Stanford Pragmatiec Effectiveness Comparison (SPEC) protocol: Comparing long-term effectiveness of high-frequency and burst spinal cord stimulation in real-world application.

OBJECTIVES: High-frequency and burst stimulation are newer waveforms that have demonstrated promise compared to traditional tonic spinal cord stimulation (SCS), but more studies are needed to compare their effectiveness. We report the study methods for an ongoing, single center, pragmatic randomized clinical trial to compare the effectiveness of high-frequency and burst SCS in patients with chronic back and/or leg pain. MATERIALS AND METHODS: Participants who are candidates for spinal cord stimulation are enrolled and screened. Participants will be randomly assigned using point-of-care randomization to receive either high-frequency or burst SCS. Data collection will be through Stanford Pain Management Center's learning healthcare system: CHOIR. CHOIR surveys include National Institutes of Health Patient Reported Outcomes Measurement Information System item banks, a body map, questions about pain intensity, pain catastrophizing scale, and questions about patients' pain experience and healthcare utilization. Participants will complete online surveys at baseline and then 1, 3, 6, 12, 18, 24 and 36 months after their device implant. All participants will use our routine process of trial and implant. Reported adverse events are monitored throughout the study. Our primary outcome is change from baseline in pain intensity at 12 months. RESULTS: We hypothesize that high-frequency SCS is more effective than burst SCS in improving pain, physical function and pain interference in participants with chronic low back and/or leg pain. CONCLUSIONS: The pragmatic nature of our proposed trial enables us to recruit a larger participant cohort faster and to follow up these participants longer than currently published clinical trials.

Performance gaps and improvement plans from a 5-hospital simulation programme for anaesthesiology providers: a retrospective study.

Background: Simulation is increasingly employed in healthcare provider education, but usage as a means of identifying system-wide practitioner gaps has been limited. We sought to determine whether practice gaps could be identified, and if meaningful improvement plans could result from a simulation course for anaesthesiology providers. Methods: Over a 2-year cycle, 288 anaesthesiologists and 67 certified registered nurse anaesthetists (CRNAs) participated in a 3.5 hour, malpractice insurer-mandated simulation course, encountering 4 scenarios. 5 anaesthesiology departments within 3 urban academic healthcare systems were represented. A real-time rater scored each individual on 12 critical performance items (CPIs) representing learning objectives for a given scenario. Participants completed a course satisfaction survey, a 1-month postcourse practice improvement plan (PIP) and a 6-month follow-up survey. Results: All recorded course data were retrospectively reviewed. Course satisfaction was generally positive (88-97% positive rating by item). 4231 individual CPIs were recorded (of a possible 4260 rateable), with a majority of participants demonstrating remediable gaps in medical/technical and non-technical skills (97% of groups had at least one instance of a remediable gap in communication/non-technical skills during at least one of the scenarios). 6 months following the course, 91% of respondents reported successfully implementing 1 or more of their PIPs. Improvements in equipment/environmental resources or personal knowledge domains were most often successful, and several individual reports demonstrated a positive impact on actual practice. Conclusions: This professional liability insurer-initiated simulation course for 5 anaesthesiology departments was feasible to deliver and well received. Practice gaps were identified during the course and remediation of gaps, and/or application of new knowledge, skills and resources was reported by participants.

Relationship of central choroidal thickness with age-related macular degeneration status.

PURPOSE: To compare choroidal thickness in patients with intermediate or advanced age-related macular degeneration (AMD) and control subjects using enhanced-depth imaging optical coherence tomography (EDI-OCT). DESIGN: Retrospective cross-sectional study of 325 eyes from 164 subjects who underwent EDI-OCT for the Age-Related Eye Disease Study (AREDS) 2 Ancillary Spectral Domain OCT study. METHODS: Choroidal thickness was measured by semi-automated segmentation of EDI-OCT images from 1.5 mm nasal to 1.5 mm temporal to the fovea. Multivariate linear regression was used to evaluate the association of subfoveal choroidal thickness or average choroidal thickness across the central 3-mm segment with systemic and ocular variables. Choroidal thickness measurements were compared between eyes with no AMD (n = 154) (ie, controls), intermediate AMD (n = 109), and advanced AMD (n = 62). RESULTS: Both subfoveal and average choroidal thicknesses were associated with age (P < .001) and refractive error (P < .001), but not other variables tested. Mean average choroidal thickness was significantly reduced in advanced AMD as compared with control eyes (P = .008), with no significant difference between advanced and intermediate AMD eyes (P = .152) or between intermediate AMD and control eyes (P = .098). Choroidal thinning was also noted from 1.5 mm nasal to 1.5 mm temporal to the fovea when comparing advanced AMD with control eyes (P < .05 at all 0.5 mm interval locations). After adjustment for age and refractive error, however, there was no significant difference in subfoveal (P = .675) or average choroidal thickness (P = .746) across all 3 groups. CONCLUSIONS: When adjusted for age and refractive error, central choroidal thickness may not be significantly influenced by AMD status based on AREDS categorization.

Intravitreal sirolimus for the treatment of geographic atrophy: results of a phase I/II clinical trial.

PURPOSE: To investigate the safety and effects of intravitreal sirolimus for the potential treatment of geographic atrophy (GA). METHODS: The study was a single-center, open-label, phase I/II trial enrolling six participants with bilateral GA treated with intravitreal sirolimus in only one randomly assigned eye, with the fellow eye as control. The primary efficacy outcome measure was the change in total GA area from baseline on color fundus photography (CFP); secondary outcomes included changes in GA area on fundus autofluorescence (FAF), visual acuity, central retinal thickness (CRT), and macular sensitivity from baseline. RESULTS: Although no systemic adverse events were attributed to treatment, two of six participants had ocular adverse events that were possibly associated. The treated eye of one participant developed abnormal paralesional changes on FAF that were associated with accelerated retinal thinning. This accelerated retinal thinning was also seen in the treated eye of a second participant. Because of concern that these events were associated with treatment, treatment was suspended. Comparisons of treated and fellow eyes for change in visual acuity, change in GA area, and change in CRT showed no evidence of treatment benefit and generally favored the untreated fellow eye. CONCLUSIONS: While paralesional FAF changes and rapid retinal thinning observed are potentially part of the natural course of GA, they may possibly be related to treatment. No general evidence of anatomical or functional benefit was detected in treated eyes. Further data on intravitreal sirolimus for GA treatment will be available from a larger phase II trial. (ClinicalTrials.gov number, NCT01445548.).

Oral minocycline for the treatment of diabetic macular edema (DME): results of a phase I/II clinical study.

PURPOSE: Inflammation contributes significantly to the pathogenesis of diabetic macular edema (DME). In particular, retinal microglia demonstrate increased activation and aggregation in areas of DME. Study authors investigated the safety and potential efficacy of oral minocycline, a drug capable of inhibiting microglial activation, in the treatment of DME. METHODS: A single-center, prospective, open-label phase I/II clinical trial enrolled five participants with fovea-involving DME who received oral minocycline 100 mg twice daily for 6 months. Main outcome measurements included best-corrected visual acuity (BCVA), central retinal subfield thickness (CST), and central macular volume using spectral domain optical coherence tomography (SD-OCT) and late leakage on fluorescein angiography (FA). RESULTS: Findings indicated that the study drug was well tolerated and not associated with significant safety issues. In study eyes, mean BCVA improved continuously from baseline at 1, 2, 4, and 6 months by +1.0, +4.0, +4.0, and +5.8 letters, respectively, while mean retinal thickness (CST) on OCT decreased by -2.9%, -5.7%, -13.9, and -8.1% for the same time points. At month 6, mean area of late leakage on FA decreased by -34.4% in study eyes. Mean changes in contralateral fellow eyes also demonstrated similar trends. Improvements in outcome measures were not correlated with concurrent changes in systemic factors. CONCLUSIONS: In this pilot proof-of-concept study of DME, minocycline as primary treatment was associated with improved visual function, central macular edema, and vascular leakage, comparing favorably with historical controls from previous studies. Microglial inhibition with oral minocycline may be a promising therapeutic strategy targeting the inflammatory etiology of DME. (ClinicalTrials.gov number, NCT01120899.).

One-pot synthesis of alpha-carbolines via sequential palladium-catalyzed aryl amination and intramolecular arylation.

A one-pot synthesis of alpha-carbolines via a palladium-catalyzed aryl amination followed by intramolecular arylation is described. 2,3-Dichloro- and 2,3-dibromopyridines have been shown to react with readily available anilines to obtain various substituted alpha-carbolines in moderate to excellent yields.