Treatment of Refractory Low Back Pain Using Passive Recharge Burst in Patients Without Options for Corrective Surgery: Findings and Results From the DISTINCT Study, a Prospective Randomized Multicenter Controlled Trial.

OBJECTIVE: Spinal cord stimulation (SCS) is effective for relieving chronic intractable pain conditions. The Dorsal spInal cord STImulatioN vs mediCal management for the Treatment of low back pain study evaluates the effectiveness of SCS compared with conventional medical management (CMM) in the treatment of chronic low back pain in patients who had not undergone and were not candidates for lumbar spine surgery. METHODS AND MATERIALS: Patients were randomized to passive recharge burst therapy (n = 162) or CMM (n = 107). They reported severe pain and disability for more than a decade and had failed a multitude of therapies. Common diagnoses included degenerative disc disease, spondylosis, stenosis, and scoliosis-yet not to a degree amenable to surgery. The six-month primary end point compared responder rates, defined by a 50% reduction in pain. Hierarchical analyses of seven secondary end points were performed in the following order: composite responder rate (numerical rating scale [NRS] or Oswestry Disability Index [ODI]), NRS, ODI, Pain Catastrophizing Scale responder rate, Patient Global Impression of Change (PGIC) responder rate, and Patient-Reported Outcome Measure Information System-29 in pain interference and physical function. RESULTS: Intention-to-treat analysis showed a significant difference in pain responders on NRS between SCS (72.6%) and CMM (7.1%) arms (p < 0.0001). Of note, 85.2% of those who received six months of therapy responded on NRS compared with 6.2% of those with CMM (p < 0.0001). All secondary end points indicated the superiority of burst therapy over CMM. A composite measure on function or pain relief showed 91% of subjects with SCS improved, compared with 16% of subjects with CMM. A substantial improvement of 30 points was observed on ODI compared with a

Teleprogramming Service Provides Safe and Remote Stimulation Options for Patients with DRG-S and SCS Implants.

BACKGROUND: Chronic pain patients implanted with a neurostimulation device typically require follow-up and device programming visits to address changes in symptoms or treatment. Follow-up visits require access to specialty care and necessitate patients to take time off work, commute long distances, arrange for travel, and/or work with a caregiver's schedule. Telemedicine was adopted for some patient management as a result of the Sars-Cov-2 pandemic; however, remote optimization for neuromodulation still required an in-person visit to adjust device parameters. An FDA-approved digital platform enables remote programming of an implanted neuromodulation device using a real-time audio-video link from the clinical programmer to the patient controller. The Remote Optimization, Adjustment, and Measurement for Chronic Pain Therapy (ROAM-CPT) is a multi-center, prospective study that is currently underway to access the effectiveness of the teleprogramming system in fulfilling patients' clinical demands. METHODS: This pilot study surveyed 16 patients to determine the ability of the teleprogramming platform to provide a rapid solution safely and effectively for patient's chronic pain. Data were collected using a questionnaire that asked 6 clinician-centric questions and 5 patient-centric questions. RESULTS: 4/4 surveyed physicians were able to address patients' needs. 16/16 surveyed patients reported a quick resolution to pain and 15/16 did not require additional follow-up. Data curated from this pilot study show that the teleprogramming application greatly improves patient care, is preferred by both clinicians and patients with minimal disruptions to patients' everyday lives. CONCLUSION: Teleprogramming provides real-time virtual programming capabilities and optimizes patients' therapy. PERSPECTIVE: This article describes remote device programming and analysis as an alternative to in-person programming/treatment sessions for neuromodulation patients. This remote option gives patients access to timely and clinically appropriate device management when in-person care may not be available.

Effectiveness and Safety of Dorsal Root Ganglion Stimulation for the Treatment of Chronic Pain: A Pooled Analysis.

INTRODUCTION: Since it became available in the mid-2010s, dorsal root ganglion (DRG) stimulation has become part of the armamentarium to treat chronic pain. To date, one randomized controlled trial, and several studies of moderate sample size and various etiologies have been published on this topic. We conducted a pooled analysis to investigate the generalizability of individual studies and to identify differences in outcome between chronic pain etiologic subgroups and/or pain location. MATERIALS AND METHODS: One prospective, randomized comparative trial and six prospective, single-arm, observational studies were identified that met pre-defined acceptance criteria. Pain scores and patient-reported outcome (PRO) measures were weighted by study sample sizes and pooled. Safety data are reported in aggregate form. RESULTS: Our analysis included 217 patients with a permanent implant at 12-month follow-up. Analysis of pooled data showed an overall weighted mean pain score of 3.4, with 63% of patients reporting ≥50% pain relief. Effectiveness sub-analyses in CRPS-I, causalgia, and back pain resulted in a mean reduction in pain intensity of 4.9, 4.6, and 3.9 points, respectively. Our pooled analysis showed a pain score for primary affected region ranging from 1.7 (groin) to 3.0 (buttocks) and responder rates of 80% for foot and groin, 75% for leg, and 70% for back. A substantial improvement in all PROs was observed at 12 months. The most commonly reported procedural or device complications were pain at the IPG pocket site, lead fracture, lead migration, and infection. CONCLUSIONS: DRG stimulation is an effective and safe therapy for various etiologies of chronic pain.

Analytical Validation of a Highly Sensitive, Multiplexed Chronic Myeloid Leukemia Monitoring System Targeting BCR-ABL1 RNA.

This study describes the analytical performance of the QuantideX qPCR BCR-ABL IS Kit, the first Food and Drug Administration-cleared assay designed to monitor breakpoint cluster region-Abelson tyrosine-protein kinase 1 (BCR-ABL1) fusion transcripts isolated from peripheral blood specimens from patients with chronic myeloid leukemia. This multiplex real-time quantitative RT-PCR assay amplifies both e13a2 and e14a2 Major BCR-ABL1 transcripts and the reference target ABL1. The test results are provided in international scale (IS) values by incorporating armored RNA-based calibrators that have defined IS values tied directly to the World Health Organization BCR-ABL1 Primary Reference Materials, without the necessity of determining and maintaining conversion factors. For each batch run, the integrated interpretive software evaluates run and specimen quality control metrics (including a sufficient amount of ABL1 control transcripts to ensure a minimal limit of detection) and calculates both molecular response (MR) and %IS values for each specimen. The test has a limit of detection of MR4.7 (0.002%IS) and a linear range from MR0.3 (50%IS) to MR4.7 (0.002%IS) for both Major transcripts. Single-site and multisite precision studies demonstrated a maximum SD of 0.13 MR (30% CV within the assay range between MR0.7 and MR3.7). The performance of this BCR-ABL1 monitoring test meets all of the clinical guideline recommendations for sensitivity and IS reporting for the management of chronic myeloid leukemia patients.

GPS-Prot: a web-based visualization platform for integrating host-pathogen interaction data.

BACKGROUND: The increasing availability of HIV-host interaction datasets, including both physical and genetic interactions, has created a need for software tools to integrate and visualize the data. Because these host-pathogen interactions are extensive and interactions between human proteins are found within many different databases, it is difficult to generate integrated HIV-human interaction networks. RESULTS: We have developed a web-based platform, termed GPS-Prot http://www.gpsprot.org, that allows for facile integration of different HIV interaction data types as well as inclusion of interactions between human proteins derived from publicly-available databases, including MINT, BioGRID and HPRD. The software has the ability to group proteins into functional modules or protein complexes, generating more intuitive network representations and also allows for the uploading of user-generated data. CONCLUSIONS: GPS-Prot is a software tool that allows users to easily create comprehensive and integrated HIV-host networks. A major advantage of this platform compared to other visualization tools is its web-based format, which requires no software installation or data downloads. GPS-Prot allows novice users to quickly generate networks that combine both genetic and protein-protein interactions between HIV and its human host into a single representation. Ultimately, the platform is extendable to other host-pathogen systems.

Gene expression, intron density, and splice site strength in Drosophila and Caenorhabditis.

In this paper we investigate the relationships among intron density (number of introns per kilobase of coding sequence), gene expression level, and strength of splicing signals in two species: Drosophila melanogaster and Caenorhabditis elegans. We report a negative correlation between intron density and gene expression levels, opposite to the effect previously observed in human. An increase in splice site strength has been observed in long introns in D. melanogaster. We show this is also true of C. elegans. We also examine the relationship between intron density and splice site strength. There is an increase in splice site strength as the intron structure becomes less dense. This could suggest that introns are not recognized in isolation but could function in a cooperative manner to ensure proper splicing. This effect remains if we control for the effects of alternative splicing on splice site strength.

Maternally and paternally silenced imprinted genes differ in their intron content.

Imprinted genes exhibit silencing of one of the parental alleles during embryonic development. In a previous study imprinted genes were found to have reduced intron content relative to a non-imprinted control set (Hurst et al., 1996). However, due to the small sample size, it was not possible to analyse the source of this effect. Here, we re-investigate this observation using larger datasets of imprinted and control (non-imprinted) genes that allow us to consider mouse and human, and maternally and paternally silenced, imprinted genes separately. We find that, in the human and mouse, there is reduced intron content in the maternally silenced imprinted genes relative to a non-imprinted control set. Among imprinted genes, a strong bias is also observed in the distribution of intronless genes, which are found exclusively in the maternally silenced dataset. The paternally silenced dataset in the human is not different to the control set; however, the mouse paternally silenced dataset has more introns than the control group. A direct comparison of mouse maternally and paternally silenced imprinted gene datasets shows that they differ significantly with respect to a variety of intron-related parameters. We discuss a variety of possible explanations for our observations.