Paramedic Interventions and Adverse Patient Events during Prolonged Interfacility Ground Transport in a "Drip and Ship" Pharmacoinvasive Model of STEMI Care.

OBJECTIVE: Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for patients with ST-segment elevation myocardial infarction (STEMI). However, when primary PCI is not available in a timely fashion, fibrinolysis and early transfer for routine PCI is recommended. Prince Edward Island (PEI) is the only province in Canada without a PCI facility, and distances to the nearest PCI-capable facilities are between 290 and 374 kilometers. This results in prolonged out-of-hospital time for critically ill patients. We sought to characterize and quantify paramedic interventions and adverse patient events during prolonged ground transport to PCI facilities post-fibrinolysis. METHODS: We performed a retrospective chart review of patients presenting to any of four emergency departments (ED) on PEI during the calendar years 2016 and 2017. We identified patients through administrative discharge data and cross referenced with emergent out-of-province ambulance transfers. All included patients were managed as STEMIs in the EDs and subsequently transferred (primary PCI, pharmacoinvasive) directly from the EDs to PCI facilities. We excluded patients having STEMIs on inpatient wards and those transported by other means. We reviewed electronic and paper ED charts plus paper EMS records. We performed summary statistics. RESULTS: We identified 149 patients meeting inclusion criteria. Most patients were males (77.9%), mean age 62.1 (SD 13.8) years. The mean transport interval was 202 (SD 29.0) minutes. Thirty-two adverse events occurred during 24 transports (16.1%). There was one death, and four patients required diversion to non-PCI facilities. Hypotension was the most common adverse event (n = 13, 8.7%), and fluid bolus (n = 11, 7.4%) was the most common intervention. Three (2.0%) patients required electrical therapy. Nitrates (n = 65, 43.6%) and opioid analgesics (n = 51, 34.2%) were the most common drugs administered during transport. CONCLUSION: In a setting where primary PCI is not feasible due to distance, a pharmacoinvasive model of STEMI care is associated with a 16.1% proportion of adverse events. Crew configuration including ALS clinicians is the key in managing these events.

Evaluating the Impact of a Novel Mobile Care Team on the Prevalence of Ambulatory Care Sensitive Conditions Presenting to Emergency Medical Services in Nova Scotia.

INTRODUCTION: Hospitalization due to ambulatory care sensitive conditions (ACSC) is a proxy measure for access to primary care. Emergency Medical Services (EMS) are increasingly called when primary care cannot be accessed. A novel paramedic-nurse EMS Mobile Care Team (MCT) was implemented in an under-serviced community. The MCT responds in a non-transport unit to referrals from EMS, emergency and primary care, and to low-acuity 911 calls in a defined geographic region. Our objective was to compare the prevalence of ACSC in ground ambulance (GA) responses before and after the introduction of the MCT. METHODS: A cross-sectional analysis of GA and MCT patients with ACSC (determined by chief complaint, clinical impression, treatment protocol, and medical history) from one year pre-MCT implementation to one year post-MCT implementation was conducted for the period of October 1, 2012, to September 30, 2014. Demographics were described. ACSC prevalence was compared using the chi-squared test. RESULTS: There were 975 calls pre-MCT and 1208 GA/95 MCT calls post-MCT. ACSC in GA patients pre- and post-MCT was similar: n=122, 12.5% vs. n=185, 15.3%; p=0.06. ACSC in patients seen by EMS (GA plus MCT) increased in the post-MCT period: 122 (12.5%) vs. 204 (15.7%) p=0.04. Pre-MCT implementation vs post-implementation, GA ACSC calls differed significantly by sex with higher female utilization (n=50 vs. n=105; p=0.007), but not age (65.38, ± 15.12 vs. 62.51 ± 20.48; p=0.16). Post-MCT, the prevalence of specific ACSC increased for GA: hypertension (p<0.001) and congestive heart failure (p=0.04). MCT patients with ACSC were less likely to have a primary care provider compared to GA (90.2% and 87.6% vs. 63.2%; p=0.003, p=0.004). CONCLUSION: The prevalence of ACSC did not decrease for GA with the introduction of the MCT, but ACSC in the overall patient population served by EMS increased. It is possible more patients with ACSC call, or are referred to EMS, for the new MCT service. Given that MCT patients were less likely to have a primary care provider, this may represent an increase in access to care or a shift away from other emergency/episodic care. These associations must be further studied to inform the ideal utility of adding such services to EMS and healthcare systems.

Paramedic Clinical Consults with a Paramedic or Nurse in an EMS Communications Center Compared to Traditional Online Physician Consults.

OBJECTIVES: In many emergency medical services (EMS) systems, a direct medical oversight physician is available to paramedics for mandatory and/or elective consultations. At the time of this study, a clinical support desk (CSD) was being implemented within the medical communications center of a provincial EMS system in addition to the physician resource. The CSD was initially staffed with a registered nurse or an advanced care paramedic. The objective of the current study was to compare CSD "peer to peer" consults versus physician consults with regards to consultation patterns, transport dispositions, and patient safety measures. METHODS: This retrospective cohort study analyzed 2 months before (September 1 to October 31, 2012) and 2 months after (September 1 to October 31, 2013) implementation of the CSD. In the before period, all clinical consults were fielded by the direct medical oversight physician. In the after period, consults were fielded by the physician, CSD or both. EMS databases were queried, and manual chart review and abstraction of audio recordings were done. Relapses back to EMS within 48 hours of non-transport were measured. RESULTS: 1621 consults were included, with 764 consults in the before period and 857 after (p = 0.02). The number of physician consults decreased from 764 before to 464 after (39.2%, p < 0.001), with the CSD taking 325 (37.9%) consults. The CSD was consulted more for police custody and trip destination. The physician was consulted more for cease resuscitation and clinical consults prior to medication administration. Overall non-transport rates were 595/764 before (77.9%), and 646/857 after (75.4%) (p = 0.2). Non-transports were 233/325 (71.7%) via the CSD, 364/464 (78.4%) via the physician, and 49/68 (72.1%) when both were involved (p = 0.07). Rate of relapse to EMS was similar before (25/524, 4.8%) and after (26/568, 4.6%) (p = 0.76), and between CSD (12/216, 5.5%) and physician consults (13/325, 4.0%) in the after period (p = 0.41). CONCLUSION: The introduction of a novel "peer-to-peer" consult program was associated with an increased total number of consults made and reduced call volume for direct medical oversight physicians. There was no change in the patient safety measure studied.

Potential Candidates for Emergency Department Initiated Extracorporeal Cardiopulmonary Resuscitation (ECPR) in a Canadian Institution.

Introduction Out-of-hospital cardiac arrest (OHCA) patients experience poor survival. The use of extracorporeal membrane oxygenation (ECMO), a form of heart-lung bypass, in the setting of cardiac arrest, termed extracorporeal cardiopulmonary resuscitation (ECPR), has promise in improving survival with good neurologic outcomes. The study objective was to determine the number of potential annual ECPR candidates among the OHCA population in a health region within the Atlantic Canadian province of Nova Scotia. Methods A retrospective chart review was conducted over a five-year period: January 1st, 2012 to December 31st, 2016. Consecutive non-traumatic OHCA and emergency department (ED) cardiac arrests occurring in a pre-determined catchment area (20-minute transport to ECMO center) defined by a geographic bounding box were identified. Criteria for ECPR were developed to identify candidates for activation of a "Code ECPR": (1) age 16-70, (2) witnessed arrest, (3) no flow duration (time to CPR, including bystander) <10 minutes, (4) resuscitation >10 minutes without return of spontaneous circulation (ROSC), (5) emergency medical service (EMS) transport to hospital <20 minutes, (6) no patient factors precluding ongoing resuscitation (do not resuscitate status (DNR), palliative care involvement, or metastatic cancer), and (7) initial rhythm not asystole. Candidates were stratified by initial rhythm. Candidates were considered ultimately ED ECPR eligible if they failed conventional treatment, defined by death or resuscitation >30 minutes. Clinical data related to candidacy was extracted by an electronic query from prehospital and ED electronic records and manual chart review by three researchers. Results Our search yielded 561 cases of EMS-treated OHCA or in-ED arrests. Of those 204/561 (36%; 95% CI 33-40%) met the criteria for activation of a "Code ECPR". Ultimately 79/204 (34%; 95% CI 28-41%) of those who met activation criteria were considered ED ECPR eligible; which is 14% (95% CI 11-17%) of the total number of arrests-of the total number of arrests, the initial rhythms were pulseless electrical activity (PEA) 33/79 (42%; 95% CI 32-53%) and shockable 46/79 (58%; 95% CI 47-69%). Conclusion Of all cardiac arrests in the area surrounding our ECMO center, approximately 41 per year met the criteria for a Code ECPR activation, with 16 per year ultimately being eligible for ED ECPR. This annual estimate varies based on the inclusion of initial rhythm. This provides insight into both prehospital and hospital implications of an ED ECPR program and will help guide the establishment of a program within our Nova Scotian health region. This study also provides a framework for similar investigation at other institutions contemplating ED ECPR program implementation.

Spatiotemporal Coupling of DNA Supercoiling and Genomic Sequence Organization-A Timing Chain for the Bacterial Growth Cycle?

In this article we describe the bacterial growth cycle as a closed, self-reproducing, or autopoietic circuit, reestablishing the physiological state of stationary cells initially inoculated in the growth medium. In batch culture, this process of self-reproduction is associated with the gradual decline in available metabolic energy and corresponding change in the physiological state of the population as a function of "travelled distance" along the autopoietic path. We argue that this directional alteration of cell physiology is both reflected in and supported by sequential gene expression along the chromosomal OriC-Ter axis. We propose that during the E. coli growth cycle, the spatiotemporal order of gene expression is established by coupling the temporal gradient of supercoiling energy to the spatial gradient of DNA thermodynamic stability along the chromosomal OriC-Ter axis.

Urban-Rural Differences in Cardiac Arrest Outcomes: A Retrospective Population-Based Cohort Study.

Background: Approximately 10% of people who suffer an out-of-hospital cardiac arrest (OHCA) treated by paramedics survive to hospital discharge. Survival differs by up to 19.2% between urban centres and rural areas. Our goal was to investigate the differences in OHCA survival between urban centres and rural areas. Methods: This was a retrospective cohort study of OHCA patients treated by Nova Scotia Emergency Medical Services (EMS) in 2017. Cases of traumatic, expected, and noncardiac OHCA were excluded. Data were collected from the Emergency Health Service electronic patient care record system and the discharge abstract database. Geographic information system analysis classified cases as being in urban centres (population > 1000 people) or rural areas, using 2016 Canadian Census boundaries. The primary outcome was survival to hospital discharge. Multivariable logistic regression covariates were age, sex, bystander resuscitation, whether the arrest was witnessed, public location, and preceding symptoms. Results: A total of 510 OHCAs treated by Nova Scotia Emergency Medical Services were included for analysis. A total of 12% (n = 62) survived to discharge. Patients with OHCAs in urban centres were 107% more likely to survive than those with OHCAs in rural areas (adjusted odds ratio = 2.1; 95% confidence interval = 1.1 to 3.8; P = 0.028). OHCAs in urban centres had a significantly shorter mean time to defibrillation of shockable rhythm (11.2 minutes ± 6.2) vs those in rural areas (17.5 minutes ± 17.3). Conclusions: Nova Scotia has an urban vs rural disparity in OHCA care that is also seen in densely populated OHCA centres. Survival is improved in urban centres. Further improvements in overall survival, especially in rural areas, may arise from community engagement in OHCA recognition and optimized healthcare delivery.

Contexte: Environ 10 % des personnes qui subissent un arrêt cardiaque en milieu extrahospitalier (ACEH), traité par des intervenants paramédicaux, survivent jusqu'à leur congé de l'hôpital. Le taux de survie peut différer de 19,2 % entre les centres urbains et les régions rurales. Notre étude visait à étudier les différences en matière de survie après un ACEH entre les centres urbains et les régions rurales. Méthodologie: Il s'agissait d'une étude de cohorte rétrospective portant sur des patients ayant subi un ACEH traité par les services médicaux d'urgence de la Nouvelle-Écosse en 2017. Les cas d'ACEH traumatique, prévu et non cardiaque ont été exclus. Les données ont été recueillies à partir du système de dossiers électroniques de soins aux patients des services médicaux d'urgence et de la Base de données sur les congés des patients. L'analyse du système d'information géographique a classé les cas selon qu'ils sont survenus dans un centre urbain (population de plus de 1 000 personnes) ou dans une région rurale, en utilisant les limites du recensement canadien de 2016. Le principal paramètre d'évaluation était la survie à la sortie de l'hôpital. Les covariables utilisées dans la régression logistique multivariée étaient l'âge, le sexe, la réanimation effectuée par des témoins si présents lors de l'arrêt cardiaque, l'emplacement public et les symptômes précédents. Résultats: Au total, 510 ACEH traités par les services médicaux d'urgence de la Nouvelle-Écosse ont été inclus aux fins de l'analyse. En tout, 12 % (n = 62) des sujets ont survécu jusqu'à leur congé hospitalier. Les patients ayant subi un ACEH dans un centre urbain étaient 107 % plus susceptibles de survivre que ceux ayant subi un ACEH dans une région rurale (rapport de cotes ajusté : 2,1; intervalle de confiance à 95 % : 1,1 ­ 3,8; p = 0,028). Le temps moyen de délivrance d'un choc lors d'un ACEH avec rythme défibrillable est significativement plus court (11,2 ± 6,2 minutes) dans un centre urbain que dans une région rurale (17,5 ± 17,3 minutes). Conclusions: La Nouvelle-Écosse fait état d'une disparité dans les soins de l'ACEH entre les régions urbaines et les régions rurales, que l'on observe également dans les villes densément peuplées. La survie est plus longue dans les centres urbains. Il est possible de prolonger davantage la survie globale, en particulier dans les régions rurales, en sensibilisant la communauté à l'ACEH et en optimisant la prestation des soins de santé.

The Prevalence and Characteristics of Non-Transports in a Provincial Emergency Medical Services System: A Population-Based Study.

BACKGROUND: Emergency Medical Services (EMS) provide patients with out-of-hospital care, but not all patients are transported to the hospital. Non-transport represents an often undefined yet potentially significant risk for poor clinical outcomes. Few North American studies have quantified this risk. OBJECTIVE: The objectives of this study were to determine the prevalence of non-transport and 48-h adverse event (composite of relapse responses that resulted in transport or death) and to identify characteristics associated with either outcome. METHODS: An analysis of pooled cross-sectional, population-based administrative data from the provincial EMS electronic charting system in 2014 was conducted. Determination of non-transport was based on recorded call outcome. The data were searched by patient identifiers to determine the 48-h adverse event rate. Paramedic-documented patient, operational, and environmental characteristics were included in the logistic regression models. RESULTS: Of 74,293 emergency responses, 14,072 (18.9%) were non-transport and, of those, 798 (5.6%) resulted in a 48-h adverse event. The characteristics statistically significantly and independently associated with non-transport and 48-h adverse event were younger age (odds ratio [OR] 1.72; 99.9% confidence interval [CI] 1.46-2.02), nonspecific paramedic clinical impression (OR 5; 99.9% CI 4.48-5.57), more than 7 comorbidities (OR 0.47; 99.9% CI 0.42-0.53), and incident location (jail) (OR 2.88; 99.9% CI 2.22-3.74). CONCLUSIONS: This study provides an estimate of prevalence of non-transports and 48-h adverse event in a provincial mixed rural-urban EMS system. The results of this study describe the scope of non-transport and present several characteristics associated with non-transport. Future study should examine the appropriateness of EMS responses and methods to mitigate risk of adverse event after non-transport.

Cardiovascular Outcomes in Nova Scotia During the Early Phase of the COVID-19 Pandemic.

BACKGROUND: This study sought to determine the impact of the COVID-19 pandemic response to healthcare delivery on outcomes in patients with cardiovascular disease. METHODS: This is a population-based cohort study performed in the province of Nova Scotia, Canada (population 979,499), between the pre-COVID (March 1, 2017-March 16, 2020) and in-COVID (March 17, 2020-December 31, 2020) periods. Adult patients (age ≥ 18 years) with new-onset or existing cardiovascular disease were included for comparison between periods. The main outcome measures included the following: cardiovascular emergency department visits or hospitalizations, mortality, and out-of-hospital cardiac arrest. RESULTS: In the first month of the in-COVID period, emergency department visits (n = 51,750) for cardiac symptoms decreased by 20.8% (95% confidence interval [CI] 14.0%-27.0%, P < 0.001). Cardiovascular hospitalizations (n = 20,609) declined by 48.1% (95% CI 40.4% to 54.9%, P < 0.001). The in-hospital mortality rate increased in patients with cardiovascular admissions in secondary care institutions by 55.1% (95% CI 10.1%-118%, P = 0.013). A decline of 20.4%-44.0% occurred in cardiovascular surgical/interventional procedures. The number of out-of-hospital cardiac arrests (n = 5528) increased from a monthly mean of 115 ± 15 to 136 ± 14, beginning in May 2020. Mortality for ambulatory patients awaiting cardiac intervention (n = 14,083) increased from 0.16% (n = 12,501) to 2.49% (n = 361) in the in-COVID period (P < 0.0001). CONCLUSIONS: This study demonstrates increased cardiovascular morbidity and mortality during restrictions maintained during the COVID-19 period, in an area with a low burden of COVID-19. As the healthcare system recovers or enters subsequent waves of COVID-19, these findings should inform communication to the public regarding cardiovascular symptoms, and policy for delivery of cardiovascular care.

CONTEXTE: Cette étude visait à déterminer les répercussions de la réponse à la pandémie de COVID-19 sur la prestation des soins de santé et son incidence sur les résultats obtenus par les patients atteints d'une maladie cardiovasculaire. MÉTHODOLOGIE: Il s'agit d'une étude de cohorte représentative de la population réalisée dans la province de la Nouvelle-Écosse, au Canada (population de 979 499 habitants), entre la période précédant le début de la pandémie de COVID-19 (du 1er mars 2017 au 16 mars 2020) et la période de pandémie (du 17 mars 2020 au 31 décembre 2020). Des patients adultes (âge ≥ 18 ans) atteints d'une maladie cardiovasculaire préexistante ou d'apparition récente ont été inclus pour la comparaison entre les périodes. Les principaux paramètres d'évaluation comprenaient les visites ou hospitalisations dans un service d'urgences cardiovasculaires, la mortalité et l'arrêt cardiaque en milieu extrahospitalier. RÉSULTATS: Au cours du premier mois de la période de pandémie, les visites aux services des urgences (n = 51 750) pour des symptômes cardiaques ont diminué de 20,8 % (intervalle de confiance [IC] à 95 % : 14,0 % ­ 27,0 %, p < 0,001). Les hospitalisations en raison d'un événement cardiovasculaire (n = 20 609) ont décliné de 48,1 % (IC à 95 % : 40,4 % ­ 54,9 %, p < 0,001). Le taux de mortalité hospitalière parmi les patients admis dans des établissements de soins secondaires a augmenté de 55,1 % (IC à 95 % : 10,1 % ­ 118 %, p = 0,013). Une baisse de 20,4 à 44,0 % du nombre d'interventions chirurgicales ou interventionnelles visant à prendre en charge un événement cardiovasculaire a également été enregistrée. Le nombre d'arrêts cardiaques survenus en milieu extrahospitalier (n = 5 528) est passé d'une moyenne mensuelle de 115 ± 15 à 136 ± 14, à compter de mai 2020. La mortalité des patients ambulatoires en attente d'une intervention cardiaque (n = 14 083) a augmenté, passant de 0,16 % (n = 12 501) à 2,49 % (n = 361) pendant la période de pandémie (p < 0,0001). CONCLUSIONS: Cette étude révèle une augmentation de la morbidité et de la mortalité cardiovasculaires durant le maintien des restrictions liées à la COVID-19 dans une région où le fardeau associé à cette maladie est faible. À mesure que le système de santé se rétablit ou affronte les vagues subséquentes de COVID-19, ces résultats devraient éclairer les communications au public concernant les symptômes cardiovasculaires et orienter la politique de prestation de soins cardiovasculaires.

Composition of Transcription Machinery and Its Crosstalk with Nucleoid-Associated Proteins and Global Transcription Factors.

The coordination of bacterial genomic transcription involves an intricate network of interdependent genes encoding nucleoid-associated proteins (NAPs), DNA topoisomerases, RNA polymerase subunits and modulators of transcription machinery. The central element of this homeostatic regulatory system, integrating the information on cellular physiological state and producing a corresponding transcriptional response, is the multi-subunit RNA polymerase (RNAP) holoenzyme. In this review article, we argue that recent observations revealing DNA topoisomerases and metabolic enzymes associated with RNAP supramolecular complex support the notion of structural coupling between transcription machinery, DNA topology and cellular metabolism as a fundamental device coordinating the spatiotemporal genomic transcription. We analyse the impacts of various combinations of RNAP holoenzymes and global transcriptional regulators such as abundant NAPs, on genomic transcription from this viewpoint, monitoring the spatiotemporal patterns of couplons-overlapping subsets of the regulons of NAPs and RNAP sigma factors. We show that the temporal expression of regulons is by and large, correlated with that of cognate regulatory genes, whereas both the spatial organization and temporal expression of couplons is distinctly impacted by the regulons of NAPs and sigma factors. We propose that the coordination of the growth phase-dependent concentration gradients of global regulators with chromosome configurational dynamics determines the spatiotemporal patterns of genomic expression.

Outcomes of a Provincial Myocardial Infarction Reperfusion Strategy: A Population-Based, Retrospective Cohort Study.

BACKGROUND: Fibrinolysis is an acceptable treatment for acute ST-segment elevation myocardial infarction (STEMI) when primary percutaneous coronary intervention (PCI) cannot be performed within 120 minutes. The American Heart Association has recommended Emergency Medical Services (EMS) interventions such as prehospital fibrinolysis (PHF), prehospital electrocardiogram (ECG), and hospital bypass direct to PCI center. Nova Scotia, Canada has incorporated these interventions into a unique province-wide approach to STEMI care. A retrospective cohort analysis comparing the primary outcome of 30-day mortality for patients receiving either prehospital or emergency department (ED) fibrinolysis (EDF) to patients transported directly by EMS from community or regional ED for primary PCI was conducted. METHODS: This retrospective, population-based cohort study included all STEMI patients in Nova Scotia who survived to hospital admission from July 2011 through July 2013. Three provincial databases were used to collect demographic, 30-day mortality, hospital readmission, and rescue PCI data. The results were grouped and compared according to reperfusion strategy received: PHF, EDF, patients brought by ambulance via EMS direct to PCI (EMS to PCI), and ED to PCI (ED to PCI). RESULTS: There were 1,071 STEMI patients included with 145 PHF, 606 EDF, 98 EMS to PCI, and 222 ED to PCI. There were no significant differences in 30-day mortality across groups (n, %): PHF 5(3); EDF 36(6); EHS to PCI <5(2); and ED to PCI 10(4); P = .28. There was no significant difference in patients receiving fibrinolysis who underwent rescue PCI. CONCLUSIONS: Prehospital fibrinolysis incorporated into a province-wide approach to STEMI treatment is feasible with no observed difference in patient 30-day mortality outcomes observed.

Chromosomal Organization and Regulation of Genetic Function in Escherichia coli Integrates the DNA Analog and Digital Information.

In this article, we summarize our current understanding of the bacterial genetic regulation brought about by decades of studies using the Escherichia coli model. It became increasingly evident that the cellular genetic regulation system is organizationally closed, and a major challenge is to describe its circular operation in quantitative terms. We argue that integration of the DNA analog information (i.e., the probability distribution of the thermodynamic stability of base steps) and digital information (i.e., the probability distribution of unique triplets) in the genome provides a key to understanding the organizational logic of genetic control. During bacterial growth and adaptation, this integration is mediated by changes of DNA supercoiling contingent on environmentally induced shifts in intracellular ionic strength and energy charge. More specifically, coupling of dynamic alterations of the local intrinsic helical repeat in the structurally heterogeneous DNA polymer with structural-compositional changes of RNA polymerase holoenzyme emerges as a fundamental organizational principle of the genetic regulation system. We present a model of genetic regulation integrating the genomic pattern of DNA thermodynamic stability with the gene order and function along the chromosomal OriC-Ter axis, which acts as a principal coordinate system organizing the regulatory interactions in the genome.

Generation of Remosomes by the SWI/SNF Chromatin Remodeler Family.

Chromatin remodelers are complexes able to both alter histone-DNA interactions and to mobilize nucleosomes. The mechanism of their action and the conformation of remodeled nucleosomes remain a matter of debates. In this work we compared the type and structure of the products of nucleosome remodeling by SWI/SNF and ACF complexes using high-resolution microscopy combined with novel biochemical approaches. We find that SWI/SNF generates a multitude of nucleosome-like metastable particles termed "remosomes". Restriction enzyme accessibility assay, DNase I footprinting and AFM experiments reveal perturbed histone-DNA interactions within these particles. Electron cryo-microscopy shows that remosomes adopt a variety of different structures with variable irregular DNA path, similar to those described upon RSC remodeling. Remosome DNA accessibility to restriction enzymes is also markedly increased. We suggest that the generation of remosomes is a common feature of the SWI/SNF family remodelers. In contrast, the ACF remodeler, belonging to ISWI family, only produces repositioned nucleosomes and no evidence for particles associated with extra DNA, or perturbed DNA paths was found. The remosome generation by the SWI/SNF type of remodelers may represent a novel mechanism involved in processes where nucleosomal DNA accessibility is required, such as DNA repair or transcription regulation.

Modelling and DNA topology of compact 2-start and 1-start chromatin fibres.

We have investigated the structure of the most compact 30-nm chromatin fibres by modelling those with 2-start or 1-start crossed-linker organisations. Using an iterative procedure we obtained possible structural solutions for fibres of the highest possible compaction permitted by physical constraints, including the helical repeat of linker DNA. We find that this procedure predicts a quantized nucleosome repeat length (NRL) and that only fibres with longer NRLs (≥197 bp) can more likely adopt the 1-start organisation. The transition from 2-start to 1-start fibres is consistent with reported differing binding modes of the linker histone. We also calculate that in 1-start fibres the DNA constrains more torsion (as writhe) than 2-start fibres with the same NRL and that the maximum constraint obtained is in accord with previous experimental results. We posit that the coiling of the fibre is driven by overtwisting of linker DNA which, in the most compact forms - for example, in echinoderm sperm and avian erythrocytes - could adopt a helical repeat of ∼10 bp/turn. We argue that in vivo the total twist of linker DNA could be modulated by interaction with other abundant chromatin-associated proteins and by epigenetic modifications of the C-terminal tail of linker histones.

Methodology of a Cross-sectional Study Evaluating the Impact of a Novel Mobile Care Team on the Prevalence of Ambulatory Care Sensitive Conditions Presenting to Emergency Medical Services.

Introduction Hospitalization due to ambulatory care sensitive conditions (ACSC) is often used as a proxy measure for access to primary care. The prevalence of ACSC has not been measured in the prehospital setting. Emergency medical services (EMS) are being used by patients who lack access to primary care for ACSC. Many novel models of care have been implemented within Canada and internationally, utilizing paramedics to ease the burden of poor primary care access. Recently, a mobile care team (MCT) consisting of a paramedic/nurse configuration has been deployed in the community of New Waterford, Nova Scotia. The team responds to low acuity 911 calls and follow-up appointments booked by primary care clinicians. This study will identify the prevalence of patients with ACSC presenting to EMS before and after the implementation of MCT and the differences after the implementation of the MCT. Methods Secondary data will be collected from the centralized EMS electronic patient care report (ePCR) database. All patients presenting to the ground ambulance with ACSC during the year prior to MCT implementation, all patients presenting to the ground ambulance with ACSC during the year post-MCT implementation, and all patients presenting to the MCT with ACSC will be included for analysis, allowing for a calculation of ACSC prevalence. Descriptive methods will be used for age, sex, primary care practitioner, and ASCS complaints. Prevalence data will be compared via the chi-squared test. A subgroup analysis of age, sex, and individual presenting conditions will also be analyzed using the chi-squared test. Confounding will be dealt with via multivariate logistic regression. Results The study results are pending; however, a literature review reveals a paucity of data on ACSC in EMS. Conclusions Due to the paucity of literature surrounding ACSC prevalence in EMS, the methodology developed to study these prevalence rates is a novel protocol of importance to prehospital research and the epidemiology of ACSC more broadly.

Highly disordered histone H1-DNA model complexes and their condensates.

Disordered proteins play an essential role in a wide variety of biological processes, and are often posttranslationally modified. One such protein is histone H1; its highly disordered C-terminal tail (CH1) condenses internucleosomal linker DNA in chromatin in a way that is still poorly understood. Moreover, CH1 is phosphorylated in a cell cycle-dependent manner that correlates with changes in the chromatin condensation level. Here we present a model system that recapitulates key aspects of the in vivo process, and also allows a detailed structural and biophysical analysis of the stages before and after condensation. CH1 remains disordered in the DNA-bound state, despite its nanomolar affinity. Phase-separated droplets (coacervates) form, containing higher-order assemblies of CH1/DNA complexes. Phosphorylation at three serine residues, spaced along the length of the tail, has little effect on the local properties of the condensate. However, it dramatically alters higher-order structure in the coacervate and reduces partitioning to the coacervate phase. These observations show that disordered proteins can bind tightly to DNA without a disorder-to-order transition. Importantly, they also provide mechanistic insights into how higher-order structures can be exquisitely sensitive to perturbation by posttranslational modifications, thus broadening the repertoire of mechanisms that might regulate chromatin and other macromolecular assemblies.

Evolution of a high-performance emergency health services system in Nova Scotia.

Since 1997, Emergency Health Services in Nova Scotia (NS) has evolved from a program providing prehospital care for patients in transport to a system providing integrated healthcare in both traditional (ie, ambulance) and non-traditional settings (eg, patient homes, hospital settings). This article highlights (1) the reorganization of the emergency medical service system design, (2) the strategies enabling efficient operation of this design, and (3) resultant innovations evolving from both system redesign and strategy application. Emergency Health Services has utilized a Public Utility Model (PUM) design providing prehospital healthcare, public safety, and public health responses to the population of NS. The success of the PUM has been complimented by three strategies: (1) co-leadership model operations, (2) common languages to translate evidence into practice, and (3) collaborative and integrated relationships with other regulated healthcare providers. This prehospital system design and application strategies could be applied in other sectors of community and hospital systems of care.

State of the Evidence for Emergency Medical Services (EMS) Care: The Evolution and Current Methodology of the Prehospital Evidence-Based Practice (PEP) Program.

Background: Emergency medical services (EMS) leaders and clinicians need to incorporate evidence into safe and effective clinical practice. Access to high-quality evidence, and the time to synthesize it, can be barriers to evidence-based practice. The Prehospital Evidence-Based Practice (PEP) program is an online, freely accessible, repository of critically appraised evidence specific to EMS. This paper describes the evolution and current methodology of the PEP program. Methods|design: The purpose of PEP is to identify, catalog and critically appraise relevant studies. Following regular systematic searches, two trained appraisers critically appraise included studies and assign a score on three-point level of evidence (LOE) and direction of evidence (DOE) scales. Each clinical intervention is plotted on a 3 × 3 (LOE × DOE) evidence matrix, which provides a summary recommendation. Discussion: The PEP program is a unique knowledge translation tool, specific to EMS. End-users can easily identify which clinical interventions are, or are not, supported by evidence.

ILCOR Scientific Knowledge Gaps and Clinical Research Priorities for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: A Consensus Statement.

Despite significant advances in the field of resuscitation science, important knowledge gaps persist. Current guidelines for resuscitation are based on the International Liaison Committee on Resuscitation 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations, which includes treatment recommendations supported by the available evidence. The writing group developed this consensus statement with the goal of focusing future research by addressing the knowledge gaps identified during and after the 2015 International Liaison Committee on Resuscitation evidence evaluation process. Key publications since the 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations are referenced, along with known ongoing clinical trials that are likely to affect future guidelines. © 2018 European Resuscitation Council and American Heart Association, Inc. Published by Elsevier B.V. All rights reserved.