The Mycobacterium tuberculosis Ku C-terminus is a multi-purpose arm for binding DNA and LigD and stimulating ligation.

Bacterial non-homologous end joining requires the ligase, LigD and Ku. Ku finds the break site, recruits LigD, and then assists LigD to seal the phosphodiester backbone. Bacterial Ku contains a core domain conserved with eukaryotes but has a unique C-terminus that can be divided into a minimal C-terminal region that is conserved and an extended C-terminal region that varies in sequence and length between species. Here, we examine the role of Mycobacterium tuberculosis Ku C-terminal variants, where we removed either the extended or entire C-terminus to investigate the effects on Ku-DNA binding, rates of Ku-stimulated ligation, and binding affinity of a direct Ku-LigD interaction. We find that the extended C-terminus limits DNA binding and identify key amino acids that contribute to this effect through alanine-scanning mutagenesis. The minimal C-terminus is sufficient to stimulate ligation of double-stranded DNA, but the Ku core domain also contributes to stimulating ligation. We further show that wildtype Ku and the Ku core domain alone directly bind both ligase and polymerase domains of LigD. Our results suggest that Ku-stimulated ligation involves direct interactions between the Ku core domain and the LigD ligase domain, in addition to the extended Ku C-terminus and the LigD polymerase domain.

Emergency department return visits and hospital admissions in trauma team assessed patients initially discharged from the emergency department: A population-based cohort study.

BACKGROUND: Many injured patients are transported directly to trauma centers, found to be minimally injured, and discharged directly home from the emergency department (ED). Our objectives were to characterize the short-term outcomes in this discharged patient population and to identify patient factors predictive of ED return visits. METHODS: We conducted a retrospective population-based cohort study using linked administrative data sets involving patients assessed at trauma centers in Ontario, Canada between April 1, 2009, and March 31, 2020. Patients who were assessed by a trauma team and discharged directly home from ED were included. The primary outcome was the percentage of patients with an ED return visit within 14 days. We used multivariate logistic regression analyses to identify patient characteristics predictive of at least one ED return visit. RESULTS: There were 5,550 patients included in the study. A total of 1,004 (18.1%) of patients had at least one ED return visit, but only 100 patients (1.8%) were admitted to hospital following initial discharge. Common reasons for ED return visits included wound care concerns (17.2%), head injury complaints (15.6%), and substance misuse (6.8%). Rural residence (odds ratio [OR], 1.83; 95% CI, 1.45-2.29), history of anxiety disorder (OR, 2.05; 95% CI, 1.54-2.73), high baseline ED usage (OR, 2.58; 95% CI, 2.03-3.28), penetrating injury (OR, 1.42; 95% CI, 1.20-1.68), and extremity fracture (OR, 1.52; 95% CI, 1.24-1.88) predicted return visits. CONCLUSION: Patients discharged directly have high rates of ED return visits but low rates of hospital admission or delayed surgical intervention. Trauma services should expand quality assurance initiatives to capture return visits, understand any gaps in clinical service provision, and aim to minimize unnecessary ED return visits. LEVEL OF EVIDENCE: Prognostic/Epidemiological; Level IV.

Using chart reviews to evaluate a continuing medical education (CME) program.

Context Moore's Expanded Outcomes Framework is a 7 level framework commonly used to assess the outcomes of continuing medical education (CME) programs. Levels 1 to 5 are provider-level outcomes (participation, satisfaction, knowledge, competence, and performance) while levels 6 and 7 are patient- and community-level outcomes. Chart reviews are one method to assess level 5 (performance). ECHO Ontario Chronic Pain and Opioid Stewardship ("ECHO") is a CME telementoring program that aims to increase capacity and access for primary care providers (PCPs) who manage patients with chronic pain. Objective This study uses chart reviews to evaluate ECHO's impact on PCP performance and to discuss the feasibility of performing chart reviews for evaluation purposes as per Moore's framework. Study Design Retrospective chart review Setting The practices of 12 primary care providers across Ontario who attended ECHO between June 2014 to August 2018. The inclusion criteria for PCPs was 1) attended a minimum of four ECHO sessions, and 2) clinic site must be approving of a site visit for chart reviews. Population Studied 47 patient charts were included. For each patient chart reviewed, PCPs were asked to choose patients in their practice on whom they had used ECHO-taught knowledge. Inclusion criteria for patients was 1) have chronic pain and be managed by the ECHO-participating PCP, 2) was prescribed opioids during the time frame of the study, and 3) not presented during ECHO sessions. Informed consent was obtained prior to each site visit. 1) Increased use of ECHO-taught pain and opioid management strategies 2) Feasibility of using chart reviews to evaluate PCP performance following a CME activity Results 25 (53%) patients were male and the average age was 59 (± 14) years. 24 (51%) patients had two or more pain diagnoses at baseline, with musculoskeletal pain being the most prevalent at 81%. 26 (55%) patients had comorbid mental health conditions and 13 (28%) had sleep disorders. Trends in results showed marginal, but non-significant, improvements in PCP performance after ECHO as indicated by increased use of pain and opioid management strategies. Conclusions Conducting chart reviews was a challenging method to assess provider performance. Future work to assess provider performance should include a qualitative component (in-depth interviews or focus groups) in order to complement the quantitative data and provide context for care and management decisions.