A Call to Action toward Optimizing the Electrical Dose Received by Neural Targets in Spinal Cord Stimulation Therapy for Neuropathic Pain

Spinal cord stimulation has seen unprecedented growth in new technology in the 50 years since the first subdural implant. As we continue to grow our understanding of spinal cord stimulation and relevant mechanisms of action, novel questions arise as to electrical dosing optimization. Programming adjustment — dose titration — is often a process of trial and error that can be time-consuming and frustrating for both patient and clinician. In this report, we review the current preclinical and clinical knowledge base in order to provide insights that may be helpful in developing more rational approaches to spinal cord stimulation dosing. We also provide key conclusions that may help in directing future research into electrical dosing, given the advent of newer waveforms outside traditional programming parameters

Active robotic training improves locomotor function in a stroke survivor

Abstract Background Clinical outcomes after robotic training are often not superior to conventional therapy. One key factor responsible for this is the use of control strategies that provide substantial guidance. This strategy not only leads to a reduction in volitional physical effort, but also interferes with motor relearning. Methods We tested the feasibility of a novel training approach (active robotic training) using a powered gait orthosis (Lokomat) in mitigating post-stroke gait impairments of a 52-year-old male stroke survivor. This gait training paradigm combined patient-cooperative robot-aided walking with a target-tracking task. The training lasted for 4-weeks (12 visits, 3 × per week). The subject’s neuromotor performance and recovery were evaluated using biomechanical, neuromuscular and clinical measures recorded at various time-points (pre-training, post-training, and 6-weeks after training). Results Active robotic training resulted in considerable increase in target-tracking accuracy and reduction in the kinematic variability of ankle trajectory during robot-aided treadmill walking. These improvements also transferred to overground walking as characterized by larger propulsive forces and more symmetric ground reaction forces (GRFs). Training also resulted in improvements in muscle coordination, which resembled patterns observed in healthy controls. These changes were accompanied by a reduction in motor cortical excitability (MCE) of the vastus medialis, medial hamstrings, and gluteus medius muscles during treadmill walking. Importantly, active robotic training resulted in substantial improvements in several standard clinical and functional parameters. These improvements persisted during the follow-up evaluation at 6 weeks. Conclusions The results indicate that active robotic training appears to be a promising way of facilitating gait and physical function in moderately impaired stroke survivors.http://deepblue.lib.umich.edu/bitstream/2027.42/112853/1/12984_2011_Article_375.pd

Morphological and Functional Correlates in Goldmann-Favre Syndrome: A Case Series

The purpose of this study is to describe the correlation of findings between results from spectral domain optical coherence tomography (SD-OCT) and microperimetry in a case series regarding patients with Goldmann-Favre syndrome. Goldmann-Favre syndrome is a rare autosomal recessive hereditary vitreo-retinal degeneration that impacts the functionality of vision in subjects. Three men with this condition were assessed and subjected to microperimetry and SD-OCT. Two of the men were brothers. This study finds that the retinoschisis and macular cystoid changes noted in the SD-OCT matched the scotomas revealed by the microperimetry. The findings of each of the individual cases are reported herein

Non-Caseating Granulomatous Infective Spondylitis: Melioidotic Spondylitis

Study DesignRetrospective clinical analysis.PurposeTo delineate the clinical presentation of melioidosis in the spine and to create awareness among healthcare professionals, particularly spine surgeons, regarding the diagnosis and treatment of melioidotic spondylitis.Overview of LiteratureMelioidosis is an emerging disease, particularly in developing countries, associated with a high mortality rate. Its causative pathogen, Burkholderia pseudomallei, has been labeled as a bio-terrorism agent.MethodsWe performed a retrospective analysis of patients who were culture positive for B. pseudomallei. Assessment of patients was performed using clinical, radiological, and blood parameters. Clinical measures included pain, neurological deficit, and return to work. Radiological measures included plain radiography of the spine and magnetic resonance imaging. Blood tests included erythrocyte sedimentation rate and C-reactive protein levels.ResultsFour patients having melioidosis with spondylitis were evaluated. All of them had diabetes mellitus; three had multiple abscesses which required incision and drainage. Their clinical spectrum was similar to that of tuberculous spondylitis; all had back pain and radiology revealed infective spondylodiscitis with prevertebral and paravertebral collections with psoas abscess. Three patients underwent ultrasound-guided drainage of the psoas abscess and one had aspiration of the subcutaneous abscess. Bacteriological cultures showed presence of B. pseudomallei, and histopathology showed non-caseating granulomatous inflammation. All patients were treated with intravenous Ceftazidime for 2 weeks, followed by oral bactrim double strength and Doxycycline for 20 weeks. All patients improved with treatment and were healed at follow up.ConclusionsMelioidosis presents with a clinical spectrum similar to that of tuberculosis. A diagnosis of melioidotic spondylitis should be considered, particularly in patients with diabetes with neutrophilic leukocytosis and clinical-radiological features suggestive of infective spondylodiscitis. Bacteriological culture and histopathology helps in differentiating the two conditions. Health education for healthcare professionals is important for correctly diagnosing this disease

Complaint-driven Training Data Debugging for Query 2.0

As the need for machine learning (ML) increases rapidly across all industry sectors, there is a significant interest among commercial database providers to support "Query 2.0", which integrates model inference into SQL queries. Debugging Query 2.0 is very challenging since an unexpected query result may be caused by the bugs in training data (e.g., wrong labels, corrupted features). In response, we propose Rain, a complaint-driven training data debugging system. Rain allows users to specify complaints over the query's intermediate or final output, and aims to return a minimum set of training examples so that if they were removed, the complaints would be resolved. To the best of our knowledge, we are the first to study this problem. A naive solution requires retraining an exponential number of ML models. We propose two novel heuristic approaches based on influence functions which both require linear retraining steps. We provide an in-depth analytical and empirical analysis of the two approaches and conduct extensive experiments to evaluate their effectiveness using four real-world datasets. Results show that Rain achieves the highest recall@k among all the baselines while still returns results interactively.Comment: Proceedings of the 2020 ACM SIGMOD International Conference on Management of Dat

Pressor therapy in acute ischaemic stroke: an updated systematic review

Background Low blood pressure (BP) in acute ischaemic stroke (AIS) is associated with poor functional outcome, death, or severe disability. Increasing BP might benefit patients with post-stroke hypotension including those with potentially salvageable ischaemic penumbra. This updated systematic review considers the present evidence regarding the use of vasopressors in AIS. Methods We searched the Cochrane Database of Systematic Reviews, MEDLINE, EMBASE and trial databases using a structured search strategy. We examined reference lists of relevant publications for additional studies examining BP elevation in AIS. Results We included 27 studies involving 1886 patients. Nine studies assessed increasing BP during acute reperfusion therapy (intravenous thrombolysis, mechanical thrombectomy, intra-arterial thrombolysis or combined). Eighteen studies tested BP elevation alone. Phenylephrine was the most commonly used agent to increase BP (n = 16 studies), followed by norepinephrine (n = 6), epinephrine (n = 3) and dopamine (n = 2). Because of small patient numbers and study heterogeneity, a meta-analysis was not possible. Overall, BP elevation was feasible in patients with fluctuating or worsening neurological symptoms, large vessel occlusion with labile BP, sustained post-stroke hypotension and ineligible for intravenous thrombolysis or after acute reperfusion therapy. The effects on functional outcomes were largely unknown and close monitoring is advised if such intervention is undertaken. Conclusion Although theoretical arguments support increasing BP to improve cerebral blood flow and sustain the ischaemic penumbra in selected AIS patients, the data are limited and results largely inconclusive. Large, randomised controlled trials are needed to identify the optimal BP target, agent, duration of treatment and effects on clinical outcomes.acceptedVersio

The impact of canagliflozin on the risk of neuropathy events:A post-hoc exploratory analysis of the CREDENCE trial

Aim: Canagliflozin reduces the risk, and progression, of diabetic kidney disease. We hypothesized that it may improve the microvascular complication of neuropathy. Methods: The CREDENCE trial randomized participants with type 2 diabetes and kidney disease to canagliflozin 100 mg daily or placebo. Neuropathy events were defined post-hoc as any reported adverse event consistent with a peripheral or autonomic neuropathy event. The effect of canagliflozin and predictors of neuropathy events were estimated using Cox regression analysis. In sensitivity analyses the endpoint was restricted to sensorimotor polyneuropathy, diabetic neuropathy, and non-autonomic neuropathy events. Results: Almost half (48.8%) of the 4401 participants had a diagnosis of neuropathy at baseline. Over a median of 2.45 years of follow up, 657 people experienced a neuropathy event (63.2 per 1000 patient-years). Independent factors associated with higher risk of experiencing neuropathy events were non-white race, younger age, higher glycated haemoglobin and lower estimated glomerular filtration rate. The incidence of neuropathy events was similar in people randomized to canagliflozin and placebo (334/2202 vs. 323/2199; HR 1.04, 95% CI 0.89 to 1.21, P = 0.66). Canagliflozin had no impact on sensorimotor polyneuropathy (HR 0.93, 95% CI 0.69 to 1.25, P = 0.63), diabetic neuropathy (HR 0.91, 95% CI 0.68 to 1.22, P = 0.52), or non-autonomic neuropathy (HR 1.03, 95% CI 0.87 to 1.21, P = 0.77). The lack of effect on neuropathy events was consistent in subgroup analyses. Conclusion: Canagliflozin did not affect the risk of neuropathy events in the CREDENCE trial. Future large randomized studies with prespecified neuropathy endpoints are required to determine the impact of sodium glucose cotransporter 2 inhibitors on diabetic neuropathy

Revising the WHO verbal autopsy instrument to facilitate routine cause-of-death monitoring.

OBJECTIVE: Verbal autopsy (VA) is a systematic approach for determining causes of death (CoD) in populations without routine medical certification. It has mainly been used in research contexts and involved relatively lengthy interviews. Our objective here is to describe the process used to shorten, simplify, and standardise the VA process to make it feasible for application on a larger scale such as in routine civil registration and vital statistics (CRVS) systems. METHODS: A literature review of existing VA instruments was undertaken. The World Health Organization (WHO) then facilitated an international consultation process to review experiences with existing VA instruments, including those from WHO, the Demographic Evaluation of Populations and their Health in Developing Countries (INDEPTH) Network, InterVA, and the Population Health Metrics Research Consortium (PHMRC). In an expert meeting, consideration was given to formulating a workable VA CoD list [with mapping to the International Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) CoD] and to the viability and utility of existing VA interview questions, with a view to undertaking systematic simplification. FINDINGS: A revised VA CoD list was compiled enabling mapping of all ICD-10 CoD onto 62 VA cause categories, chosen on the grounds of public health significance as well as potential for ascertainment from VA. A set of 221 indicators for inclusion in the revised VA instrument was developed on the basis of accumulated experience, with appropriate skip patterns for various population sub-groups. The duration of a VA interview was reduced by about 40% with this new approach. CONCLUSIONS: The revised VA instrument resulting from this consultation process is presented here as a means of making it available for widespread use and evaluation. It is envisaged that this will be used in conjunction with automated models for assigning CoD from VA data, rather than involving physicians

Thermal decomposition of ammonium hexachloroosmate

Structural changes of (NH4)2[OsCl6] occurring during thermal decomposition in a reduction atmosphere have been studied in situ using combined energy-dispersive X-ray absorption spectroscopy (ED-XAFS) and powder X-ray diffraction (PXRD). According to PXRD, (NH4)2[OsCl6] transforms directly to metallic Os without the formation of any crystalline intermediates but through a plateau where no reactions occur. XANES and EXAFS data by means of Multivariate Curve Resolution (MCR) analysis show that thermal decomposition occurs with the formation of an amorphous intermediate {OsCl4}x with a possible polymeric structure. Being revealed for the first time the intermediate was subjected to determine the local atomic structure around osmium. The thermal decomposition of hexachloroosmate is much more complex and occurs within a minimum two-step process, which has never been observed before