Li Ka Shing Knowledge Institute Research Articles

Feasibility of a 4 French resuscitative endovascular balloon occlusion of the aorta (REBOA) device for nontraumatic cardiac arrest in a randomized controlled study using a large porcine model

AimThe objectives of this study were to assess the return of spontaneous circulation rates and hemodynamic response of large swine (>65Kg) during cardiopulmonary resuscitation after nontraumatic cardiac arrest using the COBRA-OS® aortic occlusion balloon and to address limitations of large swine closed-chest cardiopulmonary resuscitation by comparing closed-chest vs. open-chest cardiopulmonary resuscitation. MethodsYorkshire pigs (n = 10) weighing >65 kg were anesthetized and ventilated. After 7 min of untreated ventricular fibrillation (VF), animals were randomized to receive mechanical closed-chest cardiopulmonary resuscitation or open-chest cardiac massage. Following a 5-minute low-flow state, advanced cardiac life support algorithms were started and the COBRA-OS® was inflated in the thoracic aorta. Animals that achieved return of spontaneous circulation were re-started on mechanical ventilation and medications, CPR, defibrillation, and aortic occlusion were discontinued. The primary outcome was return of spontaneous circulation and secondary outcomes were mean arterial pressures generated in the low flow and aortic occlusion states before return of spontaneous circulation. Groups were compared with a t-test or Mann-Whitney U test for normal and non-parametric data, respectively, while categorical data was compared with the chi square test. ResultsReturn of spontaneous circulation was obtained in 4 animals (80%) in the open cardiac massage group and none in the mechanical closed-chest CPR group (p < 0.05). The COBRA-OS® successfully occluded all aortas and animals experienced higher mean arterial pressures in both groups with aortic occlusion (median 15 mm Hg, IQR 13–23 mm Hg), but with a higher MAP difference in the open cardiac massage group (−12.2 mm Hg, [−2.581, −21.819]). ConclusionsConsideration should be given to intra-thoracic cardiac massage to increase cardiopulmonary resuscitation effectiveness and therefore return of spontaneous circulation rates in large (>65 kg) swine models of nontraumatic cardiac arrest. The COBRA-OS® demonstrated feasibility for use in this model.The Keenan Research Center, Li Ka Shing Knowledge Institute of St. Michael’s Hospital Animal Care Committee: ACC Protocol #726.

A Dollar a Day May Keep the Doctor Away: Putting Spending on Food and Healthcare on a Scale

A Dollar a Day May Keep the Doctor Away: Putting Spending on Food and Healthcare on a Scale Katerina Maximova PhD, MAP Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, St. Michael’s Hospital; Dalla

Increased patency with comparable mortality and revascularization risk: Is the case for no-touch vein harvesting open and shut?

Journal of Cardiac SurgeryVolume 36, Issue 11 p. 4376-4377 COMMENTARY Increased patency with comparable mortality and revascularization risk: Is the case for no-touch vein harvesting open and shut? Makoto Hibino MD, MPH, PhD, Corresponding Author Makoto Hibino MD, MPH, PhD [email protected] orcid.org/0000-0002-0017-8744 Division of Cardiac Surgery, The Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, Canada CorrespondenceMakoto Hibino, MD, MPH, PhD, Division of Cardiac Surgery, The Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, 30 Bond St., Toronto, ON M5B 1W8, Canada. Email: [email protected]Search for more papers by this authorNitish K. Dhingra BHSc, Nitish K. Dhingra BHSc Division of Cardiac Surgery, The Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, CanadaSearch for more papers by this authorSubodh Verma MD, PhD, Subodh Verma MD, PhD Division of Cardiac Surgery, The Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, CanadaSearch for more papers by this author Makoto Hibino MD, MPH, PhD, Corresponding Author Makoto Hibino MD, MPH, PhD [email protected] orcid.org/0000-0002-0017-8744 Division of Cardiac Surgery, The Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, Canada CorrespondenceMakoto Hibino, MD, MPH, PhD, Division of Cardiac Surgery, The Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, 30 Bond St., Toronto, ON M5B 1W8, Canada. Email: [email protected]Search for more papers by this authorNitish K. Dhingra BHSc, Nitish K. Dhingra BHSc Division of Cardiac Surgery, The Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, CanadaSearch for more papers by this authorSubodh Verma MD, PhD, Subodh Verma MD, PhD Division of Cardiac Surgery, The Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, CanadaSearch for more papers by this author First published: 03 September 2021 https://doi.org/10.1111/jocs.15973Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume36, Issue11November 2021Pages 4376-4377 RelatedInformation

Parent engagement in co-design of clinical trials: the PARENT trial

Evidence generated from partnering with parents to design and conduct research together may be used to refine, adjust, and modify future research approaches. This study aimed to describe the initial approaches to parent engagement in the design of the PARENT trial as well as understand parent perspectives on the acceptability and relevance of the PARENT trial and potential barriers and facilitators to participation.Parents participating in the TARGet Kids! cohort were invited to participate in a focus group, called the PARENT panel, to co-design the PARENT trial. This focus group was conducted to capture diverse individual and collective parents’ experiences. Overall methodological approaches for the PARENT panel were informed by the CIHR Strategy for Patient Oriented Research (SPOR) guiding principles (mutual respect, co-building, inclusiveness, and support) for patient engagement in research, and facilitated through the Knowledge Translation Program in the Li Ka Shing Knowledge Institute at Unity Health Toronto. Using a Nominal Group Technique, the PARENT panel provided feedback on the feasibility, relevance, and acceptability of the proposed intervention. Findings from this work will be used to further refine, adjust, and modify the next iteration of the PARENT trial, which will also serve as an opportunity to discuss the efforts made by researchers to incorporate parent suggestions and what additional steps are required for improved patient engagement.

Editorial introductions.

Editorial introductions.

Editorial introductions

Editorial introductions

Editorial introductions

Editorial introductions

Point: Glycemic Index—An Important but Oft Misunderstood Marker of Carbohydrate Quality

AuthorsEffie Viguiliouk,1,2 Stephanie K. Nishi,1,2 Thomas M. S. Wolever,1–4 and John L. Sievenpiper1–5 Affiliations1 Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.2 Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael’s Hospital, Toronto, ON, Canada.3 Division of Endocrinology and Metabolism, Department of Medicine, St. Michael’s Hospital, Toronto, ON, Canada.4 Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, ON, Canada.5 Corresponding author. Dr. John L. Sievenpiper, MD, PhD, FRCPC, St. Michael’s Hospital, #6138-61 Queen St E, Toronto, ON M5C 2T2, Canada. Tel: +1.416.867.3732; Fax: +1.416.867.7495; E-mail: john.sievenpiper@utoronto.ca

Reply.

aTerrence Donnelly Heart Centre, St Michael's Hospital bUniversity of Toronto cDivision of Nephrology, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada Correspondence to Andrew T. Yan, MD, Division of Cardiology, St. Michael's Hospital, 30 Bond Street, Rm 6-030 Donnelly, Toronto, ON M5B 1W8, Canada. Tel: +416 864 5465; fax: +416 864 5159; e-mail: [email protected]

The spleen dictates platelet destruction, anti-platelet antibody production, and lymphocyte distribution patterns in a murine model of immune thrombocytopenia.

For many years, splenectomy has been used to treat immune thrombocytopenia (ITP), and this procedure benefits approximately two-thirds of the treated patients. Although splenectomy may raise platelet counts, antibody-coated platelets and cytotoxic T lymphocytes appear to persist or can change over time. To better understand how the spleen may affect anti-platelet immune responses, we used a murine model of ITP demonstrating both antibody-mediated and T lymphocyte-mediated thrombocytopenia. Mice with severe combined immunodeficiency (SCID) were either splenectomized or not and transfused with splenocytes from CD61 (GPIIIa) knockout mice immunized against CD61(+) platelets. Platelet counts and anti-platelet antibody levels were performed weekly. After 4weeks, the mice were sacrificed, and lymphoid organs were harvested and examined by flow cytometry to quantify CD4(+)CD25(+)FoxP3(+) Tregs and conventional cross-presenting XCR1(+) and tolerizing SIRPα+ dendritic cells. The results indicate that compared with control non-splenectomized mice, thrombocytopenia was improved and anti-platelet antibody production was significantly diminished in all splenectomized mice that received immune splenocytes. Splenectomized SCID mice also had a marked reduction in Tregs in the thymus together with an increased proportion of both thymic dendritic cell subsets that correlated with increased platelet counts. Of interest, although splenectomy diminished anti-platelet antibody production and raised platelet counts, marrow megakaryocyte densities were still significantly reduced in mice that received immune splenocytes. These results suggest that the spleen in murine ITP not only is the primary site responsible for platelet destruction, but it also controls, to a significant extent, the antibody response against platelets and the migration patterns of lymphocyte subsets.

In Response

In Response

Being more conscientious, collaborative, and confident in addressing patients&#39; fears and anxieties: nurses&#39; perspectives

Being more conscientious, collaborative, and confident in addressing patients&#39; fears and anxieties: nurses&#39; perspectives Susan E Beswick,1 Sandee Westell,1 Sarah Sweetman,1 Charmaine Mothersill,1 Lianne P Jeffs1,21St Michael&#39;s Hospital, Toronto, ON, Canada; 2Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael&#39;s Hospital, Toronto, ON, Canada Background: Developing a therapeutic partnership between patient and nurse is key to ensuring the patient&#39;s needs and preferences are identified, addressed, and valued as a key patient safety goal. There is growing recognition that patients living with chronic lung diseases often experience increased levels of stress, anxiety, and depression compared to their healthy counterparts. Creating strategies for early identification and management of patients&#39; fears and anxieties is a strategy to minimize anxiety and depressive symptoms.Methods: This article provides an overview of a qualitative study which explored nurses&#39; perceptions and experiences associated with the implementation of the Registered Nurses&#39; Association of Ontario&#39;s Establishing Therapeutic Relationships Best Practice Guideline that focused on strategies to alleviate patients&#39; fears and anxieties on one respirology unit.Results: Study findings suggest that involvement in Best Practice Guideline implementation enabled nurses to address patients&#39; fears and anxieties in a focused, conscientious manner and to be more collaborative and confident in their care.Conclusion: Providing opportunities for nurses to learn and apply evidence-based practice around therapeutic patient-centered care is a key step in ensuring a quality patient experience.Keywords: evidence-based practice, best practice guideline, therapeutic relationship, fear and anxiety, collaborative practice

The role of HDL and its modulators in the development of diabetes

aKeenan Research Centre, Li Ka Shing Knowledge Institute, Department of Medicine, St Michael's Hospital bDepartment of Physiology, Faculty of Medicine cDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada Correspondence to Dominic S. Ng, PhD, MD, Keenan Research Center, St. Michael's Hospital, Shuter Wing Room 3-041, 30 Bond Street, Toronto, ON, Canada M5B1W8. Tel: +1 416 864 5197; fax: +1 416 864 5584; e-mail: [email protected]

Trends in selective abortions of girls in India: analysis of nationally representative birth histories from 1990 to 2005 and census data from 1991 to 2011

India's 2011 census revealed a growing imbalance between the numbers of girls and boys aged 0-6 years, which we postulate is due to increased prenatal sex determination with subsequent selective abortion of female fetuses. We aimed to establish the trends in sex ratio by birth order from 1990 to 2005 with three nationally representative surveys and to quantify the totals of selective abortions of girls with census cohort data.We assessed sex ratios by birth order in 0·25 million births in three rounds of the nationally representative National Family Health Survey covering the period from 1990 to 2005. We estimated totals of selective abortion of girls by assessing the birth cohorts of children aged 0-6 years in the 1991, 2001, and 2011 censuses. Our main statistic was the conditional sex ratio of second-order births after a firstborn girl and we used 3-year rolling weighted averages to test for trends, with differences between trends compared by linear regression.The conditional sex ratio for second-order births when the firstborn was a girl fell from 906 per 1000 boys (99% CI 798-1013) in 1990 to 836 (733-939) in 2005; an annual decline of 0·52% (p for trend=0·002). Declines were much greater in mothers with 10 or more years of education than in mothers with no education, and in wealthier households compared with poorer households. By contrast, we did not detect any significant declines in the sex ratio for second-order births if the firstborn was a boy, or for firstborns. Between the 2001 and 2011 censuses, more than twice the number of Indian districts (local administrative areas) showed declines in the child sex ratio as districts with no change or increases. After adjusting for excess mortality rates in girls, our estimates of number of selective abortions of girls rose from 0-2·0 million in the 1980s, to 1·2-4·1 million in the 1990s, and to 3·1-6·0 million in the 2000s. Each 1% decline in child sex ratio at ages 0-6 years implied 1·2-3·6 million more selective abortions of girls. Selective abortions of girls totalled about 4·2-12·1 million from 1980-2010, with a greater rate of increase in the 1990s than in the 2000s.Selective abortion of girls, especially for pregnancies after a firstborn girl, has increased substantially in India. Most of India's population now live in states where selective abortion of girls is common.US National Institutes of Health, Canadian Institute of Health Research, International Development Research Centre, and Li Ka Shing Knowledge Institute.

The how and why of “negative” research studies

In this issue of the Journal, Bryson et al. present a singlecentre study that evaluates the inter-relationship between postoperative delirium, postoperative cognitive dysfunction (POCD), and the apolipoprotein E-e4 (APOE-e4) genetic polymorphism. This prospective cohort study, involving 88 individuals who underwent open abdominal aortic aneurysm repair, has many strong points, including strict inclusion criteria, systematic surveillance for delirium and POCD using valid instruments, and clear documentation of postoperative follow-up. The authors found no statistically significant association of delirium with early POCD (odds ratio [OR] 2.86; 95% confidence interval [CI], 0.99 to 8.27) or with late POCD (OR 2.10; 95% CI, 0.28 to 15.92). They also found no statistically significant association of APOE-e4 with delirium (OR 1.63; CI, 0.59 to 4.56), early POCD (OR 1.33; CI, 0.44 to 4.04), or late POCD (OR 3.64; CI, 0.47 to 28.22). Thus, all of the key study findings were statistically non-significant at the traditional 0.05 level. How then should readers interpret these results? In this article, we present some general approaches both for interpreting these non-statistically significant results and for understanding why the study may have failed to identify associations. For the purpose of our discussion, we focus on the estimated association between APOE-e4 and postoperative delirium (OR 1.63; CI, 0.59 to 4.56). Rather than interpreting this estimate as showing no association (which the study results do not prove), the authors appropriately interpreted this estimate as showing no statistically significant association between APOE-e4 and delirium. However, the key question for most readers is not whether there was a statistically significant association between APOE-e4 and delirium but whether there was a clinically significant association. Man-Son-Hing et al. have proposed an approach for evaluating the clinical significance of study findings. In this approach, readers must consider both the point estimate (OR 1.63) and the confidence interval (0.59 to 4.56). The CI can be interpreted as the plausible range of values for the true odds ratio within the study population. The CI in this study was quite wide, indicating the imprecision of the study results, likely due to the small sample size. Readers can then define a threshold that they will accept as a clinically meaningful result. For example, if the threshold is defined as an OR of C 3.81(the value used in this study for estimating the sample size), the point estimate (1.63) is lower than the threshold, whereas the upper CI (4.56) exceeds the threshold. In this scenario, a clinically significant association is deemed to be ‘‘possible’’. Another approach is to consider primarily the CI for the OR, i.e., 0.59 to 4.56. Based on this CI, readers can confidently rule out population odds ratios \0.6 and [4.6. However, what of all the values in-between? The CI is not ‘‘flat’’, i.e., all of the values within the interval are not equally likely. Values towards the extremes of the interval are less likely than those towards the centre. However, knowing that the values are not equally likely may not be very satisfying to readers D. N. Wijeysundera, MD, PhD (&) Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael’s Hospital, 80 Bond Street, Toronto, ON M5B 1W8, Canada e-mail: d.wijeysundera@utoronto.ca

Geriatrics: An Interview with Dr. Sharon Straus

Dr. Sharon Straus is the Division Director of Geriatric Medicine at the University of Toronto and practices geriatric and general internal medicine at St. Michael's Hospital. She is the Director of the Knowledge Translation Program at the Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael's Hospital. Her research interests include knowledge translation, quality of care, mentorship, and education, often with an evidence-based medicine approach. She has co-authored several books about the practice of evidence-based medicine in various clinical settings.

Causes of neonatal and child mortality in India: a nationally representative mortality survey

More than 2·3 million children died in India in 2005; however, the major causes of death have not been measured in the country. We investigated the causes of neonatal and child mortality in India and their differences by sex and region. The Registrar General of India surveyed all deaths occurring in 2001-03 in 1·1 million nationally representative homes. Field staff interviewed household members and completed standard questions about events that preceded the death. Two of 130 physicians then independently assigned a cause to each death. Cause-specific mortality rates for 2005 were calculated nationally and for the six regions by combining the recorded proportions for each cause in the neonatal deaths and deaths at ages 1-59 months in the study with population and death totals from the United Nations. There were 10,892 deaths in neonates and 12,260 in children aged 1-59 months in the study. When these details were projected nationally, three causes accounted for 78% (0·79 million of 1·01 million) of all neonatal deaths: prematurity and low birthweight (0·33 million, 99% CI 0·31 million to 0·35 million), neonatal infections (0·27 million, 0·25 million to 0·29 million), and birth asphyxia and birth trauma (0·19 million, 0·18 million to 0·21 million). Two causes accounted for 50% (0·67 million of 1·34 million) of all deaths at 1-59 months: pneumonia (0·37 million, 0·35 million to 0·39 million) and diarrhoeal diseases (0·30 million, 0·28 million to 0·32 million). In children aged 1-59 months, girls in central India had a five-times higher mortality rate (per 1000 livebirths) from pneumonia (20·9, 19·4-22·6) than did boys in south India (4·1, 3·0-5·6) and four-times higher mortality rate from diarrhoeal disease (17·7, 16·2-19·3) than did boys in west India (4·1, 3·0-5·5). Five avoidable causes accounted for nearly 1·5 million child deaths in India in 2005, with substantial differences between regions and sexes. Expanded neonatal and intrapartum care, case management of diarrhoea and pneumonia, and addition of new vaccines to immunisation programmes could substantially reduce child deaths in India. US National Institutes of Health, International Development Research Centre, Canadian Institutes of Health Research, Li Ka Shing Knowledge Institute, and US Fund for UNICEF.

Adult and child malaria mortality in India: a nationally representative mortality survey

National malaria death rates are difficult to assess because reliably diagnosed malaria is likely to be cured, and deaths in the community from undiagnosed malaria could be misattributed in retrospective enquiries to other febrile causes of death, or vice-versa. We aimed to estimate plausible ranges of malaria mortality in India, the most populous country where the disease remains common. Full-time non-medical field workers interviewed families or other respondents about each of 122,000 deaths during 2001-03 in 6671 randomly selected areas of India, obtaining a half-page narrative plus answers to specific questions about the severity and course of any fevers. Each field report was sent to two of 130 trained physicians, who independently coded underlying causes, with discrepancies resolved either via anonymous reconciliation or adjudication. Of all coded deaths at ages 1 month to 70 years, 2681 (3·6%) of 75,342 were attributed to malaria. Of these, 2419 (90%) were in rural areas and 2311 (86%) were not in any health-care facility. Death rates attributed to malaria correlated geographically with local malaria transmission ratesderived independently from the Indian malaria control programme. The adjudicated results show 205,000 malaria deaths per year in India before age 70 years (55,000 in early childhood, 30,000 at ages 5-14 years, 120,000 at ages 15-69 years); 1·8% cumulative probability of death from malaria before age 70 years. Plausible lower and upper bounds (on the basis of only the initial coding) were 125,000-277,000. Malaria accounted for a substantial minority of about 1·3 million unattended rural fever deaths attributed to infectious diseases in people younger than 70 years. Despite uncertainty as to which unattended febrile deaths are from malaria, even the lower bound greatly exceeds the WHO estimate of only 15,000 malaria deaths per year in India (5000 early childhood, 10 000 thereafter). This low estimate should be reconsidered, as should the low WHO estimate of adult malaria deaths worldwide. US National Institutes of Health, Canadian Institute of Health Research, Li Ka Shing Knowledge Institute.

Hypoxemia during surgery: learning from history, science, and current practice

Prevention of hypoxemia remains one of the primary goals related to the safe practice of anesthesia. Development of the pulse oximeter has allowed for the reliable detection and prompt treatment of hypoxemia. As reviewed by Drs. Ehrenfeld et al. in this issue of the Journal, routine intraoperative application of pulse oximetry coupled with parallel increases in patient safety has made a significant impact on the practice of anesthesia. Careful conduct of anesthesia based on real-time knowledge of blood oxygenation (SpO2) stands in stark contrast with anesthesia practice patterns of previous eras in which short-term maintenance of anesthesia with high concentrations of nitrous oxide was regarded as effective and safe in healthy pre-oxygenated patients. With the invention and use of the oxygen electrode, it gradually became apparent that profound decreases in arterial oxygen tension occurred with the former method of anesthetic induction. Nonetheless, several clinical studies were continued wherein high concentrations of nitrous oxide with reciprocally low concentrations of inspired oxygen were explored. This practice led to the frequent occurrence of clinically significant hypoxemia. In their classic article published a half century ago, Heller et al. reported the following with respect to induction of anesthesia: ‘‘It is preferable to start with an 80/20 mixture of N2O and O2 rather than to subject the anxious wakeful patient to a preliminary period of (100%) oxygen breathing.’’ Although such approaches were developed at a time of limited availability of anesthetic agents, this practice – thankfully differs dramatically from our current approach. These days, we often advocate the avoidance of nitrous oxide, and pre-oxygenation is advocated routinely as one means to prevent hypoxemia. The large database of the current study helps us to appreciate further the frequency and risks of perioperative hypoxia, moving us forward from the days of ‘‘black gas anesthesia’’. In their report in this issue of the Journal, Ehrenfeld et al. present the incidence of hypoxemia during surgery using data they derived from a sizeable series of electronic records from two large medical centres. The authors report that hypoxemia (SpO2 90%) is infrequent (6.8%) but perhaps too common for an entity that anesthesiologists always try to avoid. Indeed, severe hypoxemia (SpO2 85%) occurred in 3.5% of patients. They also reported that transient hypoxemia occurred during all phases of anesthesia, especially during induction and emergence and particularly in patients who were American Society of Anesthesiologists (ASA) physical status III or IV. Aside from recognizing that we have not ‘‘conquered’’ intraoperative hypoxemia, what other important lessons can be learned from these data? First, we should reiterate the most obvious positive news. Acceptable levels of SpO2 ([ 90%) were maintained G. M. T. Hare, MD, PhD Department of Anesthesia, Keenan Research Centre in the Li Ka Shing Knowledge Institute and the Cara Phelan Centre for Trauma Research, St. Michael’s Hospital, Toronto, ON, Canada

Effects of circadian rhythm on ventilator-induced lung injury

The Keenan Research Centre in the Li Ka Shing Knowledge Institute, Saint Michael's Hospital, Toronto, Canada