Assimilation of GOSAT Methane in the Hemispheric CMAQ; Part II: Results Using Optimal Error Statistics

We applied the parametric variance Kalman filter (PvKF) data assimilation designed in Part I of this two-part paper to GOSAT methane observations with the hemispheric version of CMAQ to obtain the methane field (i.e., optimized analysis) with its error variance. Although the Kalman filter computes error covariances, the optimality depends on how these covariances reflect the true error statistics. To achieve more accurate representation, we optimize the global variance parameters, including correlation length scales and observation errors, based on a cross-validation cost function. The model and the initial error are then estimated according to the normalized variance matching diagnostic, also to maintain a stable analysis error variance over time. The assimilation results in April 2010 are validated against independent surface and aircraft observations. The statistics of the comparison of the model and analysis show a meaningful improvement against all four types of available observations. Having the advantage of continuous assimilation, we showed that the analysis also aims at pursuing the temporal variation of independent measurements, as opposed to the model. Finally, the performance of the PvKF assimilation in capturing the spatial structure of bias and uncertainty reduction across the Northern Hemisphere is examined, indicating the capability of analysis in addressing those biases originated, whether from inaccurate emissions or modelling error.

Six-month outcomes of an integrated primary care prevention and management program for chronic low back pain (LBP)

Background Accessible interdisciplinary, patient-centered and integrated primary care programs for chronic pain are needed for averting chronicity and improving patient outcomes. We sought 1) to develop an interdisciplinary low back pain (LBP) primary care program, and 2) to evaluate the program’s implementation and impact on patients’ physical and mental health over 6 months. A quasi-experimental pre-test/post-test design was used, and participants completed baseline, 3 and 6 months post-intervention evaluations. Referral and program process indicators were measured. Methods Clinically meaningful change in patient reported outcome measures of pain interference and intensity, physical function, depression and anxiety were defined a priori and evaluated. A multilevel regression analysis was performed to evaluate the impact of the program on change in individuals’ pain interference over 6 months. Results Forty six percent of participants were seen within 60 days of referral to the LBP program, and 464 individuals completed the program. The majority (≥ 60%) experienced a clinically meaningful improvement for pain intensity and interference at six months. A greater proportion of those with moderate (71%) or high risk (81%) of chronicity showed an improvement in pain interference than those with low risk (51%). A similar pattern emerged for depression and self-efficacy, but not for anxiety. Significant predictors of improvements in pain interference included higher prognostic risk of chronicity, younger age, sex, and lower baseline disability. Conclusion Results supported an improvement in participants’ confidence to manage their LBP. Future research will compare alternative modes of delivery (e.g. telehealth) and stratification approaches to further tailor resources to individuals’ needs.

Novel Splice-Site and Missense Variant of PNPLA6 in an Austrian Family Causing Spastic Paraplegia-39 with Cerebellar Oculomotor Disorder

Background The term hereditary spastic paraplegia comprises an ever-expanding array of neurological disorders with distinct aetiologies. Spastic paraplegia 39 is one of the many variants with additional features of other organs and neurological systems. We describe a large kindred with two hitherto undescribed mutations of PNPLA6 and a novel clinical phenotype as, in addition to spastic paraplegia, affected subjects suffered from a prominent cerebellar oculomotor dysfunction. Methods Three of five genetically tested family members of a large kindred were affected by spastic gait and cerebellar oculomotor dysfunction. Clinical, imaging, laboratory and electrophysiological data were analyzed. Genetic analysis was done using next-generation sequencing. Segregation analyses were performed by Sanger sequencing. To assess the pathogenicity of genetic variants on the encoded protein, in silico assessments were carried out. Results Two hitherto unknown sequence variants in the PNPLA6 gene, a splice-site variant c.1635+3G>T and a missense variant c.3401A>T, p.(Asp1134Val), were detected. Compound-heterozygous siblings presented with lower limb spasticity and a marked cerebellar oculomotor disorder accompanied by moderate hypogonadotropic hypogonadism in the female. A paternal uncle being homozygous for the splice-site variant of PNPLA6 presented with increased lower limb reflexes, an unstable gait and cerebellar oculomotor dysfunction. Treatment with 4-aminopyridin, a potassium channel blocker, lead to meaningful improvement of clinical symptoms. Conclusion PNPLA6 gene variants are associated with a broad phenotypic spectrum to which we add cerebellar oculomotor dysfunction. In our kindred, the full clinical manifestation only occurred in compound-heterozygous subjects indicating that biallelic pathogenic variants lead to more serious and earlier onset of symptoms. Our findings emphasize the role of PNPLA6 in different neurodegenerative disorders.

A Review of Intelligent Sensor-Based Systems for Pressure Ulcer Prevention

Pressure ulcers are a critical issue not only for patients, decreasing their quality of life, but also for healthcare professionals, contributing to burnout from continuous monitoring, with a consequent increase in healthcare costs. Due to the relevance of this problem, many hardware and software approaches have been proposed to ameliorate some aspects of pressure ulcer prevention and monitoring. In this article, we focus on reviewing solutions that use sensor-based data, possibly in combination with other intrinsic or extrinsic information, processed by some form of intelligent algorithm, to provide healthcare professionals with knowledge that improves the decision-making process when dealing with a patient at risk of developing pressure ulcers. We used a systematic approach to select 21 studies that were thoroughly reviewed and summarized, considering which sensors and algorithms were used, the most relevant data features, the recommendations provided, and the results obtained after deployment. This review allowed us not only to describe the state of the art regarding the previous items, but also to identify the three main stages where intelligent algorithms can bring meaningful improvement to pressure ulcer prevention and mitigation. Finally, as a result of this review and following discussion, we drew guidelines for a general architecture of an intelligent pressure ulcer prevention system.

Oral and Topical Treatment of Painful Diabetic Polyneuropathy: Practice Guideline Update Summary

ObjectiveTo update the 2011 American Academy of Neurology (AAN) guideline on the treatment of painful diabetic neuropathy (PDN) with a focus on topical and oral medications and medical class effects.MethodsThe authors systematically searched the literature from January 2008 to April 2020 using a structured review process to classify the evidence and develop practice recommendations using the AAN 2017 Clinical Practice Guideline Process Manual.ResultsGabapentinoids (standardized mean difference [SMD] 0.44; 95% confidence interval [CI], 0.21–0.67), serotonin-norepinephrine reuptake inhibitors (SNRIs) (SMD 0.47; 95% CI, 0.34–0.60), sodium channel blockers (SMD 0.56; 95% CI, 0.25–0.87), and SNRI/opioid dual mechanism agents (SMD 0.62; 95% CI, 0.38–0.86) all have comparable effect sizes just above or just below our cutoff for a medium effect size (SMD 0.5). Tricyclic antidepressants (TCAs) (SMD 0.95; 95% CI, 0.15–1.8) have a large effect size, but this result is tempered by a low confidence in the estimate.Recommendations SummaryClinicians should assess patients with diabetes for PDN (Level B) and those with PDN for concurrent mood and sleep disorders (Level B). In patients with PDN, clinicians should offer TCAs, SNRIs, gabapentinoids, and/or sodium channel blockers to reduce pain (Level B) and consider factors other than efficacy (Level B). Clinicians should offer patients a trial of medication from a different effective class when they do not achieve meaningful improvement or experience significant adverse effects with the initial therapeutic class (Level B) and not use opioids for the treatment of PDN (Level B).

Rehabilitation of Persistent Neurocognitive Deficits Following Sports-Related Concussion in an Amateur Football Athlete: Case Study

ObjectiveDemonstrate neurocognitive improvements in an inactive, amateur football athlete following a functional neurology approach to multimodal neurorehabilitation.BackgroundAmerican Football has been reported to have one of the highest incidences of concussion in all contact sports. Given the high rate of concussive blows during play, the investigation of treatment modalities is warranted. This case study presents a 23-year-old male amateur football player who has sustained 3 diagnosed concussions with additional suspected concussions throughout his time participating in football. In addition, his symptoms persisted years after ceasing participation in all contact sports.Design/MethodsThe athlete was prescribed 10 treatment sessions over 5 consecutive days at an outpatient neurorehabilitation center specializing in functional neurology. The C3Logix neurocognitive assessment and Graded Symptom Checklist were utilized on intake and discharge. Multimodal treatment interventions included transcranial photobiomodulation, non-invasive neuromodulation of the lingual branch of the trigeminal nerve, neuromuscular reeducation of the limbs bilaterally, hand-eye coordination training, vestibular rehabilitation utilizing a three-axis whole-body off-axis rotational device, and cognitive training.ResultsOn intake, composite symptom score was reported as 10/162, Trails Making Test Part A was 20.8 seconds, Part B was 41.9 seconds, Digit Symbol Matching score was 53, Simple Reaction Time was 277 milliseconds, and Choice Reaction Time was 412 milliseconds. On discharge, the patient experienced a 70% in self-reported symptoms, Trails A improved to 14.8 seconds (+29%), Trails B improved to 30.3 seconds (+28%), Simple Reaction Time was 248 milliseconds (10% faster), and Choice Reaction Time was 340 milliseconds (17% faster).ConclusionsThe present case study demonstrates a meaningful improvement in symptoms and neurocognitive performance of a patient with multiple sports-related concussions. Therefore, the Press suggest further investigation into a functional neurology approach to multi-modal, intensive care to improve neurocognitive impairment in athletes that sustained concussions participating in footballs.

Modified prolotherapy by 5% dextrose: Two years experiences of a traditional and complementary medicine practice center in Turkey

BACKGROUND: Prolotherapy (PrT) is an increasingly popular regenerative injection treatment for the management of musculoskeletal injuries. The diagnostic injection is a method for selecting suitable patients to apply PrT using subcutaneous 5% dextrose solution. OBJECTIVE: The study aims to assess the PrT usage and modifications in the treatment of chronic low back pain and lumbar disc herniation and to define diagnostic injection procedure for PrT. METHOD: Two thousand three hundred and eighty-two patients with low back pain or lumbar disc herniation were evaluated at the Traditional and Complementary Medicine Practice Center in Ankara, Turkey. Six hundred fifty-four patients were included in the study. Diagnostic injections were performed on all patients who were thought to be eligible candidates for PrT indications. A 4-or-6 week interval was allowed between treatment sessions. RESULTS: Xix hundred and fifty-four patient treatments were completed. The Visual Analogue Scale (VAS) scores decreased to 5.1 ± 1.4 while 7.2 ± 1.1 before the diagnostic injection (p< 000.1). The VAS scores decreased from 7.2 ± 1.1 before the treatment to 0.9 ± 0.9 after 52 weeks of the treatment (p< 000.1). Thirty-four patients’ treatments resulted in poor clinical results (5.2%), and 620 of the patients’ pain improved (94.8%). CONCLUSION: PrT can be regarded as a safe way of providing a meaningful improvement in pain and musculoskeletal function compared to the initial status. Diagnostic injection is an easy way to eliminate patients and may become a favorite treatment modality. 5% dextrose is a more simple and painless solution for PrT and also has a high success.

Psychometric validation and interpretation of the Nocturia Impact Diary in a clinical trial setting

Purpose Psychometric evaluation of the Nocturia Impact (NI) Diary was conducted to support its use as a trial endpoint. Methods As part of a randomized, controlled Phase 2 clinical trial investigating a novel drug candidate for nocturnal polyuria, adult nocturia patients completed the NI Diary and a voiding diary for three nights preceding their clinic visit at Baseline and Weeks 1, 4, 8, and 12 (end of treatment). Exit interviews were conducted to obtain patient impressions of the NI Diary. Results A total of N = 302 participants were included. Confirmatory factor analysis (CFA) indicated that the 11-item measure is unidimensional with values of CFI, TLI, and RMSEA meeting relevant thresholds. Good internal consistency (Cronbach’s α 0.941) and test–retest reliability (intra-class correlation coefficients 0.730–0.880). Convergent validity with two reference measures was demonstrated with strong correlations of 0.573–0.730 were shown. Significant differences (P = 0.0018, standardized effect size = 0.372) between groups defined by number of night-time voids supported known-groups validity. Exit interviews in 66 patients indicated all participants experienced improvement in at least 1 NI Diary item and that a 1-point improvement on the item response scale and 1-void reduction per night (associated with an average best cut point on ROC analysis of − 11.6) constituted meaningful improvement. Anchor and distribution-based analyses identified a meaningful change threshold of − 15 to − 18 points on the NI Diary. Conclusion The NI Diary is a reliable and valid patient-reported psychometric instrument which is fit-for-purpose to evaluate the impact of nocturia on patient quality of life in the clinical trial setting. Trial registration number and registration date NCT03201419; June 28, 2017.