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Healing of deep cutaneous wounds often results in detrimental sequelae, including painful and debilitating scars. Current therapies for full-thickness injuries that target specific phases of wound healing have moderate success; however, full resolution remains incomplete and negative consequences persist if skin homeostasis is not achieved. Photoactivated molecules can modulate cellular responses by generating reactive oxygen species and may provide a novel therapeutic option to improve wound healing. In the current study, we investigated the effects of Rose bengal (RB) dye in a preclinical model of full-thickness cutaneous injury. Monochromatic green light activates RB to generate ROS in the presence of oxygen, subsequently crosslinking collagen fibrils. In in vitro studies, we show that photoactivated RB is well tolerated by epidermal keratinocytes and dermal fibroblasts and can mitigate fibrotic signalling by downregulating collagen production. In a murine model of full-thickness injury, topically-applied and photoactivated RB closed wounds faster than control and vehicle treatments and showed significantly improved wound healing outcomes, including enhanced early granulation, better collagen organisation and increased vascularity in the presence of protracted tissue ROS. These data support an overall improved cutaneous wound healing profile after RB phototherapy and warrant further investigations into this versatile molecule.
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The evidence-based quantification of the relation between changes in movement quality and functionality can assist clinicians in achieving more effective structuring or adapting of therapy. In this paper, clinicians rated task, segment, and composite movement feature performance for 478 videos of stroke survivors executing upper extremity therapy tasks. We used the clinician ratings to develop a Hierarchical Bayesian Model (HBM) with task, segment, and composite layers for computing the statistical relation of movement quality changes to function. The model was enhanced through a detailed correlation graph (ΔHBM) that links computationally extracted kinematics with clinician-rated composite features for different task-segment combinations. Utilizing the weights and correlation graphs, we finally derive reverse cascading probabilities of the proposed HBM from kinematics to composite features, segments, and tasks. In a test involving 98 cases where clinician ratings differed, the HBM resolved 95% of these discrepancies. The model effectively aligned kinematic data with specific task-segment combinations in over 90% of cases. Once the HBM is expanded and refined through additional data it can be used for the automated calculation of statistical relations between changes in kinematics and performance of functional tasks and the generation of therapy assessment recommendations for clinicians. While our work primarily focuses on the upper extremities of stroke survivors, the HBM can be adapted to many other neurorehabilitation contexts.
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Background: Despite physical and emotional distress in patients with gynecologic malignancies, palliative care (PC) is underutilized. Objectives: We characterize referral practices, symptom burden and functional status at the time of initial PC encounter for patients with gynecologic cancer. Design: Data were extracted from the standardized Quality Data Collection Tool for Palliative Care (QDACT-PC). We describe symptom burden and performance status. Results: At initial specialty PC encounter, patients with gynecologic cancers reported a mean of 3.3 moderate/severe symptoms. Outpatients experienced the most moderate/severe symptoms (mean 3.9) versus inpatient (mean 2.1) or home (mean 1.5). A total of 72.7% of patients had significantly impaired functional status (palliative performance scale [PPS] <70) at initial encounter. Inpatients had a more impaired functional status (mean PPS 48.8) than outpatients (mean PPS 67.0). Conclusions: The symptom burden for gynecologic cancer patients at initial PC encounter is high. Despite better functional status, patients referred in the outpatient setting had the highest symptom burden.
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PURPOSE: The standard of care for burned patients experiencing hyperglycemia associated with the hypermetabolic response is insulin therapy. Insulin treatment predisposes burn patients to hypoglycemia, which increases morbidity and mortality. Metformin has been suggested as an alternative to insulin therapy for glycemic control in burn patients given its safety profile, but further research is warranted. This study investigated whether metformin use in burn patients is associated with improved glycemic control and morbidity/mortality outcomes compared to insulin use alone. MATERIALS AND METHODS: Using the TriNetX database, we conducted a retrospective study of burned patients who were administered insulin, metformin, or both within one week of injury. Demographic, comorbidity, and burn severity information were collected. Patients were categorized by treatment type, propensity score-matched, and compared for the following outcomes within 3 months: hyperglycemia, hypoglycemia, sepsis, lactic acidosis, and death. Statistical significance was set a priori at p ≤ 0.05. RESULTS: The insulin cohort was at increased risk for all outcomes (all p < 0.0001) compared to the metformin cohort, and an increased risk for sepsis, lactic acidosis, and death (all p ≤ 0.0002) compared to the insulin/metformin combination cohort. When compared to the metformin cohort, the combination cohort was at increased risk for all outcomes (all p ≤ 0.0107) except death. CONCLUSIONS: Treatment with metformin after burn is associated with a reduced risk of morbidity and mortality compared to insulin. The combination of insulin and metformin is no more effective in reducing the risk of hyperglycemia and hypoglycemia than insulin alone but is less effective than metformin alone.
Subject(s)
Burns , Hyperglycemia , Hypoglycemic Agents , Insulin , Metformin , Sepsis , Humans , Metformin/therapeutic use , Burns/mortality , Burns/drug therapy , Burns/complications , Male , Female , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Retrospective Studies , Middle Aged , Adult , Hyperglycemia/drug therapy , Sepsis/drug therapy , Sepsis/mortality , Aged , Hypoglycemia/chemically induced , Hypoglycemia/epidemiology , Acidosis, Lactic/chemically induced , Acidosis, Lactic/epidemiology , Propensity Score , Drug Therapy, Combination , Glycemic Control/methodsABSTRACT
BACKGROUND: Changes in regional levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) may indicate the potential for favorable responses to the treatment of stroke affecting the upper extremity. By selectively altering GABA levels during training, we may induce long-term potentiation and adjust excitatory/inhibitory balance (E/I balance). However, the impact of this alteration may be limited by neural damage or aging. Aerobic exercise has been shown to increase GABA levels in the sensorimotor cortex and improve motor learning by widening the dynamic range of E/I balance. The cross-sectional project, Effects of Acute Exercise on Functional Magnetic Resonance Spectroscopy Measures of GABA in Aging and Chronic Stroke (EASE), is designed to assess the functional relevance of changes in GABA concentration within the sensorimotor cortex before and after an acute aerobic exercise session. METHODS/DESIGN: EASE will enroll 30 participants comprised of healthy younger adults (18-35 years; n = 10), older adults (60+ years; n = 10), and persons with chronic stroke (n = 10) affecting distal upper extremity function. We will use resting magnetic resonance spectroscopy to measure all participants' GABA levels at rest before and after aerobic exercise. In addition, we will employ functional magnetic resonance spectroscopy using motor skill acquisition and recall tasks in healthy adults. We hypothesize that acute aerobic exercise will increase resting sensorimotor GABA concentration and that higher GABA resting levels will predict better motor learning performance on measures taken both inside and outside the magnet. We also hypothesize that a higher dynamic range of GABA during task-based spectroscopy in healthy adults will predict better motor skill acquisition and recall. DISCUSSION: The EASE project will evaluate the effect of acute exercise on GABA levels as a biomarker of upper extremity motor skill learning with two populations (aging adults and those with chronic stroke). We predict that acute exercise, higher sensorimotor GABA levels, and broader dynamic range will be related to better motor skill acquisition.
Subject(s)
Aging , Exercise , Magnetic Resonance Spectroscopy , Stroke , gamma-Aminobutyric Acid , Humans , gamma-Aminobutyric Acid/metabolism , Adult , Middle Aged , Stroke/metabolism , Stroke/physiopathology , Stroke/therapy , Exercise/physiology , Aging/physiology , Aging/metabolism , Aged , Male , Magnetic Resonance Spectroscopy/methods , Female , Young Adult , Adolescent , Cross-Sectional Studies , Stroke Rehabilitation/methods , Sensorimotor Cortex/metabolism , Sensorimotor Cortex/physiopathologyABSTRACT
CONTEXT: Early specialist palliative care (PC) involvement in metastatic non-small cell lung cancer (mNSCLC) is associated with improved quality of life, less aggressive end of life (EoL) care, and longer survival. As treatment paradigms for NSCLC have evolved, PC utilization remains low. OBJECTIVES: This work examines how the timing and extent of PC involvement impacts outcomes and the patient experience in mNSCLC in the era of immunotherapy. METHODS: This retrospective review analyzed patients with mNSCLC who initiated first-line treatment with chemotherapy, immunotherapy, or combined chemoimmunotherapy at Duke University between March 2015 and July 2019. PC consultation and outcomes data were abstracted through November 2022. EoL care variables were analyzed using descriptive statistics. RESULTS: 152 patients were stratified based on whether PC was consulted during their disease course. 80 patients (53%) never saw PC, while the 72 patients (47%) who saw PC were further stratified by time to first PC encounter and total number of PC visits. 31% were seen within two months of diagnosis (early), 33% between two and six months (intermediate), and 36% after 6 months (late). Patients who received early PC had longer median time on hospice (35 days), had lower rates of aggressive EoL care (43%), and experienced less frequent in-hospital death (14%) compared to other groups. CONCLUSION: This real-world study reveals that referrals to PC still occur late or not at all in mNSCLC despite demonstrated benefits of early PC integration. Early outpatient PC referrals resulted in longer time on hospice, lower frequency of aggressive EoL care, and lower rates of in-hospital death.
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BACKGROUND AND PURPOSE: Implantable vagus nerve stimulation (VNS) paired with volitional upper extremity rehabilitation can improve impairment and function among moderately to severely impaired, chronic stroke survivors. This study is a retrospective analysis of the in-clinic rehabilitation phase of the blinded, placebo-controlled, randomized pivotal VNS-REHAB trial to determine whether dosing parameters during in-clinic paired VNS therapy were associated with responder status and whether covariates might impact that determination. METHODS: Data were limited to 53 participants in the active VNS group who had received VNS implants prior to undergoing 6 weeks of in-clinic rehabilitation paired with VNS. Tasks were standardized across all participants. Dosing parameters included number of stimulations and task time. The primary outcome was the Fugl-Meyer Upper Extremity Assessment (FMA-UE), evaluated at the end of 6 weeks (Post-1). Participants were classified a priori as responders based on an improvement of ≥6 points on the FMA-UE from baseline to Post-1. RESULTS: Dosing parameters were not associated with FMA-UE responder status at the end of 6 weeks. Covariates including age, gender, paretic hand, baseline severity, and chronicity of stroke were also not significant associations of response. DISCUSSION AND CONCLUSIONS: While responders to VNS could be defined, therapy dosing and participant attributes did not provide greater specification for association of responder status. Limitations of this study include small sample size and non-linearity of the FMA-UE. Future studies will include reassessing responder categorization using more linear scales and examining stroke lesion characteristics to determine whether these measures are more sensitive to dosing parameters. VIDEO ABSTRACT AVAILABLE: for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://www.w3.org/1999/xlink).
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Background: Recent findings suggest increased excitatory heteronymous feedback from quadriceps onto soleus may contribute to abnormal coactivation of knee and ankle extensors after stroke. However, there is lack of consensus on whether persons post-stroke exhibit altered heteronymous reflexes and, when present, the origin of increased excitation (i.e. increased excitation alone and/or decreased inhibition). This study examined heteronymous excitation and inhibition from quadriceps onto soleus in paretic, nonparetic, and age-matched control limbs to determine whether increased excitation was due to excitatory and/or reduced inhibitory reflex circuits. A secondary purpose was to examine whether heteronymous reflex magnitudes were related to clinical measures of lower limb recovery, walking-speed, and dynamic balance. Methods: Heteronymous excitation and inhibition from quadriceps onto soleus were examined in fourteen persons post-stroke and fourteen age-matched unimpaired participants. Heteronymous feedback was elicited by femoral nerve and quadriceps muscle stimulation in separate trials while participants tonically activated soleus at 20% max. Fugl-Myer assessment of lower extremity, 10-meter walk test, and Mini-BESTest were assessed in stroke survivors. Results: Heteronymous excitation and inhibition onsets, durations, and magnitudes were not different between paretic, nonparetic or age-matched unimpaired limbs. Quadriceps stimulation elicited excitation that was half the magnitude of femoral nerve stimulation. Femoral nerve elicited paretic limb heteronymous excitation was positively correlated with walking speed but did not reach significance because only a subset of paretic limbs exhibited excitation (n = 8, Spearman r = 0.69, P = 0.058). Conclusions: Heteronymous feedback from quadriceps onto soleus assessed in a seated posture was not impaired in persons post-stroke. Despite being unable to identify whether reduced inhibition contributes to abnormal excitation reported in prior studies, our results indicate quadriceps stimulation may allow a better estimate of heteronymous inhibition in those that exhibit exaggerated excitation. Heteronymous excitation magnitude in the paretic limb was positively correlated with self-selected walking speed suggesting paretic limb excitation at the higher end of a normal range may facilitate walking ability after stroke. Future studies are needed to identify whether heteronymous feedback from Q onto SOL is altered after stroke in upright postures and during motor tasks as a necessary next step to identify mechanisms underlying motor impairment.
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Genital burns are unique and complex injuries that impact patients physically and emotionally. This study investigates the specific impact of genital burns on psychosocial and physical outcomes. A retrospective cohort study was conducted using the TriNetX database, encompassing over 117 million patients from U.S. healthcare institutions. Patients with genital burns were identified and categorized into sub-cohorts based on TBSA and burn degree. Propensity score matching and cohort balancing were performed based on age, gender, race, and ethnicity. Outcomes were analyzed both short-term (1 month) and long-term (5 years), focusing on psychiatric and physical aspects. This study identified 3,496 genital burn patients over a 15-year period. Analyses revealed that genital burns significantly increased short-term risk of death (RR: 2.8), anxiety (RR: 2.656), hospitalization (RR: 2.167), and any anxiety, PTSD, or depression (RR: 2.363), and long-term risk of death (RR: 1.658) and pruritus (RR: 1.58) (all p<0.05). Interestingly, genital burn patients showed a lower risk of chronic joint pain compared to other burn injuries (RR: 0.815) (p<0.05). These results occurred independently of the extent of TBSA. Genital burns have a distinctive impact on patients, leading to higher rates of certain psychiatric morbidities and physical complications. This study highlights the need for tailored care and consideration of the unique challenges faced by patients with genital burns, both in the immediate aftermath and in the long term. Understanding the specific impacts of genital burns is vital for healthcare practitioners to develop care strategies and better support for patients recovering from such injuries.
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BACKGROUND: Vagus nerve stimulation (VNS) combined with rehabilitation is a Food and Drug Administration approved intervention for moderate to severe upper extremity deficits in chronic ischemic stroke patients. Previous studies demonstrated that VNS improves upper extremity motor impairments, using the Fugl Meyer Assessment of Upper Extremity (FMA-UE); however, delineating where these improvements occur, and the role of VNS dosage parameters were not reported. OBJECTIVE: This study explored the relationship between dosing (time over which task repetitions were executed and number of VNS stimulations) and changes within proximal and distal components of the FMA-UE. METHODS: Participants underwent VNS implantation, with 1 group receiving VNS paired with rehabilitation (Active VNS) and the other group receiving rehabilitation with sham stimulation (Controls). Both groups received 6 weeks of in-clinic therapy followed by a 90-day at-home, self-rehabilitation program. Participants who completed at least 12 of 18 in-clinic sessions were included in the analyses (n = l06). Pearson correlations and analysis of covariance were used to investigate the relationship between dosing and FMA-UE outcome change along with the effect of covariates including baseline severity, time since stroke, age, and paretic side. RESULTS: Compared to Controls, active VNS favorably influenced distal function with sustained improvement after the home program. Significant improvements were observed in only distal components (FMdist) at both post day-1 (1.80 points, 95% Cl [0.85, 2.73], P < .001) and post-day 90 (1.62 points, 95% CI [0.45, 2.80], P < .007). CONCLUSIONS: VNS paired with rehabilitation resulted in significant improvements in wrist and hand impairment compared to Controls, despite similar in-clinic dosing across both groups.NCT03131960.
Subject(s)
Ischemic Stroke , Stroke Rehabilitation , Upper Extremity , Vagus Nerve Stimulation , Humans , Male , Female , Upper Extremity/physiopathology , Middle Aged , Stroke Rehabilitation/methods , Aged , Ischemic Stroke/rehabilitation , Ischemic Stroke/physiopathology , Chronic Disease , Combined Modality Therapy , Adult , Outcome Assessment, Health CareABSTRACT
BACKGROUND: Epilepsy surgery is an underutilized resource for children with drug-resistant epilepsy. Palliative and definitive surgical options can reduce seizure burden and improve quality of life. Palliative epilepsy surgery is often seen as a "last resort" compared to definitive surgical options. We compare patient characteristics between palliative and definitive epilepsy surgical patients and present palliative surgical outcomes from the Pediatric Epilepsy Research Consortium surgical database. METHODS: The Pediatric Epilepsy Research Consortium Epilepsy Surgery database is a prospective registry of patients aged 0-18 years undergoing evaluation for epilepsy surgery at 20 pediatric epilepsy centers. We included all children with completed surgical therapy characterized as definitive or palliative. Demographics, epilepsy type, age of onset, age at referral, etiology of epilepsy, treatment history, time-to-referral/evaluation, number of failed anti-seizure medications (ASMs), imaging results, type of surgery, and postoperative outcome were acquired. RESULTS: Six hundred forty patients undergoing epilepsy surgery were identified. Patients undergoing palliative procedures were younger at seizure onset (median: 2.1 vs 4 years, P= 0.0008), failed more ASM trials before referral for presurgical evaluation (P=<0.0001), and had longer duration of epilepsy before referral for surgery (P=<0.0001). During presurgical evaluation, patients undergoing palliative surgery had shorter median duration of video-EEG data collected (P=0.007) but number of cases where ictal data were acquired was similar between groups. The most commonly performed palliative procedure was corpus callosotmy (31%), followed by lobectomy (21%) and neuromodulation (82% responsive neurostimulation vs 18% deep brain stimulation). Palliative patients were further categorized into traditionally palliative procedures vs traditionally definitive procedures. The majority of palliative patients had 50% reduction or better in seizure burden. Seizure free outcomes were significantly higher among those with traditional definitive surgeries, 41% (95% confidence interval: 26% to 57%) compared with traditional palliative surgeries and 9% (95% confidence interval: 2% to 17%). Rate of seizure freedom was 46% at 24 months or greater of follow-up in the traditional definitive group. CONCLUSIONS: Patients receiving palliative epilepsy surgery trialed more ASMs, were referred later after becoming drug resistant, and had longer gaps between drug resistance and epilepsy surgery compared with patients undergoing definitive epilepsy surgery. The extent of surgical evaluation is impacted if surgery is thought to be palliative. A majority of palliative surgery patients achieved >50% seizure reduction at follow-up, both in groups that received traditionally palliative and traditionally definitive surgical procedures. Palliative surgical patients can achieve greater seizure control and should be referred to an epilepsy surgery center promptly after failing two appropriate anti-seizure medications.
Subject(s)
Databases, Factual , Drug Resistant Epilepsy , Palliative Care , Humans , Child , Child, Preschool , Male , Female , Infant , Adolescent , Drug Resistant Epilepsy/surgery , Neurosurgical Procedures , Registries , Infant, Newborn , Treatment Outcome , Epilepsy/surgeryABSTRACT
INTRODUCTION: An area of rehabilitation research in burns is the impact of co-morbidities on disease trajectory. Obesity is a comorbidity of increasing public health concern, but its role remains controversial regarding burn injury and physical recovery. Our aim was to evaluate the association between body mass index (BMI) categories as a measure of obesity at discharge and self-reported physical function (PF) during recovery of adult burn survivors. METHODS: This is a retrospective study on data collected by four major US burn centers, which contribute to the Burn Model System National Database. The data included BMI obtained at hospital discharge and self-reported PF-mobility, using the PROMIS measures assessed at 6, 12, and 24 months after burn. Subjects were classified into weight status categories based on BMI: underweight (BMI <18.5), normal weight (18.5 ≤ BMI <25), overweight (25 ≤ BMI <30), obesity class 1 (30 ≤ BMI <35), obesity class 2 (35 ≤ BMI <40), and obesity class 3 (BMI ≥40). Mixed-effects linear regression models were used to assess the association between BMI categories and PF scores over time, adjusted for patient and injury characteristics. RESULTS: A total of 496 adult burn patients aged 47 ± 16 years were included, with mean total body surface area (TBSA) burned of 18 ± 19 % and mean BMI at discharge of 28 ± 7 kg/m2. PROMIS PF scores significantly improved over time in the recovery phase after burn (time effect, p < 0.001). Compared to overweight burn patients, normal-underweights exhibited lower PF score by an average of 4.06 units (p = 0.001) but scores increased linearly by an estimated 0.17 units per month (p = 0.01) over the 24 months after discharge. Similarly, compared to overweight burn patients, class 1 obese reported lower PF score by a mean 2.67 units (p = 0.07) but PF increased linearly by 0.15 units per month (p = 0.07) over the 24 months after discharge. These findings were independent of the effects of age at discharge, sex, TBSA burned, and hand and leg burn. CONCLUSION: Being overweight was associated with improved and faster recovery of PF scores compared to normal, underweight, and obese burn patients during long-term recovery. Hence, our data suggests that long-term recovery and restoration of PF in adult burn survivors is not compromised by a small excess in body weight.
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PURPOSE: To compare the efficacy of a novel fusion template "reduced six-core systemic template and multiparametric magnetic resonance imaging/transrectal ultrasound (mpMRI/TRUS) fusion targeted biopsy" (TBx+6c), with mpMRI/TRUS fusion-targeted biopsy and 12-core systematic biopsy template (TBx+12c) in the diagnosis of prostate cancer (PCa). MATERIALS AND METHODS: This is an institutional review board approved single-center observational study involving adult men undergoing fusion-targeted biopsies for the diagnosis of PCa. Patients were sorted into cohorts of TBx+6c or TBx+12c based on the systematic biopsy template used. The study's main objective was to determine the cancer detection rate (CDR) for overall PCa and clinically significant PCa (csPCa) and the secondary objectives were to compare complication rates and functional outcome differences between the cohort. RESULTS: A total of 204 patients met study's inclusion criteria. TBx+6c group had 120 patients, while TBx+12c cohort had 84 patients. The groups had similar baseline characteristics and overall CDR in the TBx+6c cohort was 71.7% versus 79.8%, compared to the TBx+12c (p = 0.18) whereas, the csPCa detection rate in the TBx+6c group was 50.8% versus 54.8% in the TBx+12c group (p = 0.5). TBx+6c cohort had lower overall complication rate of 3% versus 13%, (p = 0.01) and ≥ grade 2 complication rates (1 (1%) vs. 3(4%), p = 0.03) compared to the TBx+12c cohort. There were no differences in IIEF-5 (p = 0.5) or IPSS (p = 0.1) scores at baseline and 2-weeks and 6-weeks post-biopsy. CONCLUSION: TBx+6c cohort, when compared to the TBx+12c cohort, demonstrated comparable diagnostic performance along with similar functional outcomes and lower complication rates. These results suggest the importance of further exploring the clinical implications of adopting a TBx+6c schema for PCa diagnosis in comparison to the widely used TBx+12c schema through a multicenter randomized controlled trial.
Subject(s)
Image-Guided Biopsy , Multiparametric Magnetic Resonance Imaging , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnostic imaging , Image-Guided Biopsy/methods , Image-Guided Biopsy/adverse effects , Middle Aged , Aged , Multiparametric Magnetic Resonance Imaging/methods , Ultrasonography, Interventional/methods , Prostate/pathology , Prostate/diagnostic imagingABSTRACT
Heteronymous inhibition between lower limb muscles is primarily attributed to recurrent inhibitory circuits in humans but could also arise from Golgi tendon organs (GTOs). Distinguishing between recurrent inhibition and mechanical activation of GTOs is challenging because their heteronymous effects are both elicited by stimulation of nerves or a muscle above motor threshold. Here, the unique influence of mechanically activated GTOs was examined by comparing the magnitude of heteronymous inhibition from quadriceps (Q) muscle stimulation onto ongoing soleus electromyographic at five Q stimulation intensities (1.5-2.5× motor threshold) before and after an acute bout of stimulation-induced Q fatigue. Fatigue was used to decrease Q stimulation evoked force (i.e., decreased GTO activation) despite using the same pre-fatigue stimulation currents (i.e., same antidromic recurrent inhibition input). Thus, a decrease in heteronymous inhibition after Q fatigue and a linear relation between stimulation-evoked torque and inhibition both before and after fatigue would support mechanical activation of GTOs as a source of inhibition. A reduction in evoked torque but no change in inhibition would support recurrent inhibition. After fatigue, Q stimulation-evoked knee torque, heteronymous inhibition magnitude and inhibition duration were significantly decreased for all stimulation intensities. In addition, heteronymous inhibition magnitude was linearly related to twitch-evoked knee torque before and after fatigue. These findings support mechanical activation of GTOs as a source of heteronymous inhibition along with recurrent inhibition. The unique patterns of heteronymous inhibition before and after fatigue across participants suggest the relative contribution of GTOs, and recurrent inhibition may vary across persons.
Subject(s)
Electromyography , Muscle Fatigue , Quadriceps Muscle , Humans , Muscle Fatigue/physiology , Male , Adult , Quadriceps Muscle/physiology , Female , Muscle, Skeletal/physiology , Young Adult , Neural Inhibition/physiology , Electric Stimulation , TorqueABSTRACT
OBJECTIVE: To evaluate the Refractory Epilepsy Screening Tool for Lennox-Gastaut Syndrome (REST-LGS) for real-world identification of LGS in adults and to develop a scoring system for the tool. METHODS: A retrospective chart review of adults with drug resistant epilepsy (DRE) and intellectual development disorder (IDD) was conducted by 2 primary care providers blinded to diagnosis. The REST-LGS was designed via the Modified Delphi Consensus and was previously validated. This tool consists of 8 criteria (4 major, 4 minor) considered indicative of LGS. To account for missing data in the earlier validation study and to evaluate applicability in a real-world setting, the REST-LGS was refined to include a scoring system in which major criteria were more heavily weighted than minor criteria, producing categories of "likely" (>11 points), "possible" (8-11 points), and "unlikely" (<8 points) LGS. Statistical analyses were descriptive. RESULTS: Of the 100 patients included in the analysis, data for slow spike-waves in electroencephalography and seizure onset age - both major REST-LGS criteria - were missing for 46% and 42% of patients, respectively. The majority of patients met 4 of the 8 REST-LGS criteria (cognitive impairment since childhood, 71%; persistent seizures despite a trial of ≥2 antiseizure medications, 65%; seizure onset before the age of 12 years, 57%; ≥2 seizure types, 56%). All 4 major criteria were met in 22 patients (22%). The percentages of patients considered "likely," "possible," or "unlikely" to have LGS were 26%, 30%, and 44%, respectively. Of the 74 patients without a previous LGS diagnosis, 42 (57%) were identified as "possible" or "likely" to have LGS using REST-LGS. SIGNIFICANCE: In this analysis, the validated REST-LGS was evaluated in a real-world setting. The majority of previously undiagnosed patients were identified via REST-LGS as "possible" or "likely" to have LGS. Extensive missing data highlights challenges of LGS diagnosis in adults. PLAIN LANGUAGE SUMMARY: There is a need to identify adult patients with Lennox-Gastaut syndrome (LGS) so they can receive appropriate treatment. The Refractory Epilepsy Screening Tool for LGS (REST-LGS) questionnaire was designed by experts to identify whether patients with seizures that are not controlled by medications may have LGS. In this study, 2 physicians completed the REST-LGS using charts for 100 patients who experience seizures not controlled by medications. Of the patients who were previously diagnosed as not having LGS, the majority were "likely" or "possible" to have LGS based on the REST-LGS; therefore, the REST-LGS can identify patients for further evaluation.
Subject(s)
Drug Resistant Epilepsy , Electroencephalography , Lennox Gastaut Syndrome , Humans , Lennox Gastaut Syndrome/diagnosis , Male , Female , Adult , Retrospective Studies , Drug Resistant Epilepsy/diagnosis , Drug Resistant Epilepsy/drug therapy , Young Adult , Intellectual Disability/diagnosis , Adolescent , Middle AgedABSTRACT
OBJECTIVE: This study was undertaken to estimate incidence of rare epilepsies and compare with literature. METHODS: We used electronic health record text search to identify children with 28 rare epilepsies in New York City (2010-2014). We estimated cumulative incidence and compared with literature. RESULTS: Eight of 28 rare epilepsies had five or more prior estimates, and our measurements were within the published range for all. The most common were infantile epileptic spasms syndrome (1 in 2920 live births), Lennox-Gastaut syndrome (1 in 9690), and seizures associated with tuberous sclerosis complex (1 in 14 300). Fifteen of 28 had fewer than five prior estimates, and of these, we provided additional estimates for early infantile developmental and epileptic encephalopathy (1 in 32 700), epilepsy with myoclonic-atonic seizures (1 in 34 100), Sturge-Weber syndrome plus seizures/epilepsy (1 in 40 900), epilepsy in infancy with migrating focal seizures (1 in 54 500), Aicardi syndrome plus seizures/epilepsy (1 in 71 600), hypothalamic hamartoma with seizures (1 in 225 000), and Rasmussen syndrome (1 in 450 000). Five of 28 rare epilepsies had no prior estimates, and of these, we provided a new estimate for developmental/epileptic encephalopathy with spike-and-wave activation in sleep and/or continuous spikes and waves during sleep (1 in 34 100). Data were limited for the remaining 12 rare epilepsies, which were all genetic epilepsies, including PCDH19, CDKL5, Alpers disease, SCN8A, KCNQ2, SCN2A, GLUT1 deficiency, Phelan-McDermid syndrome, myoclonic epilepsy with ragged-red fibers, dup15q syndrome, ring chromosome 14, and ring chromosome 20. SIGNIFICANCE: We estimated the incidence of rare epilepsies using population-based electronic health record data and literature review. More research is needed to better estimate the incidence of genetic epilepsies with nonspecific clinical features. Electronic health records may be a valuable data source for studying rare epilepsies and other rare diseases, particularly as genetic testing becomes more widely adopted.
Subject(s)
Epilepsy , Urban Population , Humans , Male , Female , Infant , Child , Incidence , Epilepsy/epidemiology , Epilepsy/genetics , Child, Preschool , Adolescent , New York City/epidemiology , Urban Population/statistics & numerical data , Infant, Newborn , United States/epidemiologyABSTRACT
OBJECTIVE: To evaluate differences in upper-extremity (UE) segment-specific (proximal or distal segment) recovery after vagus nerve stimulation (VNS) paired with UE rehabilitation (Paired-VNS) compared with rehabilitation with sham-VNS (Control). We also assessed whether gains in specific UE segments predicted clinically meaningful improvement. DESIGN: This study reports on a secondary analysis of Vagus nerve stimulation paired with rehabilitation for UE motor function after chronic ischemic stroke (VNS-REHAB), a randomized, triple-blinded, sham-controlled pivotal trial. A Rasch latent regression was used to determine differences between Paired-VNS and Controls for distal and proximal UE changes after in-clinic therapy and 3 months later. Subsequently, we ran a random forest model to assess candidate predictors of meaningful improvement. Each item of the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and Wolf Motor Function Test (WMFT) was evaluated as a predictor of response to treatment. SETTING: Nineteen stroke rehabilitation centers in the USA and UK. PARTICIPANTS: Dataset included 108 participants (N=108) with chronic ischemic stroke and moderate-to-severe UE impairments. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: FMA-UE and WMFT. RESULTS: Distal UE improvement was significantly greater in the Paired-VNS group than in Controls immediately after therapy (95% confidence interval, 0.27-0.73; P≤.001) and after 3 months (95% confidence interval, 0.16-0.75; P=.003). Both groups showed similar improvement in proximal UE at both time points. A subset of both distal and proximal items from the FMA-UE and WMFT were predictors of meaningful improvement. CONCLUSIONS: Paired-VNS improved distal UE impairment in chronic stroke to a greater degree than intensive rehabilitation alone. Proximal improvements were equally responsive to either treatment. Given that meaningful UE recovery is predicted by improvements across both proximal and distal segments, Paired-VNS may facilitate improvement that is otherwise elusive.
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Objective: The aim of this study is to explore the impact of internally guided (IG) versus externally guided (EG) adapted tango (AT) dance training (i.e., dancing the IG "Leader" role or the EG "Follower" role), on motor and non-motor functions in individuals with Parkinson's disease and freezing of gait (PD-FOG). The "Leader" role, a proxy for IG movements, conveys direction, timing, and amplitude of steps with tactile cues. The "Follower" role, a proxy for EG movements, detects and responds to the leader's tactile cues. Case description: Six participants were randomly assigned to the IG ("Leader") or EG ("Follower") roles for 20, 90-min AT lessons over 12 weeks. Participants were assessed for PD-specific and non-PD-specific functions before and twice after the end of the 12-week intervention, at 1-week and 1-month post-intervention. Results: EG participants improved and/or maintained performance on more outcomes across all domains than IG participants. Five participants improved in PD motor symptoms, dynamic gait, global cognitive function, and the FOG Questionnaire immediately or 1 month after intervention. All participants expressed positive attitudes toward the intervention, including improvements in walking, balance, and endurance. Conclusion: AT training in the follower role may benefit individuals with PD-FOG to a greater extent compared to the leader role. Impact: This case series study could inform additional research with the goal of enhancing physical therapy or music-based therapy approaches for addressing PD-FOG.
ABSTRACT
Severely burned patients often developed cardiac dysfunction and heart failure. The purpose of this retrospective study is to evaluate the role of Cardiac Troponin I (cTI) and its association to patients with burns. Patients deidentified data were collected from a national database in May 2023. Adult burn patients who had cTnI lab counted were enrolled in this study. Patients were grouped by the cTnI mean level within 72 hours including patients with elevated cTnI levels at >0.3 ng/mL (n= 2188 patients), and patients with non-elevated cTnI level (< 0.04 ng/mL) (n= 3200). The cohorts were further stratified by less than 20% TBSA mild burn population and >20% TBSA severe burn population to replicate the severity of burns. The 30-days incidences of acute myocardial infarction (MI), sepsis, and mortality were investigated after the cohorts were propensity matching balanced. The odds ratios (ORs) with 95%CI for MI were (9.829/7.081-13.645), sepsis (1.527/1.269-1.959) and mortality (2.586/2.110- 3.170) respectively (p<0.05). The groups that were further stratified into mild burn and severe burn had the following results: The mild burn ORs and 95% CI for MI was (6.237/3.986-9.785), sepsis (1.603/1.132-2.270), and mortality was (2.298/1.629-3.242). The severe burn cohort had ORs and 95% CI for MI (3.145/1.469-6.732), sepsis (0.993/0.555-1.777), mortality (2.934/1.924-4.475). In conclusion, the patients with earlier elevated cTnI level had worse outcomes of MI and mortality in both severe and mild burns.