A randomized, placebo-controlled trial of long-acting dexamethasone viscous gel delivered by transforaminal injection for lumbosacral radicular pain

Epidural steroid injections are used to treat lumbosacral radicular pain. However, there are no Food and Drug Administration–approved corticosteroids for lumbosacral radicular pain and all currently available injectable corticosteroids carry safety warnings about their use in epidural steroid injection procedures. SP-102 (dexamethasone injectable viscous gel) was developed to provide a safer option with extended local effect. In a randomized, double-blind, placebo-controlled, multicenter trial, 401 patients with moderate-to-severe leg pain from unilateral intervertebral lumbar disc herniation were randomized (1:1) to receive transforaminal SP-102 or sham intramuscular (IM) placebo injection and followed for 24 weeks. If clinically warranted, a repeat open-label SP-102 injection was allowed between 4 and 20 weeks for both groups. Primary and key secondary end points were change in average daily pain on the Numeric Pain Rating Scale in the affected leg and disability measured by Oswestry Disability Index over 4 weeks. Other secondary end points included time to repeat injection, pain, and quality of life assessments. Over 4 weeks, SP-102 demonstrated statistically significant pain relief compared with placebo (least-squares mean group difference −0.52 [SE 0.163] [ P = 0.002]) in the intent-to-treat population. Oswestry Disability Index mean improvement was −3.38 (1.388) (least-squares mean group difference [SE]) for SP-102 vs placebo ( P = 0.015). Median time to repeat injection was 84 days for SP-102 vs 58 days for placebo ( P = 0.001). Most other secondary end points were statistically significant for SP-102 compared with placebo. There were no serious adverse events related to study medication or procedure, no adverse events leading to death, and no AEs of special interest (paraplegia, hematoma, or infection)

Dorsal root ganglion stimulation yielded higher treatment success rate for complex regional pain syndrome and causalgia at 3 and 12 months: a randomized comparative trial

Animal and human studies indicate that electrical stimulation of dorsal root ganglion (DRG) neurons may modulate neuropathic pain signals. ACCURATE, a pivotal, prospective, multicenter, randomized comparative effectiveness trial, was conducted in 152 subjects diagnosed with complex regional pain syndrome or causalgia in the lower extremities. Subjects received neurostimulation of the DRG or dorsal column (spinal cord stimulation, SCS). The primary end point was a composite of safety and efficacy at 3 months, and subjects were assessed through 12 months for long-term outcomes and adverse events. The predefined primary composite end point of treatment success was met for subjects with a permanent implant who reported 50% or greater decrease in visual analog scale score from preimplant baseline and who did not report any stimulation-related neurological deficits. No subjects reported stimulation-related neurological deficits. The percentage of subjects receiving ≥50% pain relief and treatment success was greater in the DRG arm (81.2%) than in the SCS arm (55.7%, P < 0.001) at 3 months. Device-related and serious adverse events were not different between the 2 groups. Dorsal root ganglion stimulation also demonstrated greater improvements in quality of life and psychological disposition. Finally, subjects using DRG stimulation reported less postural variation in paresthesia (P < 0.001) and reduced extraneous stimulation in nonpainful areas (P = 0.014), indicating DRG stimulation provided more targeted therapy to painful parts of the lower extremities. As the largest prospective, randomized comparative effectiveness trial to date, the results show that DRG stimulation provided a higher rate of treatment success with less postural variation in paresthesia intensity compared to SCS

Measuring the Semantic Priming Effect Across Many Languages

Semantic priming has been studied for nearly 50 years across various experimental manipulations and theoretical frameworks. These studies provide insight into the cognitive underpinnings of semantic representations in both healthy and clinical populations; however, they have suffered from several issues including generally low sample sizes and a lack of diversity in linguistic implementations. Here, we will test the size and the variability of the semantic priming effect across ten languages by creating a large database of semantic priming values, based on an adaptive sampling procedure. Differences in response latencies between related word-pair conditions and unrelated word-pair conditions (i.e., difference score confidence interval is greater than zero) will allow quantifying evidence for semantic priming, whereas improvements in model fit with the addition of a random intercept for language will provide support for variability in semantic priming across languages

Risk of COVID-19 after natural infection or vaccinationResearch in context

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health

Risk of COVID-19 after natural infection or vaccinationResearch in context

Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health