Li Ka Shing Knowledge Institute

Toronto, Canada

Li Ka Shing Knowledge Institute

Toronto, Canada

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News Article | May 9, 2017
Site: www.eurekalert.org

People who have received organ transplants are at higher risk of developing and dying of cancer than the general population. Yet their rates of cancer screening do not meet existing guidelines, a new study has found TORONTO, May 4, 2017--People who have received organ transplants are at higher risk of developing and dying of cancer than the general population. Yet their rates of cancer screening do not meet existing guidelines, a new study has found. The study, published online today in the American Journal of Transplantation, examined the health records of 6,392 patients who had organ transplants in Ontario between 1997 and 2010. "Most of the organ transplant recipients had periods when they were not up-to-date on colorectal, cervical or breast cancer screening," said senior author Dr. Nancy Baxter, a colorectal surgeon at St. Michael's Hospital and senior scientist at the Institute for Clinical Evaluative Sciences. In fact, a sizeable portion of them had no cancer screening at all during the study, said Dr. Baxter. "Many patients don't see cancer screening as a high priority, because their main health concern is their transplant," she said. "Transplant recipients should be aware they have a heightened risk of developing and dying from cancer and should advocate with their health-care providers to be screened." Current cancer screening guidelines for transplant recipients in Canada generally parallel the guidelines for the general population. Researchers identified 6,392 solid organ transplant recipients who were eligible for cancer screening: 4,436 for colorectal cancer screening, 2,252 eligible for cervical cancer screening, and 1,551 eligible for breast cancer screening. Of those, 3,436 (78 per cent), 1,572 (70 per cent), and 1,417 (91per cent) were not continuously screened for colorectal, cervical and breast cancer, respectively. Dr. Sergio Acuna, the study's lead author and a PhD candidate in clinical epidemiology and health-care research at St. Michael's, said transplant recipients who were routinely seeing their family physician were more likely to be screened for cancer than those followed by a transplant specialist alone. Comorbidities--additional conditions including heart disease and diabetes--and life expectancy also had an effect on recipients' likelihood of being screened, according to the authors. The study found that patients with more comorbidities were less likely to be up-to-date with cancer screening. Previous work by Drs. Baxter and Acuna found that people who had organ transplants were three times more likely to die from cancer than the general population and that cancer was a leading cause of death among these patients. It is well known among clinicians and researchers that cancer screening leads to the detection of cancer at early stages, according to Dr. Acuna. "We have evidence of increased incidence of cancer in transplant recipients, we have some good evidence for the performance of screening tests in transplant recipients, and although we have no direct evidence of the effect of treatment on outcomes, it is likely that early detection in this population would lead to improved outcomes," said Dr. Acuna. Although there are no clinical trials demonstrating that this screening benefit applies to organ transplant recipients, it is unlikely to change given that clinical trials require large numbers of people to provide accurate data and the transplant population is relatively small, he said. In another study, Drs. Baxter and Acuna found cancer screening guidelines for this group are inconsistent as is the use of these guidelines. Their review found only 13 sets of clinical practice guidelines--recommendations for optimizing patient care generally based on evidence--for cancer screening of transplant recipients. Most were for kidney transplant recipients as kidneys are the most commonly transplanted organ. Dr. Acuna said this inconsistency could be one reason for low screening rates in this population, and patients and their physicians should be aware of the need for cancer screening. "In Canada, the guidelines are not comprehensive, and there are no specific guidelines for most types of solid organ transplant," he said. "Family doctors, transplant specialists and transplant recipients should all be aware that cancer screening guidelines for the general population should also apply to them or their patients." Today's study received funding from the Canadian Institutes of Health Research. St. Michael's Hospital provides compassionate care to all who enter its doors. The hospital also provides outstanding medical education to future health care professionals in 27 academic disciplines. Critical care and trauma, heart disease, neurosurgery, diabetes, cancer care, care of the homeless and global health are among the hospital's recognized areas of expertise. Through the Keenan Research Centre and the Li Ka Shing International Healthcare Education Centre, which make up the Li Ka Shing Knowledge Institute, research and education at St. Michael's Hospital are recognized and make an impact around the world. Founded in 1892, the hospital is fully affiliated with the University of Toronto. The Institute for Clinical Evaluative Sciences (ICES) is an independent, non-profit organization that uses population-based health information to produce knowledge on a broad range of health care issues. Our unbiased evidence provides measures of health system performance, a clearer understanding of the shifting health care needs of Ontarians, and a stimulus for discussion of practical solutions to optimize scarce resources. ICES knowledge is highly regarded in Canada and abroad, and is widely used by government, hospitals, planners, and practitioners to make decisions about care delivery and to develop policy. For the latest ICES news, follow us on Twitter: @ICESOntario For more information or to arrange an interview, please contact: Deborah Creatura Media Advisor, ICES (o) 416-480-4780 or (c) 647-406-5996 deborah.creatura@ices.on.ca


Women who were exposed to colder temperatures during pregnancy had a lower rate of gestational diabetes than those exposed to hotter temperatures TORONTO, May 15, 2017 - Women who were exposed to colder temperatures during pregnancy had a lower rate of gestational diabetes than those exposed to hotter temperatures, according to a study published online today in the Canadian Medical Association Journal. The prevalence of gestational diabetes was 4.6 per cent among women exposed to extremely cold average temperatures (equal to or below -10 C) in the 30-day period prior to being screened for gestational diabetes, and increased to 7.7 per cent among those exposed to hot average temperatures (above 24 C). The study also found that for every 10-degree Celsius rise in temperature, women were six to nine per cent more likely to develop gestational diabetes. The study examined 555,911 births among 396,828 women over a 12-year period. All the women studied lived in the Greater Toronto Area, but some were pregnant when the average temperature was warmer, and some when it was cooler. Researchers looked at the relationship between the average 30-day air temperature prior to the time of gestational diabetes screening in the second trimester, and the likelihood of gestational diabetes diagnosis. Dr. Gillian Booth, a researcher at St. Michael's and the Institute for Clinical Evaluative Sciences (ICES) and lead author of the study, said the finding might seem counterintuitive, but can be explained by emerging science about how humans make different kinds of fat. "Many would think that in warmer temperatures, women are outside and more active, which would help limit the weight gain in pregnancy that predisposes a woman to gestational diabetes," said Dr. Booth. "However, it fits a pattern we expected from new studies showing that cold exposure can improve your sensitivity to insulin, by turning on a protective type of fat called brown adipose tissue." A similar effect was seen for each 10-degree Celsius rise in the temperature difference between two consecutive pregnancies compared within the same woman. "By further limiting our analysis to pregnancies within the same woman, we controlled for a whole number of factors," said Dr. Joel Ray, a researcher at St. Michael's and ICES who co-led the study. "Doing so allowed us to eliminate factors like ethnicity, income, activity and eating habits that would differ between two different women." In addition to a higher rate of gestational diabetes among women who were exposed to hotter temperatures during pregnancy, there was also a lower rate of gestational diabetes among Canadian women born in cooler climates versus those who were born in hot climates. Those women born in cooler climates, including Canada and the United States, and who were exposed to cold temperatures during the 30-day period prior to screening had a gestational diabetes rate of 3.6 per cent, while those exposed to hot temperatures had a rate of gestational diabetes of 6.3 per cent. In comparison, women who were born in hot climates, including South Asia, Africa and the Middle East, had rates of gestational diabetes of 7.7 and 11.8 per cent, respectively. According to Drs. Booth and Ray, the findings, combined with the continued rise in global temperatures, could signal an increase in the future number of gestational diabetes cases worldwide. "While changes in temperature of this magnitude may lead to a small relative increase in the risk of gestational diabetes, the absolute number of women impacted in Canada and elsewhere may be substantial," they wrote. Gestational diabetes is new onset diabetes in the second trimester of pregnancy and is usually temporary, but the risk factors for gestational diabetes and adult onset type 2 diabetes are virtually the same. The results of this study could foreshadow the effects of rising world-wide temperatures on type 2 diabetes in general, according to the researchers. "This is like the canary in the coal mine for the possible effects of global warming on adult onset diabetes," said Drs. Booth and Ray. This study was funded by the St. Michael's Hospital Foundation and the Canadian Institutes of Health Research (CIHR). St. Michael's Hospital provides compassionate care to all who enter its doors. The hospital also provides outstanding medical education to future health care professionals in 29 academic disciplines. Critical care and trauma, heart disease, neurosurgery, diabetes, cancer care, care of the homeless and global health are among the hospital's recognized areas of expertise. Through the Keenan Research Centre and the Li Ka Shing International Healthcare Education Centre, which make up the Li Ka Shing Knowledge Institute, research and education at St. Michael's Hospital are recognized and make an impact around the world. Founded in 1892, the hospital is fully affiliated with the University of Toronto. ICES is an independent, non-profit organization that uses population-based health information to produce knowledge on a broad range of health care issues. Our unbiased evidence provides measures of health system performance, a clearer understanding of the shifting health care needs of Ontarians, and a stimulus for discussion of practical solutions to optimize scarce resources. ICES knowledge is highly regarded in Canada and abroad, and is widely used by government, hospitals, planners, and practitioners to make decisions about care delivery and to develop policy. For the latest ICES news, follow us on Twitter: @ICESOntario For more information, or to arrange an interview with one of the authors, please contact: Deborah Creatura Media Advisor, ICES deborah.creatura@ices.on.ca (o) 416-480-4780 or (c) 647-406-5996


News Article | May 4, 2017
Site: www.eurekalert.org

TORONTO, May 4, 2017--A study published today suggests that a select group of patients with rectal cancer who undergo chemotherapy and radiation may have low rates of recurrence and good survival rates regardless of whether they go on to have surgery. The conventional treatment for people with cancer of the rectum - the final part of the large intestine, ending at the anus - that has spread to nearby tissues or lymph nodes but not to other organs is chemoradiation to shrink the tumour, followed by surgery. But the surgery can result in complications, a permanent colostomy and poor quality of life. Some patients have such a dramatic response to chemotherapy and radiation that there is no detectable tumour at the time of surgery, said Dr. Fahima Dossa, the study's lead author and a surgical resident at St. Michael's Hospital. These patients, termed complete responders, have excellent survival and low rates of cancer recurrence, which raises questions about whether they benefit from surgery, said Dr. Dossa. Since 2004, some surgeons have offered these patients the option of surgery or a "watch-and-wait" approach that involves close followup. However, the safety of that approach remains unclear. In a paper published online today in The Lancet Gastroenterology & Hepatology, Dr. Dossa and her team conducted a systematic review and meta-analysis of 23 studies involving 867 patients who adopted the "watch-and-wait" approach. Cancer returned in the rectum of only 15.7 per cent of these patients. "What is striking is not only the low rate of cancer recurrence, but also that almost all the patients who had a recurrence could still be treated with surgery or radiation at the time the recurrence was detected," said Dr. Dossa. Only three patients with a recurrence could not undergo further treatment -- either surgery or more radiation - due to the extent of the renewed cancer. The analysis did not find differences in mortality between those who took the watch-and-wait approach and those who underwent surgery. Dr. Nancy Baxter, the study's senior author and chief of general surgery at St. Michael's, said that while many of the studies were small, the evidence to support a "watch-and-wait" approach is growing, challenging the current standards of care for rectal cancer. "The fact that patients in these studies chose to avoid surgery despite not knowing the safety of this approach is a reminder of the various factors that go into cancer treatment decisions," said Dr. Baxter. "At the very least, we are hopeful that this study will open the door to discussions between select patients and their surgeons about the option of a watch-and-wait approach. St. Michael's Hospital provides compassionate care to all who enter its doors. The hospital also provides outstanding medical education to future health care professionals in more than 29 academic disciplines. Critical care and trauma, heart disease, neurosurgery, diabetes, cancer care, and care of the homeless are among the Hospital's recognized areas of expertise. Through the Keenan Research Centre and the Li Ka Shing International Healthcare Education Center, which make up the Li Ka Shing Knowledge Institute, research and education at St. Michael's Hospital are recognized and make an impact around the world. Founded in 1892, the hospital is fully affiliated with the University of Toronto. For more information or to arrange an interview, please contact:


Review found health-care personnel assessed players in only 15 percent of head collisions during last World Cup and for average 107 seconds TORONTO, June 27, 2017--International recommendations for assessing whether athletes had suffered a concussion were not followed during the 2014 World Cup, according to research published today. Researchers led by Dr. Michael Cusimano, a neurosurgeon at St. Michael's Hospital in Toronto, reviewed videotapes of all 64 games played in the international soccer tournament in Brazil. Their findings were published online today as a research letter in the journal JAMA. The researchers found that concerning head collisions happened 72 times (1.13 times per match) and affected 81 players. Fourteen of the players (17 per cent) showed no sign or one sign of a concussion, 45 (56 per cent) had two signs and 22 (27 per cent) exhibited three or more signs. The consensus statement from the 2012 and 2016 International Conference on Concussion in Sports says symptoms of a sports-related concussion include a range of clinical symptoms, physical signs and cognitive impairment such as headache, feeling like being in a fog, loss of consciousness, an unsteady gait, and slowed reaction times. The guidelines, adopted by the Federation Internationale de Football Association, or FIFA, soccer's international governing body, say that players showing any signs of concussion should be immediately withdrawn from play and assessed by sideline health-care officials. Yet Dr. Cusimano's review found that health-care personnel assessed players in only 12 cases (15 per cent) of head collisions during the last World Cup and these assessments averaged 107 seconds (the range being 64 seconds to 180 seconds). Another 45 players (56 per cent) were assessed by another player, referee or health-care personnel on the field, and 21 players (26 per cent) received no assessment. Of greater concern, Dr. Cusimano said, was that of the 67 players who showed two or more signs of concussion, 11 players (16 per cent) received no assessment and returned to play immediately. Another 42 (63 per cent) immediately returned to play after an on-field assessment by another player (15), referee (12) or health-care worker on the field (15). Eleven players (16 per cent) were assessed on the sideline by health-care personnel and returned to play, and three (5 per cent) were removed from the match or tournament. One of the three who were removed initially was allowed to return to play after an on-pitch assessment by health-care personnel. Among the 22 players with three or more concussion signs, 19 (86 per cent) returned to play during the same game after an average assessment of 84 seconds. "In the 2014 World Cup, we found that players received no or very cursory assessment for a concussion after sustaining a collision and showing concerning physical signs for a concussion," Dr. Cusimano said. Noting that 265 million people, or four per cent of the world's population, play soccer, and viewership and media coverage have reached record levels, Dr. Cusimano said it was important for the sport's governing body to set an example for other to follow, especially in amateur leagues and those involving children. In addition, the 81 head collision events his researchers identified were far more than the 19 injuries to the head reported by team physicians to FIFA. Dr. Cusimano said team physicians may have reported only the most obvious and severe injuries and players may have under-reported their symptoms to avoid losing playing time. He recommended that independent physicians be authorized to make concussion assessments and playing decisions rather than those employed by soccer clubs whose jobs may be at risk if they make unpopular calls. St. Michael's Hospital provides compassionate care to all who enter its doors. The hospital also provides outstanding medical education to future health care professionals in more than 29 academic disciplines. Critical care and trauma, heart disease, neurosurgery, diabetes, cancer care, and care of the homeless are among the Hospital's recognized areas of expertise. Through the Keenan Research Centre and the Li Ka Shing International Healthcare Education Center, which make up the Li Ka Shing Knowledge Institute, research and education at St. Michael's Hospital are recognized and make an impact around the world. Founded in 1892, the hospital is fully affiliated with the University of Toronto. For more information or to arrange an interview, please contact:


News Article | July 26, 2017
Site: www.eurekalert.org

TORONTO, July 26, 2017--Opinion is still divided on whether strictly limiting the number of hours surgical residents can work and train impacts patient outcomes, the residents' quality of life or the caliber of their training, according to a paper published today. "The implementation of restrictions on residents' duty hours was one of the most significant transformations in medical and surgical education in recent history," Dr. Najma Ahmed, a trauma surgeon at St. Michael's Hospital, wrote in the journal Academic Medicine. "Opinions from the surgical community highlight the complexity of the issues surrounding residents' duty hours and suggest that recent changes are not achieving the desired outcomes and have resulted in unintended consequences." Traditionally, doctors in the residency phase of their training spent long hours in a hospital -often around-the-clock -- so they are able to see and treat e a wide variety and high volume of patients. In the last 15 years, health authorities started limiting those hours in the hopes of improving patient safety and the education and well-being of doctors. In 2003, the Accreditation Council for Graduate Medical Education in the United States limited all residents, regardless of their specialty, to 80 hours per week and in 2015 prohibited first-year residents from working more than 16 hours in a row. In Canada, on-call shifts were limited to 16 hours in Quebec after a provincial arbitrator ruled that in 2011 that a 24-hour on-call shift posed a danger to residents' health and violated the Charter of Rights. A National Steering Committee on Resident Duty Hours then urged all provinces and health-care institutions to develop comprehensive strategies to minimize fatigue and fatigue-related risks during residency. Dr. Ahmed, who was a member of the national group and is vice chair of education in the University of Toronto's Department of Surgery, published a systematic review of 135 articles in 2014 that concluded too-restricted hours may work for some residents, but not may not work as well for surgical residents. That paper found shorter hours for residents means more shift handovers, which means less continuity of care and more opportunities for information to get lost or not passed along. Shorter shifts may also reduce residents' ability to observe the natural course of a patient's recovery and recognize when a patient starts to experience complications, and how best to treat them - a critical skill for surgeons. While conducting that review of literature published in academic and scientific journals, Dr. Ahmed found hundreds of other non-research based articles that did not meet the criteria for inclusion in a systematic review, "yet these articles offered critical insight into the state of affairs of restrictions on working hours for surgical residents." More than 200 of those articles, mostly from authors in the United States, were subjected to a thematic review, the results of which were published today. Dr. Ahmed said the articles showed differing opinions within the surgical community around whether restricted hours improved residents' quality of life and improved patient care by decreasing surgical errors. These articles also found that that interns working fewer hours meant that more work was falling on senior residents or staff surgeons, resulting in potential burnout among this group of surgeons. . But she said their writings were consistent on several important aspects: the need for more research into the impact of restricted hours on resident training, that a one-size-fits-all approach is likely not the best approach for resident training across specialties and the unique nature of the surgical culture. . "Part of this unique culture is surgeons' ability to withstand longer work periods without rest, the emergency nature of surgical care and the need to monitor patients before and after surgery," she said. "Trainees are also intrinsically highly motivated." Some authors spoke of greater use of simulation facilities and urged hospitals to develop policies not just to manage physician fatigue, beyond duty hours and to create a culture of high-functioning surgical teams where fatigue is identified and addressed without persecution. She said the writers also expressed a desire for "data-driven policy changes, evidence supporting the implementation of these restrictions and adequate metrics to evaluate the impact of these changes on surgical training." She welcomed the Flexibility In duty hour Requirements for Surgical Trainees (FIRST) Trial underway in general surgery residency programs in accredited U.S. hospitals. First published results from the trial suggest that less-restrictive and more flexible policies are feasible without impacting patient outcomes or worsening resident wellness or the perceived quality of education. St. Michael's Hospital provides compassionate care to all who enter its doors. The hospital also provides outstanding medical education to future health care professionals in more than 29 academic disciplines. Critical care and trauma, heart disease, neurosurgery, diabetes, cancer care, and care of the homeless are among the hospital's recognized areas of expertise. Through the Keenan Research Centre and the Li Ka Shing International Healthcare Education Center, which make up the Li Ka Shing Knowledge Institute, research and education at St. Michael's Hospital are recognized and make an impact around the world. Founded in 1892, the hospital is fully affiliated with the University of Toronto. For more information or to interview Dr. Ahmed, contact: Leslie Shepherd Manager, Media Strategy, Phone: 416-864-6094 shepherdl@smh.ca


Jaqaman K.,Harvard University | Grinstein S.,Li Ka Shing Knowledge Institute
Trends in Cell Biology | Year: 2012

There is mounting evidence that the plasma membrane is highly dynamic and organized in a complex manner. The cortical cytoskeleton is proving to be a particularly important regulator of plasmalemmal organization, modulating the mobility of proteins and lipids in the membrane, facilitating their segregation, and influencing their clustering. This organization plays a critical role in receptor-mediated signaling, especially in the case of immunoreceptors, which require lateral clustering for their activation. Based on recent developments, we discuss the structures and mechanisms whereby the cortical cytoskeleton regulates membrane dynamics and organization, and how the nonuniform distribution of immunoreceptors and their self-association may affect activation and signaling. © 2012 Elsevier Ltd.


Kamel K.S.,Li Ka Shing Knowledge Institute | Halperin M.L.,Li Ka Shing Knowledge Institute
New England Journal of Medicine | Year: 2015

This review focuses on three issues facing clinicians who care for patients with diabetic ketoacidosis; all of the issues are related to acid-base disorders. The first issue is the use of the plasma anion gap and the calculation of the ratio of the change in this gap to the change in the concentration of plasma bicarbonate in these patients; the second concerns the administration of sodium bicarbonate; and the third is the possible contribution of intracellular acidosis to the development of cerebral edema, particularly in children with diabetic ketoacidosis. In this article, we examine the available data and attempt to integrate the data with principles of physiology and metabolic regulation and provide clinical guidance. Copyright © 2015 Massachusetts Medical Society.


Fairn G.D.,Li Ka Shing Knowledge Institute | Grinstein S.,Li Ka Shing Knowledge Institute
Trends in Immunology | Year: 2012

Phagocytosis mediates the clearance of apoptotic bodies and also the elimination of microbial pathogens. The nascent phagocytic vacuole formed upon particle engulfment lacks microbicidal and degradative activity. These capabilities are acquired as the phagosome undergoes maturation; a progressive remodeling of its membrane and contents that culminates in the formation of phagolysosomes. Maturation entails orderly sequential fusion of the phagosomal vacuole with specialized endocytic and secretory compartments. Concomitantly, the phagosomal membrane undergoes both inward and outward vesiculation and tubulation followed by fission, thereby recycling components and maintaining its overall size. Here, we summarize what is known about the molecular machinery that governs this complex metamorphosis of phagosome maturation. © 2012 Elsevier Ltd.


Gilbert R.E.,Li Ka Shing Knowledge Institute
Circulation Journal | Year: 2013

Although seemingly diverse, the tissue injury at sites of diabetic complications, whether in the heart, kidneys or eyes, shares the common histopathological feature of endothelial cell loss, a consequence of both increased cell death and deficient regeneration. In medium-sized and larger arteries the loss of the protective lining contributes to the atherosclerotic process, while at sites of microvascular disease endothelial cell loss leads to capillary rarefaction and ischemia. The pathophysiology of these changes and their consequences on organ structure and function in diabetes are reviewed, and the potential for endothelial regenerative strategies to enhance repair and ameliorate the long-term complications of diabetes is explored.


Slutsky A.S.,Li Ka Shing Knowledge Institute
American journal of respiratory and critical care medicine | Year: 2015

Mechanical ventilation is a life-saving therapy that catalyzed the development of modern intensive care units. The origins of modern mechanical ventilation can be traced back about five centuries to the seminal work of Andreas Vesalius. This article is a short history of mechanical ventilation, tracing its origins over the centuries to the present day. One of the great advances in ventilatory support over the past few decades has been the development of lung-protective ventilatory strategies, based on our understanding of the iatrogenic consequences of mechanical ventilation such as ventilator-induced lung injury. These strategies have markedly improved clinical outcomes in patients with respiratory failure.

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