History of etidronate.

Etidronate is a non-nitrogen-containing bisphosphonate. Because it binds with calcium and inhibits crystal formation and dissolution, it was considered by Procter & Gamble as an additive to toothpaste (to prevent build-up of tartar) and detergent (to bind calcium and increase sudsing in "hard" water). The first clinical use (1968) was for fibrodysplasia ossificans progressiva. The first approved clinical use (1977) was for treatment of Paget's disease of bone. Other approved indications are hypercalcemia of malignancy and heterotopic ossification, with a host of off-label uses (including fibrous dysplasia, periodontal disease, multiple myeloma, neuropathic arthropathy, pulmonary microlithiasis, diabetic retinopathy, bone metastases, melorheostosis, urinary stone disease, periodontal disease, etc.). Unique among bisphosphonates, etidronate (oral therapy) results in hyperphosphatemia, increased tubular reabsorption of phosphorus and increased levels of 1,25-dihydroxyvitamin D. The dose that reduces bone resorption is close to the dose that impairs mineralization; prolonged high-dose use can result in osteomalacia and bone fractures. Intermittent cyclic etidronate for osteoporosis resulted in favorable changes in bone density and histomorphometry (no mineralization defect) as well as a decrease in vertebral fracture rates in postmenopausal women with osteoporosis. Later studies showed similar effects in men with osteoporosis and patients with glucocorticoid-induced osteoporosis. Although its use for osteoporosis has given way to newer bisphosphonates and other agents, because of its unique properties, it remains the bisphosphonate of choice for treatment of heterotopic ossification.

A High Definition Noninvasive Neuromuscular Electrical Stimulation System for Cortical Control of Combinatorial Rotary Hand Movements in a Human With Tetraplegia.

OBJECTIVE: Paralysis resulting from spinal cord injury (SCI) can have a devastating effect on multiple arm and hand motor functions. Rotary hand movements, such as supination and pronation, are commonly impaired by upper extremity paralysis, and are essential for many activities of daily living. In this proof-of-concept study, we utilize a neural bypass system (NBS) to decode motor intention from motor cortex to control combinatorial rotary hand movements elicited through stimulation of the arm muscles, effectively bypassing the SCI of the study participant. We describe the NBS system architecture and design that enabled this functionality. METHODS: The NBS consists of three main functional components: 1) implanted intracortical microelectrode array, 2) neural data processing using a computer, and, 3) a noninvasive neuromuscular electrical stimulation (NMES) system. RESULTS: We address previous limitations of the NBS, and confirm the enhanced capability of the NBS to enable, in real-time, combinatorial hand rotary motor functions during a functionally relevant object manipulation task. CONCLUSION: This enhanced capability was enabled by accurate decoding of multiple movement intentions from the participant's motor cortex, interleaving NMES patterns to combine hand movements, and dynamically switching between NMES patterns to adjust for hand position changes during movement. SIGNIFICANCE: These results have implications for enabling complex rotary hand functions in sequence with other functionally relevant movements for patients suffering from SCI, stroke, and other sensorimotor dysfunctions.

Neuroprosthetic-enabled control of graded arm muscle contraction in a paralyzed human.

Neuroprosthetics that combine a brain computer interface (BCI) with functional electrical stimulation (FES) can restore voluntary control of a patients' own paralyzed limbs. To date, human studies have demonstrated an "all-or-none" type of control for a fixed number of pre-determined states, like hand-open and hand-closed. To be practical for everyday use, a BCI-FES system should enable smooth control of limb movements through a continuum of states and generate situationally appropriate, graded muscle contractions. Crucially, this functionality will allow users of BCI-FES neuroprosthetics to manipulate objects of different sizes and weights without dropping or crushing them. In this study, we present the first evidence that using a BCI-FES system, a human with tetraplegia can regain volitional, graded control of muscle contraction in his paralyzed limb. In addition, we show the critical ability of the system to generalize beyond training states and accurately generate wrist flexion states that are intermediate to training levels. These innovations provide the groundwork for enabling enhanced and more natural fine motor control of paralyzed limbs by BCI-FES neuroprosthetics.

Reducing concussion symptoms among teenage youth: Evaluation of a mobile health app.

OBJECTIVE: To evaluate whether a mobile health application that employs elements of social game design could compliment medical care for unresolved concussion symptoms. DESIGN: Phase I and Phase II (open-label, non-randomized, ecological momentary assessment methodology). SETTING: Outpatient concussion clinic. PARTICIPANTS: Youth, aged 13-18 years, with concussion symptoms 3+ weeks after injury; Phase I: n = 20; Phase II: n = 19. INTERVENTIONS: Participants received standard of care for concussion. The experimental group also used a mobile health application as a gamified symptoms journal. OUTCOME MEASURES: Phase I: feasibility and satisfaction with intervention (7-point Likert scale, 1 high). Phase II: change in SCAT-3 concussion symptoms (primary), depression and optimism. RESULTS: Phase 1: A plurality of participants completed the intervention (14 of 20) with high use (110 +/- 18% play) and satisfaction (median +/- interquartile range (IQR) = 2.0+/- 0.0). Phase II: Groups were equivalent on baseline symptoms, intervention duration, gender distribution, days since injury and medication prescription. Symptoms and optimism improved more for the experimental than for the active control cohort (U = 18.5, p = 0.028, effect size r = 0.50 and U = 18.5, p = 0.028, effect size r = 0.51, respectively). CONCLUSIONS: Mobile apps incorporating social game mechanics and a heroic narrative may promote health management among teenagers with unresolved concussion symptoms.

Using an Artificial Neural Bypass to Restore Cortical Control of Rhythmic Movements in a Human with Quadriplegia.

Neuroprosthetic technology has been used to restore cortical control of discrete (non-rhythmic) hand movements in a paralyzed person. However, cortical control of rhythmic movements which originate in the brain but are coordinated by Central Pattern Generator (CPG) neural networks in the spinal cord has not been demonstrated previously. Here we show a demonstration of an artificial neural bypass technology that decodes cortical activity and emulates spinal cord CPG function allowing volitional rhythmic hand movement. The technology uses a combination of signals recorded from the brain, machine-learning algorithms to decode the signals, a numerical model of CPG network, and a neuromuscular electrical stimulation system to evoke rhythmic movements. Using the neural bypass, a quadriplegic participant was able to initiate, sustain, and switch between rhythmic and discrete finger movements, using his thoughts alone. These results have implications in advancing neuroprosthetic technology to restore complex movements in people living with paralysis.

Restoring cortical control of functional movement in a human with quadriplegia.

Millions of people worldwide suffer from diseases that lead to paralysis through disruption of signal pathways between the brain and the muscles. Neuroprosthetic devices are designed to restore lost function and could be used to form an electronic 'neural bypass' to circumvent disconnected pathways in the nervous system. It has previously been shown that intracortically recorded signals can be decoded to extract information related to motion, allowing non-human primates and paralysed humans to control computers and robotic arms through imagined movements. In non-human primates, these types of signal have also been used to drive activation of chemically paralysed arm muscles. Here we show that intracortically recorded signals can be linked in real-time to muscle activation to restore movement in a paralysed human. We used a chronically implanted intracortical microelectrode array to record multiunit activity from the motor cortex in a study participant with quadriplegia from cervical spinal cord injury. We applied machine-learning algorithms to decode the neuronal activity and control activation of the participant's forearm muscles through a custom-built high-resolution neuromuscular electrical stimulation system. The system provided isolated finger movements and the participant achieved continuous cortical control of six different wrist and hand motions. Furthermore, he was able to use the system to complete functional tasks relevant to daily living. Clinical assessment showed that, when using the system, his motor impairment improved from the fifth to the sixth cervical (C5-C6) to the seventh cervical to first thoracic (C7-T1) level unilaterally, conferring on him the critical abilities to grasp, manipulate, and release objects. This is the first demonstration to our knowledge of successful control of muscle activation using intracortically recorded signals in a paralysed human. These results have significant implications in advancing neuroprosthetic technology for people worldwide living with the effects of paralysis.

Improved Function After Deep Brain Stimulation for Chronic, Severe Traumatic Brain Injury.

BACKGROUND: Severe traumatic brain injury (TBI) damages the frontal lobes and connecting networks, which impairs executive functions, including the ability to self-regulate. Despite significant disabling effects, there are few treatment options in the chronic phase after injury. OBJECTIVE: To investigate the safety and potential effectiveness of deep brain stimulation (DBS) for individuals with chronic, disabling TBI and problems of behavioral and emotional self-regulation. METHODS: This study was an open-label, prospective design with serial assessments of behavioral outcomes and positron emission tomography 2 years after DBS implantation. Four participants 6 to 21 years after severe TBIs from automobile crashes were included. Although alert and volitional, all experienced significant executive impairments, including either impulsivity or reduced initiation. DBS implants were placed bilaterally in the nucleus accumbens and anterior limb of the internal capsule to modulate the prefrontal cortex. RESULTS: The procedure was safe, and all participants had improved functional outcomes. Two years after implantation, 3 met a priori criteria for improvement on the Mayo-Portland Adaptability Inventory-4. Improvement was due largely to better emotional adjustment, although 1 participant showed marked increases in multiple domains. Significant improvement in a composite score of functional capacity indicated improved independence in self-care and activities of daily living. The pattern of change in cognition corresponded with changes in activation of the prefrontal cortex observed in serial scanning. CONCLUSION: This first study of DBS to this target for severe TBI supports its safety and suggests potential effectiveness to improve function years after injury. The primary impact was on behavioral and emotional adjustment, which in turn improved functional independence. ABBREVIATIONS: DBS, deep brain stimulationIC, internal capsuleMPAI-4, Mayo-Portland Adaptability Inventory-4NAcc, nucleus accumbensTBI, traumatic brain injury.

Sleep duration, cognitive decline, and dementia risk in older women.

INTRODUCTION: Consistent evidence linking habitual sleep duration with risks of mild cognitive impairment (MCI) and dementia is lacking. METHODS: We conducted a prospective study on 7444 community-dwelling women (aged 65-80 y) with self-reported sleep duration, within the Women's Health Initiative Memory Study in 1995-2008. Incident MCI/dementia cases were ascertained by validated protocols. Cox models were used to adjust for multiple sociodemographic and lifestyle factors, depression, cardiovascular disease (CVD), and other clinical characteristics. RESULTS: We found a statistically significant (P = .03) V-shaped association with a higher MCI/dementia risk in women with either short (≤6 hours/night) or long (≥8 hours/night) sleep duration (vs. 7 hours/night). The multicovariate-adjusted hazard for MCI/dementia was increased by 36% in short sleepers irrespective of CVD, and by 35% in long sleepers without CVD. A similar V-shaped association was found with cognitive decline. DISCUSSION: In older women, habitual sleep duration predicts the future risk for cognitive impairments including dementia, independent of vascular risk factors.

Big data challenges in decoding cortical activity in a human with quadriplegia to inform a brain computer interface.

Recent advances in Brain Computer Interfaces (BCIs) have created hope that one day paralyzed patients will be able to regain control of their paralyzed limbs. As part of an ongoing clinical study, we have implanted a 96-electrode Utah array in the motor cortex of a paralyzed human. The array generates almost 3 million data points from the brain every second. This presents several big data challenges towards developing algorithms that should not only process the data in real-time (for the BCI to be responsive) but are also robust to temporal variations and non-stationarities in the sensor data. We demonstrate an algorithmic approach to analyze such data and present a novel method to evaluate such algorithms. We present our methodology with examples of decoding human brain data in real-time to inform a BCI.

Insights into the epidemiology of postmenopausal osteoporosis: the Women's Health Initiative.

Osteoporosis and its associated increased risk for fragility fracture is one of the most disabling consequences of aging in women. To successfully reduce the public health burden of this pervasive disease, it is necessary to develop strategies that permit the earlier identification of women at risk for fracture and ensure that preventive interventions to reduce the risk for fracture are both safe and effective. The Women's Health Initiative offers the unprecedented opportunity to systematically address both of these issues. Eleven clinically available risk factors (age, race/ethnicity, self-reported health, weight, height, physical activity, parental hip fracture, fracture history after age 54, current smoking, corticosteroid use, and history of treated diabetes), have been identified to predict 5-year hip fracture risk in white women. Two of these factors (age and fracture history) also predict risk for total fractures in women irrespective of race-ethnicity. Biomarkers including low vitamin D or bioavailable testosterone and/or high cystatin C, pro-inflammatory cytokines, osteoprotegerin and sex hormone-binding globulin also predict risk for hip fracture independent of clinical risk factors. Two cornerstones of therapy for postmenopausal osteoporosis-postmenopausal hormone therapy and calcium plus vitamin D supplementation- were rigorously studied. Estrogen with or without a progestin was effective at preventing bone loss and reducing risk for hip, clinical vertebral and total fractures but the balance of risks and benefits failed to show an overall benefit of taking estrogen-alone or estrogen plus progestin as a preventive strategy for skeletal health. Calcium plus vitamin D supplementation also demonstrated a small but significant favorable effect on hip bone density but in contrast, the modest effect did not translate into a significant reduction in the risk of fractures in intent-to-treat analyses. Data such as these have helped to lay a foundation for the more effective management of postmenopausal osteoporosis.

Significance of preradiographic magnetic resonance imaging lesions in persons at increased risk of knee osteoarthritis.

OBJECTIVE: Little is known about early knee osteoarthritis (OA). The significance of lesions on magnetic resonance imaging (MRI) in older persons without radiographic OA is unclear. Our objectives were to determine the extent of tissue pathology by MRI and evaluate its significance by testing the following hypotheses: cartilage damage, bone marrow lesions, and meniscal damage are associated with prevalent frequent knee symptoms and incident persistent symptoms; bone marrow lesions and meniscal damage are associated with incident tibiofemoral (TF) cartilage damage; and bone marrow lesions are associated with incident patellofemoral (PF) cartilage damage. METHODS: In a cohort study of 849 Osteoarthritis Initiative (OAI) participants who had a bilateral Kellgren/Lawrence (K/L) score of 0, we assessed cartilage damage, bone marrow lesions, and meniscal damage using the MRI OA Knee Score, as well as prevalent frequent knee symptoms, incident persistent symptoms, and incident cartilage damage. Multiple logistic regression (one knee per person) was used to evaluate associations between MRI lesions and each of these outcomes. RESULTS: Of the participants evaluated, 76% had cartilage damage, 61% had bone marrow lesions, 21% had meniscal tears, and 14% had meniscal extrusion. Cartilage damage (any; TF and PF), bone marrow lesions (any; TF and PF), meniscal extrusion, and body mass index (BMI) were associated with prevalent frequent symptoms. Cartilage damage (isolated PF; TF and PF), bone marrow lesions (any; isolated PF; TF and PF), meniscal tears, and BMI were associated with incident persistent symptoms. Hand OA, but no individual lesion type, was associated with incident TF cartilage damage, and bone marrow lesions (any; any PF) with incident PF damage. Having more lesion types was associated with a greater risk of outcomes. CONCLUSION: MRI-detected lesions are not incidental and may represent early disease in persons at increased risk of knee OA.

Relation of physical activity time to incident disability in community dwelling adults with or at risk of knee arthritis: prospective cohort study.

OBJECTIVE: To investigate whether objectively measured time spent in light intensity physical activity is related to incident disability and to disability progression. DESIGN: Prospective multisite cohort study from September 2008 to December 2012. SETTING: Baltimore, Maryland; Columbus, Ohio; Pittsburgh, Pennsylvania; and Pawtucket, Rhode Island, USA. PARTICIPANTS: Disability onset cohort of 1680 community dwelling adults aged 49 years or older with knee osteoarthritis or risk factors for knee osteoarthritis; the disability progression cohort included 1814 adults. MAIN OUTCOME MEASURES: Physical activity was measured by accelerometer monitoring. Disability was ascertained from limitations in instrumental and basic activities of daily living at baseline and two years. The primary outcome was incident disability. The secondary outcome was progression of disability defined by a more severe level (no limitations, limitations to instrumental activities only, 1-2 basic activities, or ≥3 basic activities) at two years compared with baseline. RESULTS: Greater time spent in light intensity activities had a significant inverse association with incident disability. Less incident disability and less disability progression were each significantly related to increasing quartile categories of daily time spent in light intensity physical activities (hazard ratios for disability onset 1.00, 0.62, 0.47, and 0.58, P for trend=0.007; hazard ratios for progression 1.00, 0.59, 0.50, and 0.53, P for trend=0.003) with control for socioeconomic factors (age, sex, race/ethnicity, education, income) and health factors (comorbidities, depressive symptoms, obesity, smoking, lower extremity pain and function, and knee assessments: osteoarthritis severity, pain, symptoms, prior injury). This finding was independent of time spent in moderate-vigorous activities. CONCLUSION: These prospective data showed an association between greater daily time spent in light intensity physical activities and reduced risk of onset and progression of disability in adults with osteoarthritis of the knee or risk factors for knee osteoarthritis. An increase in daily physical activity time may reduce the risk of disability, even if the intensity of that additional activity is not increased.

A feasibility study using interactive graphic art feedback to augment acute neurorehabilitation therapy.

BACKGROUND: Interactive arts technologies, designed to augment the acute neurorehabilitation provided by expert therapists, may overcome existing barriers of access for patients with low motor and cognitive function. OBJECTIVES: Develop an application prototype to present movement feedback interactively and creatively. Evaluate feasibility of use within acute neurorehabilitation. METHODS: Record demographics and Functional Independent Measure™ scores among inpatients who used the technology during physical, occupational or recreational therapy. Record exercises performed with the technology, longest exercise duration performed (calculated from sensor data), user feedback, and therapist responses to a validated technology assessment questionnaire. RESULTS: Inpatients (n = 21) between the ages of 19 and 86 (mean 57 ± 18; 12 male/9 female) receiving treatment for motor deficits associated with neuropathology used the application in conjunction with occupational, recreational, or physical therapy during 1 to 7 sessions. Patients classified on the Functional Independence Measure™ as requiring 75%+ assistance for cognitive and motor function were able to use the interactive application. CONCLUSIONS: Customized interactive arts applications are appropriate for further study as a therapeutic modality. In addition to providing interactivity to individuals with low motor function, interactive arts applications might serve to augment activity-based medicine among inpatients with low problem-solving and memory function.

Prestroke factors associated with poststroke mortality and recovery in older women in the Women's Health Initiative.

OBJECTIVES: To examine prestroke lifestyle factors associated with poststroke mortality and recovery in older women. DESIGN: Longitudinal prospective cohort study. SETTING: The Women's Health Initiative (WHI, clinical trials and observational study), 40 clinical centers in the United States. PARTICIPANTS: WHI participants, women aged 50 to 79, who were stroke-free at baseline (1993/98), with incident stroke before 2005. MEASUREMENTS: Participants were followed for mortality through 2010. Prestroke characteristics were from the last examination before the stroke event. Annual follow-up for clinical events ascertained hospitalization for stroke that was subsequently physician adjudicated with medical records. Multivariable regression models were used to analyze factors associated with poststroke mortality and poststroke recovery at hospital discharge (poststroke Glasgow score), adjusting for stroke type. RESULTS: Of 3,173 women with incident stroke, 1,111 (35%) died. Individuals who were overweight or obese before stroke had lower poststroke mortality than those who were normal weight (obese: hazard ratio (HR) = 0.69, 95% confidence interval (CI) = 0.53-0.88; overweight: HR = 0.72, 95% CI = 0.58-0.90); individuals who were underweight before stroke had nonsignificantly greater poststroke mortality (HR = 2.02, 95% CI = 0.98-4.16, P = .06). Other prestroke factors associated with poststroke mortality included diabetes mellitus (HR = 1.28, 95% CI = 1.01-1.64), current smoking (vs nonsmoker, HR = 2.13, 95% CI = 1.53-3.00), physical inactivity (vs >150 min of exercise per week, HR = 1.39, 95% CI = 1.09-1.78), and lowest physical function quartile (vs highest, HR = 1.54, 95% CI = 1.18-2.02). Prestroke diabetes mellitus was associated with lower odds of good recovery after stroke (odds ratio (OR) = 0.60, 95% CI = 0.44-0.82). Current hormone use before stroke was associated with greater odds of moderate than of severe disability after stroke (OR = 1.29, 95% CI = 1.00-1.66). CONCLUSION: Potentially modifiable factors before stroke, including smoking, diabetes mellitus, and being underweight, were associated with greater poststroke mortality in older women. Being overweight or obese and physical activity before stroke were associated with lower poststroke mortality in older women.

Obesity and other modifiable factors for physical inactivity measured by accelerometer in adults with knee osteoarthritis.

OBJECTIVE: To investigate the public health impact of obesity and other modifiable risk factors related to physical inactivity in adults with knee osteoarthritis (OA). METHODS: The frequency of inactivity as defined by the US Department of Health and Human Services was assessed from objective accelerometer monitoring of 1,089 participants (ages 49-84 years) with radiographic knee OA during the Osteoarthritis Initiative 48-month visit (2008-2010). The relationship between modifiable factors (weight status, dietary fat, fiber, smoking, depressive symptoms, knee function, knee pain, and knee confidence) with inactivity was assessed using odds ratios (ORs) and attributable fractions (AFs), controlling for descriptive factors (age, sex, race, education, lives alone, employment, frequent knee symptoms, and comorbidity). RESULTS: Almost half (48.9%) of participants with knee OA were inactive. Being overweight (OR 1.8, 95% confidence interval [95% CI] 1.2-2.5) or obese (OR 3.9, 95% CI 2.6-5.7), having inadequate dietary fiber intake (OR 1.6, 95% CI 1.2-2.2), severe knee dysfunction (OR 1.9, 95% CI 1.3-2.8), and severe pain (OR 1.7, 95% CI 1.1-2.5) were significantly related to inactivity, controlling for descriptive factors. Modifiable factors with significant average AFs were being overweight or obese (AF 23.8%, 95% CI 10.5-38.6%) and inadequate dietary fiber (AF 12.1%, 95% CI 0.1-24.5%), controlling for all factors. CONCLUSION: Being obese or overweight, the quality of the diet, severe pain, and severe dysfunction are significantly associated with physical inactivity in adults with knee OA. All components should be considered in designing physical activity interventions that target arthritis populations with low activity levels.

Depressive symptoms, antidepressant use, and future cognitive health in postmenopausal women: the Women's Health Initiative Memory Study.

BACKGROUND: Antidepressants are commonly prescribed medications in the elderly, but their relationship with incident mild cognitive impairment (MCI) and probable dementia is unknown. METHODS: The study cohort included 6,998 cognitively healthy, postmenopausal women, aged 65-79 years, who were enrolled in a hormone therapy clinical trial and had baseline depressive symptoms and antidepressant use history assessments at enrollment, and at least one postbaseline cognitive measurement. Participants were followed annually and the follow-up averaged 7.5 years for MCI and probable dementia outcomes. A central adjudication committee classified the presence of MCI and probable dementia based on extensive neuropsychiatric examination. RESULTS: Three hundred and eighty-three (5%) women were on antidepressants at baseline. Antidepressant use was associated with a 70% increased risk of MCI, after controlling for potential covariates including the degree of depressive symptom severity. Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) were both associated with MCI (SSRIs: hazard ratios (HR), 1.78 [95% CI, 1.01-3.13]; TCAs: HR, 1.78 [95% CI, 0.99-3.21]). Depressed users (HR, 2.44 [95% CI, 1.24-4.80]), non-depressed users (HR, 1.79 [95% CI, 1.13-2.85]), and depressed non-users (HR, 1.62 [95% CI, 1.13-2.32]) had increased risk of incident MCI. Similarly, all three groups had increased risk of either MCI or dementia, relative to the control cohort. CONCLUSIONS: Antidepressant use and different levels of depression severity were associated with subsequent cognitive impairment in a large cohort of postmenopausal women. Future research should examine the role of antidepressants in the depression-dementia relationship and determine if antidepressants can prevent incident MCI and dementia in individuals with late-life depression subtypes with different levels of severity.

Objective physical activity measurement in the osteoarthritis initiative: Are guidelines being met?

OBJECTIVE: Osteoarthritis (OA) clinical practice guidelines identify a substantial therapeutic role for physical activity, but objective information about the physical activity of this population is lacking. The aim of this study was to objectively measure levels of physical activity in adults with knee OA and report the prevalence of meeting public health physical activity guidelines. METHODS: Cross-sectional accelerometry data from 1,111 adults with radiographic knee OA (49-84 years old) participating in the Osteoarthritis Initiative accelerometry monitoring ancillary study were assessed for meeting the aerobic component of the 2008 Physical Activity Guidelines for Americans (≥150 minutes/week moderate-to-vigorous-intensity activity lasting ≥10 minutes). Quantile regression was used to test median sex differences in physical activity levels. RESULTS: Aerobic physical activity guidelines were met by 12.9% of men and 7.7% of women with knee OA. A substantial proportion of men and women (40.1% and 56.5%, respectively) were inactive, having done no moderate-to-vigorous activity that lasted 10 minutes or more during the 7 days. Although men engaged in significantly more moderate-to-vigorous activity (average daily minutes 20.7 versus 12.3), they also spent more time in no or very-low-intensity activity than women (average daily minutes 608.2 versus 585.8). CONCLUSION: Despite substantial health benefits from physical activity, adults with knee OA were particularly inactive based on objective accelerometry monitoring. The proportions of men and women who met public health physical activity guidelines were substantially less than those previously reported based on self-reported activity in arthritis populations. These findings support intensified public health efforts to increase physical activity levels among people with knee OA.

DTI at 7 and 3 T: systematic comparison of SNR and its influence on quantitative metrics.

Diffusion tensor imaging (DTI) and advanced related methods such as diffusion spectrum and kurtosis imaging are limited by low signal-to-noise ratio (SNR) at conventional field strengths. DTI at 7 T can provide increased SNR; however, B0 and B1 inhomogeneity and shorter T2⁎ still pose formidable challenges. The purpose of this study was to quantify and compare SNR at 7 and 3 T for different parallel imaging reduction factors, R, and TE, and to evaluate SNRs influences on fractional anisotropy (FA) and apparent diffusion coefficient (ADC). We found that R>4 at 7 T and R≥2 at 3 T were needed to reduce geometric distortions due to B0 inhomogeneity. For these R at 7 T, SNR was 70-90 for b=0 s/mm(2) and 22-28 for b=1000s/mm(2) in central brain regions. SNR was lower at 3 T (40 for b=0 s/mm(2) and 15 for b=1000 s/mm(2)) and in lateral brain regions at 7 T due to B1 inhomogeneity. FA and ADC did not change with MRI field strength, SENSE factor or TE in the tested range. However, the coefficient of variation for FA increased for SNR <15 and for SNR <10 in ADC, consistent with published theoretical studies. Our study demonstrates that 7 T is advantageous for DTI and lays the groundwork for further development. Foremost, future work should further address challenges with B0 and B1 inhomogeneity to take full advantage for the increased SNR at 7 T.

Application of machine learning methods to describe the effects of conjugated equine estrogens therapy on region-specific brain volumes.

Use of conjugated equine estrogens (CEE) has been linked to smaller regional brain volumes in women aged ≥65 years; however, it is unknown whether this results in a broad-based characteristic pattern of effects. Structural magnetic resonance imaging was used to assess regional volumes of normal tissue and ischemic lesions among 513 women who had been enrolled in a randomized clinical trial of CEE therapy for an average of 6.6 years, beginning at ages 65-80 years. A multivariate pattern analysis, based on a machine learning technique that combined Random Forest and logistic regression with L(1) penalty, was applied to identify patterns among regional volumes associated with therapy and whether patterns discriminate between treatment groups. The multivariate pattern analysis detected smaller regional volumes of normal tissue within the limbic and temporal lobes among women that had been assigned to CEE therapy. Mean decrements ranged as high as 7% in the left entorhinal cortex and 5% in the left perirhinal cortex, which exceeded the effect sizes reported previously in frontal lobe and hippocampus. Overall accuracy of classification based on these patterns, however, was projected to be only 54.5%. Prescription of CEE therapy for an average of 6.6 years is associated with lower regional brain volumes, but it does not induce a characteristic spatial pattern of changes in brain volumes of sufficient magnitude to discriminate users and nonusers.

Assessing physical activity in persons with knee osteoarthritis using accelerometers: data from the osteoarthritis initiative.

OBJECTIVE: Physical activity measured by accelerometers requires basic assumptions to translate the output into meaningful measures. We used accelerometer data from the Osteoarthritis Initiative to investigate in the context of knee osteoarthritis (OA) the following data processing assumptions derived from the general US adult population: nonwear (a period the monitor was removed), based on zero activity exceeding 60 minutes; and a valid day of monitoring, based on wear time evidence exceeding 10 hours. METHODS: We examined the influence of nonwear thresholds ranging from 20 to 300 minutes of zero activity on mean daily activity minutes (counts>0), mean daily activity counts, and mean daily moderate to vigorous physical activity minutes. The effect of selecting minimums of 8, 10, or 12 wear hours to signify a valid day of monitoring on data retention was examined. RESULTS: Our sample of 3,536 days of accelerometer data from 519 persons with knee OA showed that mean daily activity minutes increased with the nonwear threshold until stabilizing at 463 minutes per day, corresponding to the 90-minute nonwear threshold. Similar patterns were observed for mean daily activity counts. Varying the nonwear threshold had no effect on mean daily moderate to vigorous physical activity minutes. Choosing the 90-minute nonwear threshold and a minimum of 10 wear hours to constitute a valid day provided 94% data retention. CONCLUSION: Data supported applying the 90-minute nonwear threshold to the knee OA population instead of the 60-minute threshold for the general population, while retaining the 10-hour valid day threshold.