Molecular MRD is strongly prognostic in patients with NPM1-mutated AML receiving venetoclax-based nonintensive therapy.

ABSTRACT: Assessment of measurable residual disease (MRD) by quantitative reverse transcription polymerase chain reaction is strongly prognostic in patients with NPM1-mutated acute myeloid leukemia (AML) treated with intensive chemotherapy; however, there are no data regarding its utility in venetoclax-based nonintensive therapy, despite high efficacy in this genotype. We analyzed the prognostic impact of NPM1 MRD in an international real-world cohort of 76 previously untreated patients with NPM1-mutated AML who achieved complete remission (CR)/CR with incomplete hematological recovery following treatment with venetoclax and hypomethylating agents (HMAs) or low-dose cytarabine (LDAC). A total of 44 patients (58%) achieved bone marrow (BM) MRD negativity, and a further 14 (18%) achieved a reduction of ≥4 log10 from baseline as their best response, with no difference between HMAs and LDAC. The cumulative rates of BM MRD negativity by the end of cycles 2, 4, and 6 were 25%, 47%, and 50%, respectively. Patients achieving BM MRD negativity by the end of cycle 4 had 2-year overall of 84% compared with 46% if MRD was positive. On multivariable analyses, MRD negativity was the strongest prognostic factor. A total of 22 patients electively stopped therapy in BM MRD-negative remission after a median of 8 cycles, with 2-year treatment-free remission of 88%. In patients with NPM1-mutated AML attaining remission with venetoclax combination therapies, NPM1 MRD provides valuable prognostic information.

Turning the spotlight on bone marrow adipocytes in haematological malignancy and non-malignant conditions.

Whilst bone marrow adipocytes (BMAd) have long been appreciated by clinical haemato-pathologists, it is only relatively recently, in the face of emerging data, that the adipocytic niche has come under the watchful eye of biologists. There is now mounting evidence to suggest that BMAds are not just a simple structural entity of bone marrow microenvironments but a bona fide driver of physio- and pathophysiological processes relevant to multiple aspects of health and disease. Whilst the truly multifaceted nature of BMAds has only just begun to emerge, paradigms have shifted already for normal, malignant and non-malignant haemopoiesis incorporating a view of adipocyte regulation. Major efforts are ongoing, to delineate the routes by which BMAds participate in health and disease with a final aim of achieving clinical tractability. This review summarises the emerging role of BMAds across the spectrum of normal and pathological haematological conditions with a particular focus on its impact on cancer therapy.

Patient and Prehospital Predictors of Hospital Admission for Patients With and Without Histories of Diabetes Treated by Paramedics for Hypoglycemia: A Health Record Review Study.

OBJECTIVES: The objectives of this study were to describe the characteristics, management, and outcomes of patients treated by paramedics for hypoglycemia, and to determine the predictors of hospital admission for these patients within 72 hours of the initial hypoglycemia event. METHODS: We performed a health record review of paramedic call reports and emergency department records over a 12-month period. We queried prehospital databases to identify cases, which included all patients ⩾18 years with prehospital glucose readings of <72 mg/dl (<4.0 mmol/L) and excluded terminally ill and cardiac arrest patients. We developed and piloted a standardized data collection tool and obtained consensus on all data definitions before initiation of data extraction by trained investigators. Data analyses included descriptive statistics univariate and logistic regression presented as adjusted odds ratios (aOR) with 95% confidence intervals (95%CI). RESULTS: There were 791 patients with the following characteristics: mean age 56.2, male 52.3%, type 1 diabetes 11.6%, on insulin 43.3%, median initial glucose 54.0 mg/dl (3.0 mmol/L), from home 56.4%. They were treated by advanced care paramedics 80.1%, received intravenous D50 37.8%, intramuscular glucagon 17.8%, oral complex carbs/protein 25.7%, and accepted transport to hospital 70.2%. Among those transported, 134 (24.3%) were initially admitted and four more were admitted within 72 hours. One patient was admitted, discharged, and admitted again within 72 hours. Patients without documented histories of diabetes (aOR 2.35, CI 1.13-4.86), with cardiovascular disease (aOR 1.81, CI 1.10-3.00), on corticosteroids (aOR 4.63, CI 2.15-9.96), on oral hypoglycemic agent(s) (aOR 1.92, CI 1.02-3.62), or those given glucagon (aOR 1.77, CI 1.07-2.93) on scene were more likely to be admitted to hospital, whereas patients on insulin (aOR 0.49, CI 0.27-0.91), able to tolerate complex oral carbs/protein (aOR 0.22, CI 0.10-0.48), with final GCS scores of 15 (aOR 0.53, CI 0.34-0.83), or from public locations (aOR 0.40, CI 0.21-0.75) were less likely to be admitted. CONCLUSIONS: There are several patient and prehospital management characteristics which, in combination, could be incorporated into a safe clinical decision tool for patients who present with hypoglycemia.

Artificial intelligence, machine learning, and deep learning in rhinology: a systematic review.

PURPOSE: This PRISMA-compliant systematic review aims to analyze the existing applications of artificial intelligence (AI), machine learning, and deep learning for rhinological purposes and compare works in terms of data pool size, AI systems, input and outputs, and model reliability. METHODS: MEDLINE, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov databases. Search criteria were designed to include all studies published until December 2021 presenting or employing AI for rhinological applications. We selected all original studies specifying AI models reliability. After duplicate removal, abstract and full-text selection, and quality assessment, we reviewed eligible articles for data pool size, AI tools used, input and outputs, and model reliability. RESULTS: Among 1378 unique citations, 39 studies were deemed eligible. Most studies (n = 29) were technical papers. Input included compiled data, verbal data, and 2D images, while outputs were in most cases dichotomous or selected among nominal classes. The most frequently employed AI tools were support vector machine for compiled data and convolutional neural network for 2D images. Model reliability was variable, but in most cases was reported to be between 80% and 100%. CONCLUSIONS: AI has vast potential in rhinology, but an inherent lack of accessible code sources does not allow for sharing results and advancing research without reconstructing models from scratch. While data pools do not necessarily represent a problem for model construction, presently available tools appear limited in allowing employment of raw clinical data, thus demanding immense interpretive work prior to the analytic process.

Severe Acute Respiratory Syndrome Coronavirus 2 and Respiratory Virus Sentinel Surveillance, California, USA, May 10, 2020-June 12, 2021.

State and local health departments established the California Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Respiratory Virus Sentinel Surveillance System to conduct enhanced surveillance for SARS-CoV-2 and other respiratory pathogens at sentinel outpatient testing sites in 10 counties throughout California, USA. We describe results obtained during May 10, 2020‒June 12, 2021, and compare persons with positive and negative SARS-CoV-2 PCR results by using Poisson regression. We detected SARS-CoV-2 in 1,696 (19.6%) of 8,662 specimens. Among 7,851 specimens tested by respiratory panel, rhinovirus/enterovirus was detected in 906 (11.5%) specimens and other respiratory pathogens in 136 (1.7%) specimens. We also detected 23 co-infections with SARS-CoV-2 and another pathogen. SARS-CoV-2 positivity was associated with male participants, an age of 35-49 years, Latino race/ethnicity, obesity, and work in transportation occupations. Sentinel surveillance can provide useful virologic and epidemiologic data to supplement other disease monitoring activities and might become increasingly useful as routine testing decreases.

Relationship Between Duration of Targeted Temperature Management, Ischemic Interval, and Good Functional Outcome From Out-of-Hospital Cardiac Arrest.

OBJECTIVES: Tailoring hypothermia duration to ischemia duration may improve outcome from out-of-hospital cardiac arrest. We investigated the association between the hypothermia/ischemia ratio and functional outcome in a secondary analysis of data from the Resuscitation Outcomes Consortium Amiodarone, Lidocaine, or Placebo Study trial. DESIGN: Cohort study of out-of-hospital cardiac arrest patients screened for Resuscitation Outcomes Consortium-Amiodarone, Lidocaine, or Placebo Study. SETTING: Multicenter study across North America. PATIENTS: Adult, nontraumatic, out-of-hospital cardiac arrest patients screened for Resuscitation Outcomes Consortium-Amiodarone, Lidocaine, or Placebo Study who survived to hospital admission and received targeted temperature management between May 2012 and October 2015. INTERVENTIONS: Targeted temperature management in comatose survivors of out-of-hospital cardiac arrest. We defined hypothermia/ischemia ratio as total targeted temperature management time (initiation through rewarming) divided by calculated total ischemia time (approximate time of arrest [9-1-1 call or emergency medical services-witnessed] to return of spontaneous circulation). MEASUREMENTS AND MAIN RESULTS: The primary outcome was hospital survival with good functional status (modified Rankin Score, 0-3) at hospital discharge. We fitted logistic regression models to estimate the association between hypothermia/ischemia ratio and the primary outcome, adjusting for demographics, arrest characteristics, and Resuscitation Outcomes Consortium enrolling site. A total of 3,429 patients were eligible for inclusion, of whom 36.2% were discharged with good functional outcome. Patients had a mean age of 62.0 years (SD, 15.8), with 69.7% male, and 58.0% receiving lay-rescuer cardiopulmonary resuscitation. Median time to return of spontaneous circulation was 21.1 minutes (interquartile range, 16.1-26.9), and median duration of targeted temperature management was 32.9 hours (interquartile range, 23.7-37.8). A total of 2,579 had complete data and were included in adjusted regression analyses. After adjustment for patient characteristics and Resuscitation Outcomes Consortium site, a greater hypothermia/ischemia ratio was associated with increased survival with good functional outcome (odds ratio, 2.01; 95% CI, 1.82-2.23). This relationship, however, appears to be primarily driven by time to return of spontaneous circulation in this patient cohort. CONCLUSIONS: Although a larger hypothermia/ischemia ratio was associated with good functional outcome after out-of-hospital cardiac arrest in this cohort, this association is primarily driven by duration of time to return of spontaneous circulation. Tailoring duration of targeted temperature management based on duration of time to return of spontaneous circulation or patient characteristics requires prospective study.

Oxygen therapy in the pre-hospital setting for acute exacerbations of chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a global leading cause of morbidity and mortality, characterised by acute deterioration in symptoms. During these exacerbations, people are prone to developing alveolar hypoventilation, which may be partly caused by the administration of high inspired oxygen concentrations. OBJECTIVES: To determine the effect of different inspired oxygen concentrations ("high flow" compared to "controlled") in the pre-hospital setting (prior to casualty/emergency department) on outcomes for people with acute exacerbations of COPD (AECOPD). SEARCH METHODS: The Cochrane Airways Group Specialised Register, reference lists of articles and online clinical trial databases were searched. Authors of identified randomised controlled trials (RCTs) were also contacted for details of other relevant published and unpublished studies. The most recent search was conducted on 16 September 2019. SELECTION CRITERIA: We included RCTs comparing oxygen therapy at different concentrations or oxygen therapy versus placebo in the pre-hospital setting for treatment of AECOPD. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. The primary outcome was all-cause and respiratory-related mortality. MAIN RESULTS: The search identified a total of 824 citations; one study was identified for inclusion and two studies are awaiting classification. The 214 participants involved in the included study were adults with AECOPD, receiving treatment by paramedics en route to hospital. The mean age of participants was 68 years. A reduction in pre/in-hospital mortality was observed in favour of the titrated oxygen group (two deaths in the titrated oxygen group compared to 11 deaths in the high-flow control arm; risk ratio (RR) 0.22, 95% confidence interval (CI) 0.05 to 0.97; 214 participants). This translates to an absolute effect of 94 per 1000 (high-flow oxygen) compared to 21 per 1000 (titrated oxygen), and a number needed to treat for an additional beneficial outcome (NNTB) of 14 (95% CI 12 to 355) with titrated oxygen therapy. Other than mortality, no other adverse events were reported in the included study. Wide confidence intervals were observed between groups for arterial blood gas (though this may be confounded by protocol infidelity in the included study for this outcome measure), treatment failure requiring invasive or non-invasive ventilation or hospital utilisation. No data were reported for quality of life, lung function or dyspnoea. Risk of bias within the included study was largely unclear, though there was high risk of bias in domains relating to performance and attrition bias. We judged the evidence to be of low certainty, according to GRADE criteria. AUTHORS' CONCLUSIONS: The one included study found a reduction in pre/in-hospital mortality for the titrated oxygen arm compared to the high-flow control arm. However, the paucity of evidence somewhat limits the reliability of these findings and generalisability to other settings. There is a need for robust, well-designed RCTs to further investigate the effect of oxygen therapies in the pre-hospital setting for people with AECOPD.

CD209+ monocyte-derived myeloid dendritic cells were increased in patients with leukemic cutaneous T-cell lymphoma undergoing extracorporeal photopheresis via the CELLEXTM system.

BACKGROUND/PURPOSE: We previously reported that myeloid dendritic cells (mDC) were increased in patients with leukemic cutaneous T-cell lymphoma (L-CTCL) following extracorporeal photopheresis (ECP) using the Therakos UVAR XTS™ system. We now assessed monocyte-derived mDCs (Mo-DCs) in L-CTCL patients treated with the CELLEXTM photopheresis system. CD209, a transmembrane receptor, was used to define Mo-DCs. METHODS: Peripheral blood samples from baseline pre-ECP and at Day 2, 1 month, 3 months, and 6 months post-ECP were analyzed by flow cytometry for Lin- HLA-DR+ CD123+ plasmacytoid dendritic cells (pDCs), Lin- HLA-DR+ CD11c+ mDCs, and CD209+ mDCs. The expression of CD209 mRNA was assessed by real-time PCR. RESULTS: At baseline, 7 of 19 patients had lower than normal mDCs, and all patients had lower than normal CD209+ mDCs in peripheral blood mononuclear cells (0.005% in patients, n = 19, vs 0.50% in healthy donors, n = 7, P < .0001). The CD209+ mDC numbers only accounted for 3.28% out of total mDCs in patients compared with 66.51% in healthy donors. After treatment, the CD209+ mDC numbers showed increasing trends in patients. The average absolute numbers of CD209+ mDCs went up by 4.8-fold at 3 months (n = 10, P = .103) and by 6.4-fold at 6 months (n = 9, P = .100). CD209 mRNA expression went up in two patients responsive to therapy, parallel to CD209+ mDC numbers. L-CTCL patients achieved 70% overall clinical response rate (7/10) following ECP therapy with the CELLEXTM system. CONCLUSIONS: Our results suggest that the CELLEXTM photopheresis system is effective for treating L-CTCL patients like the UVAR XTS™ system, and in vivo-generated Mo-DCs increase following ECP.

Association of Intra-arrest Transport vs Continued On-Scene Resuscitation With Survival to Hospital Discharge Among Patients With Out-of-Hospital Cardiac Arrest.

Importance: There is wide variability among emergency medical systems (EMS) with respect to transport to hospital during out-of-hospital cardiac arrest (OHCA) resuscitative efforts. The benefit of intra-arrest transport during resuscitation compared with continued on-scene resuscitation is unclear. Objective: To determine whether intra-arrest transport compared with continued on-scene resuscitation is associated with survival to hospital discharge among patients experiencing OHCA. Design, Setting, and Participants: Cohort study of prospectively collected consecutive nontraumatic adult EMS-treated OHCA data from the Resuscitation Outcomes Consortium (ROC) Cardiac Epidemiologic Registry (enrollment, April 2011-June 2015 from 10 North American sites; follow-up until the date of hospital discharge or death [regardless of when either event occurred]). Patients treated with intra-arrest transport (exposed) were matched with patients in refractory arrest (at risk of intra-arrest transport) at that same time (unexposed), using a time-dependent propensity score. Subgroups categorized by initial cardiac rhythm and EMS-witnessed cardiac arrests were analyzed. Exposures: Intra-arrest transport (transport initiated prior to return of spontaneous circulation), compared with continued on-scene resuscitation. Main Outcomes and Measures: The primary outcome was survival to hospital discharge, and the secondary outcome was survival with favorable neurological outcome (modified Rankin scale <3) at hospital discharge. Results: The full cohort included 43 969 patients with a median age of 67 years (interquartile range, 55-80), 37% were women, 86% of cardiac arrests occurred in a private location, 49% were bystander- or EMS-witnessed, 22% had initial shockable rhythms, 97% were treated by out-of-hospital advanced life support, and 26% underwent intra-arrest transport. Survival to hospital discharge was 3.8% for patients who underwent intra-arrest transport and 12.6% for those who received on-scene resuscitation. In the propensity-matched cohort, which included 27 705 patients, survival to hospital discharge occurred in 4.0% of patients who underwent intra-arrest transport vs 8.5% who received on-scene resuscitation (risk difference, 4.6% [95% CI, 4.0%- 5.1%]). Favorable neurological outcome occurred in 2.9% of patients who underwent intra-arrest transport vs 7.1% who received on-scene resuscitation (risk difference, 4.2% [95% CI, 3.5%-4.9%]). Subgroups of initial shockable and nonshockable rhythms as well as EMS-witnessed and unwitnessed cardiac arrests all had a significant association between intra-arrest transport and lower probability of survival to hospital discharge. Conclusions and Relevance: Among patients experiencing out-of-hospital cardiac arrest, intra-arrest transport to hospital compared with continued on-scene resuscitation was associated with lower probability of survival to hospital discharge. Study findings are limited by potential confounding due to observational design.

Service Coordination by Public Sector Managers in a Human Service Contracting Environment.

Despite emerging evidence of contracting for evidence-based practices (EBP), little research has studied how managers lead contract-based human service delivery. A 2015 survey of 193 managers from five San Francisco Bay Area county human service departments examined the relationship between contract-based service coordination (i.e., structuring cross-sector services, coordinating client referrals and eligibility, overseeing EBP implementation) and the predictors of managerial role, involvement, and boundary spanning. Multivariate regression results suggested that county managers identified fewer service coordination challenges if they were at the executive and program levels, had greater contract involvement, and engaged in contract-focused boundary spanning. In conclusion, we underscore the organizational and managerial dimensions of contract-based service delivery.

Barriers to Self-Reporting Patient Safety Incidents by Paramedics: A Mixed Methods Study.

BACKGROUND: A minimal amount of research exists examining the extent to which patient safety events occur within paramedicine and even fewer studies investigating patient safety systems for self-reporting by paramedics. The purpose of this study was to identify barriers to paramedic self-reporting of patient safety incidents (PSIs). METHODS: We randomly distributed paper-based surveys among 1,153 paramedics in an Ontario region in Canada. The survey described one of 5 different PSI clinical scenarios (near miss, adverse event, and minor, major or critical patient care variances) and listed 18 potential barriers to self-reporting PSIs as statements presented for rating on a 5-point Likert scale (very significant = 1 - very insignificant = 5). We invited comments on PSI self-reporting with 2 open-ended questions. We analyzed data with descriptive statistics, chi-square tests and Kruskal-Wallis H test. We used an inductive approach to qualitatively analyze emerging themes. RESULTS: We received responses from 1,133 paramedics (98.3%). Almost one third (28.4%) were Advanced Care Paramedics and 45.1% had >10 years' experience. The top 5 barriers to PSI self-reporting (very significant or significant, %) were the fear of being: punished (81.4%), suspended (79.6%), terminated (79.1%), investigated by Ministry of Health and Long-Term Care (78.4%), and decertified (78.0%). Overall, 64.1% responded they would self-report a given PSI. Intention to self-report a PSI varied according to scenario (22.8% near miss, 46.6% adverse event, 74.4% minor, 92.6% major, 95.6% critical). No association was found between level of training (p = 0.55) or years of experience (p = 0.10) and intention to self-report a PSI. Seven themes to improve PSI self-reporting by paramedics emerged from the qualitative data. CONCLUSIONS: A high proportion of fear-based barriers to self-reporting of PSIs exist among this study population. This suggests that a culture change is needed to facilitate the identification of future patient safety threats.

The Safety of Bypass to Percutaneous Coronary Intervention Facility by Basic Life Support Providers in Patients with ST-Elevation Myocardial Infarction in Prehospital Setting.

BACKGROUND: Most patients transferred from a non-percutaneous coronary intervention (PCI) facility for primary PCI do not meet target reperfusion times. Direct transportation of patients with ST-elevation myocardial infarction (STEMI) from the scene by advanced life support (ALS) paramedics has been shown to improve reperfusion times and outcomes. OBJECTIVE: The aim of this study was to determine whether it is safe to bypass the closest hospital and transport by basic life support (BLS) provider to a PCI facility. METHODS: This was a health records review of consecutive patients transported to a regional PCI center under an STEMI bypass protocol. Under the PCI bypass protocol, patients were eligible if they presented with symptoms of chest pain, a 12-lead electrocardiogram meeting STEMI criteria, and if transported to the regional PCI center within 60 min. The occurrence of predefined adverse events during transport was determined, which included bradycardia < 50 beats/min, tachycardia > 140 beats/min, hypotension, cardiac arrest, and death. RESULTS: There were 46 cases of STEMI bypass between February 2005 and February 2013. Mean transport time was 29.9 min (range 20-62 min). Mean contact-to-balloon time was 95.2 min (range 68-159 min). Twenty-five adverse events occurred in 20 patients during transport. In 16 of the 20 patients, the adverse events were transiently abnormal vital sign requiring no intervention. In 3 of the patients, the adverse event was clinically significant and it is believed that the patient would have benefitted from advanced cardiac life support care not within the scope of practice of the BLS providers. CONCLUSIONS: In our region, STEMI patients can be diagnosed accurately and transported safely on bypass to a PCI center for primary PCI while respecting target reperfusion times.

Toward Financially Viable Phytoextraction and Production of Plant-Based Palladium Catalysts.

Although a promising technique, phytoextraction has yet to see significant commercialization. Major limitations include metal uptake rates and subsequent processing costs. However, it has been shown that liquid-culture-grown Arabidopsis can take up and store palladium as nanoparticles. The processed plant biomass has catalytic activity comparable to that of commercially available catalysts, creating a product of higher value than extracted bulk metal. We demonstrate that the minimum level of palladium in Arabidopsis dried tissues for catalytic activity comparable to commercially available 3% palladium-on-carbon catalysts was achieved from dried plant biomass containing between 12 and 18 g·kg-1 Pd. To advance this technology, species suitable for in-the-field application: mustard, miscanthus, and 16 willow species and cultivars, were tested. These species were able to grow, and take up, palladium from both synthetic and mine-sourced tailings. Although levels of palladium accumulation in field-suitable species are below that required for commercially available 3% palladium-on-carbon catalysts, this study both sets the target, and is a step toward, the development of field-suitable species that concentrate catalytically active levels of palladium. Life cycle assessment on the phytomining approaches described here indicates that the use of plants to accumulate palladium for industrial applications has the potential to decrease the overall environmental impacts associated with extracting palladium using present-day mining processes.

Emergent decarboxylase activity and attenuation of α/ß-hydrolase activity during the evolution of methylketone biosynthesis in tomato.

Specialized methylketone-containing metabolites accumulate in certain plants, in particular wild tomatoes in which they serve as toxic compounds against chewing insects. In Solanum habrochaites f. glabratum, methylketone biosynthesis occurs in the plastids of glandular trichomes and begins with intermediates of de novo fatty acid synthesis. These fatty-acyl intermediates are converted via sequential reactions catalyzed by Methylketone Synthase2 (MKS2) and MKS1 to produce the n-1 methylketone. We report crystal structures of S. habrochaites MKS1, an atypical member of the α/ß-hydrolase superfamily. Sequence comparisons revealed the MKS1 catalytic triad, Ala-His-Asn, as divergent to the traditional α/ß-hydrolase triad, Ser-His-Asp. Determination of the MKS1 structure points to a novel enzymatic mechanism dependent upon residues Thr-18 and His-243, confirmed by biochemical assays. Structural analysis further reveals a tunnel leading from the active site consisting mostly of hydrophobic residues, an environment well suited for fatty-acyl chain binding. We confirmed the importance of this substrate binding mode by substituting several amino acids leading to an alteration in the acyl-chain length preference of MKS1. Furthermore, we employ structure-guided mutagenesis and functional assays to demonstrate that MKS1, unlike enzymes from this hydrolase superfamily, is not an efficient hydrolase but instead catalyzes the decarboxylation of 3-keto acids.

Evaluating the impact of a specialized and centralized online medical consultation system for paramedics: pilot study.

INTRODUCTION: There are many limitations to utilizing on-duty emergency department (ED) physicians as Base Hospital Physicians for paramedic telephone consultations. We aimed to examine the impact of a specialized and centralized Online Medical Consultation program for paramedic consultations on system-relevant performance. METHODS: This is a before-after study with concurrent control using health record review of audio recordings over a 6-month period before and after implementation of the Online Medical Consultation program. The primary outcome was the duration of paramedic consultation calls. The secondary outcomes included number of calls with orders that contradicted existing medical directives, number of calls with orders outside of paramedic scope of practice, number of calls with Base Hospital Physician requiring clarification on medical directives, and number of calls with Base Hospital Physician interrupting the paramedic during the call. RESULTS: We included 220 consultation calls. The patients' mean age was 54.5 years. Most consultation calls (70.5%) were for mandatory consultations and 22.7% were voluntary. Most consultations were related to cardiac arrest (43.6%), combative patients (15.0%), and analgesia (13.6%). Before-after comparisons for total call duration showed that mean call duration decreased in Ottawa from 4:28 to 4:05 min (p = 0.77) and decreased in Kingston from 4:50 to 4:13 min (p = 0.49). There were no significant differences in our secondary outcomes. CONCLUSIONS: The Online Medical Consultation program was implemented and removed the responsibility of responding to online medical consultations for on-duty emergency physicians in Ottawa. The total call duration was not significantly different between groups. Additional time intervals and adherence to protocol benefits were also not statistically significant due to low baseline incidence.

RéSUMé: INTRODUCTION: Il existe de nombreuses limites à l'utilisation des médecins en service d'urgence (DE) comme médecins de base pour les consultations téléphoniques des ambulanciers paramédicaux. Nous avons cherché à examiner l'impact d'un programme de consultation médicale en ligne spécialisé et centralisé pour les consultations paramédicales sur le rendement pertinent du système. MéTHODES: Il s'agit d'une étude avant-après avec contrôle simultané utilisant l'examen du dossier de santé des enregistrements audio sur une période de 6 mois avant et après la mise en œuvre du programme de consultation médicale en ligne. Le principal résultat était la durée des appels de consultation des paramédicaux. Les résultats secondaires comprennent le nombre d'appels avec des ordonnances qui contredisent les directives médicales existantes, le nombre d'appels avec des ordonnances en dehors du champ de pratique paramédical, le nombre d'appels avec un médecin de l'hôpital de base demandant des éclaircissements sur les directives médicales, et nombre d'appels avec le médecin de l'hôpital de base interrompant le paramédical pendant l'appel. RéSULTATS: Nous avons inclus 220 consultations. L'âge moyen des patients était de 54,5 ans. La plupart des consultations (70,5 %) étaient obligatoires et 22,7 % volontaires. La plupart des consultations étaient liées à l'arrêt cardiaque (43,6 %), aux patients combatifs (15,0 %) et à l'analgésie (13,6 %). Les comparaisons avant-après pour la durée totale des appels ont montré que la durée moyenne des appels a diminué à Ottawa de 4 h 28 à 4 h 05 min (p=0,77) et à Kingston de 4 h 50 à 4 h 13 min (p=0,49). Il n'y avait pas de différences significatives dans nos résultats secondaires. CONCLUSIONS: Le programme de consultation médicale en ligne a été mis en œuvre et a éliminé la responsabilité de répondre aux consultations médicales en ligne pour les médecins urgentistes en service à Ottawa. La durée totale de l'appel n'était pas significativement différente entre les groupes. Les intervalles de temps supplémentaires et l'adhésion aux avantages du protocole n'étaient pas non plus statistiquement significatifs en raison de la faible incidence initiale.

Evaluation of a prehospital endovascular therapy stroke bypass program.

INTRODUCTION: Prehospital stroke endovascular therapy bypass transports patients with suspected large vessel occlusion directly to an endovascular therapy capable center. Our objective was to determine if an endovascular therapy bypass protocol improved access to stroke treatments. Secondary objectives were to determine safety, effectiveness, and rate of subsequent interfacility transfers. METHODS: Endovascular therapy bypass in 2018 was implemented in Eastern Ontario, for patients with a Los-Angeles-Motor-Scale ≥ 4 (positive large vessel occlusion screen) with a 90-min transport time if < 6 h from last seen well. A before-after health record review was conducted from Dec 1, 2017 to Nov 30, 2019. A piloted data form was used to extract demographics, times, primary outcomes (endovascular therapy and intravenous (IV) tissue plasminogen activator (tPA) rate), and secondary outcomes (redirect to closer hospital, airway intervention, and subsequent interfacility transfer). We present descriptive statistics and odds ratios (OR) with 95% confidence intervals (CI) from multivariable logistic regression. RESULTS: We included 379 stroke patients (165 pre and 214 post-implementation). The endovascular therapy rate between groups was similar (14.1% vs 15.1%). The bypass had an OR of 0.98 (95% CI 0.54-1.78) for receiving endovascular therapy. IV tPA was given to 25.4% of patients pre vs 27.4% post-implementation (OR 1.06, 95% CI 0.65-1.74). No patients became unstable during transport, only one patient had an intubation attempt. The inappropriate bypass (false positive) rate was 12.7% pre vs 12.8% post-implementation (positive predictive value 87%). The bypass protocol had an OR of 1.06 (95% CI 0.58-1.95) for subsequent interfacility transfer with a mean of 2.7 h at the community site before transfer. CONCLUSIONS: Endovascular therapy stroke bypass with 90-min transport radius and Los-Angeles-Motor-Scale ≥ 4 was safe and well executed by paramedics. Our study did not show any difference in endovascular therapy rate from its implementation. The IV tPA rate was similar between groups despite potentially bypassing thrombolysis capable centers.

ABSTRAIT: INTRODUCTION: Le pontage de la thérapie endovasculaire pré-hospitalière transporte les patients présentant une occlusion suspectée de gros vaisseaux directement vers un centre capable de thérapie endovasculaire. Notre objectif était de déterminer si un protocole de pontage endovasculaire améliore l'accès aux traitements d'AVC. Les objectifs secondaires étaient de déterminer l'innocuité, l'efficacité et le taux des transferts d'interfacilité subséquents. MéTHODES: Le pontage par thérapie endovasculaire en 2018 a été mis en œuvre dans l'Est de l'Ontario, pour les patients ayant un test Los-Angeles-Motor-Scale 4 (test positif d'occlusion des gros vaisseaux) avec un temps de transport de 90 minutes si < 6 heures après la dernière observation. Un examen du dossier de santé avant-après a été effectué du 1er décembre 2017 au 30 novembre 2019. Un formulaire de données pilote a été utilisé pour extraire les données démographiques, les heures, les résultats primaires (traitement endovasculaire et taux d'activation du plasminogène par voie intraveineuse (IV) et les résultats secondaires (réorientation vers un hôpital plus proche, intervention sur les voies respiratoires et transfert d'interfacilité subséquent). Nous présentons des statistiques descriptives et des rapports de cotes (RC) avec des intervalles de confiance (IC) à 95 % à partir d'une régression logistique multivariée. RéSULTATS: Nous avons inclus 379 AVC (165 avant et 214 après la mise en œuvre). Le taux de traitement endovasculaire entre les groupes était similaire (14,1 % vs 15,1 %). Le pontage avait un RC de 0,98 (IC à 95 %, 0,54-1,78) pour le traitement endovasculaire. Le tPA IV a été administré à 25,4% des patients avant vs 27,4% après la mise en œuvre (OR 1,06, 95%CI 0,65-1,74). Aucun patient n'est devenu instable pendant le transport, seulement 1 patient a eu une tentative d'intubation. Le taux de pontage inapproprié (faux positif) était de 12,7 % avant et de 12,8 % après la mise en œuvre (valeur prédictive positive de 87 %). Le protocole de contournement avait un RC de 1,06 (IC à 95 % 0,58-1,95) pour le transfert d'interfacilité ultérieur avec une moyenne de 2,7 heures sur le site de la communauté avant le transfert. CONCLUSIONS: Le pontage d'AVC de thérapie endovasculaire avec un rayon de transport de 90 minutes et Los-Angeles-Motor-Scale 4 était sûr et bien exécuté par les ambulanciers. Notre étude n'a montré aucune différence dans le taux de thérapie endovasculaire par rapport à sa mise en œuvre. Le taux de tPA IV était similaire entre les groupes malgré le fait que les centres capables de contourner la thrombolyse étaient potentiellement contournés.

Impact of the COVID-19 pandemic on Canadian emergency medical system management of out-of-hospital cardiac arrest: A retrospective cohort study.

AIM: We sought to describe the impact of the COVID-19 pandemic on the care provided by Canadian emergency medical system (EMS) clinicians to patients suffering out of hospital cardiac arrest (OHCA), and whether any observed changes persisted beyond the initial phase of the pandemic. METHODS: We analysed cases of adult, non-traumatic, OHCA from the Canadian Resuscitation Outcome Consortium (CanROC) registry who were treated between January 27th, 2018, and December 31st, 2021. We used adjusted regression models and interrupted time series analysis to examine the impact of the COVID-19 pandemic (January 27th, 2020 - December 31st, 2021)on the care provided to patients with OHCA by EMS clinicians. RESULTS: There were 12,947 cases of OHCA recorded in the CanROC registry in the pre-COVID-19 period and 17,488 during the COVID-19 period. We observed a reduction in the cumulative number of defibrillations provided by EMS (aRR 0.91, 95% CI 0.89 - 0.93, p < 0.01), a reduction in the odds of attempts at intubation (aOR 0.33, 95% CI 0.31 - 0.34, p < 0.01), higher rates of supraglottic airway use (aOR 1.23, 95% CI 1.16-1.30, p < 0.01), a reduction in vascular access (aOR for intravenous access 0.84, 95% CI 0.79 - 0.89, p < 0.01; aOR for intraosseous access 0.89, 95% CI 0.82 - 0.96, p < 0.01), a reduction in the odds of epinephrine administration (aOR 0.89, 95% CI 0.85 - 0.94, p < 0.01), and higher odds of resuscitation termination on scene (aOR 1.38, 95% CI 1.31 - 1.46, p < 0.01). Delays to initiation of chest compressions (2 min. vs. 3 min., p < 0.01), intubation (16 min. vs. 19 min., p = 0.01), and epinephrine administration (11 min. vs. 13 min., p < 0.01) were observed, whilst supraglottic airways were inserted earlier (11 min. vs. 10 min., p < 0.01). CONCLUSION: The COVID-19 pandemic was associated with substantial changes in EMS management of OHCA. EMS leaders should consider these findings to optimise current OHCA management and prepare for future pandemics.

Identifying Features of a System of Practice to Inform a Contemporary Competency Framework for Paramedics in Canada.

INTRODUCTION: Paramedic practice is highly variable, occurs in diverse contexts, and involves the assessment and management of a range of presentations of varying acuity across the lifespan. As a result, attempts to define paramedic practice have been challenging and incomplete. This has led to inaccurate or under-representations of practice that can ultimately affect education, assessment, and the delivery of care. In this study, we outline our efforts to better identify, explore, and represent professional practice when developing a national competency framework for paramedics in Canada. METHODS: We used a systems-thinking approach to identify the settings, contexts, features, and influences on paramedic practice in Canada. This approach makes use of the role and influence of system features at the microsystem, mesosystem, exosystem, macrosystem, supra-macrosystem, and chronosystem levels in ways that can provide new insights. We used methods such as rich pictures, diagramming, and systems mapping to explore relationships between these contexts and features. FINDINGS: When we examine the system of practice in paramedicine, multiple layers become evident and within them we start to see details of features that ought to be considered in any future competency development work. Our exploration of the system highlights that paramedic practice considers the person receiving care, caregivers, and paramedics. It involves collaboration within co-located and dispersed teams that are composed of other health and social care professionals, public safety personnel, and others. Practice is enacted across varying geographical, cultural, social, and technical contexts and is subject to multiple levels of policy, regulatory, and legislative influence. CONCLUSION: Using a systems-thinking approach, we developed a detailed systems map of paramedic practice in Canada. This map can be used to inform the initial stages of a more representative, comprehensive, and contemporary national competency framework for paramedics in Canada.

Venous sinus stenting versus ventriculoperitoneal shunting: comparing clinical outcomes for idiopathic intracranial hypertension.

BACKGROUND: Venous sinus stenting (VSS) has been shown to reduce intracranial venous pressures and improve symptoms in patients with idiopathic intracranial hypertension (IIH). However, long-term follow-up data are limited, raising concerns about sustained symptom improvement. We aimed to assess long-term outcomes of VSS compared with ventriculoperitoneal shunting (VPS). METHODS: A retrospective case-control study assessed 87 patients with IIH who met inclusion criteria and underwent either VSS (n=27) or VPS (n=60) between 2017 and 2022. Descriptive statistics for baseline characteristics and outcomes were calculated, followed by multivariate logistic regression to identify factors associated with headache recurrence. RESULTS: Baseline characteristics were similar between VSS and VPS groups, including age (p=0.58), sex (p=0.74), body mass index (p=0.47), and preoperative lumbar puncture opening pressure (p=0.62). Preoperative symptoms of headaches (p=0.42), papilledema (p=0.35), and pulsatile tinnitus (p=0.56) were also similar. Initial headache improvement was comparable (96% vs 91%, p=0.42). However, headache recurrence was less common in the VSS group (31% vs 60%, p=0.015) at the last follow-up, averaging over 1 year. Multivariate analysis showed VSS was independently associated with reduced odds of headache recurrence (OR 0.24, p=0.015). Longer follow-up was associated with increased odds of headache recurrence in both groups (OR 1.01, p=0.032). CONCLUSION: VSS was independently associated with reduced odds of headache recurrence compared with VPS in multivariate analysis. Longer follow-up was significantly associated with headache recurrence in both groups. This suggests that VSS may lead to better outcomes for continued headache relief, but headache recurrence may increase with longer follow-up regardless of treatment modality.

Stearoyl-CoA desaturase inhibition is toxic to acute myeloid leukemia displaying high levels of the de novo fatty acid biosynthesis and desaturation.

Identification of specific and therapeutically actionable vulnerabilities, ideally present across multiple mutational backgrounds, is needed to improve acute myeloid leukemia (AML) patients' outcomes. We identify stearoyl-CoA desaturase (SCD), the key enzyme in fatty acid (FA) desaturation, as prognostic of patients' outcomes and, using the clinical-grade inhibitor SSI-4, show that SCD inhibition (SCDi) is a therapeutic vulnerability across multiple AML models in vitro and in vivo. Multiomic analysis demonstrates that SCDi causes lipotoxicity, which induces AML cell death via pleiotropic effects. Sensitivity to SCDi correlates with AML dependency on FA desaturation regardless of mutational profile and is modulated by FA biosynthesis activity. Finally, we show that lipotoxicity increases chemotherapy-induced DNA damage and standard chemotherapy further sensitizes AML cells to SCDi. Our work supports developing FA desaturase inhibitors in AML while stressing the importance of identifying predictive biomarkers of response and biologically validated combination therapies to realize their full therapeutic potential.