W. Jerry Mysiw

Intermittent cyclical etidronate treatment of postmenopausal osteoporosis

Abstract Background. To determine the effects of etidronate (a bisphosphonate that inhibits osteoclast-mediated bone resorption) in the treatment of postmenopausal osteoporosis, we conducted a prospective, two-year, double-blind, placebo-controlled, multicenter study in 429 women who had one to four vertebral compression fractures plus radiographic evidence of osteopenia. Methods. The patients were randomly assigned to treatment with phosphate (1.0 g) or placebo twice daily on days 1 through 3, etidronate (400 mg) or placebo daily on days 4 through 17, and supplemental calcium (500 mg) daily on days 18 through 91 (group 1, placebo and placebo; group 2, phosphate and placebo; group 3, placebo and etidronate; and group 4, phosphate and etidronate). The treatment cycles were repeated eight times. The bone density of the spine was measured by dual-photon absorptiometry, and the rates of new vertebral fractures were determined from sequential radiographs. Results. After two years, the patients receiving etidro...

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.

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.

Systematic bias in outcome studies of persons with traumatic brain injury

OBJECTIVE (1) Examine systematic biases created by subjects lost at 1-year follow-up in samples of persons with traumatic brain injury; (2) identify potential threats to generalization of outcomes data. DESIGN A consecutive sample of admissions to acute rehabilitation studied 1 year following discharge. SETTING An inpatient brain injury rehabilitation unit in a large, academic medical center. SUBJECTS Eighty-eight patients with primary diagnosis of traumatic brain injury. MAIN OUTCOME MEASURES Subjects were considered lost to follow-up when phone calls, mail, clinic visits, and assistance from family failed to allow contact 1 year after discharge from acute rehabilitation. Potential effects of the biased follow-up sample were examined for seven suboptimal outcomes. RESULTS A total of 38.6% of subjects were lost to follow-up. Subjects intoxicated at time of injury and those with history of substance abuse were more-likely to be lost. Among subjects followed, the likelihood of working or being in school 1 year after discharge was significantly less for those intoxicated at time of injury and those with a history of substance abuse. CONCLUSIONS Systematic bias in longitudinal studies may result from subjects with substance use problems being lost to follow-up. Population estimates for return to work or school will be overestimated if those lost who have substance use problems resemble those followed.

The agitated brain injured patient. Part 1: definitions, differential diagnosis, and assessment

This two-part review provides a critical analysis of the scientific and clinical literature on the agitated brain injured patient. Part 1 reviews nomenclature and classification issues, differential diagnosis, and assessment instruments designed for evaluation of the patient. Pathophysiology and treatment approaches will be discussed in Part 2 in a subsequent issue of the Archives. The review was unfortunately hampered by a lack of consistency in definitions, little scientific study of the neuroanatomic and neurochemical basis for the disorder, few outcome studies, and no randomized controlled treatment trials. Part 1 sets forth an interdisciplinary definition of agitation, establishes a differential diagnostic approach, and describes and critiques the assessment instruments available for clinical evaluation of the agitated patient. Part 2 will address treatment interventions including pharmacological, environmental, and behavioral approaches to this patient population.

Measurement and treatment of agitation following traumatic brain injury: II. a survey of the brain injury special interest group of the american academy of physical medicine and rehabilitation☆☆☆

OBJECTIVE Determine national patterns of measuring and treating agitation after traumatic brain injury (TBI) by physiatrists with expressed interest in treating TBI survivors. DESIGN A 70% random sample of members of the Brain Injury Special Interest Group of the American Academy of Physical Medicine and Rehabilitation was surveyed by telephone. MAIN OUTCOME MEASURE The survey instrument was designed to determine the most common pharmacologic interventions for agitation and, where possible, match each drug with the target behavioral and cognitive characteristics for which it is prescribed. Data were also collected on the manner in which participants measured agitation and judged treatment efficacy. RESULTS One hundred twenty-nine of 157 responded, yielding an 82% response rate. The majority of respondents were not measuring agitation in a standard fashion. The five most frequently prescribed drugs by the expert stratum were carbamazepine, tricyclic antidepressants (TCAs), trazodone, amantadine, and beta-blockers. In comparison, the nonexperts most often reported prescribing carbamazepine, beta-blockers, haloperidol, TCAs, and benzodiazepines. Desyrel (p = .06) and amantadine (p = .001) were significantly more likely to be chosen by experts than by nonexperts. Experts chose haloperidol significantly less often than nonexperts (p = .01). Prescription of sedating drugs such as haloperidol or benzodiazepines was not found to be associated with the acuity of injury of TBI patients in the respondents practice, practice setting, or years of practice since completing residency. Choice of haloperidol to treat agitation was not significantly associated with the degree to which explosive anger, verbal aggression, or physical aggression were considered important to the respondents definition of agitation. CONCLUSIONS The majority of physiatrists surveyed did not formally measure agitation. Treatment strategies differ significantly between general physiatrists and those who specialize in the treatment of patients with TBI. The breadth of pharmacologic agents and strategies identified in this survey probably reflects the lack of research specific to the pathophysiology of the disorder of posttraumatic agitation.

Role of agitation in prediction of outcomes after traumatic brain injury.

Bogner JA, Corrigan JD, Fugate L, Mysiw WJ, Clinchot D: Role of Agitation in Prediction of Outcomes After Traumatic Brain Injury. Am J Phys Med Rehabil 2001;80:636–644. Objective: To determine the role of agitation in the prediction of traumatic brain injury rehabilitation outcomes. Design: A longitudinal study of 340 consecutive patients admitted to an acute traumatic brain injury rehabilitation unit was conducted. Outcomes under study included rehabilitation length of stay, discharge destination, functional independence at discharge (FIMTM instrument), productivity at 1-yr follow-up, and life satisfaction at 1-yr follow-up (Satisfaction with Life Scale). Results: Univariate analyses suggested that the presence of agitation in rehabilitation is predictive of a longer length of stay and decreased functional independence in the cognitive realm at discharge. In addition, individuals who exhibit agitation at any time during rehabilitation are less likely to be discharged to a private residence. However, multivariate analyses indicated that cognitive functioning at admission to rehabilitation (FIM cognitive) mediates the relationship between the presence of agitation and length of rehabilitation, as well as between agitation and FIM cognitive at discharge. Similar results were found when discharge residence was the dependent variable; however, agitation also contributed some unique variance to the prediction. Lower cognitive functioning at admission to rehabilitation was associated with the occurrence of agitation during rehabilitation, longer length of stay, lower cognitive functioning at discharge, and a decreased likelihood that an individual would be discharged to a private residence. Conclusions: The results of the multivariate analyses support the contention that agitation and cognition are intimately related, with the long-term effects of the former being at least partially driven by the latter. These findings support the importance of systematically monitoring both agitation and cognition when applying interventions to reduce agitation.

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

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.

The agitated brain injured patient. Part 2: Pathophysiology and treatment

The management of agitation after brain injury remains uncertain because of a lack of a consistent definition and a poor understanding of the underlying mechanism. Part 1 of this review focused on definitions, differential diagnosis, and assessment. Part 2 reviews potential mechanisms for posttraumatic agitation and common intervention strategies. The intent of this two-part series is to advocate for a consistent definition for posttraumatic agitation, to encourage the use of appropriate assessment and monitoring strategies, and to recommend that intervention decisions are based on at least a theoretical understanding of the relationship between specific target behaviors and probable brain-behavior relationships.

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.