The Association Between Sleep Disturbance and Health Outcomes in Chronic Whiplash-associated Disorders: A Series of Mediation Analyses.

OBJECTIVES: To investigate the association between sleep disturbance and clinical features of chronic whiplash-associated disorders (WAD). We also aimed to use a bootstrapped mediation analysis approach to systematically examine both direct and indirect pathways by which sleep disturbance may affect chronic pain and functional status. MATERIALS AND METHODS: One hundred sixty-five people (63% female) with chronic WAD and not taking medications for sleep disturbance completed questionnaires evaluating sleep disturbance, pain intensity, pain interference, disability, physical and mental health quality of life, stress, anxiety, depression, pain catastrophizing, and posttraumatic stress severity. RESULTS: Greater sleep disturbance was associated with increased duration of symptoms, higher levels of pain and disability, higher levels of emotional distress and pain catastrophizing, and functional impairment (reduced health-related quality of life). Mediation analyses demonstrated that sleep disturbance influenced chronic pain intensity and interference through both direct and indirect associations inclusive of stress, anxiety, and pain catastrophizing. Similarly, sleep disturbance was associated with higher levels of disability and poor health-related quality of life, both directly and also through its negative association with pain intensity and interference. DISCUSSION: Sleep disturbance in chronic WAD was associated with worse health outcomes and demonstrated both direct and indirect effects on both chronic pain and function.

Prospective Within Subject Comparison of Fluoroscopically Guided Lumbosacral Facet Joint Radiofrequency Ablation Using a Multi-Tined (Trident) Versus Conventional Monopolar Cannula.

BACKGROUND: Radiofrequency ablation (RFA) for the lumbar facet joints has demonstrated efficacy in the management of chronic low back pain. The traditional technique uses a conventional monopolar (CM) cannula placed parallel to the putative nerve to produce a thermal lesion resulting in pain relief of the facet joints. A new multi-tined (MT) cannula has come onto the market that allows targeting the putative nerve using a perpendicular to the nerve approach. OBJECTIVES: This study describes the technique using the MT cannula and compares its efficacy and procedural characteristics to the CM cannula. STUDY DESIGN: This is a pre-post crossover observational study. METHODS: Fifty-one patients were recruited between June 2015 and March 2020. Each patient underwent 2 fluoroscopic guided lumbosacral RFA procedures on 2 separate occasions at the same facet joints, using the CM and MT cannula consecutively. The primary outcome measure was change in pain on the 11-point numeric rating scale (NRS). Secondary outcome measures included change in Pain Disability Quality of Life Questionnaire (PDQQ) score, duration and magnitude of pain relief, local anesthetic use, adverse events, procedural and fluoroscopy exposure time, and radiation dose. RESULTS: There were no statistically significant difference between CM versus MT canula in terms of absolute (4.0 versus 4.3) and relative (52% versus 57%) change in NRS (P = 0.99) and PDQQ (22 versus 22, P = 0.61) at 3 months, or overall pain magnitude (71% versus 72%, P = 0.96) and duration of relief (8.7 months versus 8.4 months, P = 0.68). The procedures using the MT cannula were completed faster (37.6 minutes versus 31.1 minutes, P < 0.001) and required less local anesthetic (15.8 mL versus 11.0 mL, P < 0.001) and radiation dose (41.5 mGy versus 30.2 mGy, P = 0.05). No adverse events were observed with either cannula. LIMITATIONS: This was an observational study at a single center with the proceduralist not blinded to the intervention. CONCLUSION: This study demonstrated that the outcomes in terms of pain, disability, quality of life, adverse events, and fluoroscopy exposure time were equivalent between the 2 cannulae. However, RFA using the MT cannula was faster to perform and involved less local anesthetic and radiation.

A Retrospective Cohort Study of Healthcare Utilization Associated with Paravertebral Blocks for Chronic Pain Management in Ontario.

Background: Injections, particularly paravertebral blocks (PVBs), are frequently performed procedures in Ontario, Canada, for the management of chronic pain, despite limited evidence and risk of complications. Aim: This study examines usage patterns of PVBs to evaluate their effects on healthcare utilization and opioid prescribing. Methods: A retrospective cohort study in Ontario using administrative data. Ontario residents receiving their initial PVBs between July 1, 2013 and March 31, 2018 were included. Changes in use of other interventions, physician visits, and opioids were compared to the 12-month periods before and after index PVBs. Data use was authorized under section 45 of Ontario's Personal Health Information Protection Act. Results: 47,723 patients received their initial PVBs in the study period. The rate of index PVBs increased from 1.61 per 10,000 population (2013) to 2.26 per 10,000 (2018). Initial PVBs were performed most commonly by family physicians (N = 25,042), followed by anesthesiologists (N = 14,195). 23,386 patients (49%) received 1 to 9 repeat PVBs in the 12 months after index PVB; 12,474 patients (26.15%) received 10 or more. Use of other nonimage guided interventional pain procedures per patient (mean±SD) increased from 2.19 ± 9.35 to 31.68 ± 52.26 in the year before and after index PVB. Relevant physician visits per patient (mean±SD) also increased from 2.92 ± 3.61 to 9.64 ± 11.77. Mean opioid dosing did not change significantly between the year before and the year after index PVB. Conclusion: PVBs are associated with increases in healthcare utilization and no change in opioid use patterns.

Contexte: Les injections, en particulier les blocs paravertébraux (BPV), sont des procédures fréquemment effectuées en Ontario, Canada, pour la prise en charge de la douleur chronique, malgré des données probantes limitées et le risque de complications.Objectif: Cette étude examine les modes d'utilisation des BPV afin d'évaluer leurs effets sur l'utilisation des soins de santé et la prescription d'opioïdes.Méthodes: Étude de cohorte rétrospective utilisant les données administratives en Ontario. Les résidents de l'Ontario ayant reçu leur BPV initial entre le 1er juillet 2013 et le 31 mars 2018 ont été inclus. Les changements dans l'utilisation des autres interventions, les visites aux médecins et les opioïdes ont été comparés 12 mois avant et 12 mois après les BPV de référence. L'utilisation des données a été autorisée en vertu de la Loi sur la protection des renseignements personnels sur la santé de l'Ontario.Résultats: 47 723 patients ont reçu leur BPV initial au cours de la période étudiée. Le taux de BPV est passé de 1,61 pour 10 000 habitants (2013) à 2,26 pour 10 000 (2018). Les BPV de référence étaient effectués le plus souvent par des médecins de famille (N = 25 042), suivis par les anesthésistes (N = 14 195). 23 386 patients (49 %) ont reçu de 1 à 9 BPV répétés dans les 12 mois suivant le BPV de référence ; 12 474 patients (26,15 %) en ont reçu 10 ou plus. L'utilisation d'autres procédures interventionnelles pour la douleur non guidées par l'image par patient (moyenne ± ET) est passée de 2,19 ± 9,35 à 31,68 ± 52,26 l'année précédant et suivant le BPV. Les visites médicales pertinentes par patient (moyenne ± ET) ont également augmenté de 2,92 ± 3,61 à 9,64 ± 11,77. La dose moyenne d'opioïdes n'a pas changé de manière significative entre l'année précédant et suivant le BPV de référence.Conclusion: Les BPV sont associés à une augmentation de l'utilisation des soins de santé et ne sont associés à aucun changement dans les modes d'utilisation des opioïdes.

Alternative splicing of the first intron of the steroid receptor RNA activator (SRA) participates in the generation of coding and noncoding RNA isoforms in breast cancer cell lines.

The Steroid Receptor RNA Activator 1 (SRA1) has originally been described as a noncoding RNA specifically activating steroid receptor transcriptional activity. We have, however, identified, in human breast tissue, exon- 1 extended SRA1 isoforms containing two initiating AUG codons and encoding a protein we called SRAP. We recently reported a decreased estrogen receptor activity in breast cancer cells overexpressing SRAP, suggesting antagonist roles played by SRA1 RNA and SRAP. SRA1 appears to be the first example of a molecule active both at the RNA and at the protein level. No data are currently available regarding the mechanisms possibly involved in the generation of coding and noncoding functional SRA1 RNAs. Using 5'-Rapid Amplification of cDNA Extremities (5'-RACE), we have herein identified several putative transcription initiation sites surrounding the second methionine codon and used to generate coding SRA1 transcripts. In the process, we also identified an alternatively spliced noncoding SRA1 transcript still containing an intron-1 sequence. Using targeted RT-PCR approaches, we confirmed the presence in breast cancer cell lines of SRA1 RNAs containing a full as well as a partial intron-1 sequence and established that the relative proportion of these RNAs varied within breast cancer cell lines. Using a "minigene" strategy, we also showed that artificial RNAs containing the SRA1 intron-1 sequence are alternatively spliced in breast cancer cell lines. Interestingly, the splicing pattern of the minigene products parallels the one of the endogenous SRA1 transcripts. Altogether, our data suggest that the primary genomic sequence in and around intron-1 is sufficient to lead to a differential splicing of this intron. We propose that alternative splicing of intron-1 is one mechanism used by breast cancer cells to regulate the balance between coding and functional noncoding SRA1 RNAs.