 18 years or older whose primary physicians had ordered that their low back pain be evaluated by radiographs. The patients were recruited between November 1998 and June 2000 from 1 of 4 imaging centers in the Seattle, Wash, area: a university-based teaching program, a nonuniversity-based teaching program, and 2 private clinics., Intervention: Patients were randomly assigned to receive lumbar spine evaluation by rapid MRI or by radiograph., Main Outcome Measures: Back-related disability measured by the modified Roland questionnaire. Secondary outcomes included Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), pain, preference scores, satisfaction, and costs., Results: At 12 months, primary outcomes of functional disability were obtained from 337 (89%) of the 380 patients enrolled. The mean back-related disability modified Roland score for the 170 patients assigned to the radiograph evaluation group was 8.75 vs 9.34 for the 167 patients assigned the rapid MRI evaluation group (mean difference, -0.59; 95% CI, -1.69 to 0.87). The mean differences in the secondary outcomes were not statistically significant : pain bothersomeness (0.07; 95% CI -0.88 to 1.22), pain frequency (0.12; 95% CI, -0.69 to 1.37), and SF-36 subscales of bodily pain (1.25; 95% CI, -4.46 to 4.96), and physical functioning (2.73, 95% CI -4.09 to 6.22). Ten patients in the rapid MRI group vs 4 in the radiograph group had lumbar spine operations (risk difference, 0.34; 95% CI, -0.06 to 0.73). The rapid MRI strategy had a mean cost of 2380 dollars vs 2059 dollars for the radiograph strategy (mean difference, 321 dollars; 95% CI, -1100 to 458)., Conclusions: Rapid MRIs and radiographs resulted in nearly identical outcomes for primary care patients with low back pain. Although physicians and patients preferred the rapid MRI, substituting rapid MRI for radiographic evaluations in the primary care setting may offer little additional benefit to patients, and it may increase the costs of care because of the increased number of spine operations that patients are likely to undergo.

Purpose: To incorporate personnel and equipment use time in an activity-based cost comparison of conventional radiography and conventional and rapid magnetic resonance (MR) imaging for low back pain (LBP)., Materials and Methods: At each of four Seattle Lumbar Imaging Project (SLIP) sites, patients were randomized to undergo conventional radiography or rapid MR imaging of the lumbar spine. For sample SLIP patients and for similar non-SLIP patients undergoing conventional lumbar spine MR imaging as usual care in calendar year 2000, measured imaging room use and technologist and radiologist times were multiplied by costs per minute of standard equipment acquisition, personnel compensation, and related expenses. Resulting provider-perspective costs and Seattle area Medicare reimbursements for conventional MR imaging and radiography for calendar year 2001 were used to estimate future "normative" reimbursement for rapid MR imaging., Results: For 23 conventional radiography, 27 rapid MR imaging, and 38 conventional MR imaging examinations timed in calendar year 2000, all rapid MR imaging times exceeded those of conventional radiography but were less than those of conventional MR imaging. All 0.3- and 0.35-T MR imaging room and technologist times exceeded those for 1.5-T MR imaging. Average costs (in 2001 dollars) were $44 for conventional radiography, 126 US dollars for 1.5-T rapid MR imaging, 128 US dollars for 0.3-0.35-T rapid MR imaging, 267 US dollars for 1.5-T conventional MR imaging, and 264 US dollars for 0.3-0.35-T conventional MR imaging. Conclusions regarding cost differences between conventional radiography and rapid MR imaging were robust to plausible parameter value changes evaluated in sensitivity analyses. Conventional radiography reimbursement was 44 US dollars. Applying the ratio of reimbursement (620 US dollars) to costs (264-267 US dollars) for conventional MR imaging to rapid MR imaging costs predicted reimbursement of 292-300 US dollars for the new modality., Conclusion: Times and costs for rapid MR imaging are roughly three times those for conventional radiography but about half those for conventional MR imaging for LBP. While current conventional radiography costs exceed reimbursement, current conventional MR and projected rapid MR imaging reimbursements exceed costs.

Objectives: This study compared the relative efficiency of lumbar x-ray and rapid magnetic resonance (MR) imaging for diagnosing cancer-related low back pain (LBP) in primary care patients., Design: We developed a decision model with Markov state transitions to calculate the cost per case detected and cost per quality-adjusted life year (QALY) of rapid MR imaging. Model parameters were estimated from the medical literature. The costs of x-ray and rapid MR were calculated in an activity-based costing study., Setting and Patients: A hypothetical cohort of primary care patients with LBP referred for imaging to exclude cancer as the cause of their pain., Main Results: The rapid MR strategy was more expensive due to higher initial imaging costs and larger numbers of patients requiring conventional MR and biopsy. The overall sensitivity of the rapid MR strategy was higher than that of the x-ray strategy (62% vs 55%). However, because of low pre-imaging prevalence of cancer-related LBP, this generates <1 extra case per 1,000 patients imaged. Therefore, the incremental cost per case detected using rapid MR was high ($213,927). The rapid MR strategy resulted in a small increase in quality-adjusted survival (0.00043 QALYs). The estimated incremental cost per QALY for the rapid MR strategy was $296,176., Conclusions: There is currently not enough evidence to support the routine use of rapid MR to detect cancer as a cause of LBP in primary care patients.