The ROK kinase N-acetylglucosamine kinase uses a sequential random enzyme mechanism with successive conformational changes upon each substrate binding.

N-acetyl-d-glucosamine (GlcNAc) is a major component of bacterial cell walls. Many organisms recycle GlcNAc from the cell wall or metabolize environmental GlcNAc. The first step in GlcNAc metabolism is phosphorylation to GlcNAc-6-phosphate. In bacteria, the ROK family kinase N-acetylglucosamine kinase (NagK) performs this activity. Although ROK kinases have been studied extensively, no ternary complex showing the two substrates has yet been observed. Here, we solved the structure of NagK from the human pathogen Plesiomonas shigelloides in complex with GlcNAc and the ATP analog AMP-PNP. Surprisingly, PsNagK showed distinct conformational changes associated with the binding of each substrate. Consistent with this, the enzyme showed a sequential random enzyme mechanism. This indicates that the enzyme acts as a coordinated unit responding to each interaction. Our molecular dynamics modeling of catalytic ion binding confirmed the location of the essential catalytic metal. Additionally, site-directed mutagenesis confirmed the catalytic base and that the metal-coordinating residue is essential. Together, this study provides the most comprehensive insight into the activity of a ROK kinase.

Using OR Black Box Technology to Determine Quality Improvement Outcomes for In-situ Timeout and Debrief Simulation.

OBJECTIVE: The purpose of this study was to determine quality improvement outcomes following the pilot implementation of an in-situ simulation designed to enhance surgical safety checklist performance. BACKGROUND: OR Black Box (ORBB) technology allows near real-time assessment for surgical safety checklist performance. Before our study, timeout quality was 73.3%, compliance was 99.9%, and engagement was 89.7% (n=1993 cases); Debrief Quality was 76.0%, compliance was 66.9%, and engagement was 66.7% (n=1842 cases). METHODS: This IRB-approved study used prospective convergent multi-methods. During 2 months, a 15-minute in-situ simulation, incorporating rapid cycle deliberate practice, was implemented for OR teams. ORBB analytics generated Timeout and Debrief scores for actual operations performed by surgeons who participated in simulation (Sim-group) versus those who did not (No-sim group) over 6 months, including 2 months pre-intervention, during-intervention, and post-intervention. Inductive content analysis was performed based on simulation discussions to determine team member perspectives. RESULTS: Thirty simulations with 163 interprofessional participants were conducted. ORBB data from 1570 cases were analyzed. Scores were significantly better for the Sim-group compared with the No-sim group for debrief quality (84% vs. 79% P<0.001, during-intervention), compliance (73% vs. 66%, P<0.001, post-intervention), and engagement (80% vs. 73%, P=0.012, during-intervention). There were no between-group differences for Timeout scores. Thematic analysis identified 2 primary categories: "culture of safety" and "policy." CONCLUSIONS: This simulation-based QI intervention created a psychologically safe training environment for OR teams. The novel use of ORBB technology facilitated outcome analysis and showed significantly better Debrief scores for simulation-trained surgeons compared with nontrained surgeons.

The Operating Room Black Box: Understanding Adherence to Surgical Checklists.

OBJECTIVE: We report for the first time the use of the Operating Room Black Box (ORBB) to track checklist compliance, engagement, and quality. BACKGROUND: Implementation of operative checklists is associated with improved outcomes. Compliance is difficult to monitor. Most studies report either no assessment of checklist compliance or deployed in-person short-term assessment. The ORBB a novel artificially intelligence-driven data analytic platform affords the opportunity to assess checklist compliance without disrupting surgical workflow. METHODS: This was a retrospective review of prospectively collected ORBB data. Operative cases included elective surgery at a quaternary referral center. Cases were analyzed as prepolicy change (first 9 months) or as a postpolicy change (last 9 months). Measures of checklist compliance, engagement, and quality were assessed. RESULTS: There were 3879 cases that were performed and monitored for checklist compliance between August 15, 2020, and February 20, 2022. The overall scores for compliance, engagement, and quality were 81%, 84%, and 67% respectively. When broken down by phase, the scores for time-out were compliance 100%, engagement 98%, and quality 61%. Scores for the debrief phase were 81% for compliance, 98% for engagement, and 66% for quality. After a hospital policy change, the debrief scores improved significantly (85%; P <0.001 for compliance, 88%; P <0.001 for engagement and 71%; P <0.001 for quality). CONCLUSIONS: ORBB provides the unprecedented ability to assess not only compliance with surgical safety checklists but also engagement and quality. Utilization of this technology allows the assessment of compliance in near real time and to accurately address safety threats that may arise from noncompliance.

Predictors and impact of thirty-day readmission on patient outcomes and health care costs after reduced-toxicity conditioning allogeneic hematopoietic cell transplantation.

Thirty-day readmission (30-DR) has become an important quality-of-care measure. Allogeneic hematopoietic cell transplantation (allo-HCT) presents a medical setting with higher readmission rates. We analyzed factors affecting 30-DR and its impact on patient outcomes and on health care costs in 91 patients who underwent reduced-toxicity conditioning (RTC) allo-HCT with fludarabine and busulfan. The patient cohort was divided into 2: the readmission group (R-gp) or the no-readmission group (NR-gp). Overall, 38% (n = 35) required readmission with a median time to readmission of 14 days. In multivariate analysis, only documented infection during the index admission predicted 30-DR, P = .01. With a median follow-up of 18 months (range, 1 to 69) for surviving patients, the 2-year overall survival was 49% and 58% in the R-gp and NR-gp respectively, P = .48. The 1-year nonrelapse mortality in R-gp and NR-gp was 18% and 13% respectively, P = .43. The median post-transplantation hospital charges in the R-gp and NR-gp were $85,115 (range, $32,015 to $242,519) and $45,083 (range, $10,715 to $485,456), P = .0002. In conclusion, only documented infections during the index hospitalization influenced 30-DR after RTC allo-HCT. Although 30-DR did not adversely affect mortality or survival, it was associated with significantly increased 100-day post-transplantation hospital charges, thus supporting its role as a quality-of-care measure in allo-HCT patients.

Registered childminders and children with disabilities.

This article describes the role of the registered childminder in caring for children with disabilities. It explains the community childminding networks that help put parents in touch with appropriate childminders and then provide continuing support to the parents and the childminder. These networks help provide additional tailored training for childminders to enable them to meet the special needs of a particular child. The networks link in with other local authority and health services and may sometime help to fund placements.

Intravenous thrombolysis of large vessel occlusions is associated with higher hospital costs than small vessel strokes: a rationale for developing stroke severity-based financial models.

BACKGROUND: Owing to their severity, large vessel occlusion (LVO) strokes may be associated with higher costs that are not reflected in current coding systems. This study aimed to determine whether intravenous thrombolysis costs are related to the presence or absence of LVO. METHODS: Patients who had undergone intravenous thrombolysis over a 9-year period were divided into LVO and no LVO (nLVO) groups based on admission CT angiography. The primary outcome was hospital cost per admission. Secondary outcomes included admission duration, 90-day clinical outcome, and discharge destination. RESULTS: 119 patients (53%) had LVO and 104 (47%) had nLVO. Total mean±SD cost per LVO patient was $18,815±14,262 compared with $15,174±11,769 per nLVO patient (p=0.04). Hospital payments per admission were $17,338±13,947 and $15,594±16,437 for LVO and nLVO patients, respectively (p=0.4). A good outcome was seen in 33 LVO patients (27.7%) and in 69 nLVO patients (66.4%) (OR 0.2, 95% CI 0.1 to 0.3, p<0.0001). Hospital mortality occurred in 31 LVO patients (26.1%) and in 7 nLVO patients (6.7%) (OR 0.2, 95% CI 0.08 to 0.5, p<0.0001). 31 LVO patients (32.6%) were discharged to home versus 64 nLVO patients (61.5%) (OR 4.5, 95% CI 2.6 to 8, p<0.0001). Admission duration was 7.5±6.9 days in LVO patients versus 4.9±4.2 days in nLVO patients (p=0.0009). Multivariate regression analysis after controlling for comorbidities showed the presence of LVO to be an independent predictor of higher total hospital costs. CONCLUSIONS: The presence or absence of LVO is associated with significant differences in hospital costs, outcomes, admission duration, and home discharge. These differences can be important when developing systems of care models for acute ischemic stroke.

Hospital-based financial analysis of endovascular therapy and intravenous thrombolysis for large vessel acute ischemic strokes: the 'bottom line'.

BACKGROUND: Economic viability is important to any hospital striving to be a comprehensive stroke center. An inability to recover cost can strain sustained delivery of advanced stroke care. OBJECTIVE: To carry out a comparative financial analysis of intravenous (IV) recombinant tissue plasminogen activator and endovascular (EV) therapy in treating large vessel strokes from a hospital's perspective. METHODOLOGY: Actual hospital's charges, costs, and payments were analyzed for 265 patients who received treatment for large vessel strokes. The patients were divided into an EV (n=141) and an IV group (n=124). The net gain/loss was calculated as the difference between payments received and the total cost. RESULTS: The charges, costs, and payments were significantly higher for the EV than the IV group (p<0.0001 for all). Medicare A was the main payer. Length of stay was inversely related to net gain/loss (p<0.0001). Favorable outcome was associated with a net gain of $3853 (±$21,155) and poor outcome with a net deficit of $2906 (±$15,088) (p=0.003). The hospital showed a net gain for the EV group versus a net deficit for the IV group in patients who survived the admission (p=0.04), had a favorable outcome (p=0.1), or were discharged to home (p=0.03). There was no difference in the time in hospital based on in-hospital mortality for the EV group but patients who died in the IV group had a significantly shorter length of stay than those who survived (p=0.04). The favorable outcome of 42.3% in the EV group was significantly higher than the 29.4% in the IV group (p=0.03). CONCLUSIONS: Endovascular therapy was associated with better outcomes and higher cost-recovery than IV thrombolysis in patients with large vessel strokes.

Long-term spinal administration of morphine in cancer and non-cancer pain: a retrospective study.

Records of 313 patients who had been treated with spinal morphine via an implanted Port-A-Cath were reviewed. In 284 cases the Port-A-Cath was implanted for epidural delivery of morphine in patients with cancer-related pain. These patients were treated for a mean of 96 (range 1-1215) days. There was a wide variation in dose requirements, minimum daily dose ranging from 0.5 to 200 mg and maximum daily dose from 1 to 3072 mg. However, there was no clear trend to increasing dose as period of epidural morphine administration increased. The most frequent complications were pain on injection (12.0% incidence), occlusion of the portal system (10.9%), infection (8.1%) and leakage of administered morphine such that it did not all reach the epidural space (2.1%). In all but 1 case infections were limited to the area around the portal or along the catheter track. All infections resolved without sequelae following removal of the portal and/or administration of antibiotics. In 17 patients Port-A-Caths were implanted for the intrathecal delivery of morphine to control cancer-related pain. These patients also exhibited wide variations in morphine dose requirements. Port-A-Caths were also implanted for delivery of spinal morphine in 12 patients with chronic pain which was not related to cancer and which failed to respond to other therapies. These patients were treated for a mean of 155 (range 2-575) days. Port-A-Caths were removed from 7 of these patients, primarily due to infection (2 cases) and inadequate pain relief and pain on injection (2 cases).

Effect of a patient care partnership project on cost and quality of care at an academic teaching hospital.

BACKGROUND: In 1998, the Patient Care Partnership Project was conducted by general internal medicine physicians and hospital administration in an academic health care center. The project was designed to optimize cost, quality, and service results to inpatients. METHODS: The project focused on improved communication among physicians, a nurse discharge planner, and hospital administration regarding appropriate resource utilization. The outcomes were average cost per inpatient, length of hospital stay, 30-day readmission rates, mortality rates, and resident and patient satisfaction. Comparisons were made with three control groups. RESULTS: The postintervention generalist-staffed services showed significant reductions in average costs per patient and length of stay. These parameters increased in the specialist group from 1997 to 1998. Readmission rates remained stable, and mortality rates actually decreased. Patient and resident satisfaction remained unchanged. CONCLUSIONS: A collaborative effort between generalists and hospital administration led to a significant improvement in resource utilization compared with the three control groups, with no compromise in quality outcomes.