Knowledge translation and implementation in spinal cord injury: a systematic review.

OBJECTIVE: To conduct a systematic review examining the effectiveness of knowledge translation (KT) interventions in changing clinical practice and patient outcomes. METHODS: MEDLINE/PubMed, CINAHL, EMBASE and PsycINFO were searched for studies published from January 1980 to July 2012 that reported and evaluated an implemented KT intervention in spinal cord injury (SCI) care. We reviewed and summarized results from studies that documented the implemented KT intervention, its impact on changing clinician behavior and patient outcomes as well as the facilitators and barriers encountered during the implementation. RESULTS: A total of 13 articles featuring 10 studies were selected and abstracted from 4650 identified articles. KT interventions included developing and implementing patient care protocols, providing clinician education and incorporating outcome measures into clinical practice. The methods (or drivers) to facilitate the implementation included organizing training sessions for clinical staff, introducing computerized reminders and involving organizational leaders. The methodological quality of studies was mostly poor. Only 3 out of 10 studies evaluated the success of the implementation using statistical analyses, and all 3 reported significant behavior change. Out of the 10 studies, 6 evaluated the effect of the implementation on patient outcomes using statistical analyses, with 4 reporting significant improvements. The commonly cited facilitators and barriers were communication and resources, respectively. CONCLUSION: The field of KT in SCI is in its infancy with only a few relevant publications. However, there is some evidence that KT interventions may change clinician behavior and improve patient outcomes. Future studies should ensure rigorous study methods are used to evaluate KT interventions.

The effects of exercise training on physical capacity, strength, body composition and functional performance among adults with spinal cord injury: a systematic review.

STUDY DESIGN: Systematic review. OBJECTIVES: To conduct a systematic review of evidence surrounding the effects of exercise on physical fitness in people with spinal cord injury (SCI). SETTING: Canada. METHODS: The review was limited to English-language studies (published prior to March 2010) of people with SCI that evaluated the effects of an exercise intervention on at least one of the four main components of physical fitness (physical capacity, muscular strength, body composition and functional performance). Studies reported at least one of the following outcomes: oxygen uptake/consumption, power output, peak work capacity, muscle strength, body composition, exercise performance or functional performance. A total of 166 studies were identified. After screening, 82 studies (69 chronic SCI; 13 acute SCI) were included in the review. The quality of evidence derived from each study was evaluated using established procedures. RESULTS: Most studies were of low quality; however, the evidence was consistent that exercise is effective in improving aspects of fitness. There is strong evidence that exercise, performed 2-3 times per week at moderate-to-vigorous intensity, increases physical capacity and muscular strength in the chronic SCI population; the evidence is not strong with respect to the effects of exercise on body composition or functional performance. There were insufficient high-quality studies in the acute SCI population to draw any conclusions. CONCLUSIONS: In the chronic SCI population, there is good evidence that exercise is effective in improving both physical capacity and muscular strength, but insufficient quality evidence to draw meaningful conclusions on its effect on body composition or functional capacity.

The development of evidence-informed physical activity guidelines for adults with spinal cord injury.

OBJECTIVES: To systematically develop evidence-informed physical activity guidelines to improve physical fitness in people with spinal cord injury (SCI). SETTING: This study was conducted in Canada. METHODS: The Appraisal of Guidelines, Research and Evaluation II guideline development protocol was used to develop exercise guidelines to improve physical capacity and muscular strength. The evidence base for the guideline development process consisted of a systematic review and quality appraisal of research examining the effects of exercise on physical fitness among people with SCI. A multidisciplinary expert panel deliberated the evidence and generated the guidelines. Pilot testing led to refinement of the wording and presentation of the guidelines. RESULTS: The expert panel generated the following guidelines: for important fitness benefits, adults with a SCI should engage in (a) at least 20 min of moderate to vigorous intensity aerobic activity two times per week and (b) strength training exercises two times per week, consisting of three sets of 8-10 repetitions of each exercise for each major muscle group. CONCLUSION: People with SCI, clinicians, researchers and fitness programmers are encouraged to adopt these rigorously developed guidelines.

A systematic review of depression and anxiety measures used with individuals with spinal cord injury.

STUDY DESIGN: A systematic review. OBJECTIVES: To review and assess the psychometric properties of depression and anxiety instruments used with populations with spinal cord injury (SCI). SETTING: Vancouver, Canada. METHODS: Electronic databases were searched for papers reporting psychometric properties of depression and anxiety instruments. Pre-established criteria were used to assess the psychometric properties. RESULTS: Thirteen papers reporting on the psychometric properties of 13 depression and anxiety instruments are used in this review, and include BDI, BSI, CESD-20, CESD-10, DASS-21, GHQ-28, HADS, Ilfeld-PSI, MEDS, PHQ-9, PHQ-9-Short, SCL-90-R, and the Zung SRS. Reliability data are available for 10 instruments, and validity results are available for 12 instruments. Evidence spanned the spectrum of evaluation criteria varying from poor to excellent. Responsiveness data are generally lacking. CONCLUSION: Given that the reliability and validity findings range for the most part from adequate to excellent, and the large amount of work to develop cutoff scores specific for populations with SCI, at present there is no need to develop SCI-specific instruments. As psychometric properties of one measure do not clearly stand out, it is difficult to recommend the use of one over another. Overall, more psychometric data are needed, and if the instruments are to be used to evaluate treatment outcomes or change over time, responsiveness data are also required. Administering the instruments in tandem with each other and with clinical diagnostic interviews would provide valuable information, as would comparison of results to normative data specific to individuals with SCI.

Developing a Model of Care for Healing Pressure Ulcers With Electrical Stimulation Therapy for Persons With Spinal Cord Injury.

Background: Electrical stimulation therapy (EST) has been shown to be an effective therapy for managing pressure ulcers in individuals with spinal cord injury (SCI). However, there is a lack of uptake of this therapy, and it is often not considered as a first-line treatment, particularly in the community. Objective: To develop a pressure ulcer model of care that is adapted to the local context by understanding the perceived barriers and facilitators to implementing EST, and to describe key initial phases of the implementation process. Method: Guided by the Knowledge-to-Action (KTA) and National Implementation Research Network (NIRN) frameworks, a community-based participatory research (CBPR) approach was used to complete key initial implementation processes including (a) defining the practice, (b) identifying the barriers and facilitators to EST implementation and organizing them into implementation drivers, and (c) developing a model of care that is adapted to the local environment. Results: A model of care for healing pressure ulcers with EST was developed for the local environment while taking into account key implementation barriers including lack of interdisciplinary collaboration and communication amongst providers between and across settings, inadequate training and education, and lack of resources, such as funding, time, and staff. Conclusions: Using established implementation science frameworks with structured planning and engaging local stakeholders are important exploratory steps to achieve a successful sustainable best practice implementation project.

An analysis of acute changes in interleukin-6 levels after treatment of hepatitis C with consensus interferon.

Cytokine production has been implicated in the antiviral response to interferon-alpha (IFN-alpha) in hepatitis C and in the development of IFN-alpha-related side effects. We characterized acute changes in serum cytokine levels following administration of a single dose of consensus IFN (IFN-con1) and during continuous treatment of chronic hepatitis C patients. Serum samples were collected at baseline, at multiple times early after IFN administration, and weekly thereafter. Viral RNA titers were assessed by RT-PCR, and viral kinetics were followed. ELISA assays were used to measure IFN-gamma, tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-4, IL-6, and IL-16. Serum cytokine levels were low at baseline. IL-6 was detected in patients with hepatitis C but not in healthy control subjects by either ELISA or RT-PCR, indicating that low levels of circulating IL-6 were associated with hepatitis C infection. None of the cytokines measured increased significantly after IFN administration except for IL-6. IL-6 levels rose rapidly, peaked at 6-15 h in a dose-dependent manner, and returned to baseline by 48 h in both patients receiving a single dose of IFN and those receiving continuous treatment. This was confirmed by RT-PCR. Pretreatment IL-6 levels were directly correlated with area under the curve (AUC) for IL-6 during the 24 h after IFN dosing (r = 0.611, p = 0.007). Viral titers decreased within 24-48 h after a single dose of IFN-con1. Changes in hepatitis C RNA titers were not significantly associated with pretreatment IL-6 levels or with changes in IL-6 levels. In conclusion, (1) baseline serum cytokine levels, except for IL-6, were low or within the normal range in patients with hepatitis C, (2) IL-6 levels were detected in some patients with hepatitis C before treatment but not in healthy controls, (3) IL-6 levels increased acutely after a single dose of IFN-alpha, and IL-6 induction was related to baseline IL-6 level, and (4) changes in IL-6 levels did not correlate with the early virologic response to IFN.

Effects of 4-aminopyridine on motor evoked potentials in patients with spinal cord injury: a double-blinded, placebo-controlled crossover trial.

4-Aminopyridine (4-AP) is a potassium (K+) channel blocking agent that has been shown to reduce the latency and increase the amplitude of motor evoked potentials (MEPs) elicited with transcranial magnetic stimulation (TMS) in patients with chronic spinal cord injury (SCI). These effects on MEPs are thought to reflect enhanced conduction in long tract axons brought about by overcoming conduction deficits due to focal demyelination and/or by enhancing neuroneuronal transmission at one or more sites of the neuraxis. The present study was designed to obtain further evidence of reduced central motor conduction time (CMCT) and to determine whether MEPs could be recorded from paretic muscles in which they were not normally elicited. MEPs were elicited with TMS being delivered to subjects (n = 25) pre- and post-administration of 4-AP (10 mg capsule) or placebo. The principal finding was that 4-AP lowered the stimulation threshold, increased the amplitude and reduced the latency of MEPs in all muscles tested, including those that were unimpaired, but did not alter measures of the peripheral nervous system (i.e., M-wave, H-reflex, F-wave). These 4-AP-induced changes in MEPs were significantly greater than those seen with placebo (p < 0.05). The primary implication of these results is that a low dose of 4-AP (immediate-release formulation) appears to improve the impaired central motor conduction of some patients with incomplete SCI. This is most likely attributable to overcoming conduction deficits at the site of injury but may also involve an increase in cortical excitability.

Conditioning lower limb H-reflexes by transcranial magnetic stimulation of motor cortex reveals preserved innervation in SCI patients.

Conditioning of lower limb H-reflexes by transcranial magnetic stimulation of motor cortex was used to detect preserved innervation in patients with long-standing spinal cord injury (SCI). Cortical stimulation was delivered at intensities suprathreshold or subthreshold for evoking motor evoked potentials (MEPs). The conditioning (C) cortical stimulation preceded the test (T) H-reflex stimulus at intervals between C-T: 10-300 msec. Conditioned H-reflex profiles in control subjects (n = 10), following both suprathreshold and subthreshold cortical conditioning, yielded evidence of early (C-T: 10-30 msec) and late arriving (C-T: 60-130 msec) excitatory inputs to the lateral gastrocnemius (LG) motoneuron pool. Demonstration of late inputs following subthreshold cortical conditioning suggested the inputs are mediated by slow conducting or oligosynaptic descending motor tracts, as distinct from afferent consequences of short latency MEPs. In SCI patients (n = 11) the conditioned H-reflex profile varied according to the patients' ASIA impairment rating. Higher functioning SCI patients (ASIA level C and D) revealed evidence of both early and late arriving inputs to the lumbosacral motoneuron pool whereas patients with more severe impairments (ASIA levels A and B) most often failed to exhibit early or late periods of H-reflex facilitation in LG. In three patients (i.e., 1 ASIA B; 2 ASIA C) the cortical modulation of H-reflex amplitudes yielded evidence of preserved corticospinal innervation that was not detectable by other MEP reinforcement procedures. These results introduce the cortical conditioning procedure as a sensitive means of detecting latent corticospinal and/or bulbospinal innervation in SCI patients consistent with the emerging neuropathological picture of preserved axonal integrity in descending motor tracts in the face of extensive functional loss.

4-Aminopyridine-sensitive neurologic deficits in patients with spinal cord injury.

4-Aminopyridine (4-AP) is a potassium channel blocking agent with the ability to restore conduction in demyelinated internodes of axons of the spinal cord. The present investigation sought to obtain electrophysiologic evidence of the effect of 4-AP in ameliorating central conduction deficits in a group of patients (n = 6) with spinal cord injury (SCI). The group was selected on the basis of having temperature-dependent central conduction deficits. 4-AP (24-25 mg total dose) was delivered intravenously at 6 mgh-1 or 15 mgh-1 while somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) were recorded as indices of central conduction. Two patients exhibited marked increases in the amplitude of cortical SEPs, and in one of these, 4-AP brought about a reduced central conduction time from L1 to cortex. Four patients revealed increased amplitude MEPs with concomitant reduction in latency indicative of enhanced conduction in corticospinal or corticobulbospinal pathways. Two of these patients demonstrated increased voluntary motor unit recruitment following 4-AP. Clinical examination revealed reduced spasticity (n = 2), reduced pain (n = 1), increased sensation (n = 1), improved leg movement (n = 3), and restored voluntary control of bowel (n = 1). These results support the hypothesis that 4-AP induces neurologic benefits in some patients with SCI. They are also consistent with the emerging concept that pharmaceutical amelioration of central conduction deficits caused by focal demyelination may contribute to the management of a select group of patients with compressive or contusive SCI.

Pharmacokinetics of an immediate-release oral formulation of Fampridine (4-aminopyridine) in normal subjects and patients with spinal cord injury.

Plasma concentration profiles of the K+ channel-blocking compound Fampridine were obtained from (1) control subjects (n = 6) following oral administration of doses of 10, 15, 20, and 25 mg and (2) patients with spinal cord injury (SCI) (n = 11) following a single oral dose of 10 mg of an immediate-release formulation. Plasma concentrations were determined using a reversed-phase ion-pair high-performance liquid chromatography (HPLC) assay with ultraviolet light detection employing liquid extraction. The drug was rapidly absorbed with a tmax approximately 1 hour for both groups; tmax was independent of dose. Cmax and AUC0-infinity were linearly related to dose, and t 1/2 was 3 to 4 hours for both groups. There were no obvious differences in the (10-mg) plasma concentration profiles between control subjects and SCI patients. The drug was well tolerated, with only mild and transient side effects of light-headedness, dysesthesias, and dizziness.

Central conduction studies in patients with spinal cord injury and other forms of myelopathy.

Central conduction studies allow objective determination of the integrity and functional properties of corticospinal tracts compromised by trauma or other forms of myelopathy. This review briefly describes some of the neurological reinforcement techniques that may be employed to maximize the probability of detecting preserved corticospinal innervation to interneurons or motoneuron pools in myelopathic patients. This is followed by an overview of how central conduction studies are being used to evaluate the efficacy of new interventions designed to ameliorate central conduction deficits due to focal demyelination. In particular a summary is provided of studies employing induced whole body hypothermia, or the K(+) channel blocking agent 4-aminopyridine, to enhance central conduction in spinal cord injured patients.

Reinforcement of motor evoked potentials by remote muscle contraction.

We investigated the effects of remote muscle contraction on the amplitude and latency of motor-evoked potentials (MEPs) recorded from tibialis anterior and lateral gastrocnemius after transcranial magnetic stimulation of the motor cortex. In particular, consideration was given to the effects of unilateral handgrip of different strengths, jaw clench, and combined bilateral handgrip (Jendrassik maneuver) and jaw clench. Eight healthy adult volunteer subjects (six women, two men) participated in the main study. The clinical usefulness of this form of facilitation was subsequently demonstrated in three patients with myelopathy. Transcranial magnetic stimulation of the motor cortex was delivered from a Cadwell MES-10 (100% intensity) with a 9.5-cm circular coil positioned with the rim over the vertex. Stimuli were delivered ∼ 1 s after initiation of reinforcement. In the main study of normal subjects, surface recordings of the evoked compound muscle action potentials were made bilaterally from anterior tibialis and lateral gastrocnemius. In the individual studies of patients, MEPs were also recorded from abductor pollicis brevis and other muscles innervated from roots below the level of lesion. The principal results showed that unilateral handgrip (50 and 100% maximum voluntary contraction, MVC) of either hand enhanced the amplitude of MEPs bilaterally in both tibialis anterior and lateral gastrocnemius in all normal subiects (p < 0.05). The mean increase in amplitude associated with 100% MVC unilateral handgrip was >300% of the control value when the subject was relaxed (p < 0.01). The bilateral Jendrassik maneuver and jaw clench were also effective in increasing (p < 0.05) MEP amplitude in both muscle groups. These two procedures did not yield the same degree of reinforcement as 100% unilateral handgrip. Remote muscle contractions induced a reduction in MEP latency of 1-2 ms (p < 0.05). The clinical importance of these observations was demonstrated by the fact that remote muscle reinforcement enabled identification of low-amplitude MEPs that might otherwise have been missed in the three patients with spinal cord trauma.

Treatment of an acquired abdominal hernia in a polar bear (Thalarctos maritimus).

A heart rate radio-transmitter was surgically implanted in the abdomen of a captive adult male polar bear (Thalarctos maritimus), but within five weeks a purulent discharge was observed at the incision site. The transmitter was surgically removed along with many fragments of the fractured encapsulation material. The skin incision healed, but a large hernia remained. Repeated localized trauma to the hernia sac necessitated surgical repair.

Spasticity outcome measures in spinal cord injury: psychometric properties and clinical utility.

STUDY DESIGN: Comprehensive review and systematic analyses. OBJECTIVES: Assess published psychometric evidence for spinal cord injury (SCI) spasticity outcome measures. Considerations about the influence of spasticity on function have also been identified to understand treatment effects and guide service delivery. SETTING: London, Ontario and Vancouver, British Columbia, Canada. METHOD: Review of measures was based on availability of psychometric data, application in clinical settings and evaluated in SCI patients. RESULTS: Ashworth and Modified Ashworth Scales (AS, MAS), Penn Spasm Frequency Scale (PSFS), Spinal Cord Assessment Tool for Spasticity (SCATS), Visual Analogue Scale self-rated scale of spasticity (VAS) and the Wartenberg Pendulum Test (WPT) were included in this review. The most frequently used tools for SCI spasticity measurement include the AS, MAS, PSFS and VAS, of which the latter two are self-report spasticity measures. The SCATS has been partially validated for SCI, but is not widely used. The WPT has been minimally validated despite its use in a large-scale SCI spasticity randomized controlled trial. CONCLUSIONS: Since spasticity is multidimensional, focusing on one or two spasticity outcome measures can misrepresent the extent and influence of spasticity on SCI patients. Different scales measure different aspects of spasticity and individual tools correlate weakly with each other. Spasticity may be better measured with an appropriate battery of tests, including the AS or MAS, along with PSFS. These tools would benefit from further reliability and responsiveness testing. Tools that assess the influence of spasticity on patient activities, participation and quality of life are important, but lacking.

Establishing evidence-based physical activity guidelines: methods for the Study of Health and Activity in People with Spinal Cord Injury (SHAPE SCI).

STUDY DESIGN: Prospective, observational cohort study. OBJECTIVES: This paper describes the rationale and methodology for the Study of Health and Activity in People with Spinal Cord Injury (SHAPE SCI). The study aims to (1) describe physical activity levels of people with different injury levels and completeness, (2) examine the relationship between physical activity, risk and/or presence of secondary health complications and risk of chronic disease, and (3) identify determinants of physical activity in the SCI population. SETTING: Ontario, Canada. METHODS: Seven hundred and twenty men and women who have incurred a traumatic SCI complete self-report measures of physical activity, physical activity determinants, secondary health problems and subjective well-being during a telephone interview. A representative subsample (n=81) participate in chronic disease risk factor testing for obesity, insulin resistance and coronary heart disease. Measures are taken at baseline, 6 and 18 months. CONCLUSION: SHAPE SCI will provide much-needed epidemiological information on physical activity patterns, determinants and health in people with SCI. This information will provide a foundation for the establishment of evidence-based physical activity guidelines and interventions tailored to the SCI community.

Conditioning effects of sural nerve stimulation on short and long latency motor evoked potentials in lower limb muscles.

The effects of conditioning sural nerve stimulation on motor evoked potentials (MEPs) in relaxed muscles of the lower limb were examined in 11 healthy adults. The study tested the hypothesis that cutaneous afferent stimulation, in the absence of muscle afferent input, facilitates the short latency MEPs evoked in lower limb muscles following transcranial magnetic stimulation of motor cortex. Non-painful (3.6 x sensory threshold) percutaneous electrical stimulation was delivered to the sural nerve at conditioning (C)-test (T) intervals of 0-150 msec. MEPs were elicited bilaterally in the tibialis anterior (TA) and lateral gastrocnemius (LG) muscles with and without preceding cutaneous stimulation. Mean MEP amplitudes were facilitated in the ipsilateral TA by 258% (n = 10 of 11), the ipsilateral LG by 275% (n = 7 of 8) and the contralateral TA by 313% (n = 7 of 7) within C-T: 60-100 msec. These results establish that cutaneous afferent stimulation per se does lead to a facilitation of short latency MEPs. In addition, two subjects who were examined at higher stimulation intensities both exhibited late responses (70-95 msec) at C-T: 0-15 msec. These responses, which were independent of the amplitude and appearance of short latency MEPs, suggest a convergence of the cutaneous stimulation with late arriving descending cortical or cortico-bulbospinal inputs to the target motoneuron pool.(ABSTRACT TRUNCATED AT 250 WORDS)

Legal liability under an IDM program.

Integrated disability management (IDM) programs offer employers a simple, strategic approach to managing health and lost time. However, components of these programs also present potential liabilities under federal, and sometimes, state law. This article reviews the sources of these liabilities and summarizes techniques for minimizing the risk of employers (and managers individually).

Mechanism of the attenuated cardiac response to beta-adrenergic stimulation in chronic hypoxia.

A blunting of the chronotropic and inotropic responses of the heart to beta-adrenergic stimulation occurs following chronic exposure to hypobaric hypoxia. To pursue the mechanism(s) involved, observations were made in six intact, conscious goats at sea level and in another six goats maintained in a decompression chamber at 445 Torr (approximately 4,300m) for 10 days (Pao2 = 43 Torr). No significant group differences in cardiac frequency and various indices of myocardial performance (peak dP/dt, time-to-peak dP/dt, Vmax) were demonstrable either before or after cholinergic blockade with intravenous atropine methyl bromide, 1 mg/kg. Following hemodynamic studies, thoracotomies were performed and full-thickness biopsies were obtained from the free wall of each of the cardiac chambers. Neither monoamine oxidase activity nor norepinephrine level of any region of the heart was altered by chronic hypoxia. However, a twofold increase (P less than 0.001) in catechol O-methyltransferase activity above sea-level values was found in both the atria and ventricles of the hypoxic animals. Thus, the attenuation in cardiac responsiveness to beta-adrenoceptor stimulation in chronic hypoxia appears unrelated to the level of vagal activity, but may be attributable to enhanced enzymatic inactivation of catecholamines.