Publications by authors named "Andrew G Day"

162 Publications

Relationship Between Nutrition Intake and Outcome After Subarachnoid Hemorrhage: Results From the International Nutritional Survey.

J Intensive Care Med 2021 Oct;36(10):1141-1148

Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, ON, USA.

Background: A previous study suggested an association between low caloric intake(CI), negative nitrogen balance, and poor outcome after subarachnoid hemorrhage(SAH). Objective of this multinational, multicenter study was to investigate whether clinical outcomes vary by protein intake(PI) or CI in SAH patients adjusting for the nutritional risk as judged by the modified NUTrition Risk in the Critically Ill (mNUTRIC) score.

Methods: The International Nutrition Survey(INS) 2007-2014 was utilized to describe the characteristics, outcomes and nutrition use. A subgroup of patients from 2013 and 2014(when NUTRIC score was captured) examined the association between CI and PI and time to discharge alive(TTDA) from hospital using Cox regression models, adjusting for nutrition risk classified by the mNUTRIC score as low(0-4) or high(5-9).

Results: There were 489 SAH patients(57% female with a mean ± SD age 57.5 ± 13.9 years, BMI of 25.9 ± 5.3 kg/m and APACHE-2 score 19.4 ± 7.0. Majority(85%) received enteral nutrition(EN) only, with a time to initiation of EN of 35.4 ± 35.2 hours. 64% had EN interrupted. Patients received a CI of 14.6 ± 7.1 calories/kg/day and PI 0.7 ± 0.3 grams/kg/day corresponding to 59% and 55% of total prescribed CI and PI respectively. In the 2013 and 2014 subgroup there were 226 SAH patients with a mNUTRIC score of 3.4 ± 1.8. Increased CI and PI were associated with faster TTDA among high mNUTRIC patients(HR per 20% of prescription received = 1.34[95% CI,1.03 -1.76] for CI and 1.44[1.07 -1.93] for PI), but not low mNUTRIC patients(CI: HR = 0.95[0.77 -1.16] PI:0.95[0.78 -1.16]).

Conclusions: Results from this multicenter study found that SAH patients received under 60% of their prescribed CI and PI. Further, achieving greater CI and PI in hi risk SAH patients was associated with improved TTDA. mNUTRIC serves to identify SAH patients that benefit most from artificial nutrition and efforts to optimize protein and caloric delivery in this subpopulation should be maximized.
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http://dx.doi.org/10.1177/0885066620966957DOI Listing
October 2021

Relationship Between Nutrition Intake and Outcome After Subarachnoid Hemorrhage: Results From the International Nutritional Survey.

J Intensive Care Med 2021 Oct;36(10):1141-1148

Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, ON, USA.

Background: A previous study suggested an association between low caloric intake(CI), negative nitrogen balance, and poor outcome after subarachnoid hemorrhage(SAH). Objective of this multinational, multicenter study was to investigate whether clinical outcomes vary by protein intake(PI) or CI in SAH patients adjusting for the nutritional risk as judged by the modified NUTrition Risk in the Critically Ill (mNUTRIC) score.

Methods: The International Nutrition Survey(INS) 2007-2014 was utilized to describe the characteristics, outcomes and nutrition use. A subgroup of patients from 2013 and 2014(when NUTRIC score was captured) examined the association between CI and PI and time to discharge alive(TTDA) from hospital using Cox regression models, adjusting for nutrition risk classified by the mNUTRIC score as low(0-4) or high(5-9).

Results: There were 489 SAH patients(57% female with a mean ± SD age 57.5 ± 13.9 years, BMI of 25.9 ± 5.3 kg/m and APACHE-2 score 19.4 ± 7.0. Majority(85%) received enteral nutrition(EN) only, with a time to initiation of EN of 35.4 ± 35.2 hours. 64% had EN interrupted. Patients received a CI of 14.6 ± 7.1 calories/kg/day and PI 0.7 ± 0.3 grams/kg/day corresponding to 59% and 55% of total prescribed CI and PI respectively. In the 2013 and 2014 subgroup there were 226 SAH patients with a mNUTRIC score of 3.4 ± 1.8. Increased CI and PI were associated with faster TTDA among high mNUTRIC patients(HR per 20% of prescription received = 1.34[95% CI,1.03 -1.76] for CI and 1.44[1.07 -1.93] for PI), but not low mNUTRIC patients(CI: HR = 0.95[0.77 -1.16] PI:0.95[0.78 -1.16]).

Conclusions: Results from this multicenter study found that SAH patients received under 60% of their prescribed CI and PI. Further, achieving greater CI and PI in hi risk SAH patients was associated with improved TTDA. mNUTRIC serves to identify SAH patients that benefit most from artificial nutrition and efforts to optimize protein and caloric delivery in this subpopulation should be maximized.
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http://dx.doi.org/10.1177/0885066620966957DOI Listing
October 2021

Identifying neurocognitive outcomes and cerebral oxygenation in critically ill adults on acute kidney replacement therapy in the intensive care unit: the INCOGNITO-AKI study protocol.

BMJ Open 2021 08 17;11(8):e049250. Epub 2021 Aug 17.

Centre for Neuroscience Studies, Queen's University, Kingston, Ontario, Canada

Introduction: Initiation of acute kidney replacement therapy (KRT) is common in critically ill adults admitted to the intensive care unit (ICU), and associated with increased morbidity and mortality. KRT has been linked to poor neurocognitive outcomes, leading to reduced quality of life and increased utilisation of healthcare resources. Adults on dialysis in the ICU may be particularly at risk of neurocognitive impairment, as survivors of critical illness are already predisposed to developing cerebrovascular disease and cognitive dysfunction long-term relative to healthy controls. Regional cerebral oxygen saturation may provide a critical early marker of long-term neurocognitive impairment in this population. This study aims to understand cerebral oxygenation in patients undergoing KRT (continuous or intermittent) in the ICU. These findings will be correlated with long-term cognitive and functional outcomes, and structural brain pathology.

Methods And Analysis: 108 patients scheduled to undergo treatment for acute kidney injury with KRT in the Kingston Health Sciences Centre ICU will be recruited into this prospective observational study. Enrolled patients will be assessed with intradialytic cerebral oximetry using near infrared spectroscopy. Delirium will be assessed daily with the Confusion Assessment Method-ICU (CAM-ICU) and severity quantified as cumulative CAM-ICU-7 scores. Neurocognitive impairment will be assessed at 3 and 12 months after hospital discharge using the Kinarm and Repeatable Battery for the Assessment of Neuropsychological Status. Structural brain pathology on MRI will also be measured at the same timepoints. Driving safety, adverse events and medication adherence will be assessed at 12 months to evaluate the impact of neurocognitive impairment on functional outcomes.

Ethics And Dissemination: This study is approved by the Queen's University Health Sciences/Affiliated Teaching Hospitals Research Ethics Board (DMED-2424-20). Results will be presented at critical care conferences, and a lay summary will be provided to patients in their preferred format.

Trial Registration Number: NCT04722939.
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http://dx.doi.org/10.1136/bmjopen-2021-049250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372874PMC
August 2021

The effect of higher versus lower protein delivery in critically ill patients: a systematic review and meta-analysis of randomized controlled trials.

Crit Care 2021 07 23;25(1):260. Epub 2021 Jul 23.

Department of Critical Care Medicine, Queen's University and the Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, ON, Canada.

Background: The optimal protein dose in critical illness is unknown. We aim to conduct a systematic review of randomized controlled trials (RCTs) to compare the effect of higher versus lower protein delivery (with similar energy delivery between groups) on clinical and patient-centered outcomes in critically ill patients.

Methods: We searched MEDLINE, EMBASE, CENTRAL and CINAHL from database inception through April 1, 2021.We included RCTs of (1) adult (age ≥ 18) critically ill patients that (2) compared higher vs lower protein with (3) similar energy intake between groups, and (4) reported clinical and/or patient-centered outcomes. We excluded studies on immunonutrition. Two authors screened and conducted quality assessment independently and in duplicate. Random-effect meta-analyses were conducted to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes).

Results: Nineteen RCTs were included (n = 1731). Sixteen studies used primarily the enteral route to deliver protein. Intervention was started within 72 h of ICU admission in sixteen studies. The intervention lasted between 3 and 28 days. In 11 studies that reported weight-based nutrition delivery, the pooled mean protein and energy received in higher and lower protein groups were 1.31 ± 0.48 vs 0.90 ± 0.30 g/kg and 19.9 ± 6.9 versus 20.1 ± 7.1 kcal/kg, respectively. Higher vs lower protein did not significantly affect overall mortality [risk ratio 0.91, 95% confidence interval (CI) 0.75-1.10, p = 0.34] or other clinical or patient-centered outcomes. In 5 small studies, higher protein significantly attenuated muscle loss (MD -3.44% per week, 95% CI -4.99 to -1.90; p < 0.0001).

Conclusion: In critically ill patients, a higher daily protein delivery was not associated with any improvement in clinical or patient-centered outcomes. Larger, and more definitive RCTs are needed to confirm the effect of muscle loss attenuation associated with higher protein delivery. PROSPERO registration number: CRD42021237530.
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http://dx.doi.org/10.1186/s13054-021-03693-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300989PMC
July 2021

Correlation between gastric residual volumes and markers of gastric emptying: A post hoc analysis of a randomized clinical trial.

JPEN J Parenter Enteral Nutr 2021 Jul 22. Epub 2021 Jul 22.

Clinical Evaluation Research Unit, Kingston Health Science Centre, Kingston, Ontario, Canada.

Background: The correlation between gastric residual volumes (GRVs) and markers of gastric emptying (GE) in critically ill patients is unclear. This particularly applies to critically ill surgical patients, as they are underrepresented in previous studies.

Methods: We conducted a post hoc analysis of a multicenter trial that investigated the effectiveness of a promotility drug. Pharmacokinetic markers of GE (3-O-methylglucose [3-OMG] and acetaminophen) were correlated with GRV measurements. High GRV was defined as one episode of >400 ml or two consecutive episodes of >250 ml, and delayed GE was defined as <20th percentile of the pharmacokinetic GE marker that had the strongest correlation with GE.

Results: Of 77 patients, 8 (10.4%) had high GRV, and 15 (19.5%) had delayed GE. The 3-OMG concentration at 60 min had the strongest correlation with GRV (ρ = -0.631), and high GRV had low sensitivity (46.7%) but high specificity (98.4%) in discriminating delayed GE. The positive (87.5%) and negative (88.4%) predictive values were similar. Compared with medical patients, surgical patients (n = 14, 18.2%), had a significantly higher incidence of high GRV (29% vs 6%, P = .032) and a trend toward delayed GE (36% vs 16%, P = .132).

Conclusion: GRV reflects GE, and high GRV is an acceptable surrogate marker of delayed GE. From our preliminary observation, surgical patients may have a higher risk of high GRV and delayed GE. In summary, GRV should be monitored to determine whether complex investigations or therapeutic interventions are warranted.
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http://dx.doi.org/10.1002/jpen.2234DOI Listing
July 2021

Validation of the modified NUTrition Risk Score (mNUTRIC) in mechanically ventilated, severe burn patients: A prospective multinational cohort study.

Burns 2021 May 15. Epub 2021 May 15.

Clinical Evaluation Research Unit, Queen's University, Kingston, ON, K7L 2V7, Canada; Department of Critical Care Medicine, Queen's University, Kingston, ON, K7L 2V7, Canada; Research Institute, Kingston Health Sciences Centre, Kingston, ON, K7L 2V7, Canada. Electronic address:

Background: Whether nutrition therapy benefits all burn victims equally is unknown. To identify patients who will benefit the most from optimal nutrition, the modified Nutrition Risk in Critically Ill (mNUTRIC) Score has been validated in the Intensive Care Unit. However, the utility of mNUTRIC in severe burn victims is unknown. We hypothesized that a higher mNUTRIC (≥5) will be associated with worse clinical outcomes, but that greater nutritional adequacy will be associated with better clinical outcomes in patients with higher mNUTRIC score.

Methods: This prospective study included data from mechanically ventilated, severe burn patients (n = 359) from 51 Burn Units worldwide included in a randomized trial. Our primary and secondary outcomes were hospital mortality and the time to discharge alive (TTDA) from hospital. We described the association between nutrition performance and clinical outcomes.

Results: Compared to low mNUTRIC (n = 313), the high mNUTRIC group (n = 46) had higher mortality (61% vs. 19%, p = 0.001), and longer TTDA (>90 [87->90] vs. 64 [38-90] days, p = <0.0001). Only in the high mNUTRIC group, increased calorie intake (per 20% increase) was associated with lower mortality and a faster TTDA.

Conclusions: The mNUTRIC score identifies those with poor clinical outcomes and may identifies those mechanically ventilated, severe burn patients in whom optimal nutrition therapy may be more advantageous.
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http://dx.doi.org/10.1016/j.burns.2021.05.010DOI Listing
May 2021

Initial development and validation of a novel nutrition risk, sarcopenia, and frailty assessment tool in mechanically ventilated critically ill patients: The NUTRIC-SF score.

JPEN J Parenter Enteral Nutr 2021 May 22. Epub 2021 May 22.

Department of Critical Care Medicine, Queen's University and the Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, Ontario, Canada.

Background: Nutrition risk, sarcopenia, and frailty are interrelated. They may be due to suboptimal or prevented by optimal nutrition intake. The combination of nutrition risk (modified nutrition risk in the critically ill [mNUTRIC]), sarcopenia (SARC-F combined with calf circumference [SARC-CALF]), and frailty (clinical frailty scale [CFS]) in a single score may better predict adverse outcomes and prioritize resources for optimal nutrition in the intensive care unit (ICU) METHODS: This is a retrospective analysis of a single-center prospective observational study that enrolled mechanically ventilated adults with expected ≥96 h of ICU stay. SARC-F and CFS questionnaires were administered to patient's next-of-kin and mNUTRIC were calculated. Right calf circumference was measured. Nutrition data were collected from nursing record. The high-risk scores (mNUTRIC ≥ 5, SARC-CALF > 10, or CFS ≥ 4) of these variables were combined to become the nutrition risk, sarcopenia, and frailty (NUTRIC-SF) score (range: 0-3).

Results: Eighty-eight patients were analyzed. Increasing mNUTRIC was independently associated with 60-day mortality, whereas increasing SARC-CALF and CFS showed a strong trend towards a higher 60-day mortality. Discriminative ability of NUTRIC-SF for 60-day mortality is better than its component (C-statistics, 0.722; 95% confidence interval [CI], 0.677-0.868). Every increment of 300 kcal/day and 30 g/day is associated with a trend towards higher rate of discharge alive for high (≥2; adjusted hazard ratio, 1.453 [95% CI, 0.991-2.130] for energy; 1.503 [0.936-2.413] for protein) but not low (<2) NUTRIC-SF score.

Conclusion: NUTRIC-SF may be a clinically relevant risk stratification tool in the ICU.
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http://dx.doi.org/10.1002/jpen.2194DOI Listing
May 2021

Determining the psychometric properties of a novel questionnaire to measure "preparedness for the future" (Prep FQ).

Health Qual Life Outcomes 2021 Apr 15;19(1):122. Epub 2021 Apr 15.

Clinical Evaluation Research Unit, Kingston Health Science Centre, Kingston, ON, Canada.

Background: People are living longer than ever before. However, with living longer comes increased problems that negatively impact on quality of life and the quality of death. Tools are needed to help individuals assess whether they are practicing the best attitudes and behaviors that are associated with a future long life, high quality of life, high quality of death and a satisfying post-death legacy. The purpose of paper is to describe the process we used to develop a novel questionnaire ("Preparedness for the Future Questionnaire™ or Prep FQ") and to define its psychometric properties.

Methods: Using a multi-step development procedure, items were generated, for the new questionnaire after which the psychometric properties were tested with a heterogeneous sample of 502 Canadians. Using an online polling panel, respondents were asked to complete demographic questions as well as the Prep-FQ, Global Rating of Life Satisfaction, the Keyes Psychological Well-Being scale and the Short-Form 12.

Results: The final version of the questionnaire contains 34 items in 8 distinct domains ("Medico-legal", "Social", "Psychological Well-being", "Planning", "Enrichment", "Positive Health Behaviors", "Negative Health Behaviors", and "Late-life Planning"). We observed minimum missing data and good usage of all response options. The average overall Prep FQ score is 51.2 (SD = 13.3). The Cronbach alphas assessing internal reliability for the Prep FQ domains ranged from 0.33 to 0.88. The intra-class correlation coefficient (ICC) used to assess the test-retest reliability had an overall score of 0.87. For the purposes of establishing construct validity, all the pre-specified relationships between Prep FQ and the other questionnaires were met.

Conclusion: Analyses of this novel measure offered support for its face validity, construct validity, test-retest reliability, and internal consistency. With the development of this useful and valid scale, future research can utilize this measure to engage people in the process of comprehensively assessing and improving their state of preparedness for the future, tracking their progress along the way. Ultimately, this program of research aims to improve the quality and quantity of peoples live by helping them 'think ahead' and 'plan ahead' on the aspects of their daily life that matter to their future.
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http://dx.doi.org/10.1186/s12955-021-01759-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048271PMC
April 2021

Longitudinal Outcomes in Octogenarian Critically Ill Patients with a Focus on Frailty and Cardiac Surgery.

J Clin Med 2020 Dec 23;10(1). Epub 2020 Dec 23.

3CARE-Cardiovascular Critical Care & Anesthesia Evaluation and Research, D-52074 Aachen, Germany.

Cardiac surgery (CSX) can be lifesaving in elderly patients (age ≥ 80 years) but may still be associated with complications and functional decline. Frailty represents a determinant to outcomes in critically ill patients, but little is known about its influence on elderly CSX-patients. This is a secondary exploratory analysis of a multi-center, prospective observational cohort study of 610 elderly patients admitted to the ICU and followed for one year to document long-term outcomes. CSX-ICU-patients ( = 49) were compared to surgical ICU patients ( = 184) with regard to demographics, frailty, and outcomes. Of all surgical patients, 102 (43%) were considered vulnerable or frail. The subdistribution hazard ratio (SHR) of time to discharge home (TTDH) for vulnerable/frail vs. fit/well patients was 0.54 (95% confidence interval (CI), 0.34, 0.86, = 0.007). The -value for effect modification between surgery group (CSX vs. surgical ICU patients) and Clinical Frailty Scale (CFS) group was not significant ( = 0.37) suggesting that the observed difference in the CFS effect between the CSX and surgical ICU patients is consistent with random error. A further subgroup analysis shows that among surgical ICU patients, the SHR of time to discharge home (TTDH) for vulnerable/frail vs. fit/well patients was 0.49 (95% CI, 0.29, 0.83) while the corresponding SHR for CSX patients was 0.77 (0.32-1.88). In conclusion, preoperative frailty reduced the rate of discharge to home in both surgical and CSX patients, but a larger sample of CSX patients is needed to adequately address this question in this patient group.
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http://dx.doi.org/10.3390/jcm10010012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793078PMC
December 2020

Translating Evidence-Based Guidelines into Practice-Are We Getting It Right? A Multi-Centre Prospective International Audit of Nutrition Care in Patients with Foregut Tumors (INFORM).

Nutrients 2020 Dec 11;12(12). Epub 2020 Dec 11.

Royal Alexandra Hospital, Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB T5H 3V9, Canada.

Malnutrition is highly prevalent in patients with foregut tumors comprising head and neck (HNC) and esophageal (EC) cancers, negatively impacting outcomes. International evidence-based guidelines (EBGs) for nutrition care exist; however, translation of research evidence into practice commonly presents considerable challenges and consequently lags. This study aimed to describe and evaluate current international nutrition care practices compared with the best-available evidence for patients with foregut tumors who are at high risk of malnutrition. A multi-centre prospective cohort study enrolled 170 patients commencing treatment of curative intent for HNC ( = 119) or EC ( = 51) in 11 cancer care settings in North America, Europe and Australia between 2016 and 2018. Adherence criteria were derived from relevant EBG recommendations with pooled results for participating centres reported according to the Nutrition Care Model at either system or patient levels. Adherence to EBG recommendations was: good (≥80%) for performing baseline nutrition screening and assessment, perioperative nutrition assessment and nutrition prescription for energy and protein targets; moderate (≥60 to 80%) for utilizing validated screening and assessment tools and pre-radiotherapy dietitian consultation; and poor (60%) for initiating post-operative nutrition support within 24 h and also dietetic consultation weekly during radiotherapy and fortnightly for 6 weeks post-radiotherapy. In conclusion, gaps in evidence-based cancer nutrition care remain; however, this may be improved by filling known evidence gaps through high-quality research with a concurrent evolution of EBGs to also encompass practical implementation guidance. These should aim to support multidisciplinary cancer clinicians to close evidence-practice gaps throughout the patient care trajectory with clearly defined roles and responsibilities that also address patient-reported concerns.
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http://dx.doi.org/10.3390/nu12123808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763837PMC
December 2020

The initial validation of a novel outcome measure in severe burns- the Persistent Organ Dysfunction +Death: Results from a multicenter evaluation.

Burns 2021 Jun 3;47(4):765-775. Epub 2020 Oct 3.

Department of Critical Care Medicine, Queen´s University, K7L 2V7 Kingston, Canada. Electronic address:

Introduction: A need exists to improve the efficiency of clinical trials in burn care. The objective of this study was to validate "Persistent Organ Dysfunction" plus death as endpoint in burn patients and to demonstrate its statistical efficiency.

Methods: This secondary outcome analysis of a dataset from a prospective international multicenter RCT (RE-ENERGIZE) included patients with burned total body surface area >20% and a 6-month follow-up. Persistent organ dysfunction was defined as persistence of organ dysfunction with life-supportiing technologies and ICU care.

Results: In the 539 included patients, the prevalence of 0p p+ pdeath was 40% at day 14 and of 27% at day 28. At both timepoints, survivors with POD (vs. survivors without POD) had a higher mortality rate, longer ICU- and hospital-stays, and a reduced quality of life. POD + death as an endpoint could result in reduced sample size requirements for clinical trials. Detecting a 25% relative risk reduction in 28-day mortality would require a sample size of 4492 patients, whereas 1236 patients would be required were 28-day POD + death used.

Conclusions: POD + death represents a promising composite outcome measure that may reduce the sample size requirements of clinical trials in severe burns patients. Further validation in larger clinical trials is warranted.

Study Type: Prospective cohort study, level of evidence: II.
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http://dx.doi.org/10.1016/j.burns.2020.09.003DOI Listing
June 2021

Intravenous Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC): A Randomized, Controlled Trial.

Ann Emerg Med 2021 06 5;77(6):613-619. Epub 2020 Nov 5.

Department of Emergency Medicine, Queen's University, Kingston, Ontario, Canada.

Study Objective: Little is known about the cause or optimal treatment of hyperemesis in habitual cannabis users. Anecdotal evidence supports the use of haloperidol over traditional antiemetics for this newly recognized disorder. We compare haloperidol with ondansetron for cannabis hyperemesis syndrome.

Methods: We randomized cannabis users with active emesis to either haloperidol (with a nested randomization to either 0.05 or 0.1 mg/kg) or ondansetron 8 mg intravenously in a triple-blind fashion. The primary outcome was the reduction from baseline in abdominal pain and nausea (each measured on a 10-cm visual analog scale) at 2 hours after treatment. Although the trial allowed for crossover, the primary analysis used only the first treatment period because few subjects crossed over.

Results: We enrolled 33 subjects, of whom 30 (16 men, aged 29 years [SD 11 years] using 1.5 g/day [SD 0.9 g/day] since age 19 years [SD 2 years]) received at least 1 treatment (haloperidol 13, ondansetron 17). Haloperidol at either dose was superior to ondansetron (difference 2.3 cm [95% confidence interval 0.6 to 4.0 cm]; P=.01), with similar improvements in both pain and nausea, as well as less use of rescue antiemetics (31% versus 59%; difference -28% [95% confidence interval -61% to 13%]) and shorter time to emergency department (ED) departure (3.1 hours [SD 1.7] versus 5.6 hours [SD 4.5]; difference 2.5 hours [95% confidence interval 0.1 to 5.0 hours]; P=.03). There were 2 return visits for acute dystonia, both in the higher-dose haloperidol group.

Conclusion: In this clinical trial, haloperidol was superior to ondansetron for the acute treatment of cannabis-associated hyperemesis. The efficacy of haloperidol over ondansetron provides insight into the pathophysiology of this now common diagnosis in many EDs.
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http://dx.doi.org/10.1016/j.annemergmed.2020.08.021DOI Listing
June 2021

Incidence, Risk Factors, and Clinical Consequence of Enteral Feeding Intolerance in the Mechanically Ventilated Critically Ill: An Analysis of a Multicenter, Multiyear Database.

Crit Care Med 2021 01;49(1):49-59

Clinical Evaluation Research Unit, Kingston Health Science Centre, Kingston, ON, Canada.

Objectives: To determine the incidence of enteral feed intolerance, identify factors associated with enteral feed intolerance, and assess the relationship between enteral feed intolerance and key nutritional and clinical outcomes in critically ill patients.

Design: Analysis of International Nutrition Survey database collected prospectively from 2007 to 2014.

Setting: Seven-hundred eighty-five ICUs from around the world.

Patients: Mechanically ventilated adults with ICU stay greater than or equal to 72 hours and received enteral nutrition during the first 12 ICU days.

Interventions: None.

Measurement And Main Results: We defined enteral feed intolerance as interrupted feeding due to one of the following reasons: high gastric residual volumes, increased abdominal girth, distension, subjective discomfort, emesis, or diarrhea. The current analysis included 15,918 patients. Of these, 4,036 (24%) had at least one episode of enteral feed intolerance. The enteral feed intolerance rate increased from 1% on day 1 to 6% on days 4 and 5 and declined daily thereafter. After controlling for site and patient covariates, burn (odds ratio 1.46; 95% CIs, 1.07-1.99), gastrointestinal (odds ratio 1.45; 95% CI, 1.27-1.66), and sepsis (odds ratio 1.34; 95% CI, 1.17-1.54) admission diagnoses were more likely to develop enteral feed intolerance, as compared to patients with respiratory-related admission diagnosis. enteral feed intolerance patients received about 10% less enteral nutrition intake, as compared to patients without enteral feed intolerance after controlling for important covariates including severity of illness. Enteral feed intolerance patients had fewer ventilator-free days and longer ICU length of stay time to discharge alive (all p < 0.0001). The daily mortality hazard rate increased by a factor of 1.5 (1.4-1.6; p < 0.0001) once enteral feed intolerance occurred.

Conclusions: Enteral feed intolerance occurs frequently during enteral nutrition delivery in the critically ill. Burn and gastrointestinal patients had the highest risk of developing enteral feed intolerance. Enteral feed intolerance is associated with lower enteral nutrition delivery and worse clinical outcomes. Identification, prevention, and optimal management of enteral feed intolerance may improve nutrition delivery and clinical outcomes in important "at risk" populations.
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http://dx.doi.org/10.1097/CCM.0000000000004712DOI Listing
January 2021

Methacholine-Induced Cough in the Absence of Asthma: Insights From Impulse Oscillometry.

Front Physiol 2020 6;11:554679. Epub 2020 Oct 6.

Department of Medicine, School of Medicine, Faculty of Health Sciences, Queen's University, Kingston, ON, Canada.

Introduction: The pathophysiologic differences between methacholine-induced cough but normal airway sensitivity (COUGH) and healthy individuals (CONTROL) are incompletely understood and may be due to differences in the bronchodilating effect of deep inspirations (DIs). The purpose of this study is to compare the bronchodilating effect of DIs in individuals with classic asthma (CA), cough variant asthma (CVA), and COUGH with CONTROL and to assess impulse oscillometry (IOS) measures as predictors of the bronchodilating effect of DIs.

Methods: A total of 43 adults [18 female; 44.8 ± 12.3 years (mean ± SD); = 11 CA, = 10 CVA, = 7 COUGH, = 15 CONTROL] underwent modified high-dose methacholine challenge, with IOS and partial/maximal expiratory flow volume (PEFV/MEFV) maneuvers (used to calculate DI Index) to a maximum change (Δ) in FEV of 50% from baseline (MAX). Cough count and dyspnea were measured at each dose. The relation between IOS parameters and DI Index was assessed at baseline and MAX using multivariable linear regression analysis.

Results: Cough frequency, dyspnea intensity, and baseline peripheral resistance (R5-R20) were significantly greater in COUGH compared with CONTROL ( = 0.006, = 0.029, and = 0.035, respectively). At MAX, the DI Index was significantly lower in COUGH (0.01 ± 0.36) compared with CA (0.67 ± 0.97, = 0.008), CVA (0.51 ± 0.73, = 0.012), and CONTROL (0.68 ± 0.45, = 0.005). Fres and R5-R20 were independent IOS predictors of the DI Index.

Conclusion: The bronchodilating effect is impaired in COUGH and preserved in mild CA, CVA, and CONTROL. Increased peripheral airway resistance and decreased resonant frequency are associated with a decreased DI Index. COUGH is a clinical phenotype distinct from healthy normals and asthma.
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http://dx.doi.org/10.3389/fphys.2020.554679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573225PMC
October 2020

Waist circumference does not improve established cardiovascular disease risk prediction modeling.

PLoS One 2020 2;15(10):e0240214. Epub 2020 Oct 2.

School of Kinesiology and Health Studies, Queen's University, Kingston, Ontario, Canada.

Despite considerable evidence demonstrating that waist circumference (WC) is independently associated with cardiovascular disease (CVD) and/or all-cause mortality, whether the addition of WC improves risk prediction models is unclear. The objective was to evaluate the improvement in risk prediction with the addition of WC, alone or in combination with BMI, to the Framingham Risk Score (FRS) and a population specific model. 34,377 men and 9,477 women aged 20 to 79 years who completed a baseline examination at the Cooper Clinic (Dallas, TX) during 1977-2003 and enrolled in the Aerobics Center Longitudinal Study (ACLS). WC was measured at the level of the umbilicus and expressed as a continuous variable. Deaths among participants were identified using the National Center for Health Statistics National Death Index. A total of 728 fatal cardiovascular disease (CVD) events occurred over a mean follow-up period of 13.1 ± 7.5 years. WC was significantly higher in CVD decedents (P = .002). The FRS C-statistic for fatal CVD in men was 0.836 (0.816-0.855) and 0.883 (0.851-0.915) in women. The addition of WC did not improve the C-statistic in men (0.831 (0.809-0.853)) or women (0.883 (0.850-0.916)). Similar findings were observed for non-fatal CVD and all-cause mortality, and when WC was added to a population specific model. Upon adding WC, the net-reclassification index was 0.024 with an integrated discrimination improvement of -0.0004. The addition of WC, alone or in combination with BMI, did not substantively improve risk prediction for CVD or all-cause mortality compared to the Framingham Risk Score or a population specific model.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240214PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531816PMC
December 2020

Application of the modified Nutrition Risk in Critically Ill score to nutritional risk stratification of trauma victims: A multicenter observational study.

J Trauma Acute Care Surg 2020 12;89(6):1143-1148

From the Department of Surgery (C.I.), University of Mississippi, Jackson, Mississippi; Department of Surgery (G.E.O.), Harborview Medical Center, University of Washington, Seattle, Washington; Clinical Evaluation Research Unit, Kingston Health Sciences Centre (A.G.D., X.J.); and Department of Critical Care Medicine (D.K.H.), Queen's University, Kingston, Ontario, Canada.

Background: The modified Nutrition Risk in Critically Ill (mNUTRIC) score was developed to identify patients most likely to benefit from nutritional therapies and to stratify or select study subjects for clinical trials. The score is not validated in trauma victims in whom adequate nutritional support is important and difficult to achieve. We sought to determine whether a higher mNUTRIC score was associated with worse outcomes and whether caloric and protein intake improved outcome more in patients classified as high risk relative to those classified as low risk.

Methods: We analyzed a prospectively collected database of patients from intensive care units globally. The primary outcome was 60-day hospital mortality, and the secondary outcome was time to discharge alive. We compared outcomes between high and low mNUTRIC score groups and also tested whether the association between outcome and nutrition intake was modified by the mNUTRIC score.

Results: A total of 771 trauma patients were included. Most (585; 76%) had a low-risk mNUTRIC (0-4) score, and 186 (24%) had a high-risk (5-9) mNUTRIC score. The overall 60-day mortality was 13%. Patients in the high mNUTRIC group had a higher risk of death than those in the low mNUTRIC group (adjusted odds ratio, 2.6; 95% confidence interval, 1.7-4.2). Overall, there was no relationship between caloric or protein intake and clinical outcomes. However, patients in the high mNUTRIC group fared better with increasing caloric and protein intake, whereas subjects in the low mNUTRIC score group did not (p values for interaction with the mNUTRIC score for time to discharge alive was p = 0.014 for calories and was p = 0.004 for protein).

Conclusion: A high mNUTRIC score identifies trauma patients at higher risk for poor outcomes and those who may benefit from higher caloric and protein intake.

Level Of Evidence: Epidemiological/Prognostic, level III.
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http://dx.doi.org/10.1097/TA.0000000000002937DOI Listing
December 2020

Simultaneous glomerular filtration rate determination using inulin, iohexol, and Tc-DTPA demonstrates the need for customized measurement protocols.

Kidney Int 2021 04 1;99(4):957-966. Epub 2020 Aug 1.

Kidney Research Centre, Ottawa Health Research Institute, Ottawa, Ontario, Canada; Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

Urinary inulin clearance is considered the gold standard of glomerular filtration rate (GFR) measurement but plasma clearance of less expensive and more accessible tracers is more commonly performed. Many plasma sampling protocols exist but little is known about their accuracy. Here, the study objectives were to compare plasma iohexol and Tc-DTPA GFR with varying sampling strategies to the GFR measured by urinary inulin and to identify protocols with the greatest accuracy according to clinical characteristics. GFR was measured simultaneously using urinary inulin, plasma iohexol, and plasma Tc DTPA clearance. Blood was sampled from 2 to 10 hours after injection. For each method, bias, precision, and accuracy (P30 and mean absolute error) were calculated for the entire cohort and for eGFR-EPI creatinine subgroups (<30, 30-59, and ≥60 ml/min/1.73m) and the edema stage using urinary inulin clearance as the gold standard. The mean inulin GFR of the 77 participants was 33 ml/min/1.73m. Delay of both the initial and the final samples in plasma iohexol protocols yielded the highest accuracy in the setting of low GFR (<30 ml/min/1.73m). Early initial and final samples yielded the highest accuracy in the setting of high GFRs (≥60 ml/min/1.73m). No sampling strategy was accurate in edematous patients. Thus, our study demonstrates that customization of GFR protocols according to the anticipated level of GFR are required to optimize protocol accuracy.
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http://dx.doi.org/10.1016/j.kint.2020.06.044DOI Listing
April 2021

Lessening Organ dysfunction with VITamin C (LOVIT): protocol for a randomized controlled trial.

Trials 2020 Jan 8;21(1):42. Epub 2020 Jan 8.

Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec City, QC, Canada.

Background: Sepsis is a health problem of global importance; treatments focus on controlling infection and supporting failing organs. Recent clinical research suggests that intravenous vitamin C may decrease mortality in sepsis. We have designed a randomized controlled trial (RCT) to ascertain the effect of vitamin C on the composite endpoint of death or persistent organ dysfunction at 28 days in patients with sepsis.

Methods: LOVIT (Lessening Organ dysfunction with VITamin C) is a multicenter, parallel-group, blinded (participants, clinicians, study personnel, Steering Committee members, data analysts), superiority RCT (minimum n = 800). Eligible patients have sepsis as the diagnosis for admission to the intensive care unit (ICU) and are receiving vasopressors. Those admitted to the ICU for more than 24 h are excluded. Eligible patients are randomized to high-dose intravenous vitamin C (50 mg/kg every 6 h for 96 h) or placebo. The primary outcome is a composite of death or persistent organ dysfunction (need for vasopressors, invasive mechanical ventilation, or new and persisting renal replacement therapy) at day 28. Secondary outcomes include persistent organ dysfunction-free days to day 28, mortality and health-related quality of life at 6 months, biomarkers of dysoxia, inflammation, infection, endothelial function, and adverse effects (hemolysis, acute kidney injury, and hypoglycemia). Six subgroup analyses are planned.

Discussion: This RCT will provide evidence of the effect of high-dose intravenous vitamin C on patient-important outcomes in patients with sepsis.

Trial Registration: clinicaltrials.gov, NCT03680274, first posted 21 September 2018.
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http://dx.doi.org/10.1186/s13063-019-3834-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950903PMC
January 2020

Promotion of Regular Oesophageal Motility to Prevent Regurgitation and Enhance Nutrition Intake in Long-Stay ICU Patients. A Multicenter, Phase II, Sham-Controlled, Randomized Trial: The PROPEL Study.

Crit Care Med 2020 03;48(3):e219-e226

Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, ON, Canada.

Objectives: To evaluate the effect of esophageal stimulation on nutritional adequacy in critically ill patients at risk for enteral feeding intolerance.

Design: A multicenter randomized sham-controlled clinical trial.

Setting: Twelve ICUs in Canada.

Patients: We included mechanically ventilated ICU patients who were given moderate-to-high doses of opioids and expected to remain alive and ventilated for an additional 48 hours and who were receiving enteral nutrition or expected to start imminently.

Interventions: Patients were randomly assigned 1:1 to esophageal stimulation via an esophageal stimulating catheter (E-Motion Tube; E-Motion Medical, Tel Aviv, Israel) or sham treatment. All patients were fed via these catheters using a standardized feeding protocol.

Measurements And Main Results: The co-primary outcomes were proportion of caloric and protein prescription received enterally over the initial 7 days following randomization. Among 159 patients randomized, the modified intention-to-treat analysis included 155 patients: 73 patients in the active treatment group and 82 in the sham treatment group. Over the 7-day study period, the percent of prescribed caloric intake (± SE) received by the enteral route was 64% ± 2 in the active group and 65% ± 2 in sham patients for calories (difference, -1; 95% CI, -8 to 6; p = 0.74). For protein, it was 57% ± 3 in the active group and 60% ± 3 in the sham group (difference, -3; 95% CI, -10 to 3; p = 0.30). Compared to the sham group, there were more serious adverse events reported in the active treatment group (13 vs 6; p = 0.053). Clinically important arrhythmias were detected by Holter monitoring in 36 out of 70 (51%) in the active group versus 22 out of 76 (29%) in the sham group (p = 0.006).

Conclusions: Esophageal stimulation via a special feeding catheter did not improve nutritional adequacy and was associated with increase risk of harm in critically ill patients.
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http://dx.doi.org/10.1097/CCM.0000000000004176DOI Listing
March 2020

Pharmacological interventions for the prevention of acute postoperative pain in adults following brain surgery.

Cochrane Database Syst Rev 2019 11 21;2019(11). Epub 2019 Nov 21.

Queen's University, Departments of Anesthesiology & Perioperative Medicine & Biomedical & Molecular Sciences, 76 Stuart Street, Victory 2 Pavillion, Kingston, ON, Canada, K7L 2V7.

Background: Pain following brain surgery can compromise recovery. Several pharmacological interventions have been used to prevent pain after craniotomy; however, there is currently a lack of evidence regarding which interventions are most effective.

Objectives: The objectives are to assess the effectiveness of pharmacological interventions for prevention of acute postoperative pain in adults undergoing brain surgery; compare them in terms of additional analgesic requirements, incidence of chronic headache, sedative effects, length of hospital stay and adverse events; and determine whether these characteristics are different for certain subgroups.

Search Methods: We searched MEDLINE, Embase, CINAHL, CENTRAL, Web of Science and two trial registries together with reference checking and citation searching on 28th of November 2018.

Selection Criteria: We included blinded and non-blinded, randomized controlled trials evaluating pharmacological interventions for the prevention of acute postoperative pain in adults undergoing neurosurgery, which had at least one validated pain score outcome measure.

Data Collection And Analysis: We used standard Cochrane methodological procedures. We calculated mean differences for the primary outcome of pain intensity; any pain scores reported on a 0 to 100 scale were converted to a 0 to 10 scale.

Main Results: We included 42 completed studies (3548 participants) and identified one ongoing study. Nonsteroidal anti-inflammatories (NSAIDs) Nonsteroidal anti-inflammatories (NSAIDs) reduce pain up to 24 hours (0 to 6 hours, MD -1.16, 95% CI -1.57 to -0.76; 12 hours, MD -0.62, 95% CI -1.11 to -0.14; 24 hours, MD -0.66, 95% CI -1.18 to -0.13; 6 studies, 742 participants; all high-quality evidence). Results for other outcomes were imprecise (additional analgesic requirements: MD 1.29 mg, 95% CI -5.0 to 2.46, 4 studies, 265 participants; nausea and vomiting RR 1.34, 95% CI 0.30 to 5.94, 2 studies, 345 participants; both low-quality evidence). Dexmedetomidine reduces pain up to 12 hours (0 to 6 hours, MD -0.89, 95% CI -1.27 to -0.51, moderate-quality evidence; 12 hours, MD -0.81, 95% CI -1.21 to -0.42, low-quality evidence). It did not show efficacy at 24 hours (MD -0.08, 95% CI -0.32 to 0.16; 2 studies, 128 participants; low-quality evidence). Dexmedetomidine may decrease additional analgesic requirements (MD -21.36 mg, 95% CI -34.63 to -8.1 mg, 2 studies, 128 participants, low-quality evidence). Results for other outcomes were imprecise (nausea and vomiting RR -0.43, 95% CI 0.06 to 3.08, 3 studies, 261 participants; hypotension RR 0.5, 95% CI 0.05 to 5.28, 3 studies, 184 participants; both low-quality evidence). Scalp blocks may reduce pain up to 48 hours (0 to 6 hours, MD -0.98, 95% CI -1.66 to -0.3, 10 studies, 414 participants; 12 hours, MD -0.95, 95% CI -1.53 to -0.37, 8 studies, 294 participants; 24 hours, MD -0.78, 95% CI -1.52 to -0.05, 9 studies, 433 participants, all low-quality evidence; 48 hours, MD -1.34, 95% CI -2.57 to -0.11, 4 studies, 135 participants, very low-quality evidence. When studies with high risk of bias were excluded, significance remained at 12 hours only. Scalp blocks may decrease additional analgesia requirements (SMD -1.11, 95% CI -1.97 to -0.25, 7 studies, 314 participants). Results for other outcomes were imprecise (nausea and vomiting RR 0.66, 95% CI 0.33 to 1.32, 4 studies, 165 participants, very low-quality evidence). Scalp Infiltration may reduce pain postoperatively but efficacy was inconsistent, with a significant effect at 12 and 48 hours only (12 hours, MD -0.71, 95% CI -1.34 to -0.08, 7 studies, 309 participants, low-quality evidence; 48 hours, MD - 1.09, 95% CI -2.13 to - 0.06, 3 studies, 128 participants, moderate-quality evidence). No benefit was observed at other times (0 to 6 hours, MD -0.64, 95% CI -1.28 to -0.00, 9 studies, 475 participants, moderate-quality evidence; 24 hours, MD -0.39, 95% CI -1.06 to 0.27,6 studies, 260 participants, low-quality evidence. Scalp infiltration may reduce additional analgesia requirements MD -9.56 mg, 95% CI -15.64 to -3.49, 6 studies, 345 participants, very low-quality evidence). When studies with high risk of bias were excluded, scalp infiltration lost the pain benefit at 12 hours and effects on additional analgesia requirements, but retained the pain-reducing benefit at 48 hours (MD -0.56, 95% CI -1.20 to -0.32, 2 studies, 100 participants, very low-quality evidence). Results for other outcomes were imprecise (nausea and vomiting, RR 0.74, 95% CI 0.48 to 1.41, 4 studies, 318 participants, low-quality evidence). Pregabalin or gabapentin may reduce pain up to 6 hours (2 studies, 202 participants), MD -1.15,95% CI -1.66 to -0.6, 2 studies, 202 participants, low-quality evidence). One study examined analgesic efficacy at 12 hours showing significant benefit. No analgesia efficacy was shown at later times (24 hours, MD -0.29, 95% CI -0.78 to -0.19; 48 hours, MD - 0.06, 95% CI -0.86 to 0.77, 2 studies, 202 participants, low-quality evidence). Additional analgesia requirements were not significantly less (MD -0.37 (95% CI -1.10 to 0.35, 3 studies, 234 participants, low-quality evidence). Risk of nausea and vomiting was significantly reduced (RR 0.51, 95% CI 0.29 to 0.89, 3 studies, 273 participants, low-quality evidence). Results for other outcomes were imprecise (additional analgesia requirements: MD -0.37, 95% CI -1.10 to 0.35, 3 studies, 234 participants, low-quality evidence). Acetaminophen did not show analgesic benefit (0 to 6 hours, MD -0.35, 95% CI -1.00 to 0.30; 12 hours, MD -0.51, 95% CI -1.04 to 0.03, 3 studies, 332 participants, moderate-quality evidence; 24 hours, MD -0.34, 95% CI -1.20 to 0.52, 4 studies, 439 participants, high-quality evidence). Results for other outcomes remained imprecise (additional analgesia requirements, MD 0.07, 95% CI -0.86 to 0.99, 4 studies, 459 participants, high-quality evidence; length of hospitalizations, MD -3.71, 95% CI -14.12 to 6.7, 2 studies, 335 participants, moderate-quality evidence).

Authors' Conclusions: There is high-quality evidence that NSAIDs reduce pain up to 24 hours postoperatively. The evidence for reductions in pain with dexmedetomidine, pregabalin or gabapentin, scalp blocks, and scalp infiltration is less certain and of very low to moderate quality. There is low-quality evidence that scalp blocks and dexmedetomidine may reduce additional analgesics requirements. There is low-quality evidence that gabapentin or pregabalin may decrease nausea and vomiting, with the caveat that the total number of events for this comparison was low.
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http://dx.doi.org/10.1002/14651858.CD011931.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867906PMC
November 2019

Impact of a Specialized Ambulatory Clinic on Refractory Breathlessness in Subjects With Advanced COPD.

Respir Care 2020 Apr 12;65(4):444-454. Epub 2019 Nov 12.

Palliative Care and Respirology Divisions, Department of Medicine, Queen's University and Kingston Health Sciences Centre, Kingston, Ontario, Canada.

Background: Severe exertional dyspnea is a commonly reported symptom in patients with COPD, especially in the advanced stages. Our objective was to assess the preliminary impact of comprehensive, individualized management provided by a specialized tertiary center clinic on exertional dyspnea and patient-centered outcomes in patients with advanced COPD.

Methods: This retrospective analysis included 45 subjects with COPD who were evaluated in a newly established dyspnea clinic over 3 years. Those with severe exertional dyspnea (Medical Research Council dyspnea score of ≥4/5), despite optimal disease-targeted therapy were eligible for referral. We used the revised Edmonton Symptom Assessment System (ESAS-r) to assess symptoms. Responders were defined as those whose change from baseline to 2-months met the minimum clinically important difference of ≤-1 in ESAS-r score for shortness of breath.

Results: Subjects (mean ± SD age 70 ± 7 years) had an average FEV of 36 ± 18% predicted and a Medical Research Council dyspnea score of 4.7 ± 0.4. Responses to the intervention were variable and mean change in the ESAS-r score for shortness of breath in the total group was -0.32 ± 3.39, = .53. Forty-seven percent of the subjects were identified as responders, and 42, 40, 40, and 33% met the minimum clinically important difference for improvement in ESAS-r scores for tiredness, anxiety, well-being, and depression, respectively. Responders had fewer emergency department annual visits in the 2 years after their first clinic visit compared with nonresponders (mean ± SD, 1.38 ± 1.63 vs 4.45 ± 5.52, = .034).

Conclusions: Although the impact of our specialized advanced dyspnea clinic was variable, as evaluated by the ESAS-r, it provided measurable additional clinically important benefit to almost half of the subjects with advanced COPD and severe refractory dyspnea.
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http://dx.doi.org/10.4187/respcare.06950DOI Listing
April 2020

Individual Response to Standardized Exercise: Total and Abdominal Adipose Tissue.

Med Sci Sports Exerc 2020 02;52(2):490-497

Institute of Nutraceuticals and Functional Foods, Laval University, Quebec City, Quebec, CANADA.

Purpose: (1) Determine the effect of exercise amount and intensity on the proportion of individuals for whom the adipose tissue (AT) response is above the minimal clinically important difference (MCID); and (2) Examine whether clinically meaningful anthropometric changes reflect individual AT responses above the MCID.

Methods: Men (n = 41) and women (n = 62) (52.7 ± 7.6 yr) were randomized to control (n = 20); low amount low intensity (n = 24); high amount low intensity (n = 30); and high amount high intensity (n = 29) treadmill exercise for 24 wk. The AT changes were measured by MRI. 90% confidence intervals for each individual's observed response were calculated as the observed score ±1.64 × TE (technical error of measurement).

Results: For visceral AT, HAHI and HALI had a greater proportion of individuals whose AT change and 90% confidence interval were beyond the MCID compared to controls (P < 0.006). For all other AT depots, all exercise groups had significantly more individuals whose changes were beyond the MCID compared with controls. Of those who achieved a waist circumference or body weight reduction ≥ the MCID, 76% to 93% achieved abdominal, abdominal subcutaneous, and visceral AT changes ≥ the MCID.

Conclusions: Increasing exercise amount and/or intensity may increase the proportion of individuals who achieve clinically meaningful visceral AT reductions. Waist circumference or body weight changes beyond a clinically meaningful threshold are predictive of clinically meaningful abdominal adiposity changes.
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http://dx.doi.org/10.1249/MSS.0000000000002140DOI Listing
February 2020

Precision exercise medicine: understanding exercise response variability.

Br J Sports Med 2019 Sep 12;53(18):1141-1153. Epub 2019 Mar 12.

Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.

There is evidence from human twin and family studies as well as mouse and rat selection experiments that there are considerable interindividual differences in the response of cardiorespiratory fitness (CRF) and other cardiometabolic traits to a given exercise programme dose. We developed this consensus statement on exercise response variability following a symposium dedicated to this topic. There is strong evidence from both animal and human studies that exercise training doses lead to variable responses. A genetic component contributes to exercise training response variability.In this consensus statement, we (1) briefly review the literature on exercise response variability and the various sources of variations in CRF response to an exercise programme, (2) introduce the key research designs and corresponding statistical models with an emphasis on randomised controlled designs with or without multiple pretests and post-tests, crossover designs and repeated measures designs, (3) discuss advantages and disadvantages of multiple methods of categorising exercise response levels-a topic that is of particular interest for personalised exercise medicine and (4) outline approaches that may identify determinants and modifiers of CRF exercise response. We also summarise gaps in knowledge and recommend future research to better understand exercise response variability.
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http://dx.doi.org/10.1136/bjsports-2018-100328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6818669PMC
September 2019

Individual Response to Standardized Exercise: Total and Abdominal Adipose Tissue.

Med Sci Sports Exerc 2019 Feb 15. Epub 2019 Feb 15.

School of Kinesiology and Health Studies, Queen's University, Kingston, ON, Canada.

Purpose: (1) Determine the effect of exercise amount and intensity on the proportion of adipose tissue (AT) responses likely, very likely, and unlikely above the minimal clinically important difference (MCID); and (2) Examine whether clinically meaningful anthropometric changes reflect individual AT responses above the MCID.

Methods: Men (n=41) and women (n=62) (52.7 ± 7.6 years) were randomized to control (N=20); low amount low intensity (LALI, N=24); high amount low intensity (HALI, N=30); and high amount high intensity (HAHI, N=29) exercise for 24 weeks. AT changes were measured by MRI. The probability that individual responses were > MCID after adjusting for technical error of measurement were calculated for each individual and categorized as: 'Unlikely' = < 25%, 'Possibly' = 25-74%, 'Likely' = 75-94%, 'Very Likely' = 95-100% chance.

Results: The HALI (total AT) and HAHI (total AT, visceral AT) groups had a greater proportion of individuals whose response was "very likely" ≥ MCID vs controls (p<0.006). Across the abdominal AT depots, for individuals who reduced WC or body weight ≥ 2 cm or 2 kg, respectively, 51-69% of responses were "likely" or "very likely" beyond the MCID.

Conclusion: Increasing exercise amount and/or intensity may increase the proportion of individuals deemed 'very likely' to achieve clinically meaningful AT reductions. The use of anthropometric change to identify individual response for adiposity reduction remains a challenge.
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http://dx.doi.org/10.1249/MSS.0000000000001930DOI Listing
February 2019

A Patient-Centered Mobile Health System That Supports Asthma Self-Management (breathe): Design, Development, and Utilization.

JMIR Mhealth Uhealth 2019 01 28;7(1):e10956. Epub 2019 Jan 28.

Western University, London, ON, Canada.

Background: Uncontrolled asthma poses substantial negative personal and health system impacts. Web-based technologies, including smartphones, are novel means to enable evidence-based care and improve patient outcomes.

Objective: The aim of this study was to design, develop, and assess the utilization of an asthma collaborative self-management (CSM) platform (breathe) using content based on international evidence-based clinical guidelines.

Methods: We designed and developed breathe as a Web-based mobile health (mHealth) platform accessible on smartphones, tablets, or desktop with user-centered design methods and International Organization for Standardization-certified quality development processes. Moreover, breathe was envisioned as a multifunctional, CSM mHealth platform, with content based on international clinical practice guidelines and compliant with national privacy and security specifications. The system enabled CSM (patient, provider, and breathe) and self-monitoring of asthma patients through (1) assessment of asthma control, (2) real-time access to a dynamic asthma action plan, (3) access to real-time environmental conditions, and (4) risk-reduction messaging. The data collection protocol collected user data for 12 months, with clinic visits at baseline and 6 and 12 months. Utilization outcomes included user interactions with the platform, user impressions, self-reported medication use, asthma symptom profile, reported peak flow measurement, and the delivery and impact of email reminders.

Results: We enrolled 138 patients with a mean age of 45.3 years to receive the breathe intervention. Majority were female (100/138, 72.5%), had a smartphone (92/138, 66.7%), and had a mean Asthma Control Test score of 18.3 (SD 4.9). A majority reported that breathe helped in the management of their asthma. Moreover, breathe scored 71.1 (SD 18.9) on the System Usability Scale. Overall, 123 patients had complete usage analytics datasets. The platform sent 7.96 reminder emails per patient per week (pppw), patients accessed breathe 3.08 times, journaled symptoms 2.56 times, reported medication usage 0.30 times, and reported peak flow measurements 0.92 times pppw. Furthermore, breathe calculated patients' action plan zone of control 2.72 times pppw, with patients being in the green (well-controlled) zone in 47.71% (8300/17,396) of the total calculations. Usage analysis showed that 67.5% (83/123) of the participants used the app at week 4 and only 57.7% (71/123) by week 45. Physician visits, email reminders, and aged 50 years and above were associated with higher utilization.

Conclusions: Individuals with asthma reported good usability and high satisfaction levels, reacted to breathe notifications, and had confidence in the platform's assessment of asthma control. Strong utilization was seen at the intervention's initiation, followed by a rapid reduction in use. Patient reminders, physician visits, and being aged 50 years and above were associated with higher utilization.

Trial Registration: ClinicalTrials.gov NCT01964469; https://clinicaltrials.gov/ct2/show/NCT01964469.
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http://dx.doi.org/10.2196/10956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369424PMC
January 2019

Adaptation and Preliminary Validation of the Advance Care Planning Engagement Survey for Surrogate Decision Makers.

J Pain Symptom Manage 2019 05 24;57(5):980-988.e9. Epub 2019 Jan 24.

Department of Critical Care Medicine, Clinical Evaluation Research Unit, Kingston General Health Research Institute, Queen's University, Kingston, Ontario, Canada.

Context: Although measures that assess patient engagement in the advance care planning (ACP) process exist, there are no validated tools to assess surrogate decision makers' (SDMs') role in ACP.

Objectives: The objective of this study was to adapt and begin to validate a patient-oriented questionnaire for use with SDMs of patients with chronic illness.

Methods: Questions from the 55-item patient-oriented ACP engagement survey were adapted for SDMs and assessed for face validity. The resultant 47-item questionnaire was administered to 65 SDMs of patients with chronic illness. Responses were assessed and items were flagged for removal based on item redundancy, nonresponses, and ceiling effects. A preliminary exploratory factor analysis was performed, internal consistency was assessed, and domains were constructed based on findings.

Results: The 47-item questionnaire was administered to 65 participants (mean age 51.8; 81% female; 96% Caucasian). Seventeen items were removed owing to redundancy (r > 0.80), and 13 items lacking face validity were removed. In a preliminary exploratory factor analysis of the resultant 17-item questionnaire, a three-factor solution was deemed most statistically and conceptually sound. Items were organized into domains: 1) serving as an SDM (seven items); 2) contemplation (four items); 3) readiness (six items). Internal consistency for each domain was high (Cronbach alpha 0.90-0.91).

Conclusion: The 17-item ACP engagement survey for SDMs (ACP-17-SDM) is a conceptually sound and reliable questionnaire adaptation of the original ACP engagement survey. This questionnaire may be used by researchers in parallel with the patient-oriented ACP engagement survey to more fully understand the impact of ACP interventions on SDMs. Larger studies are needed to more closely examine construct validity.
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http://dx.doi.org/10.1016/j.jpainsymman.2019.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857702PMC
May 2019

Intravital imaging reveals systemic ezrin inhibition impedes cancer cell migration and lymph node metastasis in breast cancer.

Breast Cancer Res 2019 01 24;21(1):12. Epub 2019 Jan 24.

Department of Pathology and Molecular Medicine, Queen's University, Kingston, Canada.

Background: Limited understanding of the cancer biology of metastatic sites is a major factor contributing to poor outcomes in cancer patients. The regional lymph nodes are the most common site of metastasis in most solid cancers and their involvement is a strong predictor of relapse in breast cancer (BC). We have previously shown that ezrin, a cytoskeletal-membrane linker protein, is associated with lymphovascular invasion and promotes metastatic progression in BC. However, the efficacy of pharmacological inhibition of ezrin in blocking cancer cell migration and metastasis remains unexplored in BC.

Methods: We quantified ezrin expression in a BC tissue microarray (n = 347) to assess its correlation with risk of relapse. Next, we developed a quantitative intravital microscopy (qIVM) approach, using a syngeneic lymphatic reporter mouse tumor model, to investigate the effect of systemic ezrin inhibition on cancer cell migration and metastasis.

Results: We show that ezrin is expressed at significantly higher levels in lymph node metastases compared to matched primary tumors, and that a high tumor ezrin level is associated with increased risk of relapse in BC patients with regional disease. Using qIVM, we observe a subset of cancer cells that retain their invasive and migratory phenotype at the tumor-draining lymph node. We further show that systemic inhibition of ezrin, using a small molecule compound (NSC668394), impedes the migration of cancer cells in vivo. Furthermore, systemic ezrin inhibition leads to reductions in metastatic burden at the distal axillary lymph node and lungs.

Conclusions: Our findings demonstrate that the tumor ezrin level act as an independent biomarker in predicting relapse and provide a rationale for therapeutic targeting of ezrin to reduce the metastatic capacity of cancer cells in high-risk BC patients with elevated ezrin expression.
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http://dx.doi.org/10.1186/s13058-018-1079-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345049PMC
January 2019

Are all low-NUTRIC-score patients the same? Analysis of a multi-center observational study to determine the relationship between nutrition intake and outcome.

Clin Nutr 2019 12 8;38(6):2783-2789. Epub 2018 Dec 8.

Department of Critical Care Medicine, Queen's University, Kingston, Ontario, Canada; Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, Ontario, Canada. Electronic address:

Background: The NUTrition Risk in the Critically Ill (NUTRIC) scoring system is a tool useful, discriminating critically-ill patients benefiting from optimal nutrition intake (>80% of prescription). Recent recommendations advocate for withholding artificial nutrition among low-NUTRIC patients, however, we hypothesized that some low-NUTRIC patients would show an association between nutrition intake and outcome.

Methods: Patients were selected from the 2013-2014 International Nutrition Surveys when ICU length of stay (LICU) ≥72 h, baseline mNUTRIC score ≤4 and had at least three evaluable nutrition days (N = 2781). Proportion of prescription received during evaluable days was associated to 60-day hospital mortality by a logistic regression modelling. A priori, we expected that the association between proportion of prescription received and mortality might differ according to: LICU, BMI and prior unintentional weight loss or reduced oral intake.

Results: A total of 2781 patients fulfilled the inclusion criteria and participated in the study. Ten percent of the sample had a BMI <20 kg/m and 20% experienced either unintentional weight loss during the last 3 months, or reduced food intake over the last week. Sixty-day hospital mortality was 15% and median LICU reached 11.3 [6.3-21.7] days. Mean total prescription received by any means of nutritional support during the first 12 evaluable days was 57.4 ± 28.1% for energy and 53.7 ± 29.2% for protein. In the pooled, subgroup and sensitivity analyses, no significant associations were identified.

Conclusion: Low-NUTRIC (≤4) patients demonstrate a prolonged LICU, while experiencing significant mortality and a high prevalence of malnutrition risk factors. Although improvements in mortality were not achieved with increased nutritional intake, this should not be construed as a rationale for withholding artificial nutrition among this patient group.
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http://dx.doi.org/10.1016/j.clnu.2018.12.006DOI Listing
December 2019

Handheld versus conventional vascular ultrasound for assessing carotid artery plaque.

Int J Cardiol 2019 Mar 5;278:295-299. Epub 2018 Dec 5.

Department of Biomedical and Molecular Sciences, Queen's University, 18 Stuart Street, Kingston, K7L 3N6, ON, Canada; Department of Medicine, Division of Cardiology, Cardiovascular Imaging Network at Queen's (CINQ), Queen's University, 76 Stuart Street, Kingston, K7L 2V7, ON, Canada. Electronic address:

Background: Coronary Artery Disease (CAD) is the leading cause of death worldwide. Ultrasound-detected carotid plaque has been previously shown to predict significant CAD. Despite this evidence, carotid plaque assessment has not been implemented in cardiac risk screening, likely due to the cost associated with a formal carotid ultrasound examination. This study sought to determine whether a handheld vascular ultrasound device could be used as an accurate point-of-care imaging tool for the assessment of carotid artery plaque.

Methods: We performed a focused vascular ultrasound of the carotid arteries of 200 patients referred for coronary angiography using a handheld ultrasound device as well as a full-size conventional ultrasound system. For each participant, the maximum plaque height (MPH) and total plaque area (TPA) of the carotid artery bulbs were measured.

Results: Carotid plaque assessment using the handheld device was comparable to that of the conventional ultrasound system. We found a good correlation and no relevant bias between handheld and conventional ultrasound systems in measuring MPH (r = 0.84, p < 0.0001) and TPA (r = 0.94, p < 0.0001). Furthermore, there was good inter-rater reliability for online and offline measurements of MPH and offline measurements of TPA by handheld ultrasound (0.79, 0.76 and 0.85, respectively).

Conclusions: This study demonstrates that a focused ultrasound of the carotid artery using a handheld device can be used to accurately measure MPH and TPA. This protocol has the potential to provide an expedited point-of-care assessment of carotid plaque.
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http://dx.doi.org/10.1016/j.ijcard.2018.12.014DOI Listing
March 2019
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