Using simulation modelling to transform hospital planning and management to address health inequalities.

Health inequalities are a perennial concern for policymakers and in service delivery to ensure fair and equitable access and outcomes. As health inequalities are socially influenced by employment, income, and education, this impacts healthcare services among socio-economically disadvantaged groups, making it a pertinent area for investigation in seeking to promote equitable access. Researchers widely acknowledge that health equity is a multi-faceted problem requiring approaches to understand the complexity and interconnections in hospital planning as a precursor to healthcare delivery. Operations research offers the potential to develop analytical models and frameworks to aid in complex decision-making that has both a strategic and operational function in problem-solving. This paper develops a simulation-based modelling framework (SimulEQUITY) to model the complexities in addressing health inequalities at a hospital level. The model encompasses an entire hospital operation (including inpatient, outpatient, and emergency department services) using the discrete-event simulation method to simulate the behaviour and performance of real-world systems, processes, or organisations. The paper makes a sustained contribution to knowledge by challenging the existing population-level planning approaches in healthcare that often overlook individual patient needs, especially within disadvantaged groups. By holistically modelling an entire hospital, socio-economic variations in patients' pathways are developed by incorporating individual patient attributes and variables. This innovative framework facilitates the exploration of diverse scenarios, from processes to resources and environmental factors, enabling key decision-makers to evaluate what intervention strategies to adopt as well as the likely scenarios for future patterns of healthcare inequality. The paper outlines the decision-support toolkit developed and the practical application of the SimulEQUITY model through to implementation within a hospital in the UK. This moves hospital management and strategic planning to a more dynamic position where a software-based approach, incorporating complexity, is implicit in the modelling rather than simplification and generalisation arising from the use of population-based models.

Semisynthesis and biological evaluation of a focused library of unguinol derivatives as next-generation antibiotics.

In this study, we report the semisynthesis and in vitro biological evaluation of thirty-four derivatives of the fungal depsidone antibiotic, unguinol. Initially, the semisynthetic modifications were focused on the two free hydroxy groups (3-OH and 8-OH), the three free aromatic positions (C-2, C-4 and C-7), the butenyl side chain and the depsidone ester linkage. Fifteen first-generation unguinol analogues were synthesised and screened against a panel of bacteria, fungi and mammalian cells to formulate a basic structure activity relationship (SAR) for the unguinol pharmacophore. Based on the SAR studies, we synthesised a further nineteen second-generation analogues, specifically aimed at improving the antibacterial potency of the pharmacophore. In vitro antibacterial activity testing of these compounds revealed that 3-O-(2-fluorobenzyl)unguinol and 3-O-(2,4-difluorobenzyl)unguinol showed potent activity against both methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MIC 0.25-1 µg mL-1) and are promising candidates for further development in vivo.

Kcnn2 blockade reverses learning deficits in a mouse model of fetal alcohol spectrum disorders.

Learning disabilities are hallmarks of congenital conditions caused by prenatal exposure to harmful agents. These include fetal alcohol spectrum disorders (FASDs) with a wide range of cognitive deficiencies, including impaired motor skill development. Although these effects have been well characterized, the molecular effects that bring about these behavioral consequences remain to be determined. We previously found that the acute molecular responses to alcohol in the embryonic brain are stochastic, varying among neural progenitor cells. However, the pathophysiological consequences stemming from these heterogeneous responses remain unknown. Here we show that acute responses to alcohol in progenitor cells altered gene expression in their descendant neurons. Among the altered genes, an increase of the calcium-activated potassium channel Kcnn2 in the motor cortex correlated with motor learning deficits in a mouse model of FASD. Pharmacologic blockade of Kcnn2 improves these learning deficits, suggesting Kcnn2 blockers as a new intervention for learning disabilities in FASD.

In vitro antimicrobial activity of seven adjuvants against common pathogens associated with canine otitis externa.

BACKGROUND: An antibiotic adjuvant is a chemical substance used to modify or augment the effectiveness of primary antimicrobial agents against drug-resistant micro-organisms. Its use provides an alternative approach to address the global issue of antimicrobial resistance and enhance antimicrobial stewardship. HYPOTHESIS/OBJECTIVES: To determine the antimicrobial activity of a panel of potential antimicrobial adjuvants against common pathogens associated with canine otitis externa (OE). ANIMALS/ISOLATES: A number of type strains and clinical isolates (n = 110) from canine OE were tested including Staphylococcus pseudintermedius, ß-haemolytic Streptococcus spp., Pseudomonas aeruginosa, Proteus mirabilis and Malassezia pachydermatis. METHODS AND MATERIALS: Antimicrobial activities of monolaurin, monocaprin, N-acetylcysteine (NAC), polymyxin B nonapeptide, Tris-EDTA, Tris-HCL and disodium EDTA were tested using microdilution methodology according to CLSI guidelines. RESULTS: N-acetylcysteine, Tris-EDTA and disodium EDTA had antimicrobial activity against both type strains and otic pathogens. The other adjuvants tested had limited to no efficacy. NAC had a minimal inhibitory concentration (MIC) range of 2,500-10,000 µg/mL for the various organisms. Pseudomonas aeruginosa isolates were eight times more susceptible to disodium EDTA in the presence of Tris-HCL in comparison to disodium EDTA alone. Malassezia pachydermatis isolates were most susceptible to Tris-EDTA (MIC90  = 190/60 µg/mL) and disodium EDTA (MIC90  = 120 µg/mL). CONCLUSIONS AND CLINICAL RELEVANCE: N-acetylcysteine, Tris-EDTA and disodium EDTA have intrinsic antimicrobial activity and represent promising adjuvants that could be used to enhance the efficacy of existing antibiotics against Gram-negative and multidrug-resistant bacterial infections. These agents could be combined with other antimicrobial agents in a multimodal approach for mixed ear infections in dogs.

Repurposing Ionophores as novel antimicrobial agents for the treatment of bovine mastitis caused by Gram-positive pathogens.

Increasing reports of multidrug-resistant bacterial infections in animals has created a need for novel antimicrobial agents that do not promote cross-resistance to critically important antimicrobial classes used in human medicine. In response to the recent emergence of antimicrobial resistance in several bovine mastitis pathogens, in vitro antimicrobial susceptibility was determined for four polyether ionophores (lasalocid, monensin, narasin and salinomycin) against Staphylococcus spp. and Streptococcus spp. isolated from clinical cases. In addition, erythrocyte haemolysis and WST-1 cell proliferation assays were used to assess in vitro mammalian cell cytotoxicity and biofilm susceptibility testing was performed using the minimum biofilm eradication concentration (MBEC™) biofilm assay. Lasalocid, monensin, narasin and salinomycin exhibited bacteriostatic antimicrobial activity against all pathogens tested, including methicillin-resistant staphylococci, with MIC90 values <16 µg/ml. Narasin and monensin displayed the least toxicity against mammalian cell lines and all compounds significantly reduced viable cell numbers in a Staphylococcus aureus biofilm. Based on in vitro characterization, all four ionophores offer potentially novel treatments against bovine mastitis but in vivo studies will be essential to determine whether acceptable safety and efficacy is present following intramammary administration.

Giardia duodenalis mouse model for the development of novel antigiardial agents.

This study describes a neonatal mouse model of Giardia infection for development of novel antigiardials. Mice were infected with the axenically cultured Assemblage A BAH2c2 strain, with 105 trophozoites per animal recovered. This model proved to be robust and consistent for use in preliminary drug efficacy trials and drug development.

Evaluation of Transdermal Drug Permeation as Modulated by Lipoderm and Pluronic Lecithin Organogel.

The transdermal delivery of 2 fluorescent probes with similar molecular weight but different lipophilicity, into and through the skin from 2 commercially available transdermal bases, pluronic lecithin organogel, and Lipoderm® has been evaluated. First, in vitro penetration of fluorescein sodium and fluorescein (free acid) through porcine skin was evaluated. Retention and depth distribution profiles in skin were obtained by tape stripping and then followed by optical sectioning using multiphoton microscopy. The results showed that Lipoderm® led to an enhanced penetration of the hydrophilic compound, fluorescein sodium. For the lipophilic compound fluorescein (free acid), Lipoderm® performed similar to pluronic lecithin organogel base, where minimal drug was detected in either receptor phase. The skin retention and depth distribution results also showed that the hydrophilic fluorescein sodium had high skin retention with Lipoderm®, whereas fluorescein (free acid) had very low penetration and retention with increasing skin depth. Moreover, optical sectioning by multiphoton microscopy revealed an uneven distribution of probes across the skin in the x-y plane for both transdermal bases. This work showed that a hydrophilic compound has significantly increased skin penetration and retention when formulated with Lipoderm®, and the skin retention of the probe was the main determinant of its skin flux.

Intra-cardiac and peripheral levels of biochemical markers of fibrosis in patients undergoing catheter ablation for atrial fibrillation.

AIMS: Measurement of circulating biomarkers of fibrosis may have a role in selecting patients and treatment strategy for catheter ablation. Pro-collagen type III N-terminal pro-peptide (PIIINP), C-telopeptide of type I collagen (ICTP), fibroblast growth factor 23 (FGF-23), and galectin 3 (gal-3) have all been suggested as possible biomarkers for this indication, but studies assessing whether peripheral levels reflect intra-cardiac levels are scarce. METHODS AND RESULTS: We studied 93 patients undergoing ablation for paroxysmal atrial fibrillation (AF) (n = 63) or non-paroxysmal AF (n = 30). Femoral venous, left and right atrial, and coronary sinus blood were analysed using ELISA to determine biomarker levels. Levels were compared with control patients (n = 36) and baseline characteristics, including left atrial voltage mapping data. C-telopeptide of type I collagen levels were higher in AF than in non-AF patients (P = 0.007). Peripheral ICTP levels were higher than all intra-cardiac levels (P < 0.001). Peripheral gal-3 levels were higher than left atrial levels (P = 0.001). Peripheral levels of FGF-23 and PIIINP were not significantly different from intra-cardiac levels. CS levels of ICTP were higher than right and left atrial levels (P < 0.001). gal-3 was higher in women vs. men (P ≤ 0.001) and with higher body mass index (P ≤ 0.001). ICTP levels increased with reducing ejection fraction (P ≤ 0.012). CONCLUSIONS: Atrial fibrillation patients have higher levels of circulating ICTP than matched non-AF controls. In AF ablation patients, intra-cardiac sampling of FGF-23 or PIIINP gives no further information over peripheral sampling. For gal-3 and ICTP, intra-cardiac sampling may be necessary to assess their association with intra-cardiac processes. None of the biomarkers is related to fibrosis assessed by left atrial voltage.

Giving Them a Hand: Wearing a Myoelectric Elbow-Wrist-Hand Orthosis Reduces Upper Extremity Impairment in Chronic Stroke.

OBJECTIVE: To determine the immediate effect of a portable, myoelectric elbow-wrist-hand orthosis on paretic upper extremity (UE) impairment in chronic, stable, moderately impaired stroke survivors. DESIGN: Observational cohort study. SETTING: Outpatient rehabilitation clinic. PARTICIPANTS: Participants exhibiting chronic, moderate, stable, poststroke, UE hemiparesis (N=18). INTERVENTIONS: Subjects were administered a battery of measures testing UE impairment and function. They then donned a fabricated myoelectric elbow-wrist-hand orthosis and were again tested on the same battery of measures while wearing the device. MAIN OUTCOME MEASURES: The primary outcome measure was the UE Section of the Fugl-Meyer Scale. Subjects were also administered a battery of functional tasks and the Box and Block (BB) test. RESULTS: Subjects exhibited significantly reduced UE impairment while wearing the myoelectric elbow-wrist-hand orthosis (FM: t17=8.56, P<.0001) and increased quality in performing all functional tasks while wearing the myoelectric elbow-wrist-hand orthosis, with 3 subtasks showing significant increases (feeding [grasp]: z=2.251, P=.024; feeding [elbow]: z=2.966, P=.003; drinking [grasp]: z=3.187, P=.001). Additionally, subjects showed significant decreases in time taken to grasp a cup (z=1.286, P=.016) and increased gross manual dexterity while wearing a myoelectric elbow-wrist-hand orthosis (BB test: z=3.42, P<.001). CONCLUSIONS: Results suggest that UE impairment, as measured by the Fugl-Meyer Scale, is significantly reduced when donning a myoelectric elbow-wrist-hand orthosis, and these changes exceeded the Fugl-Meyer Scale's clinically important difference threshold. Further, utilization of a myoelectric elbow-wrist-hand orthosis significantly increased gross manual dexterity and performance of certain functional tasks. Future work will integrate education sessions to increase subjects' ability to perform multijoint functional movements and attain consistent functional changes.

Retention of the spacing effect with mental practice in hemiparetic stroke.

Mental practice (MP) is a promising adjuvant to physical practice that involves many of the same mechanisms and takes on many of the same properties as physical practice. This study compared efficacy of a "massed" MP regimen versus a "distributed" MP regimen on upper extremity (UE) motor impairment and functional limitation. Twenty-seven chronic stroke survivors were administered the UE section of the Fugl-Meyer (FM) and Action Research Arm Test (ARAT), followed by standardized physical practice and MP regimens. One group was administered "massed" MP (60 min of MP during a single daily session) and a second group administered distributed MP (20 min of MP occurring three times/day). After intervention, changes in FM and ARAT scores of subjects in the distributed condition were significantly higher than those of subjects in the massed condition (FM 3.65, 95 % CI 0.82-6.49, p value = 0.01; ARAT 3.95, 95 % CI 1.24-6.67, p value = 0.006). Likewise, at POST 3, subjects in the distributed group showed significantly higher change in ARAT scores (ARAT 4.90, 95 % CI 0.57-9.22, p value = 0.03); the change in FM scores at POST 3 was 3.18 points higher among subjects in the distributed condition, but only approached significance (95 % CI -1.27 to 7.63, p value = 0.15). Results suggest that a distributed MP schedule is more efficacious in bringing about paretic UE changes than a massed practice schedule, especially in terms of reducing UE functional limitation.

Upper-Limb Recovery After Stroke: A Randomized Controlled Trial Comparing EMG-Triggered, Cyclic, and Sensory Electrical Stimulation.

BACKGROUND AND PURPOSE: This study compared the effect of cyclic neuromuscular electrical stimulation (NMES), electromyographically (EMG)-triggered NMES, and sensory stimulation on motor impairment and activity limitations in patients with upper-limb hemiplegia. METHODS: This was a multicenter, single-blind, multiarm parallel-group study of nonhospitalized hemiplegic stroke survivors within 6 months of stroke. A total of 122 individuals were randomized to receive either cyclic NMES, EMG-triggered NMES, or sensory stimulation twice every weekday in 40-minute sessions, over an 8 week-period. Patients were followed for 6 months after treatment concluded. RESULTS: There were significant increases in the Fugl-Meyer Assessment [F(1, 111) = 92.6, P < .001], FMA Wrist and Hand [F(1, 111) = 66.7, P < .001], and modified Arm Motor Ability Test [mAMAT; time effect: F(1, 111) = 91.0, P < .001] for all 3 groups. There was no significant difference in the improvement among groups in the FMA [F(2, 384) = 0.2, P = .83], FMA Wrist and Hand [F(2, 384) = 0.4, P = .70], or the mAMAT [F(2, 379) = 1.2, P = .31]. CONCLUSIONS: All groups exhibited significant improvement of impairment and functional limitation with electrical stimulation therapy applied within 6 months of stroke. Improvements were likely a result of spontaneous recovery. There was no difference based on the type of electrical stimulation that was administered.

"Reps" Aren't Enough: Augmenting Functional Electrical Stimulation With Behavioral Supports Significantly Reduces Impairment in Moderately Impaired Stroke.

OBJECTIVE: To determine the impact of repetitive task-specific practice (RTP) integrating electrical stimulation and behavioral supports on upper extremity (UE) impairment, gross manual dexterity, and paretic UE amount and quality of use in chronic stroke survivors exhibiting moderate, stable UE deficits. DESIGN: Case series with 3-month follow-up. SETTING: Outpatient rehabilitation hospital. PARTICIPANTS: Persons (N=9) who experienced a stroke >12 months before enrollment and exhibiting chronic, moderate, stable UE impairment. INTERVENTIONS: After administering outcome measures, RTP was administered 3d/wk for 120 minutes with an electrical stimulation neuroprosthesis (60min in a supervised clinical setting; 60min at home) over 8 weeks. Behavioral supports (eg, behavior contract; weekly reviews of UE use) were provided during clinical sessions and integrated into home exercise sessions to increase paretic UE use and maximize carryover to subjects' community environments. MAIN OUTCOME MEASURES: The UE section of the Fugl-Meyer Impairment Scale, the Box and Block Test, and the Motor Activity Log. RESULTS: Subjects exhibited statistically significant (P<.01) increases on all measures at both time-point comparisons (ie, preintervention to postintervention; preintervention to 3mo postintervention). Subjects reported a new ability to perform valued activities they had not performed in months. CONCLUSIONS: Addition of behavioral supports to RTP augmented by electrical stimulation significantly increased paretic UE use and function. Significant motor changes were exhibited across ages and etiologies, and no other intervention was administered to this stable population, making it likely that results were not due to chance and suggests a larger trial is justified.

Integrating Mental Practice with Task-specific Training and Behavioral Supports in Poststroke Rehabilitation: Evidence, Components, and Augmentative Opportunities.

Stroke remains a leading cause of death, with most survivors experiencing long-term deficits in motor function. Upper extremity (UE) hemiparesis constitutes one of the most common and disabling poststroke impairments. Many contemporary rehabilitative methods target reacquisition of UE motor skills. One such intervention is mental practice (MP), which involves mental rehearsal without physical execution of the movement. MP has not been consistently integrated into clinical environments. This article discusses the scientific rationale for MPs, highlights evidence supporting their use, discusses components of the repetitive task-specific practice regimens accompanying MP, and discusses possible augmentative strategies and areas for research.

Development of intramammary delivery systems containing lasalocid for the treatment of bovine mastitis: impact of solubility improvement on safety, efficacy, and milk distribution in dairy cattle.

BACKGROUND: Mastitis is a major disease of dairy cattle. Given the recent emergence of methicillin-resistant Staphylococcus aureus as a cause of bovine mastitis, new intramammary (IMA) treatments are urgently required. Lasalocid, a member of the polyether ionophore class of antimicrobial agents, has not been previously administered to cows by the IMA route and has favorable characteristics for development as a mastitis treatment. This study aimed to develop an IMA drug delivery system (IMDS) of lasalocid for the treatment of bovine mastitis. METHODS: Minimum inhibitory concentrations (MICs) were determined applying the procedures recommended by the Clinical and Laboratory Standards Institute. Solid dispersions (SDs) of lasalocid were prepared and characterized using differential scanning calorimetry and Fourier transform infrared spectroscopy. IMDSs containing lasalocid of micronized, nano-sized, or as SD form were tested for their IMA safety in cows. Therapeutic efficacy of lasalocid IMDSs was tested in a bovine model involving experimental IMA challenge with the mastitis pathogen Streptococcus uberis. RESULTS: Lasalocid demonstrated antimicrobial activity against the major Gram-positive mastitis pathogens including S. aureus (MIC range 0.5-8 µg/mL). The solubility test confirmed limited, ion-strength-dependent water solubility of lasalocid. A kinetic solubility study showed that SDs effectively enhanced water solubility of lasalocid (21-35-fold). Polyvinylpyrrolidone (PVP)-lasalocid SD caused minimum mammary irritation in treated cows and exhibited faster distribution in milk than either nano or microsized lasalocid. IMDSs with PVP-lasalocid SD provided effective treatment with a higher mastitis clinical and microbiological cure rate (66.7%) compared to cloxacillin (62.5%). CONCLUSION: Lasalocid SD IMDS provided high cure rates and effectiveness in treating bovine mastitis with acceptable safety in treated cows.

Mental practice--triggered electrical stimulation in chronic, moderate, upper-extremity hemiparesis after stroke.

OBJECTIVE: To determine the feasibility and impact of home-based, mental practice-triggered electrical stimulation among stroke survivors exhibiting moderate upper-extremity (UE) impairment. METHOD: Five participants with moderate, stable UE hemiparesis were administered the Fugl-Meyer Assessment, the Box and Block Test, and the Activities of Daily Living, Hand Function, and overall recovery domains of the Stroke Impact Scale (Version 3). They were then administered an 8-wk regimen consisting of 1 hr of mental practice-triggered electrical stimulation every weekday in their home. At the end of every 2 wk, participants attended supervised stimulation to progress therapeutic exercises and stimulation levels and monitor compliance. RESULTS: Six instances of device noncompliance were reported. Participants exhibited reduced UE motor impairment and increased UE dexterity and participation in valued activities. CONCLUSION: The regimen appears feasible and had a substantial impact on UE impairment, dexterity, and participation in valued activities as well as perceptions of recovery.

Language changes coincide with motor and fMRI changes following upper extremity motor therapy for hemiparesis: a brief report.

To formally assess changes in language, affected UE movement, and motor functional activation changes via functional magnetic resonance imaging (fMRI) following participation in motor therapy without any accompanying language intervention. Pre-post case series. Five subjects with stroke exhibiting chronic, stable UE hemiparesis. The upper extremity section of the Fugl-Meyer (FM), the Western Aphasia Battery (WAB), and functional magnetic resonance imaging (fMRI), administered during performance of an affected UE motor task. All subjects were administered six weeks of repetitive task specific training (RTP), performed for approximately 2.5 hours per day, split into two sessions. For the first four weeks of the intervention period, RTP was administered every weekday, whereas, for the subsequent two weeks, RTP was administered 3 days/week. Epidural cortical stimulation was co-administered with the RTP via an electrode array and implanted pulse generator. For all sessions, one subject worked with a single therapist. Four weeks before and four weeks after the intervention period, all subjects were administered the FM, WAB, and fMRI. Three of the subjects exhibited clinically significant language changes on the WAB. These individuals exhibited the largest motor changes as measured by the FM. Functional MRI revealed distinct motor activation patterns in these subjects, characterized by more strongly right lateralized focal BOLD activity or a shift in activation toward the right hemisphere. Language changes appear to co-occur with motor changes after UE RTP. Understanding the underlying mechanisms of these findings may lead to more efficient and synergistic rehabilitative therapy delivery.

Mean diffusivity as a potential diffusion tensor biomarker of motor rehabilitation after electrical stimulation incorporating task specific exercise in stroke: a pilot study.

Changes in diffusion tensor imaging (DTI) values co-occur with neurological and functional changes after stroke. However, quantitative DTI metrics have not been examined in response to participation in targeted rehabilitative interventions in chronic stroke. The primary purpose of this pilot study was to examine whether changes in DTI metrics co-occur with paretic arm movement changes among chronic stroke patients participating in a regimen of electrical stimulation targeting the paretic arm. Three subjects exhibiting stable arm hemiparesis were administered 30-minute (n = 1) or 120-minute (n = 2) therapy sessions emphasizing paretic arm use during valued, functional tasks and incorporating an electrical stimulation device. These sessions occurred every weekday for 8 weeks. A fourth subject served as a treatment control, participating in a 30-minute home exercise regimen without electrical stimulation every weekday for 8 weeks. DTI and behavioral outcome measures were acquired at baseline and after intervention. DTI data were analyzed using a region of interest (ROI) approach, with ROIs chosen based on tract involvement in sensorimotor function or as control regions. Behavioral outcome measures were the Fugl-Meyer Scale (FM) and the Action Research Arm Test (ARAT). The treatment control subject exhibited gains in pinch and grasp, as shown by a 5-point increase on the ARAT. The subject who participated in 30-minute therapy sessions exhibited no behavioral gains. Subjects participating in 120-minute therapy sessions displayed consistent impairment reductions and distal movement changes. DTI changes were largest in subjects two and three, with mean diffusivity (MD) decreases in the middle cerebellar peduncle and posterior limb of the internal capsule following treatment. No changes in fractional anisotropy (FA) were observed for sensorimotor tracts. Our preliminary results suggest that active rehabilitative therapies augmented by electrical stimulation may induce positive behavioral changes which are underscored by DTI changes indicative of increased white matter tract integrity in regions specific to sensory-motor function.

Paretic upper extremity movement gains are retained 3 months after training with an electrical stimulation neuroprosthesis.

OBJECTIVE: To determine retention of upper extremity (UE) motor changes 3 months after participation in a regimen in which subjects with moderate UE hemiparesis engaged in repetitive task-specific training using an electrical stimulation neuroprosthesis (ESN). DESIGN: Prospective, blinded, cohort, pre-post study. SETTING: Outpatient rehabilitation hospital. PARTICIPANTS: Individuals (N=24) in the chronic stage of stroke exhibiting stable UE hemiparesis (11 men; mean age, 57.9±9.5y; age range, 39-75y; mean time since stroke at time of repetitive task-specific practice [RTP] using ESN intervention start, 36.7mo; range of onset, 7-162mo). INTERVENTION: As part of a larger trial, subjects had been randomly assigned to receive an 8-week regimen comprised of RTP on valued activities using the ESN. This observational study assessed this single group's paretic UE motor levels immediately after, and 3 months after, the intervention. MAIN OUTCOME MEASURES: The Fugl-Meyer (FM) assessment of sensorimotor impairment, the Action Research Arm Test (ARAT), the Arm Motor Ability Test (AMAT), and the Box and Block Test (BBT). RESULTS: None of the scores significantly changed from the period directly after intervention to the test 3-months follow-up (FM: t=1.64; ARAT: t=2.17; AMAT: t=.76, .92, and 1.01 for the functional ability, quality of movement, and time scales, respectively; BBT: t=.36; adjusted t critical value to reject the null [t(crit)]=2.90, 2-tailed α=.008 to preserve experiment-wise error rate of .05). CONCLUSIONS: Subjects exhibited no changes in the various functional tests, indicating that changes in paretic UE movement realized through RTP using ESN appear to be retained 3 months after the intervention has concluded. This was the first study to our knowledge to examine the longer-term effects of RTP using an ESN in any population.

Longer versus shorter daily durations of electrical stimulation during task-specific practice in moderately impaired stroke.

OBJECTIVE: To examine and compare efficacy of 30-, 60-, and 120-minute repetitive task-specific practice (RTP) sessions incorporating use of an electrical stimulation neuroprosthesis (ESN) on affected upper-extremity (UE) movement. DESIGN: Prospective, single-blinded, randomized controlled trial. SETTING: Outpatient rehabilitation hospital. PARTICIPANTS: Chronic stroke subjects (N=32) exhibiting moderate, stable affected UE motor deficits. INTERVENTIONS: Subjects participated in 30-, 60-, or 120-minute therapy sessions involving RTP incorporating the ESN, occurring every weekday for 8 weeks. During sessions, they wore the ESNs to enable performance of valued activities that they had identified. A fourth group participated in a 30-minute per weekday home exercise program. MAIN OUTCOME MEASURES: Outcomes were evaluated using the UE section of the Fugl-Meyer Assessment of Sensorimotor Impairment (FM), the Arm Motor Ability Test (AMAT), the Action Research Arm Test (ARAT), and Box and Block (B&B) 1 week before and 1 week after intervention. RESULTS: After intervention, subjects in the 120-minute condition were the only ones to exhibit significant score increases on the FM (P=.0007), AMAT functional ability scale (P=.002), AMAT quality of movement scale (P=.0002), and ARAT (P=.02). They also exhibited the largest changes in time to perform AMAT tasks and in B&B score, but these changes were nonsignificant, (P=.15 and P=.10, respectively). CONCLUSIONS: One hundred and twenty minutes a day of RTP augmented by ESN use elicits the largest and most consistent UE motor changes in moderately impaired stroke subjects.