Abstract Background Skin and soft tissue infections (SSTIs) are very common bacterial infections. Numerous clinical trials have compared antibiotics for SSTI treatment. However, trials typically have non-inferiority designs that give little insight as to which antibiotic classes have superior efficacy. Methods We performed a systematic literature review and a network meta-analysis of published SSTI treatment trials. Using standardized key words, we searched PubMed and Embase for SSTI clinical trials published from 1/1/66 to 5/31/22. We excluded trials on diabetic foot infections, non-generalizable populations (e.g., burn associated), and studies with outcomes not involving clinical resolution or cure. Abstracts with relevant clinical trial data were pulled and, if inclusion criteria met, had manuscript data abstracted. Two reviewers independently performed abstract and manuscripts reviews and data abstraction. For the network meta-analyses, the comparator antibiotic class was glycopeptides. Two analyses were performed using intention to treat (ITT) and clinically evaluable (CE) populations. Clinical trial quality was measured using the PEDro score. Results We reviewed 5,469 abstracts, of which 260 were pulled for data abstraction and 93 contained analyzable trial data (Fig. 1). Clinical trial quality varied widely (PEDro score range 2-10, median 8). We identified 26 analyzable antibiotic classes or combinations for comparison. In the ITT model, cure rate for oxazolidinones (OR 1.28 [95% CI 1.10-1.49]), flucloxacillin plus clindamycin (OR 1.61 [95% CI 1.03-2.53]), lipopeptides (OR 1.66 [95% CI 1.04-2.66]), and tetracyclines OR 1.69 [95% CI 1.24-2.30]), significantly differed from glycopeptides. (Fig. 2) In the CE model, cure rate for oxazolidinones (OR 1.29 [95% CI 1.01-1.64]) and tetracyclines (OR 2.05 [95% CI 1.37-3.06]) significantly differed. Conclusion We found that most (22/26) antibiotic classes or combinations used for SSTI treatment had similar efficacy to glycopeptides. However, oxazolidinones, lipopeptides, flucloxacillin plus clindamycin, and tetracyclines may have superior efficacy compared to glycopeptides. Treatment guidelines may wish to favor these latter classes for patients at high risk of treatment failure. Disclosures Amy Y. Kang, Pharm.D., BCIDP, Paratek: Grant/Research Support Elliot I. Miller, BS, Epic Systems, Verona, WI: Employee Loren G. Miller, MD MPH, ContraFect: Grant/Research Support|GSK: Grant/Research Support|Medline: Grant/Research Support|Merck: Grant/Research Support|Paratek: Grant/Research Support

Hispanic people compared to White people with multiple sclerosis (MS) are two times more likely to present with optic neuritis (ON). ON in dissemination in space (DIS) after a single attack is not part of the current McDonald 2017 criteria. To evaluate if adding ON in DIS (ON-modified criteria) improves the performance of the McDonald 2017 criteria in the diagnosis of MS after a single attack of ON. Retrospective study of 102 patients of Hispanic background. Cases were reviewed between 2017 and 2021. Clinical ON was reported for 35 cases. ON in DIS was verified for 28 patients via MRI, optical coherence tomography, and/or visual evoked potential. We investigated the performance of the McDonald 2017 criteria and ON-modified criteria and calculated sensitivity, specificity, positive and negative predictive values, and accuracy. The ON-modified criteria significantly improved the performance of the McDonald 2017 criteria (p = 0.003) and identified an additional nine patients. Both sensitivity and accuracy increased from 64% to 74% and 62% to 71%, respectively, while specificity remained unchanged (40% (95% confidence interval (CI): 0.10, 0.70)). This study provides evidence that the inclusion of ON in DIS improved the overall performance of the McDonald 2017 criteria among Hispanic people.

Postpartum, patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) have increased risk for disease activity. Anti-CD20 IgG1 monoclonal antibodies (mAb) are increasingly used as disease-modifying therapies (DMTs). Patients may wish to both breastfeed and resume DMT postpartum. This study aimed to determine the transfer of anti-CD20 IgG1 mAbs, ocrelizumab, and rituximab (OCR/RTX), into mature breastmilk and describe maternal and infant outcomes. Fifty-seven cis-women receiving OCR/RTX after 59 pregnancies and their infants were enrolled and followed up to 12M postpartum or 90 days post-infusion. Breastmilk was collected pre-infusion and serially up to 90 days and assayed for mAb concentration. Medical records and patients' questionnaire responses were obtained to assess neurologic, breastfeeding, and infant development outcomes. The median average concentration of mAb in breastmilk was low (OCR: 0.08 μg/mL, range 0.05-0.4; RTX: 0.03 μg/mL, range 0.005-0.3). Concentration peaked 1-7 days post-infusion in most (77%) and was nearly undetectable after 90 days. Median average relative infant dose was <1% (OCR: 0.1%, range 0.07-0.7; RTX: 0.04%, range 0.005-0.3). Forty-three participants continued to breastfeed post-infusion. At 8-12 months, the proportion of infants' growth between the 3rd and 97th World Health Organization percentiles did not differ for breastfed (36/40) and non-breastfed (14/16, p > 0.05) infants; neither did the proportion with normal development (breastfed: 37/41, non-breastfed: 11/13; p > 0.05). After postpartum infusion, two mothers experienced a clinical relapse. These confirm minimal transfer of mAb into breastmilk. Anti-CD20 mAb therapy stabilizes MS activity before conception to the postpartum period, and postpartum treatments appears to be safe and well-tolerated for both mother and infant.

Abstract The high-voltage plant power system of nuclear power plants contains various cables. When a single-phase ground fault occurs in the system, the input of a large number of cables will increase the capacitive current of the system. At the same time, in the environment of strong radiation and high temperature, the cable insulation is very easy to age. At present, the research on single-phase fault of 6.6kV system mainly focuses on simulation calculation, and lacks the verification of real-type experiment due to the cost and difficulty. Aiming at the problems faced by a domestic nuclear power plant, this paper established a 6.6kV high-voltage utility power ground fault simulation model based on the high-voltage utility cable wiring topology, and studied the fault characteristics of the system under different single-phase faults. A 6.6kV system real-type experiment platform was built to simulate metal grounding and cable insulation faults when the neutral point was not grounded and the extinction coil was grounded, and the agreement between the test and the simulation calculation results is high, but there is a difference in the arcing ground triggered by the cable insulation faults, so as to provide a reference for the maintenance and safe operation of the cable of the power system of the plant of the nuclear power plant.

Implementation of guideline-recommended depression screening in oncology presents numerous challenges. Implementation strategies that are responsive to local context may be critical elements of adoption and sustainment. We evaluated barriers and facilitators to implementation of a depression screening program for breast cancer patients in a community medical oncology setting as part of a cluster randomized controlled trial. Guided by the Consolidated Framework for Implementation Research, we employed qualitative methods to evaluate clinician, administrator, and patient perceptions of the program using semi-structured interviews. We used a team-coding approach for the data; thematic development focused on barriers and facilitators to implementation using a grounded theory approach. The codebook was refined through open discussions of subjectivity and unintentional bias, coding, and memo applications (including emergent coding), and the hierarchical structure and relationships of themes. We conducted 20 interviews with 11 clinicians/administrators and 9 patients. Five major themes emerged: (1) gradual acceptance and support of the intervention and workflow; (2) compatibility with system and personal norms and goals; (3) reinforcement of the value of and need for adaptability; (4) self-efficacy within the nursing team; and (5) importance of identifying accountable front-line staff beyond leadership "champions." Findings suggest a high degree of acceptability and feasibility due to the selection of appropriate implementation strategies, alignment of norms and goals, and a high degree of workflow adaptability. These findings will be uniquely helpful in generating actionable, real-world knowledge to inform the design, implementation, and sustainment of guideline-recommended depression screening programs in oncology. ClinicalTrials.gov #NCT02941614.

To assess 12-month safety and efficacy of pegloticase + methotrexate (MTX) versus pegloticase + placebo (PBO) cotherapy in a PBO-controlled, double-blind trial (A randomized, double-blind, placebo-controlled, multicenter, efficacy and safety study of methotrexate to increase response rates in patients with uncontrolled gout receiving pegloticase [MIRRORRCT]). Patients with uncontrolled gout (serum urate level [SU] ≥7 mg/dl, oral urate-lowering therapy failure or intolerance, and presence of one or more gout symptoms [one or more tophi, two or more flares in 12 months, gouty arthropathy]) were randomized 2:1 to receive pegloticase (8-mg infusion every 2 weeks) with blinded MTX (oral 15 mg/week) or PBO for 52 weeks. Efficacy end points included proportion of responders (SU level <6 mg/dl for ≥80% of examined month) in the intent-to-treat population (ITT) (all randomized patients) during month 6 (primary end point), month 9, and month 12; proportion with resolution of one or more tophi (ITT); mean SU reduction (ITT); and time to SU-monitoring pegloticase discontinuation. Safety was evaluated via adverse event reporting and laboratory values. Month 12 response rate was significantly higher in patients cotreated with MTX (60.0% [60 of 100] vs. 30.8% [16 of 52]; difference: 29.1% [95% confidence interval (CI): 13.2%-44.9%], P = 0.0003), with fewer SU discontinuations (22.9% [22 of 96] vs. 63.3% [31 of 49]). Complete resolution of one or more tophi occurred in 53.8% (28 of 52) versus 31.0% (9 of 29) of MTX versus PBO patients at week 52 (difference: 22.8% [95% CI: 1.2%-44.4%], P = 0.048), more than at week 24 (34.6% [18 of 52] vs. 13.8% [4 of 29]). Consistent with observations through month 6, pharmacokinetic and immunogenicity findings showed increased exposure and lower immunogenicity of pegloticase when administered with MTX, with an otherwise similar safety profile. No infusion reactions occurred after 24 weeks. Twelve-month MIRROR RCT data further support MTX cotherapy with pegloticase. Tophi resolution continued to increase through week 52, suggesting continued therapeutic benefit beyond month 6 for a favorable treatment effect.

Simulation-based training (SBT) and debriefing have increased in healthcare as a method to conduct interprofessional team training in a realistic environment. This qualitative study aimed to describe the experiences of neonatal healthcare professionals when implementing a patient safety simulation and debriefing program in a neonatal intensive care unit (NICU). Fourteen NICUs in California and Oregon participated in a 15-month quality improvement collaborative with the California Perinatal Quality Care Collaborative. Participating sites completed 3 months of preimplementation work, followed by 12 months of active implementation of the simulation and debriefing program. Focus group interviews were conducted with each site 2 times during the collaborative. Content analysis found emerging implementation themes. There were 234 participants in the 2 focus group interviews. Six implementation themes emerged: (1) receptive context; (2) leadership support; (3) culture change; (4) simulation scenarios; (5) debriefing methodology; and (6) sustainability. Primary barriers and facilitators with implementation of SBT centered around having a receptive context at the unit level (eg, availability of resources and time) and multidisciplinary leadership support. NICUs have varying environmental (context) factors and consideration of unit-level context factors and support from leadership are integral aspects of enhancing the successful implementation of a simulation and debriefing program for neonatal resuscitation. Additional research regarding implementation methods for overcoming barriers for both leaders and participants, as well as determining the optimal frequency of SBT for clinicians, is needed. A knowledge gap remains regarding improvements in patient outcomes with SBT.