Objective: The clinical, social, and economic impacts of neurogenic lower urinary tract dysfunction (NLUTD) on individuals and healthcare systems are thought to be immense, yet the true costs of care are unknown. The aims of this study are to illuminate the global costs related to the current state of care for NLUTD. Methods: A systematic review of the literature was performed using MEDLINE, the National Health Service Economic Evaluation Database, and the Cochrane Specialised Urology and Incontinence Registers. Studies reporting the healthcare costs of NLUTD were identified. All steps of the review were performed by two independent reviewers. Costs were converted to 2022 US dollars and reported for different categories of services. Findings: A total of 13 studies were included in the final review (12 from high-income economy, and one from an upper-middle-income economy). Routine maintenance care varied notably across studies in terms of included services. Annual supportive costs ranged from $2,039.69 to $12,219.07 with one study estimating lifetime costs of $112,774 when complications were considered. There was limited data on the costs of care from the patient's perspective. However, catheters and absorbent aids were estimated to be among the costliest categories of expenditure during routine care. More invasive and reconstructive treatments were associated with significant costs, ranging between $18,057 and $55,873. Conclusion: NLUTD incurs a variety of healthcare expenditures ranging from incontinence supplies to hospitalizations for management of complications and leads to a significant burden for healthcare systems over the patient's lifetime. Approaches to NLUTD that focus on functional rehabilitation and restoration, rather than on management of complications may prove to be a less costly and more effective alternative.
OBJECTIVE The primary objective of this study was to evaluate the safety of 3 escalating doses of oligodendrocyte progenitor cells (LCTOPC1; previously known as GRNOPC1 and AST-OPC1) administered at a single time point between 21 and 42 days postinjury to participants with subacute cervical spinal cord injuries (SCIs). The secondary objective was to evaluate changes in neurological function following administration of LCTOPC1. METHODS This study was designed as an open-label, dose-escalation, multicenter clinical trial. Twenty-five participants with C4–7 American Spinal Injury Association Impairment Scale grade A or B injuries received a single dose of either 2 × 10 ⁶ , 1 × 10 ⁷ , or 2 × 10 ⁷ LCTOPC1 delivered via intraparenchymal injection into the spinal cord at the site of injury using a custom-designed syringe positioning device. Low-dose tacrolimus was administered until day 60. Outcome measures included adverse event (AE) monitoring and neurological function as measured by the International Standards for Neurological Classification of Spinal Cord Injury. RESULTS All 25 participants experienced at least one AE, with a total of 534 AEs (32 study-related vs 502 study-unrelated anticipated complications of SCI) reported at the completion of 1-year follow-up. There were 29 serious AEs reported. Two grade 3 serious AEs (CSF leak in one participant and a bacterial infection in another) were considered related to the injection procedure and to immunosuppression with tacrolimus, respectively. The CSF leakage resolved with sequelae, including self-limited altered mental status, and the infection resolved with antibiotic therapy. For all participants, MRI scans demonstrated no evidence of an enlarging mass, spinal cord damage related to the injection procedure, inflammatory lesions in the spinal cord, or masses in the ventricular system. At 1-year follow-up, 21/22 (96%) of the intention-to-treat group recovered one or more levels of neurological function on at least one side of their body, and 7/22 (32%) recovered two or more levels of neurological function on at least one side of their body. CONCLUSIONS LCTOPC1 can be safely administered to participants in the subacute period after cervical SCI. The injection procedure, low-dose temporary immunosuppression regimen, and LCTOPC1 were well tolerated. The safety and neurological function data support further investigation to determine the efficacy of LCTOPC1 in the treatment of SCI. Clinical trial registration no.: NCT02302157 ( ClinicalTrials.gov )
Rationale: Deep brain stimulation (DBS) of the hippocampus is proposed for enhancement of memory impaired by injury or disease. Many pre-clinical DBS paradigms can be addressed in epilepsy patients undergoing intracranial monitoring for seizure localization, since they already have electrodes implanted in brain areas of interest. Even though epilepsy is usually not a memory disorder targeted by DBS, the studies can nevertheless model other memory-impacting disorders, such as Traumatic Brain Injury (TBI). Methods: Human patients undergoing Phase II invasive monitoring for intractable epilepsy were implanted with depth electrodes capable of recording neurophysiological signals. Subjects performed a delayed-match-to-sample (DMS) memory task while hippocampal ensembles from CA1 and CA3 cell layers were recorded to estimate a multi-input, multi-output (MIMO) model of CA3-to-CA1 neural encoding and a memory decoding model (MDM) to decode memory information from CA3 and CA1 neuronal signals. After model estimation, subjects again performed the DMS task while either MIMO-based or MDM-based patterned stimulation was delivered to CA1 electrode sites during the encoding phase of the DMS trials. Each subject was sorted (post hoc) by prior experience of repeated and/or mild-to-moderate brain injury (RMBI), TBI, or no history (control) and scored for percentage successful delayed recognition (DR) recall on stimulated vs. non-stimulated DMS trials. The subject's medical history was unknown to the experimenters until after individual subject memory retention results were scored. Results: When examined compared to control subjects, both TBI and RMBI subjects showed increased memory retention in response to both MIMO and MDM-based hippocampal stimulation. Furthermore, effects of stimulation were also greater in subjects who were evaluated as having pre-existing mild-to-moderate memory impairment. Conclusion: These results show that hippocampal stimulation for memory facilitation was more beneficial for subjects who had previously suffered a brain injury (other than epilepsy), compared to control (epilepsy) subjects who had not suffered a brain injury. This study demonstrates that the epilepsy/intracranial recording model can be extended to test the ability of DBS to restore memory function in subjects who previously suffered a brain injury other than epilepsy, and support further investigation into the beneficial effect of DBS in TBI patients.
Introduction: Partial preservation of sensory and motor functions in the contralateral extremities after hemispherectomy is likely secondary to cortical reorganization of the remaining hemisphere and can be improved by rehabilitation. This study aims to investigate behavioral and structural cerebral cortical changes that may occur after a 2-week novel robotic rehabilitation program in children with prior anatomic hemispherectomy. Methods: Five patients with prior anatomic hemispherectomy (average age 10.8 years; all female) participated in a 2-week novel robotic rehabilitation program. Pre- and post-treatment (2 time points) high-resolution structural 3D FSPGR (fast spoiled gradient echo) magnetic resonance images were analyzed to measure cortical thickness and gray matter volume using a locally designed image processing pipeline. Results: Four of the five patients showed improvement in the Fugl-Meyer score (average increase 2.5 + 2.1 SD. Individual analyses identified small increases in gray matter volume near the hand knob area of the primary cortex in three of the five patients. Group analyses identified an increase in cortical thickness near the hand knob area of the primary motor cortex, in addition to other sensorimotor regions. Conclusion: This small pilot study demonstrates that potentially rehabilitation-associated cortical changes can be identified with MRI in hemispherectomy patients.
Motor performance and learning have distinct behavioral and neural signatures and can be uniquely modulated by various informational and motivational factors. Contemporary frameworks describe four different motor learning mechanisms mapped onto specific neural regions which are key for motor skill acquisition: error-based learning (cerebellum), reinforcement learning (basal ganglia), cognitive strategies (prefrontal cortex), and use-dependent learning (motor cortex). However, little is known about the neural circuits engaged during skill acquisition that are modulated specifically by practice-based performance improvement and those that predict recall performance. Based on previous work, we hypothesize that brain activity during practice in primary motor cortex and basal ganglia (1) is associated with trial-by-trial practice performance and (2) is predictive of immediate recall performance. Leveraging the contemporary framework, we use a well-known task paradigm that primarily relies upon cognitive strategy, reinforcement, and use-based learning mechanisms to test our hypotheses. Forty neurotypical young adults were asked to practice a pinch force tracking task. Participants received performance feedback after each trial during practice. We used whole brain analysis of functional magnetic resonance imaging (fMRI) and behavioral performance measures (i.e., time-on-target and self-efficacy) during the practice phase to determine which brain activation patterns are (1) associated with trial-by-trial tracking performance and (2) predictive of immediate no-feedback retention performance. We observed brain activations in the frontal orbital cortex, putamen, amygdala, and insula correlated with tracking performance improvement during practice. In contrast, a different set of performance-related activated regions were observed that were associated with immediate retention performance that included the primary motor cortex, superior frontal gyrus, somatosensory cortex, angular gyrus, and parietal gyrus. Our findings demonstrate that improved practice performance and recall of a sensorimotor skill are correlated with distinct neural activity patterns during acquisition, drawing on different motor learning mechanisms during encoding. While motor performance improvements depend on both cortical and subcortical regions, motor skill recall depends primarily on prefrontal and motor cortices. We discuss possible interpretations for why our hypothesis regarding basal ganglia activity and retention performance was not supported. Understanding the different neural mechanisms engaged in motor performance and learning may inform novel interventions to enhance motor skill learning.
Unlike growth on tissue, microbes can grow freely on implantable devices with minimal immune system intervention and often form resilient biofilms that continuously pump out pathogenic cells. The efficacy of antibiotics used to treat infection is declining due to increased rates of pathogenic resistance. A simple, one‐step zwitterionic surface modification is developed to significantly reduce protein and microbial adhesion to synthetic materials and demonstrate the successful modification of several clinically relevant materials, including recalcitrant materials such as elastomeric polydimethylsiloxane. The treated surfaces exhibit robust adhesion resistance against proteins and microorganisms in both static and flow conditions. Furthermore, the surface treatment prevents the adhesion of mammalian fibroblast cells while displaying no cytotoxicity. To demonstrate the clinical efficacy of the novel technology in the real‐world, a surface‐treated, commercial silicone foley catheter is developed that is cleared for use by the U.S. Food and Drug Administration (K192034). 16 long‐term catheterized patients received surface‐treated catheters and completed a Patient Global Impression of Improvement (PGI‐I) questionnaire. 10 out of 16 patients described their urinary tract condition post implantation as “much better” or “very much better” and 72% (n = 13) of patients desire to continue using the surface‐treated catheter over conventional latex or silicone catheters.
Blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging of the human brain requires bulky equipment for the generation of magnetic fields. Photoacoustic computed tomography obviates the need for magnetic fields by using light and sound to measure deoxyhaemoglobin and oxyhaemoglobin concentrations to then quantify oxygen saturation and blood volumes. Yet, the available imaging speeds, fields of view (FOV), sensitivities and penetration depths have been insufficient for functional imaging of the human brain. Here, we show that massively parallel ultrasonic transducers arranged hemispherically around the human head can produce tomographic images of the brain with a 10-cm-diameter FOV and spatial and temporal resolutions of 350 µm and 2 s, respectively. In patients who had a hemicraniectomy, a comparison of functional photoacoustic computed tomography and 7 T BOLD functional magnetic resonance imaging showed a strong spatial correspondence in the same FOV and a high temporal correlation between BOLD signals and photoacoustic signals, with the latter enabling faster detection of functional activation. Our findings establish the use of photoacoustic computed tomography for human brain imaging. Massively parallel ultrasonic transducers arranged hemispherically around the human head enable functional photoacoustic computed tomography of the human brain with a 10-cm-diameter field of view and resolutions of 350 µm and 2 s.
Antibiofouling Harmful microbes can grow freely on implanted medical devices such as catheters (as shown on the right). In article number 2200254, Amir Sheikhi, Richard B. Kaner, and co‐workers, report a new method to apply a robust surface coating containing zwitterions, which creates a water layer that prevents biofilm formation (as shown on the left). This can improve the safety of the medical devices and reduce patient complications. Image credit: Amir Sheikhi/Penn State.
Background Bone deficiencies in dysplastic acetabula create technical difficulties during total hip arthroplasty (THA). Bulk femoral head autograft (FHA) is one method to increase cup coverage and bone stock of the true acetabulum; however, only limited data exist on its efficacy through a direct anterior approach (DAA). This study aimed to evaluate the outcomes of FHA during THA via a DAA in dysplastic hips. Methods Retrospective review of 34 patients (41 hips) with hip dysplasia (Crowe I-III) who underwent primary THA via a DAA with FHA at a single institution was performed. Surgical procedures were performed on a traction table with intraoperative fluoroscopy and highly porous-coated cup placement in the true acetabulum. Patients were assessed clinically and radiographically at a minimum of 2 years postoperatively (range, 2 to 7). Results The average modified Harris Hip Score improved from 31.9 ± 10.8 to 94.1 ± 5.8, Merle d'Aubigné Hip Score from 7.5 ± 2.8 to 16.6 ± 1.1, and visual analog pain score from 7.9 ± 2.7 to 1.4 ± 1.4 (all P < .001). All hips had an “anatomic” inferomedial cup position postoperatively, with an average increase in horizontal coverage of 43.4%. Mean postoperative limb-length discrepancy improved from 21.8 ± 16.1 mm to 1.6 ± 5.7 mm (P < .001). There were no cases of revision THA, nor complications such as dislocation, infection, or osteolysis. Conclusion Reconstructing dysplastic acetabula (Crowe I-III) with FHA during THA can be successfully accomplished via the DAA with increased acetabular bone stock and accurate correction of limb-length discrepancy.
Objective: The purpose of this study was to evaluate the safety of oligodendrocyte progenitor cells (LCTOPC1) derived from human pluripotent stem cells administered between 7 and 14 days postinjury to patients with T3 to T11 neurologically complete spinal cord injury (SCI). The rationale for this first-in-human trial was based on evidence that administration of LCTOPC1 supports survival and potential repair of key cellular components and architecture at the SCI site. Methods: This study was a multisite, open-label, single-arm interventional clinical trial. Participants (n = 5) received a single intraparenchymal injection of 2 × 106 LCTOPC1 caudal to the epicenter of injury using a syringe positioning device. Immunosuppression with tacrolimus was administered for a total of 60 days. Participants were followed with annual in-person examinations and MRI for 5 years at the time of this report and will be followed with annual telephone questionnaires for 6 to 15 years postinjection. The primary endpoint was safety, as measured by the frequency and severity of adverse events related to the LCTOPC1 injection, the injection procedure, and/or the concomitant immunosuppression administered. The secondary endpoint was neurological function as measured by sensory scores and lower-extremity motor scores as measured by the International Standards for Neurological Classification of Spinal Cord Injury examinations. Results: No unanticipated serious adverse events related to LCTOPC1 have been reported with 98% follow-up of participants (49 of 50 annual visits) through the first 10 years of the clinical trial. There was no evidence of neurological decline, enlarging masses, further spinal cord damage, or syrinx formation. MRI results during the long-term follow-up period in patients administered LCTOPC1 cells showed that 80% of patients demonstrated T2 signal changes consistent with the formation of a tissue matrix at the injury site. Conclusions: This study provides crucial first-in-human safety data supporting the pursuit of future human embryonic stem cell-derived therapies. While we cannot exclude the possibility of future adverse events, the experience in this trial provides evidence that this cell type can be well tolerated by patients, with an event-free period of up to 10 years. Based on the safety profile of LCTOPC1 obtained in this study, a cervical dose escalation trial was initiated (NCT02302157).
Background: Overactive bladder (OAB) affects 12 to 30% of the world's population. The accompanying urinary urgency, frequency and incontinence can have a profound effect on quality of life, leading to depression, social isolation, avoidance of sexual activity and loss of productivity. Conservative measures such as lifestyle modification and pelvic floor physical therapy are the first line of treatment for overactive bladder. Patients who fail these may go on to take medications, undergo neuromodulation or receive injection of botulinum toxin into the bladder wall. While effective, medications have side effects and suffer from poor adherence. Neuromodulation and botulinum toxin injection are also effective but are invasive and not acceptable to some patients. Methods: We have developed a novel transcutaneous spinal cord neuromodulator (SCONE™,) that delivers multifrequency electrical stimulation to the spinal cord without the need for insertion or implantation of stimulating electrodes. Previously, multifrequency transcutaneous stimulation has been demonstrated to penetrate to the spinal cord and lead to motor activation of detrusor and external urethral sphincter muscles. Here, we report on eight patients with idiopathic overactive bladder, who underwent 12 weeks of SCONE™ therapy. Results: All patients reported statistically significant clinical improvement in multiple symptoms of overactive bladder, such as urinary urgency, frequency and urge incontinence. In addition, patients reported significant symptomatic improvements as captured by validated clinical surveys. Conclusion: SCONE™ therapy represents the first of its kind therapy to treat symptoms of urgency, frequency and urge urinary incontinence in patients with OAB. Trial registration: The study was listed on clinicaltrials.gov ( NCT03753750 ).
The cortical grasp network encodes planning and execution of grasps and processes spoken and written aspects of language. High-level cortical areas within this network are attractive implant sites for brain-machine interfaces (BMIs). While a tetraplegic patient performed grasp motor imagery and vocalized speech, neural activity was recorded from the supramarginal gyrus (SMG), ventral premotor cortex (PMv), and somatosensory cortex (S1). In SMG and PMv, five imagined grasps were well represented by firing rates of neuronal populations during visual cue presentation. During motor imagery, these grasps were significantly decodable from all brain areas. During speech production, SMG encoded both spoken grasp types and the names of five colors. Whereas PMv neurons significantly modulated their activity during grasping, SMG’s neural population broadly encoded features of both motor imagery and speech. Together, these results indicate that brain signals from high-level areas of the human cortex could be used for grasping and speech BMI applications.
Spinal cord injury (SCI) is a devastating condition that impacts multiple organ systems. Neurogenic bowel dysfunction (NBD) frequently occurs after a SCI leading to reduced sensation of bowel fullness and bowel movement often leading to constipation or fecal incontinence. Spinal Neuromodulation has been proven to be a successful modality to improve sensorimotor and autonomic function in patients with spinal cord injuries. The pilot data presented here represents the first demonstration of using spinal neuromodulation to activate the anorectal regions of patients with spinal cord injuries and the acute and chronic effects of stimulation. We observed that spinal stimulation induces contractions as well as changes in sensation and pressure profiles along the length of the anorectal region. In addition, we present a case report of a patient with a SCI and the beneficial effect of spinal neuromodulation on the patient’s bowel program.
Background In the acute post injury setting, the prognostic value of sensory sparing among motor complete spinal injury patients has been well demonstrated. However, once final AIS grade is achieved one year post-injury, the value of sensory sparing alone has not been elucidated. We hypothesized that sensory sparing would lead to better outcomes in AIS B over AIS A patients at long-term, post-recovery follow-up. Purpose To evaluate for differences in medical, Physical and Social outcomes between AIS A and B patients at least one year post injury. Study Design Retrospective Cohort Patient Sample Adults over the age of 18 with AIS A or B spinal cord injury sustained between January 1, 1995 and September 13, 2019. Data Collected from the Spinal Cord Injury Model Systems Database. Outcome Measures Self Reported Measures: PHQ-9 score; SCI-QOL Resilience Short Form score; VAS pain score; Life Satisfaction Score; Self reported depression and sleep disturbances. Physiologic Measures: Body Mass Index, Diabetes Mellitus, Hypertension, Hyperlipidemia, Mortality, Incidence of Pressure Sores. Functional Measures: Bowel and Bladder Management; Illicit Substance use; Level of Education; Marital Status; Rehospitalization Rate. Methods Patient data from the Spinal Cord Injury Model Systems Database were extracted for patients with a final, recovered American Spinal Injury Association Impairment Scale (AIS) grade of A or B at 1-year post-injury. Variables related to physical, mental and social functioning were compared between the two groups. Results 2,562 AIS A and 675 AIS B patient met inclusion criteria. Occurrence of pressure ulcers was 7% less in AIS B vs. A (34.5% vs. 41.9%, p=0.003). There were no statistical differences between groups in pain, bowel or bladder accidents, urinary tract infections, or the level of assistance for bowel or bladder management. There was no statistical difference for PHQ-9 depression scores, SCI-QOL Resilience Scores, rates of suicidality or sleep disturbance. There was no difference for illicit drug or alcohol abuse, life satisfaction scores, perceived health, and marriage or divorce rates Conclusions Except for a 7% reduction in pressure ulcer occurrence, there is no apparent long-term outcome advantage for motor complete spinal cord injury patients with AIS B sensory sparing over AIS A sensory complete. All other physical function domains were not different, nor were mental and social outcomes.
Background A critical factor in healing diabetic foot ulcers is patient adherence to offloading devices. We tested a smart offloading boot (SmartBoot) combined with a smartwatch app and cloud dashboard to remotely monitor patient adherence and activity. In addition, the impact of SmartBoot on balance, gait, and user experience was investigated. Methods Fourteen volunteers (31.6±8.7 years; 64% female) performed natural activities (eg, sitting, standing, walking) with and without the SmartBoot for approximately 30 minutes. All participants completed balance tests, 10-meter walking tests at slow, normal, and fast pace while wearing the SmartBoot, and a user experience questionnaire. The accuracy of real-time adherence reporting was assessed by comparing the SmartBoot and staff observation. Center of mass (COM) sway and step counts were measured using a validated wearable system. Results Average sensitivity, specificity, and accuracy for adherence and non-adherence were 90.6%, 88.0%, and 89.3%, respectively. The COM sway area was significantly smaller with the SmartBoot than without the SmartBoot regardless of test condition. Step count error was 4.4% for slow waking, 36.2% for normal walking, 16.0% for fast walking. Most participants agreed that the SmartBoot is easy to use, relatively comfortable, nonintrusive, and innovative. Conclusions To our knowledge, this is the first smart offloading system that enables remote patient monitoring and real-time adherence and activity reporting. The SmartBoot enhanced balance performance, likely due to somatosensory feedback. Questionnaire results highlight SmartBoot’s technical and clinical potential. Future studies warrant clinical validation of real-time non-adherence alerting to improve wound healing outcomes in people with diabetic foot ulcers.
Clinicians and scientists alike have long sought to predict the course and severity of chronic post-stroke cognitive and motor outcomes, as the ability to do so would inform treatment and rehabilitation strategies. However, it remains difficult to make accurate predictions about chronic post-stroke outcomes due, in large part, to high inter-individual variability in recovery and a reliance on clinical heuristics rather than empirical methods. The neuroanatomical location of a stroke is a key variable associated with long-term outcomes, and because lesion location can be derived from routinely collected clinical neuroimaging data there is an opportunity to use this information to make empirically based predictions about post-stroke deficits. For example, lesion location can be compared to statistically weighted multivariate lesion-behavior maps (LBMs) of neuroanatomical regions that, when damaged, are associated with specific deficits based on aggregated outcome data from large cohorts. Here, our goal was to evaluate whether we can leverage LBMs based on data from two large cohorts of individuals with focal brain lesions to make predictions of 12-month cognitive and motor outcomes in an independent sample of stroke patients. Further, we evaluated whether we could augment these predictions by estimating the structural and functional networks disrupted in association with each LBM through the use of structural and functional lesion network mapping (sLNM & fLNM, respectively), which use normative structural and functional connectivity data from neurologically healthy individuals to elucidate lesion-associated networks. We derived these brain network maps using the anatomical regions with the strongest association with impairment for each cognitive and motor outcome based on LBM results. These peak regional findings became the ‘seeds’ to generate networks, an approach that offers potentially greater precision compared to previously used single-lesion approaches. Next, in an independent sample, we quantified the overlap of each lesion location with the LBM, sLNM, and fLNM and evaluated how much variance each could explain in 12-month behavioral outcomes using a latent growth curve statistical model. We found that each lesion-deficit mapping modality was able to predict a statistically significant amount of variance in cognitive and motor outcomes. Both fLNM and sLNM were able to predict variance in 12-month outcomes beyond LBM. fLNM performed best for the prediction of language deficits, and sLNM performed best for the prediction of motor deficits. Altogether, these results support the notion that lesion location and lesion network mapping can be combined to improve the prediction of post-stroke deficits at 12-months.
Navigation in total knee arthroplasty has gained popularity over the last two decades. The reported advantages of navigation include more accurate component placement with the goal of improved stability and longevity of implants. Although some advocate the widespread use of this technology, there has been no strong evidence supporting superior outcomes. Navigation has shown benefits in clinical scenarios where traditional instrumentation is not possible. Overall complication rates are low. The overall added time and cost of navigation systems need to be taken into account when considering their use.
A clinical practice guideline on Parkinson disease was developed by an American Physical Therapy Association (APTA) volunteer guideline development group that consisted of physical therapists and a neurologist. The guideline was based on systematic reviews of current scientific and clinical information and accepted approaches for management of Parkinson disease. The Spanish version of this clinical practice guideline is available as a supplement. (Suppl. Appendix 1).
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