Teaching an old pain medicine society new tweets: integrating social media into continuing medical education.

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Core patient-reported outcome measures for chronic pain patients treated with spinal cord stimulation or dorsal root ganglia stimulation

Background: Neurostimulation is a highly effective therapy for the treatment of chronic Intractable pain, however, due to the complexity of pain, measuring a subject’s long-term response to the therapy remains difficult. Frequent measurement of patient-reported outcomes (PROs) to reflect multiple aspects of subjects’ pain is a crucial step in determining therapy outcomes. However, collecting full-length PROs is burdensome for both patients and clinicians. The objective of this work is to identify the reduced set of questions from multiple validated PROs that can accurately characterize chronic pain patients’ responses to neurostimulation therapies. Methods: Validated PROs were used to capture pain, physical function and disability, as well as psychometric, satisfaction, and global health metrics. PROs were collected from 509 patients implanted with Spinal Cord Stimulation (SCS) or Dorsal Root Ganglia (DRG) neurostimulators enrolled in the prospective, international, post-market REALITY study (NCT03876054, Registration Date: March 15, 2019). A combination of linear regression, Pearson’s correlation, and factor analysis were used to eliminate highly correlated questions and find the minimal meaningful set of questions within the predefined domains of each scale. Results: The shortened versions of the questionnaires presented almost identical accuracy for classifying the therapy outcomes as compared to the validated full-length versions. In addition, principal component analysis was performed on all the PROs and showed a robust clustering of pain intensity, psychological factors, physical function, and sleep across multiple PROs. A selected set of questions captured from multiple PROs can provide adequate information for measuring neurostimulation therapy outcomes. Conclusions: PROs are important subjective measures to evaluate the physiological and psychological aspects of pain. However, these measures are cumbersome to collect. These shorter and more targeted PROs could result in better patient engagement, and enhanced and more frequent data collection processes for digital health platforms that minimize patient burden while increasing therapeutic benefits for chronic pain patients.</p

The iCook 4-H Study: Report on Physical Activity and Sedentary Time in Youth Participating in a Multicomponent Program Promoting Family Cooking, Eating, and Playing Together

Objective To report physical activity and sedentary time outcomes of youth in iCook 4-H. Study Design and Setting iCook 4-H was a 5-state, randomized, control–treatment, family-based childhood obesity prevention intervention promoting cooking, eating, and playing together. Participants and Intervention Youth aged 9–10 years and the main preparer of their meals participated in the 12-week program followed by monthly newsletters and biyearly booster sessions until 24 months. Main Outcome Measure(s) A total of 155 youth were fitted with an Actigraph GT3X+ accelerometer, which they wore for 7 days at baseline and 4, 12, and 24 months to measure mean daily minutes per hour of waking wear time for sedentary time (ST), light physical activity (PA) (LPA), moderate PA, vigorous PA, and moderate to vigorous PA. Self-reported PA was assessed using the Block Kids Physical Activity Screener and additional questions querying for the program goal of the frequency of family actively playing together. Linear mixed models were used to determine differences from baseline to 24 months. Significance was set at P ≤ .05. Results There was a significant (P \u3c .05) group × time interaction for LPA (adjusted interaction B estimate, 95% confidence interval; 0.18 [0.05, 0.30]) and ST (−0.15 [−0.26, −0.04]); ST increased and LPA decreased in the treatment group. There were no differences in other accelerometer-derived PA measures, self-report Block Kids Physical Activity Screener measures, or frequency of family actively playing together at any time point. Conclusions and Implications iCook 4-H was a multicomponent program observing youth aged 9–10 years for 24 months that focused on enhancing cooking skills, mealtime behavior and conversation, and PA through daily family activities. Greater emphasis on developing PA skills, changing environmental factors, and increasing PA both in and after school may be needed

The iCook 4-HStudy: Report on Physical Activity and Sedentary Time in Youth Participating in a Multicomponent Program Promoting Family Cooking, Eating, and Playing Together

Objective: To report physical activity and sedentary time outcomes of youth in iCook 4-H. Study Design and Setting: iCook 4-H was a 5-state, randomized, control−treatment, family-based childhood obesity prevention intervention promoting cooking, eating, and playing together. Participants and Intervention: Youth aged 9−10 years and the main preparer of their meals participated in the 12-week program followed by monthly newsletters and biyearly booster sessions until 24 months. Main Outcome Measure(s): A total of 155 youth were fitted with an Actigraph GT3X+ accelerometer, which they wore for 7 days at baseline and 4, 12, and 24 months to measure mean daily minutes per hour of waking wear time for sedentary time (ST), light physical activity (PA) (LPA), moderate PA, vigorous PA, and moderate to vigorous PA. Self-reported PA was assessed using the Block Kids Physical Activity Screener and additional questions querying for the program goal of the frequency of family actively playing together. Linear mixed models were used to determine differences from baseline to 24 months. Significance was set at P ≤ .05. Results: There was a significant (P \u3c .05) group £ time interaction for LPA (adjusted interaction B estimate, 95% confidence interval; 0.18 [0.05, 0.30]) and ST (-0.15 [-0.26, -0.04]); ST increased and LPA decreased in the treatment group. There were no differences in other accelerometer-derived PA measures, self-report Block Kids Physical Activity Screener measures, or frequency of family actively playing together at any time point. Conclusions and Implications: iCook 4-H was a multicomponent program observing youth aged 9−10 years for 24 months that focused on enhancing cooking skills, mealtime behavior and conversation, and PA through daily family activities. Greater emphasis on developing PA skills, changing environmental factors, and increasing PA both in and after school may be needed

Calibrating ensemble reliability whilst preserving spatial structure

Ensemble forecasts aim to improve decision-making by predicting a set of possible outcomes. Ideally, these would provide probabilities which are both sharp and reliable. In practice, the models, data assimilation and ensemble perturbation systems are all imperfect, leading to deficiencies in the predicted probabilities. This paper presents an ensemble post-processing scheme which directly targets local reliability, calibrating both climatology and ensemble dispersion in one coherent operation. It makes minimal assumptions about the underlying statistical distributions, aiming to extract as much information as possible from the original dynamic forecasts and support statistically awkward variables such as precipitation. The output is a set of ensemble members preserving the spatial, temporal and inter-variable structure from the raw forecasts, which should be beneficial to downstream applications such as hydrological models. The calibration is tested on three leading 15-d ensemble systems, and their aggregation into a simple multimodel ensemble. Results are presented for 12 h, 1° scale over Europe for a range of surface variables, including precipitation. The scheme is very effective at removing unreliability from the raw forecasts, whilst generally preserving or improving statistical resolution. In most cases, these benefits extend to the rarest events at each location within the 2-yr verification period. The reliability and resolution are generally equivalent or superior to those achieved using a Local Quantile-Quantile Transform, an established calibration method which generalises bias correction. The value of preserving spatial structure is demonstrated by the fact that 3×3 averages derived from grid-scale precipitation calibration perform almost as well as direct calibration at 3×3 scale, and much better than a similar test neglecting the spatial relationships. Some remaining issues are discussed regarding the finite size of the output ensemble, variables such as sea-level pressure which are very reliable to start with, and the best way to handle derived variables such as dewpoint depression

Combination Intrathecal Drug Therapy Strategies for Pain Management

Background: Numerous combination intrathecal drug therapy (CIDT) strategies exist and are utilized for varying pain syndromes, typically when monotherapy dose escalation or medication alternation is deemed untenable or unfeasible. Unfortunately, the supportive evidence basis for the use of these strategies and specific drug combinations is generally lacking and unclear, with many medications being used for off-label indications. Objective: In this manuscript, we provide a robust exploration and analysis of the literature to provide an evidence-based narrative for the use of CIDT strategies in regard to clinical indications, pharmacologic parameters, specific drug combinations, safety profiles, and future directions. Study design: Narrative review. Methods: This was an evidence based narrative performed after extensive review of the literature. Results: Variances in intrathecal pharmacokinetics and pharmacodynamics are utilized advantageously with CIDT strategies to achieve improved analgesic benefit; however, appropriate use may be limited by increased or compounded risk of adverse effects. The supportive evidence for CIDT use for chronic pain conditions is largely lacking and limited to small, uncontrolled, observational studies, with many having various confounding factors, including a lack of standardized dosing. The most evidenced CIDT strategies include polyanalgesia with morphine-ziconotide, opioid-clonidine, and morphine-bupivacaine. Notably, in addition to pain relief, morphine-bupivacaine has been shown to decrease early opioid escalation requirements. Limitations: The supportive evidence for CIDT use for chronic pain conditions is largely lacking and limited to small, uncontrolled, observational studies, with many having various confounding factors including a lack of standardized dosing. Conclusions: CIDT strategies and polyanalgesia combinations can be effective for treating various patient populations with chronic pain. The appropriate use of these strategies may be limited by increased or compounded risk of adverse effects, both of which are highly patient and scenario dependent. Therefore, practitioners should maintain a particularly low threshold of suspicion for adverse effects in patients with CIDT such that safety profiles associated with this therapy can be favorably maintained

Quantum State Diffusion, Density Matrix Diagonalization and Decoherent Histories: A Model

We analyse the quantum evolution of a particle moving in a potential in interaction with an environment of harmonic oscillators in a thermal state, using the quantum state diffusion (QSD) picture of Gisin and Percival, in which one associates the usual Markovian master equation for the density operator with a class of stochastic non-linear Schr\"odinger equations. We find stationary solutions to the Ito equation which are Gaussians, localized around a point in phase space undergoing classical Brownian motion. We show that every initial state approaches these stationary solutions in the long time limit. We recover the density operator corresponding to these solutions, and thus show, for this particular model, that the QSD picture effectively supplies a prescription for approximately diagonalizing the density operator in a basis of phase space localized states. The rate of localization is related to the decoherence time, and also to the timescale on which thermal and quantum fluctuations become comparable. We use these results to exemplify the general connection between the QSD picture and the decoherent histories approach.Comment: 32 pages, plain Tex

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin