Antimicrobial Release From Prefabricated Spacers Is Variable and the Dose Is Low

Background

High-dose antimicrobial-loaded bone cement (ALBC) is recommended to treat orthopaedic infections. Elution characteristics from prefabricated ALBC spacers and how they compare with hand-mixed ALBC are not well described.

Questions/purposes

(1) How does antimicrobial release from prefabricated spacers compare with release from hand-mixed ALBC over time? (2) Is antimicrobial release uniform across the surface of prefabricated ALBC spacers? (3) Do variations exist between different prefabricated spacer components? (4) Do textured surfaces release more antimicrobial than smooth surfaces?

Methods

Six prefabricated ALBC spacer components, two hip and four knee, and three hand-mixed ALBC formulations were studied in this comparative laboratory study. Gentamicin was eluted from 41 discrete sites over the surfaces of six spacer components and compared with elution from 15 ALBC specimens, five from each of three hand-mixed formulations. Elution was compared between spacer sites, components, and surface texture. Statistical analysis was performed by analysis of variance and Tukey’s multiple-comparison test or t-test.

Results

Gentamicin release was highest in the first 24 hours for both prefabricated ALBC spacers and hand-mixed ALBC. Elution decreased over 7 days similarly for both. At Day 7, prefabricated ALBC spacers eluted more than hand-mixed 1 g ALBC (1 g ALBC: 1.49 ± 0.34, prefabricated: 3.59 ± 1.48, mean difference = 2.1 [0.2–4.0], p = 0.04) but eluted less than 5 g ALBC (9.21 ± 1.31, mean difference = −5.6 [−3.5 to −7.7], p < 0.001) and less than 10 g ALBC (35.8 ± 1.69, mean difference = −32.2 [−29.8 to −34.6], p < 0.001). Release varied from 2.7 to 9.9 µg/mm² over the surface of the spacers and from 3.5 to 5.5 µg/mm² between components with no component different than the others (Tukey). Release from textured surfaces was inconsistent.

Conclusions

Antimicrobial release from prefabricated ALBC spacers is consistent with low-dose ALBC. Variation across the surface and between components is small compared with changes in antimicrobial load.

Clinical Relevance

Antimicrobial release from prefabricated ALBC spacers is consistent with local antimicrobial delivered from other low-dose ALBC formulations.     

Rifamycin Derivatives Are Effective Against Staphylococcal Biofilms In Vitro and Elutable From PMMA

Background

Local antimicrobial delivery through polymethylmethacrylate beads (PMMA), commonly vancomycin, is used for the treatment of contaminated open fractures but has limited activity against Staphylococcus aureus biofilms, which occur commonly in such fractures. Rifamycins have activity against biofilms and are an effective treatment for osteoarticular infections involving staphylococcal biofilms, but there are limited studies evaluating the activity of rifamycin derivatives, other than rifampin, against biofilms of S. aureus and evaluating incorporation of these drugs into PMMA for treatment of contaminated open fractures.

Questions/purposes

(1) Are rifamycin derivatives effective against established biofilms of clinical isolates of S. aureus? (2) Can PMMA be used as a carrier for rifamycin derivatives?

Methods

Biofilms were developed and evaluated for susceptibility to a panel of antimicrobials in vitro using the minimum biofilm eradication concentration high-throughput model. Susceptibility was assessed by measuring bacterial recovery at 6 and 24 hours after antimicrobial treatment. Activity of rifamycin derivatives against intracellular bacteria was also evaluated using a gentamicin protection assay. Evaluation of PMMA as a carrier for rifampin and rifamycin derivatives was determined by assessing the curing time subsequent to loading of rifamycins and characterizing the release kinetics of rifamycins at daily intervals for 14 days from PMMA by performing bioassays.

Results

Rifamycin derivatives between 1 and 8 µg/mL reduced bacteria within biofilms 5- to 9-logs and prevented bacterial recovery up to 24 hours post-treatment, indicating near to complete eradication of biofilms. Rifamycin derivatives at 32 µg/mL had activity against intracellular staphylococci, significantly reducing the number of internalized bacteria with limited effects on osteoblast viability. Rifampin was the only rifamycin observed to have a suitable release profile from PMMA, releasing 49% of the total antibiotic and maintaining a sustained released profile up to 14 days at a mean 28 ± 6 μg/mL.

Conclusions

Rifampin can be incorporated into PMMA and eluted at concentrations effective against biofilms and intracellular staphylococci.

Clinical Relevance

Our in vitro findings suggest that local delivery of rifampin may be an effective strategy for the prevention and/or treatment of open fractures where S. aureus biofilms might develop. Clinical studies are needed to characterize what role this approach might have in the prevention and treatment of infections involving biofilms.

Electronic supplementary material

The online version of this article (doi:10.1007/s11999-015-4300-3) contains supplementary material, which is available to authorized users.     

Voriconazole Is Delivered From Antifungal-Loaded Bone Cement

Background

Local delivery of antifungals is an important modality in managing orthopaedic fungal infection. Voriconazole is a powder antifungal suitable for addition to bone cement that is released from bone cement but the mechanical properties of antimicrobial-loaded bone cement (ALBC) made with voriconazole are unknown.

Questions/Purposes

(1) Is voriconazole release dose-dependent? (2) Is released voriconazole active? (3) Is the loss of ALBC’s compressive strength caused by voriconazole dose- and elution-dependent?

Methods

Sixty standard test cylinders were fabricated with ALBC: 300 or 600 mg voriconazole per batch eluted for 30 days in deionized water. Voriconizole concentration in the eluate was measured using high-performance liquid chromatography. Cumulative-released voriconizole was calculated. Biologic activity was tested. Compressive strength was measured before and after elution. The effect of dose and time on release and compressive strength were analyzed using repeated-measure analysis of variance.

Results

Fifty-seven percent and 63% of the loaded voriconazole were released by Day 30 for the 300-mg and 600-mg formulations, respectively. The released voriconazole was active on bioassay. Compressive strength was reduced from 79 MPa to 53 MPa and 69 MPa to 31 MPa by 30 days for the 300-mg and 600-mg formulations, respectively.

Conclusions

Voriconazole release from ALBC increases with dose and is bioactive. Loss in compressive strength is greater after elution and with higher dose.

Clinical Relevance

Three hundred milligrams of voriconazole in ALBC would be expected to deliver meaningful amounts of active drug in vivo. The compressive strength of ALBC with 600 mg voriconazole is less than expected compared to commonly used antibacterials.     

Chitosan Sponges to Locally Deliver Amikacin and Vancomycin: A Pilot In Vitro Evaluation

Background

Open orthopaedic wounds are ideal sites for infection. Preventing infection in these wounds is critical for reducing patient morbidity and mortality, controlling antimicrobial resistance and lowering the cost of treatment. Localized drug delivery has the potential to overcome the challenges associated with traditional systemic dosing. A degradable, biocompatible polymer sponge (chitosan) that can be loaded with clinician-selected antibiotics at the point of care would provide the patient and clinician with a desirable, adjunctive preventive modality.

Questions/purposes

We asked (1) if an adaptable, porous chitosan matrix could absorb and elute antibiotics for 72 hours for potential use as an adjunctive therapy to débridement and lavage; and (2) if the sponges could elute levels of antibiotic that would inhibit growth of Staphylococcus aureus and Pseudomonas aeruginosa?

Methods

We fabricated a degradable chitosan sponge that can be loaded with antibiotics during a 60-second hydration in drug-containing solution. In vitro evaluation determined amikacin and vancomycin release from chitosan sponges at six time points. Activity tests were used to assess the release of inhibitory levels of amikacin and vancomycin.

Results

Amikacin concentration was 881.5 μg/mL after 1 hour with a gradual decline to 13.9 μg/mL after 72 hours. Vancomycin concentration was 1007.4 μg/mL after 1 hour with a decrease to 48.1 μg/mL after 72 hours. Zone of inhibition tests were used to verify inhibitory levels of drug release from chitosan sponges. A turbidity assay testing activity of released amikacin and vancomycin indicated inhibitory levels of elution from the chitosan sponge.

Clinical Relevance

Chitosan sponges may provide a potential local drug delivery device for preventing musculoskeletal infections.     

Lower-Dose Mepivacaine Plus Fentanyl May Improve Spinal Anesthesia for Knee Arthroscopy

Background

Previous work indicates that 30 mg isobaric mepivacaine 1.5% plus 10 μg fentanyl produces reliable anesthesia for knee arthroscopy with a more rapid recovery profile than 45 mg mepivacaine.

Questions/Purposes

This randomized controlled trial compared plain mepivacaine to three reduced doses of mepivacaine with 10 μg fentanyl for spinal anesthesia.

Methods

Following written informed consent, subjects undergoing outpatient knee arthroscopy were prospectively randomized into one of four groups: mepivacaine 37.5 mg (M37.5); mepivacaine 30 mg plus fentanyl 10 μg (M30/F10); mepivacaine 27 mg plus fentanyl 10 μg (M27/F10); and mepivacaine 24 mg plus fentanyl 10 μg (M24/F10). The spinal was evaluated by the blinded anesthetist and surgeon. In the post-anesthesia care unit, sensory and motor block resolution was assessed. Subjects rated their satisfaction with the overall experience.

Results

Group M30/F10 (n = 6) had two “fair” anesthetics, and group M27/F10 (n = 10) had one “fair” and one “inadequate” anesthetic. Both groups were eliminated from further enrollment per study protocol. The recovery profiles showed little difference between groups M37.5 and M30/F10, except for motor block resolution (median (25th percentile, 75th percentile): 171 (135, 195) and 128 (120, 135), respectively). Groups M27/F10 and M24/F10 demonstrated recovery profiles that were faster than group M37.5. Patient satisfaction was 10/10 for all groups.

Conclusions

Adding fentanyl 10 μg to a lower dose of mepivacaine 1.5% can lead to quicker recovery profiles. However, this advantage of a quicker recovery must be weighed against the likelihood of an incomplete anesthetic.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-015-9454-8) contains supplementary material, which is available to authorized users.     

Voriconazole Is Cytotoxic at Locally Delivered Concentrations: A Pilot Study

Background

Fungal infections are rare but major problems when they involve orthopaedic implants. Preferred treatment in North America is two-staged: resection and then delayed reconstruction, with local delivery of an antifungal between stages. The effect of voriconazole, a hydrophobic antifungal, on local tissues and wound healing is unclear.

Questions/purposes

We asked: (1) Is voriconazole cytotoxic to fibroblasts or osteoblasts at target concentrations for local delivery? And (2) if cytotoxic, can fibroblasts or osteoblasts resume proliferation after voriconazole is removed?

Methods

We exposed 5000 fibroblasts or osteoblasts/well to voriconazole concentrations of 0, 1, 5, 10, 25, 100, 500, 1000, 5000, 10,000, and 20,000 μg/mL (n = 4 wells/concentration) in 24-well plates. At 3 and 7 days, cell growth was assessed with alamarBlue^® and light microscopy. After Day 7, exposure to voriconazole was stopped and incubation continued for 4 days in medium with no voriconazole. On Day 11, cell growth (recovery) was assessed with alamarBlue^® and light microscopy.

Results

Increasing voriconazole concentration to more than 100 μg/mL decreased osteoblast and fibroblast growth. Cell growth recovered after 7 days’ exposure to 1000 μg/mL or less.

Conclusions

Voriconazole is cytotoxic to osteoblasts and fibroblasts, but cell growth recovers over 4 days after exposure to 1000 μg/mL or less.

Clinical Relevance

Cytotoxicity seen from voriconazole to mouse osteoblasts and fibroblasts occurs at concentrations achievable clinically from local delivery. It may be prudent to limit the dose of voriconazole in antibiotic-loaded bone cement.     

Acute Suppression of Bone Turnover With Calcium Infusion in Persons With Spinal Cord Injury

Background:

Some people with chronic spinal cord injury (SCI) have low vitamin D levels and secondary hyperparathyroidism.

Objective:

To determine whether, and to what extent, an acute calcium infusion decreased levels of N-telopeptide (NTx), a marker of osteoclastic activity, in individuals with chronic SCI.

Study Design:

Case series.

Subjects:

Eight men with chronic SCI. A relatively low serum 25 hydroxyvitamin D concentration (25[OH]D ≤20 ng/mL) and/or a high parathyroid hormone (PTH) (>55 pg/mL) was a prerequisite for study inclusion.

Methods:

Calcium gluconate bolus 0.025 mmol elemental calcium/kg over 20 minutes followed by a constant infusion of 0.025 mmol/kg per hour for 6 hours was infused; blood samples were collected every 2 hours for measurement of serum total calcium, creatinine, NTx, and PTH.

Results:

All results are expressed as means (± SDs). Baseline serum 25-hydroxyvitamin D level was 14.5 ± 3.5 ng/mL (range: 10.2–19.6 ng/mL); PTH, 70 ± 25 pg/mL (range: 37–100 pg/mL); and NTx, 21 ± 7 nM bone collagen equivalents (BCE) (range: 14–34 nM). At 2, 4, and 6 hours after the calcium infusion, serum calcium rose from 9.3 ± 0.2 to 10.8 ± 0.9, 10.5 ± 0.8, and 10.6 ± 0.6 mg/d; PTH was suppressed from 70 ± 25 pg/mL to 18 ± 12, 16 ± 9, and 15 ± 9 pg/mL, respectively; NTx fell from 21 ± 8 nM BCE to 17 ± 5, 12 ± 4, and 12 ± 3 nM BCE, respectively.

Conclusions:

Serum NTx is a marker for bone collagen catabolism, and its reduction suggests that bone turnover was decreased. A relative deficiency of vitamin D associated with chronically elevated levels of PTH would be expected to increase bone turnover and to worsen the bone loss associated with immobilization.     

Pre-procedural antibiotics for endoscopic urological procedures: Initial experience in individuals with spinal cord injury and asymptomatic bacteriuria

Objective

The objective of this study was to compare the safety, efficacy, quality-of-life impact, and costs of a single dose or a longer course of pre-procedural antibiotics prior to elective endoscopic urological procedures in individuals with spinal cord injury and disorders (SCI/D) and asymptomatic bacteriuria.

Design

A prospective observational study.

Setting

Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Virginia, USA.

Participants

Sixty persons with SCI/D and asymptomatic bacteriuria scheduled to undergo elective endoscopic urological procedures.

Interventions

A single pre-procedural dose of antibiotics vs. a 3–5-day course of pre-procedural antibiotics.

Outcome measures

Objective and subjective measures of health, costs, and quality of life.

Results

There were no significant differences in vital signs, leukocytosis, adverse events, and overall satisfaction in individuals who received short-course vs. long-course antibiotics. There was a significant decrease in antibiotic cost (33.1 ± 47.6 vs. 3.6 ± 6.1 US$, P = 0.01) for individuals in the short-course group. In addition, there was greater pre-procedural anxiety (18 vs. 0%, P < 0.05) for individuals who received long-course antibiotics.

Conclusion

SCI/D individuals with asymptomatic bacteriuria may be able to safely undergo most endoscopic urological procedures with a single dose of pre-procedural antibiotics. However, further research is required and even appropriate pre-procedural antibiotics may not prevent severe infections.     

Modification of spasticity by transcutaneous spinal cord stimulation in individuals with incomplete spinal cord injury

Context/objective

To examine the effects of transcutaneous spinal cord stimulation (tSCS) on lower-limb spasticity.

Design

Interventional pilot study to produce preliminary data.

Setting

Department of Physical Medicine and Rehabilitation, Wilhelminenspital, Vienna, Austria.

Participants

Three subjects with chronic motor-incomplete spinal cord injury (SCI) who could walk ≥10 m.

Interventions

Two interconnected stimulating skin electrodes (Ø 5 cm) were placed paraspinally at the T11/T12 vertebral levels, and two rectangular electrodes (8 × 13 cm) on the abdomen for the reference. Biphasic 2 ms-width pulses were delivered at 50 Hz for 30 minutes at intensities producing paraesthesias but no motor responses in the lower limbs.

Outcome measures

The Wartenberg pendulum test and neurological recordings of surface-electromyography (EMG) were used to assess effects on exaggerated reflex excitability. Non-functional co-activation during volitional movement was evaluated. The timed 10-m walk test provided measures of clinical function.

Results

The index of spasticity derived from the pendulum test changed from 0.8 ± 0.4 pre- to 0.9 ± 0.3 post-stimulation, with an improvement in the subject with the lowest pre-stimulation index. Exaggerated reflex responsiveness was decreased after tSCS across all subjects, with the most profound effect on passive lower-limb movement (pre- to post-tSCS EMG ratio: 0.2 ± 0.1), as was non-functional co-activation during voluntary movement. Gait speed values increased in two subjects by 39%.

Conclusion

These preliminary results suggest that tSCS, similar to epidurally delivered stimulation, may be used for spasticity control, without negatively impacting residual motor control in incomplete SCI. Further study in a larger population is warranted.     

Heavy reliance on carbohydrate across a wide range of exercise intensities during voluntary arm ergometry in persons with paraplegia

Context/objective

To describe and compare substrate oxidation and partitioning during voluntary arm ergometry in individuals with paraplegia and non-disabled individuals over a wide range of exercise intensities.

Design

Cross-sectional study.

Setting

Clinical research facility.

Participants

Ten apparently healthy, sedentary men with paraplegia and seven healthy, non-disabled subjects.

Interventions

Rest and continuous progressive voluntary arm ergometry between 30 and 80% of peak aerobic capacity (VO_2peak).

Outcome measures

Total energy expenditure and whole body rates of fat and carbohydrate oxidation.

Results

A maximal whole body fat oxidation (WBFO) rate of 0.13 ± 0.07 g/minute was reached at 41 ± 9% VO_2peak for subjects with paraplegia, although carbohydrate became the predominant fuel source during exercise exceeding an intensity of 30–40% VO_2peak. Both the maximal WBFO rate (0.06 ± 0.04 g/minute) and the intensity at which it occurred (13 ± 3% VO_2peak) were significantly lower for the non-disabled subjects than those with paraplegia.

Conclusion

Sedentary individuals with paraplegia are more capable of oxidizing fat during voluntary arm ergometry than non-disabled individuals perhaps due to local adaptations of upper body skeletal muscle used for daily locomotion. However, carbohydrate is the predominant fuel source oxidized across a wide range of intensities during voluntary arm ergometry in those with paraplegia, while WBFO is limited and maximally achieved at low exercise intensities compared to that achieved by able-bodied individuals during leg ergometry. These findings may partially explain the diminished rates of fat loss imposed by acute bouts of physical activity in those with paraplegia.     

Examining implicit bias of physicians who care for individuals with spinal cord injury: A pilot study and future directions

Context

Despite evidence that healthcare providers have implicit biases that can impact clinical interactions and decisions, implicit bias among physicians caring for individuals with spinal cord injury (SCI) has not been examined.

Objective

Conduct a pilot study to examine implicit racial bias of SCI physicians and its association with functioning and wellbeing for individuals with SCI.

Design

Combined data from cross-sectional surveys of individuals with SCI and their SCI physicians.

Setting

Four national SCI Model Systems sites.

Participants

Individuals with SCI (N = 162) and their SCI physicians (N = 14).

Outcome measures

SCI physicians completed online surveys measuring implicit racial (pro-white/anti-black) bias. Individuals with SCI completed questionnaires assessing mobility, physical independence, occupational functioning, social integration, self-reported health, depression, and life satisfaction. We used multilevel regression analyses to examine the associations of physician bias and outcomes of individuals with SCI.

Results

Physicians had a mean bias score of 0.62 (SD = 0.35), indicating a strong pro-white/anti-black bias. Greater physician bias was associated with disability among individuals with SCI in the domain of social integration (odds ratio = 4.80, 95% confidence interval (CI) = 1.44, 16.04), as well as higher depression (B = 3.24, 95% CI = 1.06, 5.41) and lower life satisfaction (B = −4.54, 95% CI= −8.79, −0.28).

Conclusion

This pilot study indicates that SCI providers are susceptible to implicit racial bias and provides preliminary evidence that greater implicit racial bias of physicians is associated with poorer psychosocial health outcomes for individuals with SCI. It demonstrates the feasibility of studying implicit bias among SCI providers and provides guidance for future research on physician bias and patient outcomes.     

Physical exercise improves arterial stiffness after spinal cord injury

Objective/background

Aortic pulse wave velocity (PWV), the gold-standard assessment of central arterial stiffness, has prognostic value for cardiovascular disease risk in able-bodied individuals. The aim of this study was to compare aortic PWV in athletes and non-athletes with spinal cord injury (SCI).

Design

Cross-sectional comparison.

Methods

Aortic PWV was assessed in 20 individuals with motor-complete, chronic SCI (C2–T5; 18 ± 8 years post-injury) using applanation tonometry at the carotid and femoral arterial sites. Ten elite hand-cyclists were matched for sex to 10 non-athletes; age and time since injury were comparable between the groups. Heart rate and discrete brachial blood pressure measurements were collected throughout testing.

Outcome measures

Aortic PWV, blood pressure, heart rate.

Results

Aortic PWV was significantly lower in athletes vs. non-athletes (6.9 ± 1.0 vs. 8.7 ± 2.5 m/second, P = 0.044). There were no significant between-group differences in resting supine mean arterial blood pressure (91 ± 19 vs. 81 ± 10 mmHg) and heart rate (60 ± 10 vs. 58 ± 6 b.p.m.).

Conclusion

Athletes with SCI exhibited improved central arterial stiffness compared to non-athletes, which is in agreement with the previous able-bodied literature. This finding implies that chronic exercise training may improve arterial health and potentially lower cardiovascular disease risk in the SCI population.     

Randomized controlled trial of pharmacological replacement of melatonin for sleep disruption in individuals with tetraplegia

Objective

To determine the effectiveness of a melatonin agonist for treating sleep disturbances in individuals with tetraplegia.

Design

Placebo-controlled, double-blind, crossover, randomized control trial.

Setting

At home.

Participants

Eight individuals with tetraplegia, having an absence of endogenous melatonin production and the presence of a sleep disorder.

Interventions

Three weeks of 8 mg of ramelteon (melatonin agonist) and 3 weeks of placebo (crossover, randomized order) with 2 weeks of baseline prior to and 2 weeks of washout between active conditions.

Outcome

Change in objective and subjective sleep.

Measures

Wrist actigraphy, post-sleep questionnaire, Stanford sleepiness scale, SF-36.

Results

We observed no consistent changes in either subjective or objective measures of sleep, including subjective sleep latency (P = 0.55, Friedman test), number of awakenings (P = 0.17, Friedman test), subjective total sleep time (P = 0.45, Friedman test), subjective morning alertness (P = 0.35, Friedman test), objective wake after sleep onset (P = 0.70, Friedman test), or objective sleep efficiency (P = 0.78, Friedman test). There were significant increases in both objective total sleep time (P < 0.05, Friedman test), subjective time in bed (P < 0.05, Friedman test), and subjective sleep quality (P < 0.05, Friedman test), although these occurred in both arms. There were no significant changes in any of the nine SF-36 subscale scores (Friedman test, Ps >Bonferroni adjusted α of 0.005).

Conclusion

In this pilot study, we were unable to show effectiveness of pharmacological replacement of melatonin for the treatment of self-reported sleep problems in individuals with tetraplegia.

Trial Registration

ClinicalTrials.gov # {"type":"clinical-trial","attrs":{"text":"NCT00507546","term_id":"NCT00507546"}}NCT00507546.     

Airway complications in traumatic lower cervical spinal cord injury: A retrospective study

Objective

To investigate risk factors for pneumonia in patients with traumatic lower cervical spinal cord injury.

Design

Observational study, retrospective study.

Setting

Spinal cord unit in a maximum care hospital.

Methods

Thirty-seven patients with acute isolated traumatic spinal cord injury at levels C4–C8 and complete motor function injury (AIS A, B) treated from 2004 to 2010 met the criteria for inclusion in our retrospective analysis. The following parameters were considered: ventilation-specific parameters, re-intubation, creation of a tracheostomy, pneumonia, antibiotic treatment, and length of intensive care unit (ICU) stay and total hospitalization.

Results

Among the patients, 81% had primary invasive ventilation. In 78% of cases a tracheostomy was created; 3% of these cases were discharged with invasive ventilation and 28% with a tracheostomy without ventilation. Pneumonia according to Centers for Disease Control criteria occurred in 51% of cases within 21 ± 32 days of injury, and in 3% at a later date. The number of pre-existing conditions was significantly associated with pneumonia. Length of ICU stay was 25 ± 34 days, and average total hospital duration was 230 ± 144 days. Significant factors affecting the duration of ventilation were the number of pre-existing conditions and tetraplegia-specific complications.

Conclusions

Our results confirm that patients with traumatic lower cervical spinal cord injuries defined by lesion level and AIS constitute a homogeneous group. This group is characterized by a high rate of pneumonia during the first 4 weeks after injury. The number of pre-existing general conditions and spinal injury-specific comorbidities are the only risk factors identified for the development of pneumonia and/or duration of ventilation.     

A preliminary comparison of myoelectric and cyclic control of an implanted neuroprosthesis to modulate gait speed in incomplete SCI

Objective

Explore whether electromyography (EMG) control of electrical stimulation for walking after incomplete spinal cord injury (SCI) can affect ability to modulate speed and alter gait spatial-temporal parameters compared to cyclic repetition of pre-programmed stimulation.

Design

Single case study with subject acting as own concurrent control.

Setting

Hospital-based biomechanics laboratory.

Participants

Single subject with C6 AIS D SCI using an implanted neuroprosthesis for walking.

Interventions

Lower extremity muscle activation via an implanted system with two different control methods: (1) pre-programmed pattern of stimulation, and (2) EMG-controlled stimulation based on signals from the gastrocnemius and quadriceps.

Outcome measures

Gait speed, distance, and subjective rating of difficulty during 2-minute walks. Range of walking speeds and associated cadences, stride lengths, stride times, and double support times during quantitative gait analysis.

Results

EMG control resulted in statistically significant increases in both walking speed and distance (P < 0.001) over cyclic stimulation during 2-minute walks. Maximum walking speed with EMG control (0.48 m/second) was significantly (P < 0.001) faster than the fastest automatic pattern (0.39 m/second), with increased cadence and decreased stride and double support times (P < 0.000) but no change in stride length (z = −0.085; P = 0.932). The slowest walking with EMG control (0.25 m/second) was virtually indistinguishable from the slowest with automatic cycling (z = −0.239; P = 0.811).

Conclusion

EMG control can increase the ability to modulate comfortable walking speed over pre-programmed cyclic stimulation. While control methods did not differ at the lowest speed, EMG-triggered stimulation allowed significantly faster walking than cyclic stimulation. The expanded range of available walking speeds could permit users to better avoid obstacles and naturally adapt to various environments. Further research is required to definitively determine the robustness, generalizability, and functional implications of these results.     

The efficacy of immediate versus delayed antibiotic administration on bacterial growth and biofilm production of selected strains of uropathogenic Escherichia coli and Pseudomonas aeruginosa

Purpose

The treatment of urinary tract infections (UTI) with antibiotics is commonly used, but recurrence and antibiotic resistance have been growing and concerning clinicians. We studied whether the rapid onset of a protective biofilm may be responsible for the lack of effectiveness of antibiotics against selected bacteria.

Materials and Methods

Two established uropathogenic Escherichia coli strains, UTI89 and CFT073, and two Pseudomonas aeruginosa strains, PA01 and Boston-41501, were studied to establish a reliable biofilm formation process. Bacterial growth (BG) was determined by optical density at 600 nm (OD 600) using a spectrophotometer, while biofilm formation (BF) using crystal violet staining was measured at OD 550. Next, these bacterial strains were treated with clinically relevant antibiotics, ciprofloxacin HCl (200 ng/mL and 2 μg/mL), nitrofurantoin (20 μg/mL and 40 μg/mL) and ampicillin (50 μg/mL) at time points of 0 (T0) or after 6 hours of culture (T6). All measurements, including controls (bacteria -1% DMSO), were done in triplicates and repeated three times for consistency.

Results

The tested antibiotics effectively inhibited both BG and BF when administered at T0 for UPEC strains, but not when the antibiotic administration started 6 hours later. For Pseudomonas strains, only Ciprofloxacin was able to significantly inhibit bacterial growth at T0 but only at the higher concentration of 2 μg/mL for T6.

Conclusion

When established UPEC and Pseudomonas bacteria were allowed to culture for 6 hours before initialization of treatment, the therapeutic effect of selected antibiotics was greatly suppressed when compared to immediate treatment, probably as a result of the protective nature of the biofilm.     

Influence of different rehabilitation therapy models on patient outcomes: Hand function therapy in individuals with incomplete SCI

Objectives

The primary objective was to compare the benefits of single (COT1) versus double (COT2) dose of conventional occupational therapy (COT) in improving voluntary hand function in individuals with incomplete, sub-acute C3–C7 spinal cord injury (SCI). The secondary objective was to compare these two interventions versus functional electrical stimulation therapy plus COT (FES + COT).

Design

Retrospective analysis.

Setting

Inpatient spinal cord rehabilitation center, Toronto.

Participants

Individuals with traumatic incomplete sub-acute SCI.

Interventions

Data from Phases I and II (ClinicalTrials.gov ID {"type":"clinical-trial","attrs":{"text":"NCT00221117","term_id":"NCT00221117"}}NCT00221117) randomized control trials were pooled together for the purpose of this study. Participants in the COT1 group received 45 hours of therapy, the COT2 group received 80 hours of therapy, and the FES + COT group received 40 hours of COT therapy +40 hours of FES therapy.

Outcome measures

We analyzed the functional independence measure (FIM) and the spinal cord independence measure (SCIM) self-care sub-scores.

Results

The mean change scores on the FIM self-care sub-score for the COT1, COT2, and FES + COT groups were 12.8, 10, and 20.1 points, respectively. Similarly, the mean change scores on the SCIM self-care sub-score for the COT1, COT2, and FES + COT groups were, 2.6, 3.16, and 10.2 points, respectively.

Conclusion

Increased rehabilitation intensity alone may not always be beneficial. The type of intervention plays a significant role in determining functional changes. In this instance, receiving one (COT1) or two (COT2) doses of COT resulted in similar outcomes, however, FES + COT therapy yielded much better outcomes compared to COT1 and COT2 interventions.     

Antimicrobial Distribution From Local Delivery Depends on Dose

Background

Tissue distribution after local delivery has been quantified over a period of 5 hours on 7-T MRI in a rabbit model using gadolinium-labeled diethylenetriamine pentaacetic acid (Gd-DTPA) as an antimicrobial surrogate; however, it is unknown how the Gd-DTPA load in a local depot will affect the duration of high-concentration Gd-DTPA in local tissues after surgical débridement.

Questions/purposes

We determined whether the Gd-DTPA load in bone cement affected its local tissue distribution over a period of 1 month after local delivery.

Methods

A 1-cm³ soft tissue dead space was created in the quadriceps of seven rabbits and filled with gadolinium-loaded bone cement. At 7, 14, and 33 days, the volume of tissue with a Gd-DTPA concentration of more than 14 μg/mL was calculated from T1-weighted images using 7-T MRI. Differences in volumes of distribution were analyzed with ANOVA.

Results

The volume of tissue with more than 14 μg/mL Gd-DTPA was much larger from higher gadolinium loads on Day 7 (p = 0.02) (2121 mm³ for 10 g and 665 mm³ for 1 g) and smaller with time for the 10-g formulation (2121 mm³ on Day 7 and 1241 mm³ on Day 14).

Conclusions

Volume of distribution and duration of Gd-DTPA after local delivery increased with increasing load in the cement and decreased with time.

Clinical Relevance

For local delivery, high antimicrobial concentrations would be expected in greater volumes of tissue, for longer durations, when higher antimicrobial loads are used.     

Assessment of passive knee stiffness and viscosity in individuals with spinal cord injury using pendulum test

Objective

Stiffness and viscosity represent passive resistances to joint motion related with the structural properties of the joint tissue and of the musculotendinous complex. Both parameters can be affected in patients with spinal cord injury (SCI). The purpose of this study was to measure passive knee stiffness and viscosity in patients with SCI with paraplegia and healthy subjects using Wartenberg pendulum test.

Design

Non-experimental, cross-sectional, case–control design.

Setting

An outpatient physical therapy clinic, University of social welfare and Rehabilitation Science, Iran.

Patients

A sample of convenience sample of 30 subjects participated in the study. Subjects were categorized into two groups: individuals with paraplegic SCI (n = 15, age: 34.60 ± 9.18 years) and 15 able-bodied individuals as control group (n = 15, age: 30.66 ± 11.13 years).

Interventions

Not applicable.

Main measures

Passive pendulum test of Wartenberg was used to measure passive viscous-elastic parameters of the knee (stiffness, viscosity) in all subjects.

Results

Statistical analysis (independent t-test) revealed significant difference in the joint stiffness between healthy subjects and those with paraplegic SCI (P = 0.01). However, no significant difference was found in the viscosity between two groups (P = 0.17). Except for first peak flexion angle, all other displacement kinematic parameters exhibited no statistically significant difference between normal subjects and subjects with SCI.

Conclusions

Patients with SCI have significantly greater joint stiffness compared to able-bodied subjects.