Publications by authors named "Nathan Scales"

8 Publications

  • Page 1 of 1

Early Warning of Infection in Patients Undergoing Hematopoietic Stem Cell Transplantation Using Heart Rate Variability and Serum Biomarkers.

Transplant Cell Ther 2021 May 5. Epub 2021 May 5.

Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Departments of Critical Care Medicine and Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada.

Early warning of infection is critical to reduce the risk of deterioration and mortality, especially in neutropenic patients following hematopoietic stem cell transplantation (HCT). Given that heart rate variability (HRV) is a sensitive and early marker for infection, and that serum inflammatory biomarkers can have high specificity for infection, we hypothesized their combination may be useful for accurate early warning of infection. In this study, we developed and evaluated a composite predictive model using continuous HRV with daily serum biomarker measurements to provide risk stratification of future deterioration in HCT recipients. A total of 116 ambulatory outpatients about to undergo HCT consented to collection of prospective demographic, clinical (daily vital signs), HRV (continuous electrocardiography [ECG] monitoring, laboratory [daily serum samples frozen at -80 °C]), and infection outcome variables (defined as the time of escalation of antibiotics), all from 24 hours pre-HCT to the onset of infection or 14 days post-HCT. Indications for antibiotic escalation were adjudicated as "true infection" or not by 2 blinded HCT clinicians. A composite time series of 8 HRV metrics was created for each patient, and the probability of deterioration within the next 72 hours was estimated using logistic regression modeling of composite HRV and serum biomarkers using a rule-based naïve Bayes model if the HRV-based probability exceeded a median threshold. Thirty-five patients (30%) withdrew within <24 hours owing to intolerability of ECG monitoring, leaving 81 patients, of whom 48 (59%) had antibiotic escalation adjudicated as true infection. The combined HRV and biomarker (TNF-α, IL-6, and IL-7) predictive model began increasing at ∼48 hours on average before the diagnosis of infection, could distinguish between high risk of impending infection (>90% incidence of subsequent infection within 72 hours), average risk (∼50%), and low risk (<10%), with an area under the receiver operating characteristic curve of 0.87. However, given that prophylactic predictive ECG monitoring and daily serum collection proved challenging for many patients, further refinement in measurement is necessary for further study.
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http://dx.doi.org/10.1016/j.jtct.2021.04.023DOI Listing
May 2021

Large pH oscillations promote host defense against human airways infection.

J Exp Med 2021 Apr;218(4)

Department of Physiology, McGill University, Montréal, Québec, Canada.

The airway mucosal microenvironment is crucial for host defense against inhaled pathogens but remains poorly understood. We report here that the airway surface normally undergoes surprisingly large excursions in pH during breathing that can reach pH 9.0 during inhalation, making it the most alkaline fluid in the body. Transient alkalinization requires luminal bicarbonate and membrane-bound carbonic anhydrase 12 (CA12) and is antimicrobial. Luminal bicarbonate concentration and CA12 expression are both reduced in cystic fibrosis (CF), and mucus accumulation both buffers the pH and obstructs airflow, further suppressing the oscillations and bacterial-killing efficacy. Defective pH oscillations may compromise airway host defense in other respiratory diseases and explain CF-like airway infections in people with CA12 mutations.
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http://dx.doi.org/10.1084/jem.20201831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845918PMC
April 2021

Resumption of Cardiac Activity after Withdrawal of Life-Sustaining Measures.

N Engl J Med 2021 01;384(4):345-352

From the Children's Hospital of Eastern Ontario (S.D.), Children's Hospital of Eastern Ontario Research Institute (S.D., L.H., A. van Beinum, M.H., H.T.), Faculty of Medicine (S.D.) and Centre for Health Law, Policy, and Ethics (J.A.C.), University of Ottawa, Canadian Blood Services (L.H., S.D.S.), Carleton University (A. van Beinum), the Dynamical Analysis Lab (N.B.S., C.H., A.S.), Clinical Epidemiology Program (N.B.S., C.H., A.S.), and Clinical Epidemiology Program Methods Centre (T.R.), Ottawa Hospital Research Institute, the Departments of Critical Care and General Surgery (G.P.) and Surgery (A.S.) and Division of Thoracic Surgery (A.S.), Ottawa Hospital, and Interventional Cardiology Program, University of Ottawa Heart Institute (D. So), Ottawa, the Department of Critical Care, Trauma and Neurosurgery Program, St. Michael's Hospital (A. Baker), Li Ka Shing Knowledge Institute, Unity Health-St. Michael's Hospital (J.O.F., D. Scales), University of Toronto (J.O.F.), Mount Sinai Hospital (S.M., L.M.) and Interdepartmental Division of Critical Care Medicine (S.M., L.M., D. Scales), University of Toronto, Department of Critical Care Medicine, Sunnybrook Health Sciences Centre (D. Scales), and the Canadian Donation and Transplantation Research Program (H.T.), Toronto, the Departments of Critical Care and Anesthesia, Dalhousie University, Halifax, NS (S.B.), the Departments of Medicine and Critical Care Medicine, Queen's University, Kingston, ON (J.G.B., D.M.M.), the Department of Medicine (Critical Care), Research Centre of the University of Montreal Hospital (M.C.), the Department of Critical Care, Division of Pulmonary Medicine, McGill University (J.S.), McGill University Health Centre and Research Institute (J.S., S.D.S.), Transplant Québec (M.W.), and the Division of Critical Care, Montreal Children's Hospital (S.D.S.), Montreal, the Department of Anesthesiology, Université de Sherbrooke and Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Sherbrooke, Sherbrooke, QC (F. D'Aragon), the Departments of Critical Care Medicine, Community Health Sciences, and Medicine, Cumming School of Medicine (C.J.D.), and the Departments of Critical Care Medicine and Clinical Neurosciences (A.H.K.), University of Calgary, and Calgary Zone, Alberta Health Services (C.J.D.), Calgary, the Department of Clinical Neurological Sciences, London Health Sciences Centre (T.G.), Schulich School of Medicine and Dentistry (T.G.), the Department of Psychology, King's University College (L.N.), and the Department of Medicine and the Brain and Mind Institute (M. Slessarev), Western University, London, ON, the Division of Critical Care, Departments of Medicine and Anesthesia, University of British Columbia, Vancouver (G.I.), the Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton (D.J.K.), the Department of Medicine, McMaster University, and Hamilton Health Sciences Centre, Hamilton, ON (M.M.), and the Division of Pediatric Intensive Care, CHU de Québec, Centre Mère-Enfant Soleil, and the Department of Pediatrics, Faculté de Médecine, Université Laval, Quebec City, QC (M.W.) - all in Canada; Safar Center for Resuscitation Research, Critical Care Medicine Department, University of Pittsburgh School of Medicine, Pittsburgh (C.D.); Charles University, Third Faculty of Medicine and FNKV University Hospital (F. Duska, M. Schmidt, P.W.), and the Department of Palliative Medicine, First Faculty of Medicine, Charles University and General University Hospital (K.R.), Prague, Czech Republic; NHS Blood and Transplant, Bristol (D.G., D.H.), and Adult Critical Care, Nottingham University Hospitals NHS Trust, Nottingham (D.G., D.H.) - both in the United Kingdom; and the Department of Intensive Care Medicine, Maastricht University Medical Center, and the School of Health Professions Education, Maastricht University (W.N.K.A.M.), and the Heart and Vascular Center, Maastricht University Medical Center (J.T.W.), Maastricht, the Netherlands.

Background: The minimum duration of pulselessness required before organ donation after circulatory determination of death has not been well studied.

Methods: We conducted a prospective observational study of the incidence and timing of resumption of cardiac electrical and pulsatile activity in adults who died after planned withdrawal of life-sustaining measures in 20 intensive care units in three countries. Patients were intended to be monitored for 30 minutes after determination of death. Clinicians at the bedside reported resumption of cardiac activity prospectively. Continuous blood-pressure and electrocardiographic (ECG) waveforms were recorded and reviewed retrospectively to confirm bedside observations and to determine whether there were additional instances of resumption of cardiac activity.

Results: A total of 1999 patients were screened, and 631 were included in the study. Clinically reported resumption of cardiac activity, respiratory movement, or both that was confirmed by waveform analysis occurred in 5 patients (1%). Retrospective analysis of ECG and blood-pressure waveforms from 480 patients identified 67 instances (14%) with resumption of cardiac activity after a period of pulselessness, including the 5 reported by bedside clinicians. The longest duration after pulselessness before resumption of cardiac activity was 4 minutes 20 seconds. The last QRS complex coincided with the last arterial pulse in 19% of the patients.

Conclusions: After withdrawal of life-sustaining measures, transient resumption of at least one cycle of cardiac activity after pulselessness occurred in 14% of patients according to retrospective analysis of waveforms; only 1% of such resumptions were identified at the bedside. These events occurred within 4 minutes 20 seconds after a period of pulselessness. (Funded by the Canadian Institutes for Health Research and others.).
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http://dx.doi.org/10.1056/NEJMoa2022713DOI Listing
January 2021

Resolving fluorescent species by their brightness and diffusion using correlated photon-counting histograms.

PLoS One 2019 30;14(12):e0226063. Epub 2019 Dec 30.

Department of Physiology, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada.

Fluorescence fluctuation spectroscopy (FFS) refers to techniques that analyze fluctuations in the fluorescence emitted by fluorophores diffusing in a small volume and can be used to distinguish between populations of molecules that exhibit differences in brightness or diffusion. For example, fluorescence correlation spectroscopy (FCS) resolves species through their diffusion by analyzing correlations in the fluorescence over time; photon counting histograms (PCH) and related methods based on moment analysis resolve species through their brightness by analyzing fluctuations in the photon counts. Here we introduce correlated photon counting histograms (cPCH), which uses both types of information to simultaneously resolve fluorescent species by their brightness and diffusion. We define the cPCH distribution by the probability to detect both a particular number of photons at the current time and another number at a later time. FCS and moment analysis are special cases of the moments of the cPCH distribution, and PCH is obtained by summing over the photon counts in either channel. cPCH is inherently a dual channel technique, and the expressions we develop apply to the dual colour case. Using simulations, we demonstrate that two species differing in both their diffusion and brightness can be better resolved with cPCH than with either FCS or PCH. Further, we show that cPCH can be extended both to longer dwell times to improve the signal-to-noise and to the analysis of images. By better exploiting the information available in fluorescence fluctuation spectroscopy, cPCH will be an enabling methodology for quantitative biology.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226063PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936799PMC
April 2020

Heart Rate Variability, Clinical and Laboratory Measures to Predict Future Deterioration in Patients Presenting With Sepsis.

Shock 2019 04;51(4):416-422

Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada.

Background: Risk stratification of patients presenting to the emergency department (ED) with sepsis can be challenging. We derived and evaluated performance of a predictive model containing clinical, laboratory, and heart rate variability (HRV) measures to quantify risk of deterioration in this population.

Methods: ED patients aged 21 and older satisfying the 1992 consensus conference criteria for sepsis and able to consent (directly or through a surrogate) were enrolled (n = 1,247). Patients had clinical, laboratory, and HRV data recorded within 1 h of ED presentation, and were followed to identify deterioration within 72 h.

Results: Eight hundred thirty-two patients had complete data, of whom 68 (8%) reached at least one endpoint. Optimal predictive performance was derived from a combination of laboratory values and HRV metrics with an area under the receiver-operating curve (AUROC) of 0.80 (95% CI, 0.65-0.92). This combination of variables was superior to clinical (AUROC = 0.69, 95% CI, 0.54-0.83), laboratory (AUROC = 0.77, 95% CI, 0.63-0.90), and HRV measures (AUROC = 0.76, 95% CI, 0.61-0.90) alone. The HRV+LAB model identified a high-risk cohort of patients (14% of all patients) with a 4.3-fold (95% CI, 3.2-5.4) increased risk of deterioration (incidence of deterioration: 35%), as well as a low-risk group (61% of all patients) with 0.2-fold (95% CI 0.1-0.4) risk of deterioration (incidence of deterioration: 2%).

Conclusions: A model that combines HRV and laboratory values may help ED physicians evaluate risk of deterioration in patients with sepsis and merits validation and further evaluation.
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http://dx.doi.org/10.1097/SHK.0000000000001192DOI Listing
April 2019

Practice Variation in Spontaneous Breathing Trial Performance and Reporting.

Can Respir J 2016 29;2016:9848942. Epub 2016 Mar 29.

The Ottawa Hospital, University of Ottawa, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6.

Background. Spontaneous breathing trials (SBTs) are standard of care in assessing extubation readiness; however, there are no universally accepted guidelines regarding their precise performance and reporting. Objective. To investigate variability in SBT practice across centres. Methods. Data from 680 patients undergoing 931 SBTs from eight North American centres from the Weaning and Variability Evaluation (WAVE) observational study were examined. SBT performance was analyzed with respect to ventilatory support, oxygen requirements, and sedation level using the Richmond Agitation Scale Score (RASS). The incidence of use of clinical extubation criteria and changes in physiologic parameters during an SBT were assessed. Results. The majority (80% and 78%) of SBTs used 5 cmH2O of ventilator support, although there was variability. A significant range in oxygenation was observed. RASS scores were variable, with RASS 0 ranging from 29% to 86% and 22% of SBTs performed in sedated patients (RASS < -2). Clinical extubation criteria were heterogeneous among centres. On average, there was no change in physiological variables during SBTs. Conclusion. The present study highlights variation in SBT performance and documentation across and within sites. With their impact on the accuracy of outcome prediction, these results support efforts to further clarify and standardize optimal SBT technique.
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http://dx.doi.org/10.1155/2016/9848942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4904518PMC
July 2017

Modeling electroosmotic and pressure-driven flows in porous microfluidic devices: zeta potential and porosity changes near the channel walls.

J Chem Phys 2006 Sep;125(9):094714

Department of Electronics, Carleton University, Ottawa, Ontario K1S 5B6, Canada.

This work presents analytical solutions for both pressure-driven and electroosmotic flows in microchannels incorporating porous media. Solutions are based on a volume-averaged flow model using a scaling of the Navier-Stokes equations for fluid flow. The general model allows analysis of fluid flow in channels with porous regions bordering open regions and includes viscous forces, permitting consideration of porosity and zeta potential variations near channel walls. To obtain analytical solutions problems are constrained to the linearized Poisson-Boltzmann equation and a variation of Brinkman's equation [Appl. Sci. Res., Sect. A 1, 27 (1947); 1, 81 (1947)]. Cases include one continuous porous medium, two adjacent regions of different porosities, or one open channel adjacent to a porous region, and the porous material may have a different zeta potential than that of the channel walls. Solutions are described for two geometries, including flow between two parallel plates or in a cylinder. The model illustrates the relative importance of porosity and zeta potential in different regions of each channel.
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http://dx.doi.org/10.1063/1.2335846DOI Listing
September 2006