Medical Assistance in Dying (MAiD) as a Source of Liver Grafts: Honouring the Ultimate Gift.

OBJECTIVE: To report the clinical outcomes of liver transplants from donors after medical assistance in dying (MAiD) versus donors after cardiac death (DCD) and deceased brain death (DBD). SUMMARY BACKGROUND DATA: In North America, the number of patients needing liver transplants exceeds the number of available donors. In 2016, MAiD was legalized in Canada. METHODS: All patients undergoing deceased donor liver transplantation at Toronto General Hospital between 2016 and 2021 were included in the study. Recipient perioperative and postoperative variables and donor physiological variables were compared among 3 groups. RESULTS: Eight hundred seven patients underwent deceased donor liver transplantation during the study period, including DBD (n=719; 89%), DCD (n=77; 9.5%), and MAiD (n=11; 1.4%). The overall incidence of biliary complications was 6.9% (n=56), the most common being strictures (n=55;6.8%), highest among the MAiD recipients [5.8% (DBD) vs. 14.2% (DCD) vs. 18.2% (MAiD); P =0.008]. There was no significant difference in 1 year (98.4% vs. 96.4% vs. 100%) and 3-year (89.3% vs. 88.7% vs. 100%) ( P =0.56) patient survival among the 3 groups. The 1- and 3- year graft survival rates were comparable (96.2% vs. 95.2% vs. 100% and 92.5% vs. 91% vs. 100%; P =0.37). CONCLUSION: With expected physiological hemodynamic challenges among MAiD and DCD compared with DBD donors, a higher rate of biliary complications was observed in MAiD donors, with no significant difference noted in short-and long-term graft outcomes among the 3 groups. While ethical challenges persist, good initial results suggest that MAiD donors can be safely used in liver transplantation, with results comparable with other established forms of donation.

ED-based COVID-19 vaccination campaign finds higher vaccination rates for individuals from racial and ethnic minority groups compared with clinic setting.

BACKGROUND: Emergency department visits associated with Coronavirus Disease 2019 (COVID-19) continue to indicate racial and ethnic inequities. We describe the sociodemographic characteristics of individuals receiving COVID-19 vaccination in the emergency department and compare with an outpatient clinic population and emergency department (ED) patients who were eligible but not vaccinated. METHODS: We conducted a retrospective analysis of electronic health record data at an urban academic ED from May to July 2021. The primary aim was to characterize the ED-vaccinated population, compared with ED patients who were eligible but unvaccinated and the physically adjacent outpatient vaccination clinic population. RESULTS: A total of 627 COVID-19 vaccinations were administered in the ED. Overall, 49% of ED patients during that time had already received at least one vaccine dose prior to ED arrival. Hispanic, non-Hispanic Black patients, and patients on non-commercial insurance had higher odds of being vaccinated in the ED as compared with outpatient clinic setting. Among eligible ED patients, men and patients who were uninsured/self-pay were more likely to accept ED vaccination. CONCLUSIONS: This ED COVID-19 vaccination campaign demonstrated a higher likelihood to vaccinate individuals from racial/ethnic minority groups, those with high social vulnerability, and non-commercial insurance, when compared with a co-located outpatient vaccination clinic.

Differences in cardiac testing resource utilization using two different risk stratification schemes.

OBJECTIVE: Assess whether changing an emergency department (ED) chest pain pathway from utilizing the Thrombolysis in Myocardial Infarction (TIMI) score for risk stratification to an approach utilizing the History, EKG, Age, Risk, Troponin (HEART) score was associated with reductions in healthcare resource utilization. METHODS: A retrospective, quasi-experimental study using difference-in-differences and interrupted time series specifications evaluated all ED patients with a chest pain encounter from 8/2015 to 7/2019 at a large academic medical center. We included patients age ≥ 18 with negative troponin testing discharged from the ED. Our standardized care pathway utilized TIMI for risk stratification until 09/2017 and HEART thereafter. We evaluated patients undergoing hospital-based cardiac diagnostic testing (CDT), length of stay (LOS), and 30-day Major Adverse Cardiovascular Events (MACE) at the intervention site before and after the pathway change and compared these outcomes to a similar control site within the health system for the difference-in-differences specification. RESULTS: During the study period, 6.3% (450 of 7117) of patients in the TIMI cohort and 7.2% (546 of 7623) in the HEART cohort among 400,965 total ED visits underwent CDT. In a multivariable analysis, transition to the HEART pathway was associated with greater odds of receiving CDT (odds ratio 2.88 [95% CI 1.21 to 6.86]), a reduction in LOS of 34 min (95% CI 2.2 to 67.6), and no significant difference in 30-day MACE. CONCLUSION: The transition from TIMI to HEART was associated with mixed consequences for healthcare resource utilization, including increased CDT but reduced length of stay.

Pre-clinical and clinical evaluation of the HYPERSCINT plastic scintillation dosimetry research platform for in vivo dosimetry during radiotherapy.

PURPOSE: The purpose of this work is to evaluate the Hyperscint-RP100 scintillation dosimetry research platform (Hyperscint-RP100, Medscint Inc., Quebec, QC, Canada) designed for clinical quality assurance (QA) for use in in vivo dosimetry measurements. METHODS: The pre-clinical evaluation of the scintillator was performed using a Varian TrueBeam linear accelerator. Dependency on field size, depth, dose, dose rate, and temperature were evaluated in a water tank and compared to calibration data from commissioning and annual QA. Angularity was evaluated with a 3D printed phantom. The clinical evaluation was first performed in two cadaver dogs, and then in three companion animal dogs receiving radiation therapy for nasal tumors. A treatment planning CT scan was performed for cadavers and clinical patients. Prior to treatment, the probe was inserted into the radiation field. Radiation was then delivered and measured with the scintillator. For cadavers, the treatment was repeated after making an intentional shift in patient position to simulate a treatment error. RESULTS: In the preclinical measurements the dose differed from annual measurements as follows: field size -0.77 to 0.43%, depth dose -0.36 to 1.14%, dose -0.54 to 2.93%, dose rate 0.3 to 3.6%, and angularity -1.18 to 0.01%. Temperature dependency required a correction factor of 0.11%/°C. In the two cadavers, the dose differed by -1.17 to 0.91%. The device correctly detected the treatment error when the heads were intentionally laterally shifted. In three canine clinical patients treated in multiple fractions, the detected dose ranged from 98.33 to 103.15%. CONCLUSION: Results of this new device are promising although more work is necessary to fully validate it for clinical dosimetry.

Diurnal variation in autonomic regulation among patients with genotyped Rett syndrome.

BACKGROUND: Rett syndrome is a severe neurological disorder with a range of disabling autonomic and respiratory symptoms and resulting predominantly from variants in the methyl-CpG binding protein 2 gene on the long arm of the X-chromosome. As basic research begins to suggest potential treatments, sensitive measures of the dynamic phenotype are needed to evaluate the results of these research efforts. Here we test the hypothesis that the physiological fingerprint of Rett syndrome in a naturalistic environment differs from that of controls, and differs among genotypes within Rett syndrome. METHODS: A comprehensive array of heart rate variability, cardiorespiratory coupling and cardiac repolarisation measures were evaluated from an existing database of overnight and daytime inhome ambulatory recordings in 47 cases and matched controls. RESULTS: Differences between girls with Rett syndrome and matched controls were apparent in a range of autonomic measures, and suggest a shift towards sympathetic activation and/or parasympathetic inactivation. Daily temporal trends analysed in the context of circadian rhythms reveal alterations in amplitude and phase of diurnal patterns of autonomic balance. Further analysis by genotype class confirms a graded presentation of the Rett syndrome phenotype such that patients with early truncating mutations were most different from controls, while late truncating and missense mutations were least different from controls. CONCLUSIONS: Comprehensive autonomic measures from extensive inhome physiological measurements can detect subtle variations in the phenotype of girls with Rett syndrome, suggesting these techniques are suitable for guiding novel therapies.

The importance of pre-training gap analyses and the identification of competencies and skill requirements of medical personnel for mass casualty incidents and disaster training.

BACKGROUND: Effective preparedness to respond to mass casualty incidents and disasters requires a well-planned and integrated effort by all involved professionals, particularly those who are working in healthcare, who are equipped with unique knowledge and skills for emergencies. This study aims to investigate and evaluate the level of knowledge and skills related to mass casualty and disaster management in a cohort of healthcare professionals. METHODS: A cross-sectional brief study was conducted using a validated and anonymous questionnaire, with a sample of 134 employees at a clinical hospital in Lublin, Poland. RESULTS: The findings of this study may indicate a need for standardization of training for hospitals employees. It also suggests a knowledge gap between different professional groups, which calls for adjusting such general training, to at least, the weakest group, while special tasks and mission can be given to other groups within the training occasion. CONCLUSION: Pre-Training gap analyses and identification of participants' competencies and skills should be conducted prior to training in mass casualty incidents and disasters. Such analyses provides an opportunity to develop training curriculum at various skill and knowledge levels from basic to advance. All training in mass casualty incidents and disasters should be subject to ongoing, not just periodic, evaluation, in order to assess continued competency.

Impact of Reduced Preincision Antibiotic Infusion Time on Surgical Site Infection Rates: A Retrospective Cohort Study.

OBJECTIVE: Our objective was to determine the impact of total preincision infusion time on surgical site infections (SSIs) and establish an optimal time threshold for subsequent prospective study. BACKGROUND: SSIs remain a major cause of morbidity. Although regulated, the total time of infusion of preincision antibiotics varies widely. Impact of infusion time on SSI risk is poorly understood. METHODS: All consecutive patients (n = 46,791) undergoing inpatient surgical intervention were retrospectively enrolled (2014-2015) and monitored for 1 year. Primary outcomes: the presence of SSI infection as predicted by reduced preoperative antibiotic infusion time. SECONDARY OUTCOMES: preintervention compliance, the impact of a quality improvement algorithm to optimize infusion time compliance. Multivariate logistic regression of the retrospective cohort demonstrated predictors of infection. Receiver-operating characteristic analysis demonstrated the timing threshold predictive of infection. Cost impact of avoidable infections was analyzed. RESULTS: Only 36.1% of patients received preincision infusion of vancomycin in compliance with national and institutional standards (60-120 min). Cephalosporin infusion times were 53 times more likely to be compliant [odds ratio (OR) 53.33, P < 0.001]. Vancomycin infusion times that were not compliant with national standards (less than standard 60-120 min) did not predict infection. However, significantly noncompliant, reduced preincision infusion time, significantly predicted SSI (<24.6 min infusion, AUC = 0.762). Vancomycin infusion, initiated too close to surgical incision, predicted increased SSI (OR = 4.281, P < 0.001). Implementation of an algorithm to improve infusion time, but not powered to demonstrate infection /reduction, improved vancomycin infusion start time (257% improvement, P < 0.001) and eliminated high-risk infusions (sub-24.6 min). CONCLUSIONS: Initially, vancomycin infusion rarely met national guidelines; however, minimal compliance breach was not associated with SSI implications. The retrospective data here suggest a critical infusion time for infection reduction (24.6 min before incision). Prospective implementation of an algorithm led to 100% compliance. These data suggest that vancomycin administration timing should be studied prospectively.

A Controllable, Centrifugal-Based Hydrodynamic Microfluidic Chip for Cell-Pairing and Studying Long-Term Communications between Single Cells.

Investigation of cell-cell interactions between individual cells in a well-defined microenvironment is critical for the understanding of specific intercellular communications and interactions. However, most current studies in multicellular systems are often overwhelmed by additional complicated interactions. Cell-pairing based on a microfluidic chip provides a potential strategy to simplify the studies. Here, we report a robust and straightforward method, relying on a combination of hydrodynamic single-cell capture and centrifugation-assisted relocation of individual cells, which can be applied, in general, to various cell types for cell-pairing and studying cell interactions at the single-cell level. This microfluidic chip is simple to operate and easily controlled, which requires only two operational steps-capturing individual cells with hydrodynamic traps and subsequently relocating the capture cells by centrifugation. With this microfluidic chip, we demonstrated homotypic cell-pairing, heterotypic cell-pairing, and long-term cell coculture, which exhibited better or comparable performance compared with previous cell-pairing methods. Its single-cell trapping and cell-pairing efficiencies are ∼74% and ∼20%, respectively. As a proof of concept, we paired individual dHL-60 cells and HeLa cells (HeLa-IL8, HeLa-IL10, and wild-type HeLa cells) in multiple cell chambers. The HeLa-IL8 and HeLa-IL10, both engineered with a light-induced gene expression system, can secret interleukin-8 and interleukin-10, respectively, under blue light illumination. We found that these three HeLa cell lines have very different influences on the migration of dHL-60 cells. This platform demonstrates its potential applications in studies of intercellular communication (paracrine), and it can be extended to trap three or more individual cells for more complex biological systems.

First report of using low-titer cold-stored type O whole blood in massive postpartum hemorrhage.

BACKGROUND: In cases of massive hemorrhage in the US military, improved outcomes have been reported with the use of warm, fresh whole blood transfusions. Cold-stored low-titer type O whole blood (LTOWB) has become the preferred product for resuscitation of severe bleeding in deployed surgical units. Reports of LTOWB use in civilian trauma are becoming more frequent. CASE REPORT: We report our experience with emergency transfusion of LTOWB for a woman with massive postpartum hemorrhage. The patient had two previous cesarean section deliveries at term without complications. With her third elective cesarean section at term, blood loss during surgery was not excessive, but 3 to 4 hours later she had an estimated blood loss of 3600 mL. Despite measures to control the hemorrhage, she rapidly became hypotensive and tachycardic, and our massive transfusion protocol (MTP) was activated. The transfusion service had very recently incorporated LTOWB into Trauma Pack 1 of the MTP. She received two LTOWB units, after which her hemorrhaging ceased, blood pressure normalized, and she became alert. One hour later she received one unit of fresh frozen plasma and one unit of red blood cells (RBCs). The following morning she received one unit of crossmatched RBCs, for a hematocrit of 20.7%. She was discharged home on Day 4, and she remains healthy. CONCLUSIONS: This is the first report of which we are aware of massive postpartum hemorrhage treated using LTOWB. Our positive experience leads us to speculate that this approach could have a role in massive obstetric hemorrhage.

The Association between Chronic Obstructive Pulmonary Disease and Coronary Artery Disease in Patients Undergoing Coronary Angiography.

Chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD) are leading causes of morbidity and mortality. There are conflicting results regarding the association between COPD and CAD. We sought to measure the association between COPD and angiographically diagnosed CAD in a population-based cohort. We performed a retrospective analysis using data from the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH), a prospectively collected registry capturing all patients undergoing coronary angiography in Alberta, Canada, since 1995. We included adult patients who had undergone coronary angiogram between April 1, 2007 and March 31, 2014. CAD was present if at least one coronary artery had a significant stenosis ≥50%. COPD was present if the patient had a documented COPD history and was prescribed bronchodilators or inhaled steroids. We evaluated the association between COPD and CAD using univariable and multivariable logistic regression. There were 26,137 patients included with a mean age of 63.3 ± 12.2 years, and 19,542 (74.8%) were male. The crude odds ratio (OR) of having CAD was 0.83 (95% CI 0.74-0.92) for patients with COPD compared to those without COPD. The adjusted OR was 0.75 (95% CI 0.67-0.84) after controlling for age, sex, smoking history, body mass index, hypertension, diabetes, hyperlipidemia, peripheral artery disease and cardiac family history. In patients undergoing coronary angiography, COPD was negatively associated with CAD with and without the adjustment for classic risk factors. COPD patients should be properly examined for heart disease to reduce premature mortality.

Clinical operations of academic versus non-academic emergency departments: a descriptive comparison of two large emergency department operations surveys.

BACKGROUND: Academic and non-academic emergency departments (EDs) are regularly compared in clinical operations benchmarking despite suggestion that the two groups may differ in their clinical operations characteristics. and outcomes. We sought to describe and compare clinical operations characteristics of academic versus non-academic EDs. METHODS: We performed a descriptive, comparative analysis of academic and non-academic adult and general EDs with 40,000+ annual encounters, using the Academy of Academic Administrators of Emergency Medicine (AAAEM)/Association of Academic Chairs of Emergency Medicine (AACEM) and Emergency Department Benchmarking Alliance (EDBA) survey results. We defined academic EDs as primary teaching sites for emergency medicine (EM) residencies and non-academic EDs as sites with minimal resident involvement. We constructed the academic and non-academic cohorts from the AAAEM/AACEM and EDBA surveys, respectively, and analyzed metrics common to both surveys. RESULTS: Eighty and 454 EDs met inclusion criteria for academic and non-academic EDs, respectively. Academic EDs had more median annual patient encounters (73,001 vs 54,393), lower median proportion of pediatric patients (6.3% vs 14.5%), higher median proportion of EMS patients (27% vs 19%), and were more commonly designated as Level I or II Trauma Centers (94% vs 24%). Median patient arrival-to-provider times did not differ (26 vs 25 min). Median length-of-stay was longer (277 vs 190 min) for academic EDs, and left-before-treatment-complete was higher (5.7% vs 2.9%). MRI utilization was higher for academic EDs (2.2% patients with at least one MRI vs 1.0 MRIs performed per 100 patients). Patients-per-hour of provider coverage was lower for academic EDs with and without consideration for advanced practice providers and residents. CONCLUSIONS: Demographic and operational performance measures differ between academic and non-academic EDs, suggesting that the two groups may be inappropriate operational performance comparators. Causes for the differences remain unclear but the differences appear not to be attributed solely to the academic mission.

Antibiotic Prescribing Patterns for Sinusitis Within a Direct-to-Consumer Virtual Urgent Care.

Background:Direct-to-consumer virtual visits are increasingly popular across both for-profit and nonprofit healthcare systems.Introduction:Virtual visits offer a convenient affordable way for patients to obtain medical care for simple conditions such as sinusitis and uncomplicated urinary tract infections. However, virtual visits have been associated with increased antibiotic utilization when compared with traditional in-person care.Methods:In this retrospective cohort study, antibiotic utilization for acute sinusitis was compared between patients treated through a direct-to-consumer virtual urgent care versus a matched cohort treated through traditional urgent care.Results:Fifty-seven patients were treated for acute sinusitis within the virtual care cohort, whereas 100 patients were treated in the traditional care arm. Antibiotic utilization for acute sinusitis was lower when care was delivered virtually using live-interactive video (67%) than when using traditional urgent care (92%) (p < 0.001). When care was delivered virtually, age, gender, and care delivery modality (telephone vs. video) were not associated with antibiotic utilization for acute sinusitis.Discussion:Concerns have been raised that care delivered virtually does not meet expected quality standards when compared with traditional care. Antibiotic utilization has been used as an example of this quality gap. In this study, we demonstrate that antibiotic utilization was lower in a virtual care cohort than when care was delivered by emergency medicine physicians based in an academic setting. This suggests that awareness and sensitivity to prescribing guidelines may be more important than care delivery modality as it relates to antibiotic utilization.Conclusions:It is possible to deliver care virtually for acute sinusitis without increasing antibiotic utilization.

Mortality Associated With Emergency Department Boarding Exposure: Are There Differences Between Patients Admitted to ICU and Non-ICU Settings?

BACKGROUND: Emergency Department (ED) boarding threatens patient safety. It is unclear whether boarding differentially affects patients admitted to intensive care units (ICUs) versus non-ICU settings. RESEARCH DESIGN AND SUBJECTS: We performed a 2-hospital, 18-month, cross-sectional, observational, descriptive study of adult patients admitted from the ED. We used Kaplan-Meier estimation and Cox Proportional Hazards regression to describe differences in boarding time among patients who died during hospitalization versus those who survived, controlling for covariates that could affect mortality risk or boarding exposure, and separately evaluating patients admitted to ICUs versus non-ICU settings. MEASURES: We extracted age, race, sex, time variables, admission unit, hospital disposition, and Elixhauser comorbidity measures and calculated boarding time for each admitted patient. RESULTS: Among 39,781 admissions from the EDs (21.3% to ICUs), non-ICU patients who died in-hospital had a 1.2-fold risk (95% confidence interval, 1.03-1.36; P=0.016) of having experienced longer boarding times than survivors, accounting for covariates. We did not observe a difference among patients admitted to ICUs. CONCLUSIONS: Among non-ICU patients, those who died during hospitalization were more likely to have had incrementally longer boarding exposure than those who survived. This difference was not observed for ICU patients. Boarding risk mitigation strategies focused on ICU patients may have accounted for this difference, but we caution against interpreting that boarding can be safe. Segmentation by patients admitted to ICU versus non-ICU settings in boarding research may be valuable in ensuring that the safety of both groups is considered in hospital flow and boarding care improvements.

Short- and long-term mortality after pulmonary embolism in patients with and without cancer.

Pulmonary embolism (PE) is a major cause of mortality and morbidity. It is known that the risk of death varies by provoking factors; however, it is unknown if the risk of death persists beyond the initial diagnosis among patients with cancer-associated and non-cancer provoked patients. In this study, we aimed to investigate the effect of cancer on overall, short- and long-term mortality in a cohort of consecutive incident PE patients. Using administrative databases, we identified all incident cases of PE between 2004 and 2012 in Alberta, Canada. Cases were stratified by provoking factors (i.e. unprovoked, provoked, and cancer-associated). A multivariate Cox survival model was used to estimate the hazard ratios of short- and long-term death. We identified 8641 patients with PE, among which 42.2% were unprovoked, 37.9% were provoked and 19.9% were cancer-associated. The 1-year and 5-year survival probabilities were 60% (95% CI: 57-64%) and 39% (95% CI: 36-43%) in patients with cancer-associated PE, 93% (95% CI: 92-94%) and 80% (95% CI: 78-81%) in provoked PE, and 94% (95% CI: 93-95%) and 85% (95% CI: 83-87%) in unprovoked PE, respectively. Compared to patients with unprovoked events, both short-term and long-term survival in patients with cancer-associated PE have a higher observed risk of all-cause mortality in all age groups ( p<0.001). In contrast, patients with provoked events had a similar short- and long-term all-cause mortality. While PE has a significant mortality in all risk groups, patients with cancer have a higher risk of short-term mortality compared to patients with unprovoked PE.

Contrasting Views on the Role of Mesenchymal Stromal/Stem Cells in Tumour Growth: A Systematic Review of Experimental Design.

The effect of mesenchymal stromal/stem cells (MSCs) on tumour growth remains controversial. Experimental evidence supports both an inhibitory and a stimulatory effect. We have assessed factors responsible for the contrasting effects of MSCs on tumour growth by doing a meta-analysis of existing literature between 2000 and May 2017. We assessed 183 original research articles comprising 338 experiments. We considered (a) in vivo and in vitro experiments, (b) whether in vivo studies were syngeneic or xenogeneic, and (c) if animals were immune competent or deficient. Furthermore, the sources and types of cancer cells and MSCs were considered together with modes of cancer induction and MSC administration. 56% of all 338 experiments reported that MSCs promote tumour growth. 78% and 79% of all experiments sourced human MSCs and cancer cells, respectively. MSCs were used in their naïve and engineered form in 86% and 14% of experiments, respectively, the latter to produce factors that could alter either their activity or that of the tumour. 53% of all experiments were conducted in vitro with 60% exposing cancer cells to MSCs via coculture. Of all in vivo experiments, 79% were xenogeneic and 63% were conducted in immune-competent animals. Tumour growth was inhibited in 80% of experiments that used umbilical cord-derived MSCs, whereas tumour growth was promoted in 64% and 57% of experiments that used bone marrow- and adipose tissue-derived MSCs, respectively. This contrasting effect of MSCs on tumour growth observed under different experimental conditions may reflect differences in experimental design. This analysis calls for careful consideration of experimental design given the large number of MSC clinical trials currently underway.

Cancer Stem Cells in Head and Neck Carcinomas: Identification and Possible Therapeutic Implications.

The recurrence and/or lack of response of certain tumors to radio- and chemotherapy has been attributed to a small subpopulation of cells termed cancer stem cells (CSCs). CSCs have been identified in many tumors (including solid and hematological tumors). CSCs are characterized by their capacity for self-renewal, their ability to introduce heterogeneity within a tumor mass and its metastases, genomic instability, and their insensitivity to both radiation and chemotherapy. The latter highlights the clinical importance of studying this subpopulation since their resistance to traditional treatments may lead to metastatic disease and/or tumor relapse. Head and neck squamous cell carcinomas (HNSCCs) are the sixth most common malignancy worldwide with the highest incidence occurring in East Asia and eastern and southern Africa. Several cellular subpopulations believed to have CSC properties have been isolated from HNSCCs, but at present, identification and characterization of CSCs remains an experimental challenge with no established or standardized protocols in place to confirm their identity. In this review we discuss current approaches to the study of CSCs with a focus on HNSCCs, particularly in the context of what this might mean from a therapeutic perspective.

Deoxyribonucleic Acid Damage and Repair: Capitalizing on Our Understanding of the Mechanisms of Maintaining Genomic Integrity for Therapeutic Purposes.

Deoxyribonucleic acid (DNA) is the self-replicating hereditary material that provides a blueprint which, in collaboration with environmental influences, produces a structural and functional phenotype. As DNA coordinates and directs differentiation, growth, survival, and reproduction, it is responsible for life and the continuation of our species. Genome integrity requires the maintenance of DNA stability for the correct preservation of genetic information. This is facilitated by accurate DNA replication and precise DNA repair. DNA damage may arise from a wide range of both endogenous and exogenous sources but may be repaired through highly specific mechanisms. The most common mechanisms include mismatch, base excision, nucleotide excision, and double-strand DNA (dsDNA) break repair. Concurrent with regulation of the cell cycle, these mechanisms are precisely executed to ensure full restoration of damaged DNA. Failure or inaccuracy in DNA repair contributes to genome instability and loss of genetic information which may lead to mutations resulting in disease or loss of life. A detailed understanding of the mechanisms of DNA damage and its repair provides insight into disease pathogeneses and may facilitate diagnosis and the development of targeted therapies.

Door-to-Imaging Time for Acute Stroke Patients Is Adversely Affected by Emergency Department Crowding.

BACKGROUND AND PURPOSE: National guidelines call for door-to-imaging time (DIT) within 25 minutes for suspected acute stroke patients. Studies examining factors that affect DIT have focused primarily on stroke-specific care processes and patient-specific factors. We hypothesized that emergency department (ED) crowding is associated with longer DIT. METHODS: We conducted a retrospective investigation of 1 year of consecutive patients in our prospective Code Stroke registry, which included all ED stroke team activations. The registry and electronic health records were abstracted for 27 potential predictors of DIT, including patient, stroke care process, and ED operational factors. We fit a multivariate logistic regression model and calculated odds ratios and 95% confidence intervals. Second, we constructed a random forest recursive partitioning model to cross-validate our findings and explore the proportional importance of each category of predictor. Our primary outcome was the binary variable of DIT within the 25-minute goal. RESULTS: A total of 463 patients met inclusion criteria. In the regression model, ED occupancy rate emerged as a predictor of DIT, with odds ratio of 0.83 (95% confidence interval, 0.75-0.91) of DIT within 25 minutes per 10% absolute increase in ED occupancy rate. The secondary analysis estimated that ED operational factors accounted for nearly 14% of the algorithm's prediction of DIT. CONCLUSIONS: ED crowding is associated with reduced odds of meeting DIT goals for acute stroke. In addition to improving stroke-specific processes of care, efforts to reduce ED overcrowding should be considered central to optimizing the timeliness of acute stroke care.

Sex disparities in hospitalization and mortality rates for venous thromboembolism.

Venous thromboembolism (VTE) is a major health problem for both men and women. Whether sex disparities exist for outcomes after acute VTE is unknown. We sought to measure sex-specific rates of hospitalization for and mortality from acute VTE. We used a population-based administrative dataset from Alberta, Canada, covering the years 2002 to 2012. We used Poisson regression to measure the incidence rate ratio for hospitalization and Cox regression to test for sex disparities in short-term all-cause mortality after adjusting for potential confounders. Of those diagnosed with VTE, 55.9% were women. The proportion of hospitalized women for VTE was 24.4 versus 27.8% in men (p < 0.001). The risk adjusted incidence rate ratio for VTE hospitalization increased with age for both sex. While women younger than 80 years old were less likely to be hospitalized than men, sex disparities for the risk of hospitalization were not significant after age 80 (p = 0.93). The adjusted 90-day all-cause mortality rate for women was 4.0% compared to 4.9% in men (adjusted HR = 1.0, p = 0.49). Women with acute VTE were less likely than men to be hospitalized in most age groups, but sex disparities in short-term all-cause mortality were not found.