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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:


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.


Burns K.E.,Li Ka Shing Knowledge Institute
The Cochrane database of systematic reviews | Year: 2013

Noninvasive positive-pressure ventilation (NPPV) provides ventilatory support without the need for an invasive airway. Interest has emerged in using NPPV to facilitate earlier removal of an endotracheal tube and to decrease complications associated with prolonged intubation. We evaluated studies in which invasively ventilated adults with respiratory failure of any cause (chronic obstructive pulmonary disease (COPD), non-COPD, postoperative, nonoperative) were weaned by means of early extubation followed by immediate application of NPPV or continued IPPV weaning. The primary objective was to determine whether the noninvasive positive-pressure ventilation (NPPV) strategy reduced all-cause mortality compared with invasive positive-pressure ventilation (IPPV) weaning. Secondary objectives were to ascertain differences between strategies in proportions of weaning failure and ventilator-associated pneumonia (VAP), intensive care unit (ICU) and hospital length of stay (LOS), total duration of mechanical ventilation, duration of mechanical support related to weaning, duration of endotracheal mechanical ventilation (ETMV), frequency of adverse events (related to weaning) and overall quality of life. We planned sensitivity and subgroup analyses to assess (1) the influence on mortality and VAP of excluding quasi-randomized trials, and (2) effects on mortality and weaning failure associated with different causes of respiratory failure (COPD vs. mixed populations). We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 5, 2013), MEDLINE (January 1966 to May 2013), EMBASE (January 1980 to May 2013), proceedings from four conferences, trial registration websites and personal files; we contacted authors to identify trials comparing NPPV versus conventional IPPV weaning. Randomized and quasi-randomized trials comparing early extubation with immediate application of NPPV versus IPPV weaning in intubated adults with respiratory failure. Two review authors independently assessed trial quality and abstracted data according to prespecified criteria. Sensitivity and subgroup analyses assessed (1) the impact of excluding quasi-randomized trials, and (2) the effects on selected outcomes noted with different causes of respiratory failure. We identified 16 trials, predominantly of moderate to good quality, involving 994 participants, most with chronic obstructive pulmonary disease (COPD). Compared with IPPV weaning, NPPV weaning significantly decreased mortality. The benefits for mortality were significantly greater in trials enrolling exclusively participants with COPD (risk ratio (RR) 0.36, 95% confidence interval (CI) 0.24 to 0.56) versus mixed populations (RR 0.81, 95% CI 0.47 to 1.40). NPPV significantly reduced weaning failure (RR 0.63, 95% CI 0.42 to 0.96) and ventilator-associated pneumonia (RR 0.25, 95% CI 0.15 to 0.43); shortened length of stay in an intensive care unit (mean difference (MD) -5.59 days, 95% CI -7.90 to -3.28) and in hospital (MD -6.04 days, 95% CI -9.22 to -2.87); and decreased the total duration of ventilation (MD -5.64 days, 95% CI -9.50 to -1.77) and the duration of endotracheal mechanical ventilation (MD - 7.44 days, 95% CI -10.34 to -4.55) amidst significant heterogeneity. Noninvasive weaning also significantly reduced tracheostomy (RR 0.19, 95% CI 0.08 to 0.47) and reintubation (RR 0.65, 95% CI 0.44 to 0.97) rates. Noninvasive weaning had no effect on the duration of ventilation related to weaning. Exclusion of a single quasi-randomized trial did not alter these results. Subgroup analyses suggest that the benefits for mortality were significantly greater in trials enrolling exclusively participants with COPD versus mixed populations. Summary estimates from 16 trials of moderate to good quality that included predominantly participants with COPD suggest that a weaning strategy that includes NPPV may reduce rates of mortality and ventilator-associated pneumonia without increasing the risk of weaning failure or reintubation.


Gilbert R.E.,Li Ka Shing Knowledge Institute
Current Atherosclerosis Reports | Year: 2014

Diabetes is characterised by widespread endothelial cell dysfunction that underlies the development of both the micro- and macrovascular complications of the disease, including nephropathy, cardiomyopathy, and non-proliferative retinopathy. In the kidney, major changes are noted in glomerular endothelial cell structure in their fenestrations and glycocalyx. These changes, along with endothelial cell loss and capillary rarefaction in both the glomerulus and tubulointerstitium, lead to the progressive loss of glomerular filtration that render diabetes the most common cause of end-stage renal disease in much of the developed world. New treatments in diabetes that directly address the abnormal structure and function of the endothelial cell are desperately needed. © Springer Science+Business Media New York 2014.


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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