McMaster’s Medical Research and Health Ethics Student Journal
The Ontario Telehomecare Strategy: Phase One
Also in this issue: Progeria: the Fight against Time Curing Cancer with Viruses
HIV in the context of Science and the Law
The Quarantine Conundrum
Innovation and Implementation Issue 12 | April 2008
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Table of Contents
Issue 12 | April 2008
Research Articles Presidential Address
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MedWire
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MedBulletin
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Tyler Law
MedQuiz
HIV/AIDS in the Context of Science and the Law Michael Herman
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About The McMaster Meducator The McMaster Meducator is an undergraduate medical journal that publishes articles on current topics in health research and medical ethics. We aim to provide an opportunity for undergraduate students to publish their work and share information with their peers. Our protocol strives to maintain the highest standard of academic integrity by having each article edited by a postgraduate in the relevant field. We invite you to offer us your feedback by visting our website: www.meducator.org. The McMaster Meducator may be contacted via our e-mail address: meduemail @learnlink.mcmaster.ca or our mailing address: B.H.Sc. (Honours) Program Attention: The McMaster Meducator Michael G. DeGroote Centre for Learning and Discovery Room 3308 Faculty of Health Sciences 1200 Main Street West Hamilton, Ontario L8N 3Z5 http://www.meducator.org
Oncolytic Therapy: Curing Cancer with Viruses Jonathan Liu & Noemie Dell 3’
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Progeria: The Fight Against Time Jennifer Gao, Christine Ibrahim, Jennifer Lee, Christina Martorelli, & Penny Yin
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The Ontario Telehomecare Strategy: Phase One Sarah Mullen
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The Quarantine Conundrum Alexandra Perri
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s we are presented with the unique challenges and situations of healthcare, the intrepid innovators of new solutions do us an invaluable service. Those who engage us in dialogue, addressing the complexities of these issues, form the framework of our understanding of these problems. The solutions to modern and unfamiliar problems are rooted in discussion and the development of ideas is key to their eventual implementation. This issue of the Meducator highlights several of such innovative dialogues. Quarantining is a protocol that has been around for many years, yet privacy laws and personal rights has forced the issue into unexpected directions. Alexandra Perri guides us through some of the core problems, and how we might approach quarantine given these new circumstances. Issues of privacy and ethical responsibility concern Mike Herman’s article also, as he explores some of the legal issues involved when an individual fails to disclose their HIV-positive status to sexual partners. A solution to the increasing burden of patients on hospital resources is explored by Sarah Mullen, who explains the concept of telemedicine and demonstrates how it is being applied in Ontario to relieve that burden. On an individual level, Jennifer Gao, Christine Ibrahim, Jennifer Lee, Christina Martorelli, and Penny Yin describe the devastating disease of Hutchinson-Gilford Progeria Syndrome, how it can adversely influence an individual’s life, and what breakthrough research is being done to help those affected. Jonathan Liu and Noemie Dell focus narrower, showing how oncolytic viruses display promising advances in cancer therapy. Together, these articles represent a broad range of dialogues taking place to help explain the very difficult challenges in healthcare today. While these articles are the mainstay of the magazine, our website, www.meducator.org, contains regularly updated content. Every week new advances in medical research and health ethics are highlighted in MedBulletins, packaged into concise, digestible lengths. These MedBulletins are a great way to keep on top of interesting medical news as well as inform yourself of ethical debates. For an even quicker read, check out our MedWire section, where two-sentence summaries give a taste of the very latest in health news. Both sets of articles are available to browse on our website, and can also be subscribed to via RSS. We are proud of our website content, and hope that you will enjoy the continual updates. As this is the last issue for which I will serve as President, I would like to take a moment to recognize the exceptional individuals I have had the pleasure of working with. Thanks to Crystal Chung – your leadership and responsibility have proved that I really don’t need to be there at all. Thank you to our VP Editors, Harjot Atwal, Harman Chaudhry, Jacqueline Ho, Alexandra Perri, Jonathan Liu, Siddhi Mathur, Sarah Mullen, Navpreet Rana, and Jeannette So, for maintaining the high quality of our publication, and keeping everything on track. Thanks to Avinash Ramsaroop for maintaining the website – your work has been important for the new direction of the magazine. Thank you to Stephanie Low for responsibly managing the entire visual layout of the magazine, as well as Ran Ran and Andrew Yuen for assisting her. Lastly, thanks to our Junior Editors: Veronica Chan, Randall Lau, Simone Liang, and Fanyu Yang; I am tremendously proud of the effort you’ve put in, and you should be as well. We would not have been so successful this year without your dedication. I can’t wait to see where you take the Meducator next. As always, enjoy this issue. Please visit our website, www.meducator.org, and leave us a comment, submit an article idea, or check out our continually updated MedWire and MedBulletin sections. Sincerely,
Meducator Staff President Tyler Law Vice-President Crystal Chung VP Medical Research and Health Ethics Harman Chaudhry Jacqueline Ho Jonathan Liu Siddhi Mathur Sarah Mullen Alexandra Perri Navpreet Rana Jeannette So VP Layout Stephanie Low VP Web Design Avinash Ramsaroop VP Public Relations Harjot Atwal Junior Executives Veronica Chan Randall Lau Simone Liang Ran Ran Fanyu Yang Andrew Yuen
Post Graduate Editors Dr. Dale Guenter, M.D., MPH Dr. Robert A. Hegele, M.D., FRCPC, FACP Dr. Brian Lichty, Ph.D. Dr. Lisa Schwartz, MA, Ph.D. Dr. Jim Bolton, M.D.
Tyler Law B.H.Sc. III www.meducator.org
Presidential Address
Dear Reader,
MedWire
4 Researchers in the UK have developed a TB blood test that provides results within 48 hours, and with 99% accuracy when used with the tuberculin skin test. The new blood test specifically recognizes the immune response produced by TB infection, and has been tested on 389 patients in the UK. Doctors hope that once this test is licensed, it can be used to diagnose and treat patients more quickly. A study conducted at the University of Western Australia suggests that lower levels of testosterone in elderly men may make them more susceptible to depression. In the research, approximately 4000 men over the age of 70 gave blood samples and participated in other tests to identify depression. Though more studies have to be done for verification, the study suggests that depression in elderly men may be treated by increasing their testosterone levels.
A five year study conducted by the University of Minnesota has found that individuals who had breakfast in the morning weighed 5 pounds less than those who skipped breakfast. People who have breakfast are more active and alert throughout the day and
Issue 12 burn more calories. Though teenage girls were most likely to skip breakfast, in fear of gaining weight, this study supports the idea that people who eat breakfast are healthier than those who do not. A team of researchers from the United States National Institute of Health suggests that they have discovered a possible reason to explain why the influenza virus is more prevalent in cold conditions. Essentially, the virus particles become surrounded in a lipid-like coat which solidifies, providing protection during transmission from host to host. Pathogenesis begins inside the respiratory tract where the warmer internal temperature melts the rubber-like coating. Minute magnet particles produced by bacteria are found to have promising
the extremely drug-resistant tuberculosis, is also becoming increasingly prevalent worldwide. This form has proven to be nearly incurable and shows no response to both firstline and secondary antibiotic treatments.
The medical ethics board of the United Kingdom has recently granted approval for full facial transplants to be performed. Although partial facial transplants have been successfully performed in France since 2005, the notion
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clinical applications in cancer treatment. These particles can be guided towards sites of tumour growth magnetically, and the induction of an opposite magnetic field would subsequently cause the temperature of the nanomagnets to rise. It is suggested that the heat emitted from this process can eradicate cancerous cells.
A recent report from the World Health Organization insinuates that 5% of the 9 million global diagnoses of tuberculosis are characteristically multidrug resistant. A more severe variety, known as
of full transplants has always been intensely controversial because of its implications to adopting a key component of a deceased individual’s identity. Long-term psychological or medical consequences of full facial transplants are currently unknown. The latest study conducted by the University of Edinburgh has found that one’s genes exhibit control over approximately half of one’s personality traits, which account for happiness. External factors such as relationships and career success influence the remaining half. Measuring
the differences between personality traits in fraternal twins, compared to identical twins elucidated the magnitude of genetic influence on happiness. An ingredient in cigarette smoke, polyaromatic hydrocarbon benzo(a)pyrene (BaP), has been shown to slow the healing process in bone fractures. BaP interferes with the expression of an important transcription factor, Y-box 9 (SOX-9), slowing the conversion of mesenchymal stem cells into cartilage and inhibiting collagen type II production, reducing the rate at which two sides of a fracture meet . A large number of population studies have shown a protective effect of light or moderate alcohol drinking against the risk of death and
the development of heart disease. However, recent findings from researchers at the Peter Munk Cardiac Centre of the Toronto General Hospital placed a new spin on the beneficial effects of red wine or alcohol. Blood vessels
April 2008
Tamoxifen, typically used to treat breast cancer, has shown promise in regulating the mania of those diagnosed with bipolar disorder. A clinical trial sample of patients diagnosed with bipolar disorder or displaying a state of mania were given a combination of tamoxifen and the sedative, lorazepam, to control their symptoms. As the study continued, those given tamoxifen vastly reduced their lorazepam requirements over 2.5 times more quickly than the placebo group.
Physicians at Lucile Packard Children’s Hospital turned to an unconventional diagnostic tool to alleviate a boy’s daily episodes of seizures. The only way to pinpoint the true cause was to monitor the child’s brain activity during an event. Many children who seem to be having epileptic seizures are actually having an involuntary physical reaction to psychological stress in their lives. The physicians believe that hypnosis may be an important tool that can speed up proper diagnosis and treatment for children suffering from seizure-like events.
Researchers from the Harvard Medical School have found that the uncontrolled division of cancerous cells can be attributed to the PKM2 form of pyruvate kinase. This enzyme facilitates the atypically high rate of glucose metabolism by tumour cells that accounts for their rapid growth. Attenuation of cellular division was observed when PKM2 expression was impeded. Investigation at the Ingestive Behavior Research Center at Purdue University reveal that laboratory rats which consumed food with artificial sweeteners ate more calories than their counterparts whose food was sweetened with normal sugar. The researchers suggest that a sweet taste may cause animals to anticipate the calorie content of food. Eating artificial sweeteners with little or no calories undermines this connection and lead to an energy imbalance of increasing food intake or reducing energy expenditure.
Scientists from the University of Chicago Medical Center have shown that attachment of chromatin to the inner nuclear membrane can silence genes and prevent their transcription. This novel form of gene regulation likely involves nuclear membrane
proteins that accumulate at sites of attachment and come in contact with parts of the silenced genes. This proposes that DNA segments that encode for ‘nuclear addresses’ direct genes to associate with specific regions within the nucleus.
Researchers at the University of Illinois have uncovered a new treatment strategy for serious antibiotic-resistant Staphylococcus aureus infections. A compound (BPH652) originally designed to lower cholesterol, blocks a key enzyme in the organism’s infection pathway and allows the body’s immune cells to prevail against the infection. Such findings are particularly promising because BPH-652 has already been used in humans clinically, reducing the cost and time for development. Seven French physicians have recently been on trial for allegedly infecting more than 100 patients with the Creutzfeld-Jakob Disease, the human form of mad cow disease. The old practice of obtaining growth hormones from the pituitary glands of corpses was outlawed in the early 1980’s, yet the accused health care officials continued with this dangerous procedure without informing patients of its fatal risks.
A study conducted at the King’s College in London has found that a compound in black pepper, known as piperine, could be used to treat a skin disorder, known as vitiligo. Vitiligo occurs when patches of skin lose their pigment and become pale. The compound piperine is the secret to black pepper’s flavor, and according to researchers, piperine can also be used to invoke pigmentation. Combining piperine with the current UV radiation therapy resulted in pigmentation that developed faster and lasted longer. Researchers of Wageningen University in the Netherlands have demonstrated the importance of unsaturated dietary fats in gene expression. The breakthrough may eventually allow for targeted pharmacological intervention using synthetic triglycerides, improving upon the ambiguity of earlier dietary therapies and setting a new benchmark for nutrige-nomic studies. Preliminary research suggests that these mechanisms, regulated by the genes that respond vigorously to synthetic fatty acids, protect the liver cell from their unnecessary accumulation, while lowering plasma triglycerides and the incidence of blood clots.
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MedWire
appeared more “relaxed” or dilated after one drink of red wine or alcohol. But, after two drinks, the heart rate and action of the sympathetic nervous system all increased. The ability of the blood vessels to expand in response to an increase in blood flow was also compromised.
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Intercessory Prayer: Issues in Investigating Medicinal Faith
Issue 12
MedBulletin by Fanyu Yang
Research on intercessory prayer is a recent attempt to scientifically investigate the health benefits of religious activity. In these studies, patients are randomly assigned to receive either standard care or standard care plus the prayers of distant intercessors. To date, the empirical results of trials remain conflicting. They have however, raised growing questions on the ethical and methodological basis of intercessory prayer as an “experimental drug”. Many studies waive key precepts in the ethical conduct involving human subjects by specifically averting informed consent to avoid patient expectations that might provoke a psychosomatic ‘placebo’ response. This arguably overlooks the patient’s spiritual autonomy and well-being. In addition, problems arise in identifying subject and control groups. Even if patients are matched based upon type and stage of disease, it is highly difficult to find equivalent groups based upon faith or “receptiveness” to healing by prayer. The laws of statistical reasoning caution that with enough outcomes measured, a statistically significant difference will arise by chance even when no real difference exists. This in turn raises the question of how “much” prayer is statistically significant. Can prayer be measured by time, the degree of sincerity or fervency? Does the faith tradition (e.g., Buddhism, Christianity, etc.) of the intercessor matter? The power of personal faith and its contribution to health and healing may be indisputable. However, debate over clinical trials of intercessory prayer raises questions on how to align such faith with the scientific method, or whether it is possible at all. Medical academians should therefore engage in critical bioethical evaluation and weigh arguments for and against such trials. References Turner, D. D. (2006). Just another drug? A philosophical assessment of randomised controlled studies on intercessory prayer. J Med Ethics. 32, 487-490. Halperin, E. C. (2001). Should academic medical centers conduct clinical trials of the efficacy of intercessory prayer? Academic Medicine, 76(8), 791.
Depressed Doctors and Prescription Blunders?
MedBulletin by Veronica Chan
A recent cohort study conducted at two paediatric hospitals in the United States suggests that prescription errors by junior doctors are, to a great extent, associated with mental health state indicators like depression and burn-out. Many investigations have been conducted on medication errors and patient mortality with respect to the systems’ flaws and have proposed some appalling statistics. Preventable prescription blunders account for nearly 7000 deaths in the United States yearly, and less experienced physicians are found to be responsible for the majority of these incidents. However, the mental health of young doctors as a key factor in influencing judgment and decision-making in medical practice is rarely examined. Fahrenkopf and his research team selected children’s hospitals as sites of study since paediatric care often involves the prescription of atypical drug varieties and the re-calculation of lower dosages. This poses a heightened risk for error. In surveying 123 junior doctors, nearly 20% experience symptoms of depression and 74% suffer from burn-out. When correlated with a six-week record of medication blunders of the same physicians, it was found that those who match the criteria for depression are six times more likely to err in clinical practice. Much to the researchers’ surprise, burn-out and prescription errors were not found to have a statistically significant relationship, despite previous evidence of a correlation between burn-out and poor clinical performance. It is recognized that the findings of this short-term, considerably subjective study are far from being conclusive or constructive in the development of strategies to prevent medication errors. Nevertheless, it provides an insightful starting point for future investigation, highlighting the need to examine the effects of multifaceted personal factors like the mental health of physicians on clinical performance. Findings from prospective large-scale, standardized studies will be required before firm conclusions can be drawn in this critical issue of patient safety. References: McLay, J., & Ross, S. (2008). Medication Errors Caused by Junior Doctors. BMJ. Retrieved February 15, 2008, from http://www.bmj.com.
April 2008
Orchestrating Insulin Resistance
MedBulletin by Randall Lau
Researchers at the Salk institute for Biological Sciences have uncovered the specific molecular mechanism at the root of insulin resistance. The final enzyme in the hexosamine pathway, O-linked ß-N-acetylglucosamine transferase (OGT), has been identified as crucial for turning off the cell’s insulin response. In normal physiology, when insulin binds to its receptor on the cell surface, it immediately stimulates the production of PIP3, a specialized lipid molecule which orchestrates the synthesis and storage of complex carbohydrates, proteins, and lipids. Within minutes of the insulin pathway’s initiation, OGT is recruited from the nucleus to the plasma membrane where it combines with the same lipid responsible for initiation, PIP3, to gradually turn off the signaling system. OGT forms the necessary PIP3 binding domain by tagging key factors in the insulin signaling network with sugar molecules, namely O-linked ß-N-acetylglucosamine (O-GlcNAc). The sugars are produced by the hexosamine pathway, and their concentration is directly proportional to the availability of glucose and other high energy molecules in the bloodstream. The hexosamine pathway is now understood to act as a fuel gauge that drives the regulation of OGT activity and in turn, the duration of the cell’s insulin response. In environments where nutrients are in excess however, O-GlcNAc levels balloon quickly. Subsequently, OGT activity is over-stimulated causing the cell’s insulin response to be cut short. This mechanism has been observed in murine models to result in abnormal blood sugar levels and insulin resistance soon thereafter. If OGT activity is not strictly regulated, the prolonged insulin inhibition is a strong indicator of Type II diabetes to follow. References Salk Institute. (2008). Novel Link Between Excessive Nutrient Levels And Insulin Resistance Uncovered. ScienceDaily. Retrieved February 24, 2008, from http://www.sciencedaily.com/releases/2008/02/080221143325.htm.
Too Much of a Good Thing?
MedBulletin by Simone Liang
Many people take vitamin supplements to compensate for a lack of essential nutrients and minerals. However, researchers are beginning to question the benefits of supplements as studies begin to suggest that supplements could affect one’s risk of getting cancer. Vitamin E is an anti-oxidant, which can prevent cellular damage from unstable radicals, but scientists now wonder if high dosages of anti-oxidants may actually damage cells. A study conducted by US researchers has found that high intake of vitamin E slightly increases the risks of lung cancer, especially among smokers. Consisting of 77 000 people, researchers monitored the intake of folic acid, vitamin C and vitamin E for four years. By the end of the study, 521 people had developed lung cancer, and vitamin E was the only supplement that had affected the risk of lung cancer. The relationship between vitamin E and lung cancer was more commonly found among, but not restricted to, smokers. Researchers conclude that the daily dose of 100 milligrams of vitamin E supplement increased the risk of lung cancer by seven percent. In another study that consisted of male smokers, an 18 percent increased risk of lung cancer was correlated with the supplement beta-carotene. Inconclusive evidence shows that high dosages of supplements can increase one’s risk of getting cancer, while others show no effect, and some show benefits. However, repeated studies show that a healthy diet provides all the necessary vitamins, and does not affect one’s risk of cancer.
References: BBC News. (2008). Vitamin E linked to lung cancer. Retrieved February 29, 2008, from http://news.bbc.co.uk/2/hi/health/7271189.stm.
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Issue 12
HIV/AIDS in the Context of Science and the Law The HIV/AIDS pandemic is not simply a biomedical problem – the disease also has important social and political implications. One of the controversial issues is the criminality associated with HIV transmission. This article will examine the legal position that Canada has taken to help limit HIV/AIDS transmission. Michael Herman
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uman Immunodeficiency Virus (HIV) has become a prominent topic in the last few decades. It is a virus that can lead to Acquired Immunodeficiency Syndrome (AIDS), a disease that affects countless people worldwide. In the July 2002 issue of The Lancet, experts from various organizations, including the United Nations AIDS Agency and the World Health Organisation, announced that within the next eight years approximately 45 million people would contract HIV (Watstein & Stratton, 2003). This prediction is a terrifying reminder of the global prevalence of HIV/AIDS (Figure 1). Attention is usually focused on developing regions like Africa; however, HIV and AIDS also impact various facets of society in Europe and North America. According to famous American essayist Susan Sontag, “like the effects of industrial pollution ... the AIDS crisis is
evidence of a world in which nothing important is regional, local, limited; in which everything that can circulate does, and every problem is, or is destined to become, worldwide” (Sontag, 2006). The AIDS pandemic is not simply a biomedical problem, there are also important social and political issues to consider. This article describes the legal position that Canada has taken in the preclusion of HIV transmission.
The S cience B ehind HIV/AIDS Many experts agree that HIV most likely evolved from a retrotransposon. These are sections of genetic code that migrate from one locus to another by first being transcribed into ribonucleic acid (RNA), and then reverse transcribed back into deoxyribonucleic acid (DNA) at another location. It is
Figure 1 A United Nations’ geographical representation of the global prevalence of HIV.
April 2008 believed that after gaining additional genetic code, the retrotransposon, was able to leave the cell like a virus (Friedman-Kien, 1996). HIV is a retrovirus that contains a RNA genome associated with enzymes that allow for reverse transcription into the host cell’s genome. The capsid of the virus is covered by a lipid bilayer of gp120 surface proteins (Karp, 2008). The targets of HIV are helper T-cells (Th), particularly CD4+ cells that express a surface protein which binds to gp120, facilitating entry of the virus into host Th cells (Watstein, 2003). Once inside, the RNA genome is reverse transcribed into the CD4+ cells’ genome (Figure 2). The virus’ non-lysogenic replication cycle allows many copies of the virus to be made while the infected cell remains dormant (Figure 3). It is this characteristic of replication without CD4+ cell lysis that explains why people with HIV remain free from AIDS for varying lengths of time. As such, nonsymptomatic individuals may pass on the virus to others.
The Law B ehind HIV/AIDS When looking at the legal aspects of HIV, one encounters numerous ethical and social issues, one of the most important being the criminality of the transmission of HIV. In common law (or case law), outcomes of past cases are referenced when making decisions for new cases (Hill & Hill, 2005). Cases that are recent, local, and from higher levels of court are given greater consideration (Ross, 2006). Therefore, recent Canadian cases of HIV transmission contribute to understanding what legal steps Canada is taking to prevent the transmission of HIV. Also, these cases demonstrate the criminality and consequences associated with HIV transmission. In Canada, the ethical and legal onus
9 Figure 2 The HIV infection cycle. Processing by
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rests on individuals with HIV to disclose their HIV-positive status where sexual activity poses “significant risk of serious bodily harm” (Betteridge & Alexandrova, 2004). R. v. WALKEM The case of R. v. Walkem in 2007 is an example of a HIV transmission case that can act as precedent. The ruling by Superior Court Justice Arthur Gans in Toronto found Vincent Walkem guilty on two counts of aggravated sexual assault for “[endangering] the lives of two former girlfriends by engaging with them in repeated acts of unprotected sex when he knew he had tested positive for HIV” (Gans, 2007). Mr. Walkem, after learning he was HIV positive and being repeatedly warned
by health officials to notify his sexual partners, engaged in unprotected sexual relations with two women whilst not revealing his condition. The main ethical issue in this case is the balancing of the rights of the victims to be free of a deadly disease against the defendant’s right to privacy. However, human life is generally considered more important than privacy. When guilt has been firmly established, what kind of sentence should be given for the willing and deceitful transmission of HIV? This legal dilemma was addressed by Judge Gans: “It is in cases of this nature where an aggravated assault is perpetrated by knowing HIV-carriers that the sentencing objectives of deterrence and denunciation are paramount, requiring as it does the imposition of a sentence of imprisonment rather than a www.meducator.org
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Issue 12 very seriously, and harshly punishes individuals who fail to disclose their HIV status to their partners. It is the legal responsibility of individuals infected with HIV/AIDS to inform their sexual partners of their condition. Canada understands that social and legal deterrents need to be put in place to complement scientific approaches of controlling the spread of HIV.
Looking to the Future
Figure 3 HIV viral particles infecting a T cell.
conditional sentence” (Gans, 2007). In other words, the crime is considered serious enough that there is a pressing need to impose imprisonment, rather than alternative punishments such as house arrest, community service or probation. R. v. LEONE Carl Leone, originally charged with 20 counts of aggravated sexual assault for having sexual relations with 20 women after finding himself to be HIV-positive, pleaded guilty to 15 counts of aggravated sexual assault in April 2007 (Canadian HIV/AIDS Legal Network, 2007). Similar to the aforementioned case with R. v. Walkem, the Canadian court associated serious charges with the deceitful transmission of HIV. However, in R. v. Leone the courts took a step further and ordered the accused to undergo psychiatric evaluation to determine whether or not Leone should be classified as a dangerous offender (Canadian HIV/AIDS Legal Network, 2007). In Canada, incarceration, involving the complete removal of an individual’s personal freedom, is viewed as the most severe form of punishment. For this reason, jail sentences are usually capped at 25 years; however, if an indivudal is declared to be a dangerous offender, the 25year cap is waived and they face a sentence of indefinite imprisonment (subject to review every seven years). The fact that Leone was even evaluated as a possible dangerous offender meant that in Canada, the failure to disclose one’s HIV status to sexual partners is considered on par with the most severe of crimes. What implications do these rulings have on society? Canada is a country that takes the transmission of HIV
Society has more knowledge about HIV and AIDS now than ever before, and it is imperative to disseminate this knowledge so that everyone may benefit from it. This may include setting up more sexual health clinics so that the necessary information is more readily available, targeting schools to educate youth about the dangers of unprotected sex, and making sure the general population understands the legal responsibilities of HIV-positive individuals. HIV is a pandemic, and, in the words of Nelson Mandela, “Education is the most powerful weapon which you can use to change the world.”
References Betteridge, G., & Alexandrova, A. (2004). Disclosure of HIV status – developing resources for community based AIDS service organizations. Abstract presented at the 15th International AIDS Conference, Bangkok, Thailand, abtract no. MoPeE4127. Retrieved March 15, 2008, from the National Library of Medicine database. Canadian HIV/AIDS Legal Network. (2007). Man accused of failing to disclose HIV- positive status convicted of 15 counts of aggravated sexual assault. HIV/AIDS Policy & Law Review, 12, 2/3. Derlega, V. J. (2004). Reasons for HIV disclosure/nondisclosure in close relationships: Testing a model of HIV–disclosure decision making. Journal of Social and Clinical Psychology, 23, 747-767. Friedman-Kien, A. E., & Cockerell, C. J. (Eds.). (1996). Color Atlas of AIDS. (2nd ed.). Philadelphia: W.B. Saunders Company. Hill, G., & Hill, K. (2005). The Legal Dictionary. Viewed November 13th from http://legal-dictionary.thefreedictionary.com/case+law. Karp, G. (2008). Cell and Molecular Biology: Concepts and Experiments. Indianapolis: John Wiley & Sons, Inc. Regina v. Walkem. (2007). CanLII 742 (ON S.C.). Ross, M. (2002). An Advocates Toolbox. Michigan Bar Journal, 81, 2428. Sontag, S. (2006). “Like the effects of industrial...” The Columbia World of Quotations. Ed. Robert Andrews, Mary Biggs, and Michael Seidel. Columbia University Press, 2006. eNotes.com. 2006. Retrieved Oct 29th, http://www.enotes.com/famous-quotes/ like-the-effects-of-industrial-pollution-the-aids. Watstein, S., & Stratton, S. (2003). The Encyclopedia of HIV and AIDS. (2nd ed.). New York: Facts on File, Inc.
April 2008
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Oncolytic Therapy: Curing Cancer With Viruses
Jonathan Liu & Noemie Dell
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When we think of viruses, they are often stigmatized as something that is harmful to our bodies. However, the genetic amenability of viruses allows researchers to easily manipulate them to specifically target cancer cells. This new approach to cancer treatment is referred to as oncolytic virus therapy. In China, a new oncolytic strain of adenovirus has recently been approved for treating cancer, but the technology is lagging in North America. This article discusses some of the barriers and novel findings in the exciting field of oncolytic virus therapy.
ue to emerging cancers that are resistant to conventional chemotherapy, the field of oncolytic therapy is touted as the future of cancer treatment. Oncolytic therapy involves the use of a virus to specifically replicate and destroy tumour cells found throughout the body. Within the past decade, researchers have experimented with the poliovirus, influenza virus, and measles virus as potential candidates for oncolytic virus therapy (Russell, 2002). This may seem counter-intuitive since these viruses are generally viewed as something that is harmful. Several decades ago, Peyton Rous was awarded the Nobel Prize for discovering that viruses are the causative agents of certain tumours. Many virologists today, however, have reversed this conventional view by trying to eliminate tumours with viruses. China’s Food and Drug Administration (FDA) recently approved the first oncolytic virus called H101, created by Shanghai Sunway Biotech, for oncolytic treatment of head and neck cancers (Garber, 2006). Although a wide range of these recombinant viruses exist in the United States, oncolytic therapy is still considered an experimental procedure because of tight safety regulations imposed by the American FDA. This article discusses
the current barriers that oncolytic therapy faces, followed by a review of new directions that this field is taking, with particular focus on the use of the vesicular stomatitis virus.
Barriers to O vercome Although several viruses have been shown to possess oncolytic abilities, there are still many unanswered questions and problems that need to be addressed. Getting viruses to the site of the tumour has been problematic since most experiments require injecting high viral titers directly into the tumour site. The efficacy of eliminating metastasized cancer by using oncolytic therapy may be very low since all cancerous cells must be removed to prevent relapses. Systemic delivery of oncolytic viruses via intravenous injection is difficult because of viral tropism and activation of the immune system upon viremia. Getting the virus into specific tumour areas is the challenge that lies ahead. The fear of oncolytic viruses evolving into pathogens is another concern that is deeply rooted in the belief that viruses are harmful (Bell, Lichty, & Stojdl, 2003). The human body can place selective pressures on these viruses, but clinical trials for oncolytic viral therapy are designed to ensure that patients do not inadvertently infect other
individuals. By preventing transmission or “serial passage� of oncolytic viruses, the probability of either mutating or recombining, and eventually reverting into its original pathogenic form, is reduced. Occasionally, administration of an oncolytic virus might cause an adverse response. Although this often is not lethal, one method of administration that has been used in some experiments is to gradually increase viral dosage over the course of several injections (Bell et al., 2003). Even though adverse symptoms may appear after the first inoculation, the host will eventually become desensitized and the virus can continue its anti-tumour activity unimpeded by the immune system. Further complicating matters are the ethical and economic factors that need to be considered with regards to oncolytic therapy. As the United States biotechnology companies continue to be impeded by the FDA, they may relocate their research branches to China. This raises some ethical concerns regarding practices in recruiting test subjects. However, it is economically feasible to relocate since the bulk of their market resides in China, where oncolytic therapies seem to earn government approval faster. The economic perspective is an important consideration since it has www.meducator.org
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become extremely costly for biotechnology companies to research, produce, test and market these products. To date, only a handful of oncolytic viruses have made it into the advanced stages of FDA testing (e.g. human test trials), only to be withdrawn or rejected (Garber, 2006).
The Difference B etween Using DNA and RNA Viruses When compared to the adenovirus, a doublestranded DNA virus, RNA viruses are better candidates for oncolytic therapy. This is because they do not rely on the host nucleus and polymerases for transcription and translation of the viral genome. The requirement for viral transcripts to be exported out of the nucleus also complicates and diminishes the expediency of the DNA virus life cycle. However, the lifecycle of an RNA virus is less restrictive in terms of the host cell environment that is required for its replication. RNA viruses either carry their own polymerases or polymerase transcripts are immediately transcribed upon entry into the host cell. Furthermore, RNA viruses generally replicate faster than DNA viruses. This is a desirable characteristic since the goal of oncolytic therapy is to rapidly eliminate tumour cells before these cells can spread or become resistant (Russell, 2002). One setback is that RNA virus genomes tend to be more prone to errors during replication, possibly leading to an evolved pathogenic form of the oncolytic virus. Viral evolution is a problem that is shared by both DNA and RNA viruses even though it might be more rapid with RNA viruses.
S electively Targeting Tumour Cells There are currently three approaches used to ensure that viruses are able to specifically target tumour cells: (1) complementing a viral mutation with a tumour mutation, (2) fusing the viral genome to a tumour-driven promoter so that it can only be expressed in tumours, and (3) allowing the virus to express recombinant receptors that show high affinity to cell surface markers found on tumour cells (O’Shea, 2005). The first approach can be further divided into two ways that allow mutant viruses to exploit tumour cell-specific defects. One defect includes an inability to respond to interferon (IFN), a crucial antiviral compound that activates a whole subset of genes responsible for “arming� cells during infection. It is believed that tumour cells possess a defective IFN response because IFN normally diminishes uncontrolled growth by shifting cellular resources away from the cell and towards antiviral response. Nonetheless, this defect results in reduced cellular fitness as the cell becomes more vulnerable to viral infections. Another tumour-specific defect that can be exploited is Ras hyperactivation, resulting in uncontrolled cell proliferation (tumours). The Ras pathway is closely related to the protein kinase R (PKR) mechanism, which usually suppresses cellular translation upon detecting foreign RNA. In cells with Ras-induced cell proliferation, PKR must either be mutated or inhibited so that cellular translation can proceed in tumours (Norman, Farassati, & Lee, 2000). In normal cells, viral infection results in long, double-stranded RNA that activate PKR and arrest cellular translation in the
IFN
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Figure 1 This diagram shows how the Ras, PKR, and IFN pathways converge in a normal (noncancerous) cell to shut down cellular translation in response to an infection. The influenza virus typically encodes an NS1 protein that can inhibit the PKR-antiviral response to ensure that translation continues (Chiocca, 2002).
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Figure 2 The vesicular stomatitis virus is an enveloped negative-strand RNA virus. Its genome is segmented into five genes that encode the following proteins: large polymerase protein (L), glycoprotein (G), matrix protein (M), phosphoprotein (P), and nucleoprotein (N). The coiled structure found within the phospholipids bilayer represents the ribonucleoprotein containing RNA and proteins to ensure the viral genome is protected (Lichty et al., 2004).
host cytoplasm, thus preventing the virus from replicating and spreading. Viruses such as influenza encode a protein that can counteract this PKRantiviral response. However, if this viral protein is deleted, the virus will only be able to persist in cells with a defective PKR response and this is how tumour cells can be selectively targeted.
Vesicular Stomatitis Virus A group of Canadian researchers decided to approach the problems facing oncolytic viruses from another perspective. Rather than taking a human viral pathogen and subjecting it to specific mutations, this group decided to start with a non-pathogenic virus called the vesicular stomatitis virus (VSV). This virus is a primary candidate for oncolytic therapy because it typically does not infect humans, meaning most individuals will not be seropositive for VSV (Lichty et al., 2004). Without pre-existing neutralizing antibodies, this virus is able to reach target sites (e.g. tumours) more effectively. VSV is a negative-strand RNA virus that is spread by an arthropod vector and causes ulcerations in cattle, swine, and horses. It is part of the rhabdoviridae family, which also includes the rabies virus (Figure 2). Individuals that are
frequently in contact with livestock may become infected, but the symptoms are not lethal and are similar to those of a mild flu (Lichty et al., 2004). The broad tropism of VSV seen within humans is another characteristic that contributes to the viability of using this as an oncolytic virus (Lichty et al., 2004). The ability to infect a variety of tissues is an important property if VSV is to be used as an oncolytic treatment for metastatic cancers. One other notable characteristic of VSV is its ability to encode for a matrix (M) protein. Once translated, the M protein is capable of localizing to the nuclear pores of the host cell to block transcripts for immune system factors (e.g. cytokines, interferons) from accessing the cytoplasm. This not only prevents an antiviral response from mounting, but also induces cellular apoptosis resulting in VSV pathogenesis. The M-protein has also been studied for its ability to contribute towards viral budding and virion assembly (Jayakar, Murti, & Whitt, 2000). Here at McMaster University, Dr. Brian Lichty has continued the quest of optimizing the use of VSV for oncolytic therapy. An earlier paper by Lichty and his colleagues studied the effect of single amino acid substitutions in the M protein
of VSV (referred to as AV1 and AV2). Through microarray data, the authors discovered that VSV strains deficient in M protein function allowed carcinoma cells to upregulate genes involved with antiviral response (interferon stimulated response elements or ISREs). The normal cellular response that prevents viral infection is divided into three distinct transcriptional waves. Wild-type VSV with functional M protein blocks transcripts at the second wave. The authors were able to quantify IFN sensitivity of various cancer cell lines by IFN pre-treatment, followed by infection with wild-type VSV. Since cancer cells did not respond properly to IFN, these cells were vulnerable to infection as measured by the multiplicity of infection. In-vivo testing with mice infected by the AV1/AV2 strains showed significant reduction in tumour size while side effects were minimal. Mice were more tolerant to AV1/AV2; the lethal dose increased more than 10 000times compared to wild-type VSV and multiple doses of AV1/AV2 improved the outcome. Another notable finding was that systemic administration of the virus, rather than direct injection into the site, was equally effective at reducing the size of xenographicallyimplanted cancers (Stojdl et al., 2003). This highlights the possible systemic use of VSV and capitalizes on the virus’s broad tropism. How does all this work prove that VSV can selectively target carcinoma cells? The logic is as follows (Figure 3): 1. Mutant VSV strain (AV1/AV2) can infect any tumour cell type. 2. The infected cell releases IFN since the virus cannot produce the counteracting M protein. 3. IFN reaches surrounding tissue and cells that can respond to IFN and will mount an antiviral response to prevent viral entry. This ensures that normal cells are protected. www.meducator.org
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human body long enough to reach the target site and kill tumour cells. The idea of taking a virus and using it to treat cancer still seems abnormal due to the stigma that is associated with viruses. Public concern over the safety of this technology offers one explanation as to why the American FDA has emphasized such unyielding guidelines. This is the first of many roadblocks to come. Whether or not this method of treating cancer will continue to capture the interests of researchers depends on public response and the willingness for continual investigation. As health expenditure continues to increase, Meropol and Schulman (2007) raise an interesting point: how much is too much? Cancer has recently surpassed heart disease as the number one cause of death for Americans under the age of 85 and cancer expenditure totaled $74 billion in 2005 without any signs of slowing down. A dire need exists for a new approach to treating cancer. Oncolytic virus therapy is a promising start for a technology that can potentially save millions of lives and reduce the increasing cost of healthcare.
References Alemany, R. (2007). Cancer selective adenoviruses. Molecular Aspects of Medicine, 28, 42-58.
Figure 3 Diagram of VSV infection of tumour cells. Cells that are infected by VSV are depicted in the darkest shade. (A) VSV infects a cell and causes the release of interferon and other cytokines. (B) Normal cells (non-spiked) are protected by interferon but cancer cells (spiked) are susceptible to infection. (C) Malignant cells are lytically removed, leaving behind the normal cells (Lichty et al., 2004).
4. Tumour cells are not sensitive to IFN, therefore no antiviral response is produced and these cells remain vulnerable to infection by VSV. Although our understanding of VSV is derived from current studies on oncolytic viruses in murine models, preliminary results show that it is a promising and novel approach to overcoming the barriers surrounding oncolytic virus therapy.
Conclusion The challenge in creating the ideal oncolytic virus lies in finding the proper balance between two competing requirements. On one hand, there is the need to mutate the subset of viral genes that is normally responsible for pathogenesis. Conversely, there is the need for the virus to counteract immune responses in order to persist in the
Bell, J.C., Lichty, B., & Stojdl, D. (2003). Getting oncolytic virus therapies off the ground. Cancer Cell, 4, 7-11. Garber, K. (2006). China approves world’s first oncolytic virus therapy for cancer treatment. Journ. Nat. Cancer Ins., 98(5), 298-300. Jayakar, H.R., Murti, K.G., & Whitt, M.A. (2000). Mutations in the PPPY motif of vesicular stomatitis virus matrix protein reduces virus budding by inhibiting a late step in virion release. Journal of Virology, 74(21), 9818-9827. Lichty, B.D., Power, A.T., Stojdl, D.F., & Bell, J.C. (2004). Vesicular stomatitis virus: re-inventing the bullet. TRENDS in Molecular Medicine, 10(5), 210-216. Meropol, N.J., & Schulman, K.A. (2007). Cost of cancer: Issues and implications. Journal of Clinical Oncology, 25(2), 180-186. Norman, K.L., Farassati, F., & Lee, P.W. (2000). Oncolytic viruses and cancer therapy. Cytokine and Growth Factor, 12, 271-282. O’Shea, C.C. (2005). Viruses: tools for tumor target discovery, and agents for oncolytic therapy – an introduction. Oncogene, 24, 7636-7639. Russell, S.J. (2002). RNA viruses as virotherapy agents. Cancer Gene Therapy, 9, 961-966. Stojdl, D.F., Lichty, B., Knowles, S., Marius, R., Atkins, H., Sonenberg, N., & Bell, J.C. (2000). Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic pathway. Nature Medicine, 6(7), 821-825. Stojdl, D.F., Lichty, B.D., tenOever, B.R., Paterson, J.M., Power, A.T., Knowles, S., et al. (2003). VSV strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agent. Cancer Cell, 4, 263-275.
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Hutchinson-Gilford Progeria Syndrome: The fight against time
Jennifer Gao, Christine Ibrahim, Jennifer Lee, Christina Martorelli, & Penny Yin
Having just over one hundred documented cases worldwide, HutchinsonGilford progeria syndrome (HGPS) is a fatal disease which causes premature aging in children. This article aims to provide a thorough background on this under discussed illness by describing its pathogenesis, clinical features, diagnosis, lifestyle effects, current treatment, and potential areas for further research. Symptoms stem from a single point-mutation in the LMNA gene that disrupts a cell’s normal nuclear lamina functions. Unfortunately, there is no cure for HGPS, however, current clinical trials show that this disease may be controlled symptomatically using farnesyltransferase inhibitors. Current literature also suggests that ribonucleic acid interference (RNAi) is a potential treatment method that targets the disease at a subcellullar level.
D
erived from the Greek word meaning “prematurely old”, progeria denotes a group of disorders that impart signs of
Figure 1 A 15-year-old HGPS patient exhibiting sunken cheeks, narrow nose, and protrusion of eye sockets.
premature aging in patients of all ages. Hutchinson-Gilford progeria syndrome (HGPS) is a severe form of progeria that specifically targets infants and children (Progeria Research Foundation, 2006). Originally thought to be an autosomal recessive genetic disorder, HGPS is caused by a single, random nucleic acid mutation in the LMNA gene (Pollex & Hegele, 2004). The LMNA gene codes for lamin A and C proteins, both of which normally serve as structural microfilaments for the nuclear lamina, located within the cell’s nuclear envelope. The nuclear lamina is crucial in maintaining structural stability of the nuclear envelope, as well as regulating the gene transcription process. It embeds nuclear pores and binds to various transcription factors and proteins (Capell & Collins, 2006). Approximately 90% of HGPS cases are caused by a substitution of cytosine for thymine that yields a silent G680G mutation (Glynn & Glover, 2005). Although no change is
observed at the amino acid level, the activation of a cryptic splice donor site occurs at the nucleic acid level. Thus, an extra 150 nucleotides are lost during RNA splicing, including an important endoproteolytic cleavage site, the loss of which renders improper maturation of the lamin A protein (Glynn & Glover, 2005). This mutated protein, progerin, then becomes permanently bound to a farnesyl group, a 12-carbon lipid molecule, which is normally cleaved for proper protein function. As a result, progerin becomes erroneously embedded in the nuclear membrane (Capell & Collins, 2006). Drastic events follow, including “nuclear blebbing” formation of blister-like bubbles on the nuclear envelope, and disruption of the transcription factors essential for DNA replication and protein synthesis (Capell & Collins, 2006). All of these damages accumulate to form an unstable nucleus that may lead to mistranslated proteins, lower cell reproductive ability, and possible cell apoptosis.
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Figure 2 Structural and functional consequences due to the improper embedding of lamin A protein in the nuclear lamina.
Clinical Features Although infants with HGPS appear healthy at birth, they begin to exhibit signs of abnormal physical growth and common characteristics of aging by twelve months of age (Brown, 1992). The aging process that a HGPS patient undergoes in one year is equivalent to approximately ten years in a normal individual (Pollex & Hegele, 2004). Therefore, by the age of ten, HGPS patients would have various cardiovascular, respiratory, and orthopaedic conditions. On average, children with HGPS die at the age of thirteen due to cerebrovascular and coronary atherosclerosis (Pollex & Hegele, 2004). However, the intellectual development of these children is not affected by HGPS, as the LMNA gene is not expressed in brain cells (Progeria Research Foundation, 2006). In general, HGPS children are characterized by short stature, below average weight, and limited sexual maturation. A ten-year-old HGPS patient will be of same
height as an average three-year-old child (Sarkar & Shinton 2001). Phenotypes are most notable in the facial area, including a small jaw (micrognathia), proportionally large cranium, protruding eyes, narrow nose, and prominent veins on the scalp (Pollex & Hegele, 2004). Moreover, HGPS children all experience premature loss of hair (alopecia), eyebrows, and eyelashes. Typical dermatological features include dry, wrinkled skin, caused by the hardening of connective tissue and the loss of subcutaneous adipose tissue, as well as the uneven thickening of the skin due to the presence of scar tissue-like lesions (Uitto, 2002; Sarkar & Shinton, 2001).
Diagnosis & Lifestyle Effects Since children afflicted with progeria appear healthy at birth, it is extremely difficult to diagnose this disease in newborns. However, at around six to twelve months, a baby with HGPS will fail to gain weight and display a noticeable discolouration of the skin. The pediatrician may recommend
April 2008 testing the arterial walls of the child, as patients with HGPS often exhibit early atherosclerosis. The final determinant of the diagnosis is a blood test that confirms the presence of the mutated LMNA gene (Progeria Research Foundation, 2006). Numerous lifestyle adjustments must be made following diagnosis of HGPS. Children with progeria are placed on strict diets to ensure proper nutritional intake (Progeria Research Foundation, 2006). Also, HGPS patients are at an increased risk for cardiovascular disease and are given daily doses of Aspirin, a blood thinner that increases blood circulation and the oxygen-carrying capacity of the body. However, undesirable effects may occur. The constant ingestion of Aspirin, especially at such a young age, may lead to stomach pain, excessive bleeding, or bruising (Gordon, Leslie, Lloyd & Smoot, 2001). Since HGPS patients have weaker and more fragile
17 bones, they are placed in extensive exercise programs to maximize their range of motion, which can become restricted due to tightened skin and arthritis (Progeria Research Foundation, 2006). HGPS patients also undergo hydrotherapy to alleviate pain. Even when all these lifestyle changes are followed, the average lifespan for a child with progeria ranges from eight to twenty-one years.
Current Treatments Due to the unique pathogenesis, disease development, and limited cases of HGPS, treatments are currently at the stage of clinical trials and many impart a multitude of unwanted side effects (Pollex & Hegele, 2004). Present research for HGPS treatment focuses on the use of farnesyltransferase inhibitors (FTIs) (Yang et al., 2006). FTIs inhibit a naturally occurring process known as
“farnesylation� in the nucleus, which ensures the binding of lamin A protein to the nuclear envelope, catalyzed by farnesyltransferase (Fong et al., 2006). The farnesyl group only serves to aid in this binding of lamin A to the nuclear envelope (Fong et al., 2006). Thus, in normal cells, once the lamin A protein is bound, the farnesyl group is immediately cleaved. In HGPS patients, however, the farnesyl group remains attached to the protein, rendering abnormal nuclear morphology. This malformed structure then results in the manifestation of symptoms characteristic of HGPS patients (Glynn & Glover, 2005). FTI drugs prevent the enzyme farnesyltransferase from catalyzing the reaction between the farnesyl group and the lamin A protein, subsequently preventing lamin A from binding to the nuclear envelope. As a result, the nuclear envelope will possess a normal conformation (Gordon, 2006). Experiments conducted by Yang et al. (2006) indicate that FTIs are effective in treating mice with HGPS. While this treatment is promising, FTIs may impart undesirable side-effects such as diarrhea and liver malfunction (Gordon, 2006). Ongoing research for more effective treatments for the disease is thus required.
Future Treatment by RNAi
Figure 3 MRI and photographic images of teeth deformations in patients with HGPS.Images A and B are MRIs of an 8-month old girl and a 10.5-year-old boy; images C and D are photographs of a 10.5-year-old boy and a 10-year-old boy.
Current literature suggests that ribonucleic acid interference (RNAi) is one of the most promising therapies for HGPS. While eukaryotic cells have single stranded RNA, viruses are comprised of double stranded RNA (dsRNA). When a dsRNA is injected into a eukaryotic cell, the cell recognizes the dsRNA as foreign and attempts to destroy these molecules with a degradation process known as RNA-interference (PBS, 2005). The cell not only destroys the foreign www.meducator.org
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molecules, but also eradicates any host-made protein that contains the same complementary amino acid sequence. Scientists attempt to exploit this evolutionary process by inserting a synthesized dsRNA with the sequencing of choice. The addition of a synthesized dsRNA with the LMNA sequence would prompt the cell to eliminate all mutated lamin proteins at the post-transcriptional level, thereby reducing progerin expression (Matzke, 2004). The rationale behind attempts to use RNAi as a treatment is based on the suggestion that progeria is not caused by the absence of the correct, functioning LMNA gene
and its proteins, but rather due to an over-expression of the mutated proteins within certain locations of the cell. It is the over-expression of mutated proteins that causes toxic effects (Fong, Ng, Lammerding, Vickers, & Meta, 2006). Huang et al. (2006) discovered that reduced expression of mutated LMNA proteins not only abated abnormal nuclear morphologies on HGPS cells, but also increased cell longevity. In addition, Fong et al. (2006) showed significant symptomatic improvement in the LMNA gene knock-out mice. Thus, RNAi is a potential treatment that may help to eradicate the pathogenesis of HGPS.
References Antler, C. (2003). The science creative quarterly. Antisense RNA. Retrieved February 2, 2007 from http://www.scq.ubc.ca/?p=265. Brown, W. T. (1992). Progeria: a human-disease model of accelerated aging. American Society for Clinical Nutrition, 55, 1222-1224. Capell, B. C. & Collins, F. S. (2006). Human laminopathies: nuclei gone genetically awry. Nature Review Genetics, 7, 940-952. Faivre, L. & Cormier-Daire, V. (2005). Progeria. In V. Cormier-Daire, Orphanet Encylopedia. Retrieved February 4, 2007, from http:// www.orpha.net/data/patho/GB/uk-progeria05.pdf Fong, L. G., Ng, J. K., Lammerding, J., Vickers, T. A., & Meta, M. (2006). Prelamin A and lamina A appear to bedispensable in the nuclear lamina. American Society for Clinical Investigation, 116, 743-752. Glynn, M.W., & Glover, T.W. (2005). Incomplete Processing of Mutant Lamin A in Hutchinson-Gilford Progeria Syndrome Leads to Nuclear Abnormalities, Which are Reversed by Farnesyltransferase Inhibition. Human Molecular Genetics, 14, 2959-2969. Goldman R. D. et al., (2004). Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson– Gilford progeria syndrome. Proceedings of the National Academy of Sciences, 101(24), 8963-8968. Gordon, L. B. (2006). Update: Farnesyltransferase Inhibitors (FTIs) as Potential Drug Therapy for Children with Progeria: Recent Research Findings and Frequently Asked Questions. Retrieved December 4, 2006, from http://www.progeriaresearch.org/assets/ files/pdf/FTIQ&AAugust2006Final.pdf. Gordon, L., Feit, L. R. & Smoot, L. (2001) Important Information for You and Your Doctors About Low-Dose Aspirin Treatment and Progeria. Retrieved December 20, 2006 from http://www.progeriaresearch. org/assets/files/pdf/AspirinTrtmnt(07-04).pdf. Huang, S., Chen, L., Libina, N., Janes, J., & Martin, G. (2005). Correction of cellular phenotypes of Hutchinson-Gilford Progeria cells by RNA interference. Human Genetics, 118, 444-450.
Jansen, T. & Romiti, R. (2000). Progeria infantum (Hutchinson-Gilford Syndrome) associated with scleroderma-like lesions and acroostelysis: a case report and brief review of the literature. Pediatric Dermatology, 17(4), 282-285. Matzke, A. J, & Matzke, M. A (2004). Planting the seeds of a new paradigm. PLOS Biology. 2(5). Retrieved January 4, 2006 from http://biology.plosjournals.org/perlserv/?request=getdocument&doi=10.1371/journal.pbio.0020133. PBS (2005). Sciencenow RNAi interference. Retrieved January 11, 2006 from http://www.pbs.org/wgbh/nova/sciencenow/3210/02-explflash.html. Pollex R. L., & Hegele, R. A. (2004). Hutchinson–Gilford Progeria. Clinical Genetics, 66(5), 375-381. Progeria (2005). In Medline Plus Medical Encylopedia. U.S. Nationary Library of Medicine. Retrieved February 4, 2007 from http://www. nlm.nih.gov/medlineplus/ency/article/001657.htm. Progeria Research Foundation, The. (2006). About Progeria. Retrieved December 20, 2006 from http://www.progeriaresearch.org/ about_progeria.html Progeria Research Foundation, The. (2006). Diagnostic Testing. Retrieved December 20, 2006 from http://www.progeriaresearch. org/diagnostic_testing.html Sarkar, P. K. & Shinton, R. A. (2001). Hutchinson-Guilford progeria syndrome. Postgraduate Medicine Journal, 77, 312-317. Uitto, J. (2002). Searching for clues to premature aging. Trends in Molecular Medicine 8(4), 155-157. Yang, S. H., Meta, M., Qiao, X., Frost, D., Bauch, J., Coffinier, C., Majumdar, S., Bergo, M.O., Young, S.G., Fong, L.G. (2006). A farnesyltransferase inhibitor improves disease phenotypes in mice with a Hutchinson-Gilford progeria syndrome mutation. Journal of Clinical Investigation, 116, 2115-2122.
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The Ontario Telehomecare Strategy Phase One Program: An innovative model for chronic disease management As the prevalence of chronic illnesses in Ontario continues to rise, there is an urgent need for a strategy to combat the burden on the health care system and on caregivers.
The Ontario Telemedicine Network is currently implementing the first phase of the Ontario Telehomecare Program: an innovative, collaborative Sarah Mullen
model of chronic disease management which combines the use of technology with self-management education in order to provide care that is both high in quality and efficiency.
T
he growing demands of the aging population and those with chronic diseases are placing increasing strain on the Ontario healthcare system. The Ontario Telehomecare Strategy brings healthcare directly to a patient’s home by remotely monitoring their condition through information technology. This innovation has been found to be costeffective and user-friendly, while providing improved, timely access to healthcare without sacrificing quality. Telehomecare has the potential to provide care to high-risk patients at home who are currently cared for in hospitals. Ontario faces increasing challenges in striving to meet the needs of people with chronic diseases. As a result of the growing aging population, conditions such as asthma, diabetes, congestive heart failure (CHF), arthritis and chronic obstructive pulmonary disease (COPD) are becoming more prevalent (Ontario Ministry of Health and Long-Term Care, 2005). This poses a great financial burden to the healthcare system, as almost 80% of Ontarians aged 45 and over have a chronic condition, and approximately 70% of these individuals suffer from two or more chronic illnesses (Statistics Canada, 2003). Effective management and prevention of such conditions is thus crucial, as one chronic disease can lead to another if left untreated (Ontario Telemedicine Network, 2007). In adherence to evidence-based guidelines, the Ontario Telehomecare Strategy has been developed as a collaborative, innovative approach to managing chronic disease. With this strategy, healthcare is brought directly to a patient’s home through remote monitoring of the patient’s condition via advanced communications and information technology. The Ontario Telehomecare Strategy aims to ensure that “patients across the province have access to effective care in a timely, integrated manner that is responsive to individual and local challenges and needs” (Ontario Telemedicine Network, 2007).
What is Chronic Disease Management? The term “disease management”, first introduced in the early 1990’s, has been defined as “a systematic, populationbased approach to identify persons at risk, intervene with specific programs of care, and measure clinical and other outcomes” (Gilbert, 2007). In this sense, chronic disease management is any program encompassing assessment, diagnosis, treatment, education and follow-up for a patient with a specific condition. By educating patients about their disease, including available treatment options and self-management strategies, these specialized programs for managing chronic diseases have the potential to improve health in a cost-effective manner (Wong et al., 2004). The creation of such programs has corresponded with a growing interest in evidence-based medicine and the development of best-practice guidelines by consensus conferences. Clinical guidelines provide recommendations for optimal patient care based on relevant literature and consensus among clinical experts. These guidelines are continually reviewed and revised based on emerging research, thus assisting physicians in the prevention, diagnosis and treatment of a specific chronic condition (Wong et al., 2004). Research indicates that successful chronic disease management programs share common characteristics in that they: • • • •
are evidence-based employ multiple strategies and interventions are patient-centred empower individuals to increase control over and improve their health • promote collaboration among providers, organizations, individuals, families and community groups www.meducator.org
20 • include an evaluation component to ensure that programs are achieving their objectives (Ontario Ministry of Health and Long-Term Care, 2005).
The Ontario Telehomecare Strategy In compliance with the above guidelines, the Ontario Telehomecare Strategy Phase One Program will focus on chronic disease management and improved self-management of CHF and COPD. In Ontario, CHF is the most common diagnosis resulting in hospital admission of patients aged 65 or older. COPD is projected to be the third leading cause of death by 2020, and is currently the seventh most common cause of hospitalization (Ontario Telemedicine Network, 2007). While telemedicine applies technology to provide healthcare over a distance, telehomecare is a form of telemedicine based in the patient’s home. Studies show that telehomecare can reduce strain on the healthcare system by decreasing the number of emergency room visits, hospitalizations, hospital bed days of care, and nursing home admissions (Meyer et al., 2002). It is a communication and clinical information system that enables the interaction of voice, video, and healthrelated data over ordinary telephone lines (Bowles & Baugh, 2007). Ontario’s newlyestablished interprofessional Family Health Teams (FHT), in collaboration with local Community Care Access Centres (CCAC), will be primarily responsible for the care of patients eligible to participate in this program. The Phase One Program of this strategy is being piloted from March 2007 until October 2008 and will be delivered to 600 patients in six FHTs. A specialized Telehomecare Registered Nurse (RN) situated within each FHT will conduct eligibility assessments for patients in that region, and will also be responsible for the remote monitoring
Issue 12 of their clinical status. Participants in this program will have a telemonitoring device installed in their home, which may include a blood pressure monitor, a heart rate monitor, a pulse oximeter, a breath sound auscultation, and a glucometer (Figure 1). Based upon data generated from these devices, the Telehomecare RN will work within the established
“...research shows this model to be cost-effective and user-friendly, while providing improved, timely access to healthcare without sacrificing quality.” clinical guidelines for COPD and CHF, in consultation with the patient’s primary healthcare provider (Figure 2). The project manager for the Phase One Program is the Ontario Telemedicine Network (OTN), one of the most comprehensive telemedicine networks in Canada (Ontario Telemedicine Network, 2007).
Why Telehomecare? Although the use of telehomecare in chronic disease management is a relatively new development, research shows this model to be cost-effective and user-friendly, while providing improved, timely access to healthcare without sacrificing quality (Dansky et al., 2001). The Ontario Telehomecare Strategy promotes interprofessional collaboration and complies with evidence-based guidelines of successful chronic disease management programs. An Integrated Model In Canada, hospital care has traditionally been distinct from community care, and the transition of
patients across these sectors has been challenging (Young et al., 2004). In Ontario, chronic disease management programs are often affiliated with hospitals; this is unfavourable due to continuing hospital budget deficits (Ontario Ministry of Health and Long-Term Care, 2005). The Ontario Telehomecare Strategy is a more sustainable model as it enables the coordination of care across multiple providers by promoting communication among clinicians, health organizations and the community. Patient care largely becomes the responsibility of primary care networks, as the local FHT and CCAC play a vital role in providing chronic disease management activities (Ontario Ministry of Health and Long-Term Care, 2005). As a means of program support, collaboration among healthcare providers is further encouraged via monthly videoconferences among FHTs and Telehomecare RNs. (Ontario Telemedicine Network, 2007). Self-management Chronic disease management is a means of empowering people with chronic conditions to take responsibility for their health and wellbeing. Patients learn how to recognize signs and symptoms, how to control these symptoms through lifestyle modification, when to take medication, and when to seek medical attention (Gilbert, 2007). With this knowledge, patients can avoid unnecessary hospital admissions and emergency room visits (Bourbeau et al., 2006). Education is thus an integral component of the Ontario Telehomecare Strategy, as the Telehomecare RN is responsible for providing patients with teaching materials and educating them about important strategies to manage their conditions (Ontario Telemedicine Network, 2007). In this way, participants benefit from the sense of independence and control that they achieve through
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analysis indicated there was a cost savings of $63.00 per patient in the intervention group. Results showed no differences in quality indicators, demonstrating that telehomecare is capable of maintaining quality of care in a cost-effective manner (Dansky et al., 2007).
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Home Phone
Figure 2 The remote monitoring system consists of three main components: the patient components, the back end data repository and decision support system, and the alerting and physician reporting component. The data flow between these components is shown above (Cafazzo et al., 2004).
self-management, which also relieves the burden on the caregiver. Additionally, patients learn how to prevent acute exacerbations by enabling them to recognize and avoid possible triggers of COPD flare-ups (Bourbeau et al., 2006). This provides increased benefits to the healthcare system, as there is decreased reliance on healthcare professionals and acute care services (Gilbert, 2007). As Phase One of this program is a time-limited intervention, patients can graduate from the program once they are properly educated and thus create room for new eligible participants (Ontario Telemedicine Network, 2007). This concept is also important for program sustainability (Wong et al., 2004). Patient Satisfaction There is substantial evidence that the application of telehomecare to a chronic disease management program yields high patient satisfaction. Research shows that when telehomecare is used to help manage COPD, both patients
and caregivers were able to use the technology comfortably and without difficulty (Bowles & Baugh, 2007; Calazzo et al., 2004). Encouragingly, Jenkins and McSweeny found that the majority of participants in their study perceived the telehomecare experience as comfortable and useful, and described the physical examination as adequate. Both patients and nurses found that videoconferencing resulted in quicker and more frequent clinical consultations (Bowles & Baugh, 2007). While concerns have been raised that this use of technology could have a detrimental effect on the patient-provider relationship, research consistently shows that patients are very satisfied in substituting home visitations with video consultations (Dansky et al., 2001). In one study of patients receiving healthcare at home, the control and intervention groups both received routine home healthcare visits; however, the intervention group also participated in video consultations. After taking into account the rehospitalization rates,
Mental Health Issues Depression is very common in the elderly, and its prevalence increases in patients suffering from CHF or COPD. In fact, depression may even be a result of these diseases (van Manen et al., 2002). It is estimated that 40% of people with COPD are affected by clinical depression, while up to 42% of patients suffering from CHF are also depressed (Ng et al., 2007; Guck et al., 2003). However, depression often goes undiagnosed by healthcare providers, as patients may be unwilling to report symptoms, or depressive symptoms may be attributed to the pre-existing chronic condition (van Manen et al., 2002). In both COPD and CHF, depression is an independent risk factor for readmission to hospital, longer hospital stays, functional decline, and mortality (Ng et al., 2007; Guck et al., 2003). While telehomecare is correlated with increased adherence to chronic disease management programs, depressed patients are less likely to comply with the program’s selfmanagement strategies and lifestyle modifications (Cafazzo et al., 2004; Ng et al., 2007; Guck et al., 2003). Therefore, it is recommended that guidelines to manage depression also be established, in order to maximize program adherence, cost-effectiveness, and quality of life. Confidentiality Research indicates that participants in telehomecare programs are not concerned with confidentiality issues involved with communicating www.meducator.org
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private health-related information via telephone lines (Bowles & Baugh, 2007; Cafazzo et al., 2004). Nonetheless, the implementation of measures to ensure confidentiality of patient data is a crucial component of the program design, as substantial portions of the monitoring system operate in an uncontrolled environment (Cafazzo et al., 2004). Barriers to Access The number of patients that can be reached and the time during which this intervention will take place are both limited because the Phase One Program is the initial step in establishing a sustainable model of chronic disease management. In this phase, only English-speaking patients who have a working telephone line in their homes will be eligible for participation (Ontario Telemedicine Network, 2007). However, as the model expands, the allocation of funds to assist patients from low socioeconomic backgrounds, and the use of technology which can overcome language barriers, will be necessary in order to equalize access to healthcare.
Conclusion An aging population has prompted a push for more efficient delivery of services and increased access to healthcare at home. In addition to monitoring patients with chronic diseases such as CHF and COPD, telehomecare has the potential to provide care to high-risk patients at home who are currently cared for in hospitals. Telehomecare can also aid disabled persons, increase patient compliance, enhance caregivers’ effectiveness, and connect socially isolated individuals to their care providers. Several practical advantages of telehomecare are just beginning to emerge, and the evolution of this method of care will help meet a growing demand for successful and sustainable management of chronic illness (Dansky et al., 2001).
References Bourbeau, J., Collet, J.-P., Schwartzman, K., Ducruet, T., Nault, D., Bradley, C., & the COPD axis of the Respiratory Health Network of the Fond de la recherche en santé du Quebec. (2006). “Economic Benefits of Self-Management Education in COPD”. American College of Chest Physicians, 130, 1704 – 1711. Bowles, K., & Baugh, A. (2007). “Applying Research Evidence to Optimize Telehomecare”. Journal of Cardiovascular Nursing, 22(1), 5 – 15. Cafazzo, J., Trudel, M., Igharas, W., Hamill, M., Picton, P., Lam, J., Sathiananthan, A., Rossos, P., Logan, A., & Easty, A. (2004). “A Mobile Phone Based Tele-Monitoring System for Chronic Disease Management”. Centre for Global eHealth Innovation. University Health Network. Retrieved March 9, 2008 from http://www.ehealthinnovation.org/dh Dansky, K., Palmer, L., Shea, D., & Bowles, K. (2001). “Cost-Analysis of Telehomecare”. Telemedicine Journal and e-Health, 7(3), 225 – 232. Gilbert, J. (2007). “Chronic Disease Management: A Smart Solution to a Serious Problem”. Ontario Hospital Association. Retrieved March 9, 2008 from http://www.oha. com/Client/OHA/OHA_LP4W_LND_WebStation.nsf/page/ Chronic+Disease+Management Guck, T., Elsasser, G., Kavan, M., & Barone, E. (2003). “Depression and congestive heart failure”. Congestive Heart Failure, 9(3), 163 – 169. Meyer, M., Kobb, R., & Ryan, P. (2002). “Virtually Healthy: Chronic Disease Management in the Home”. Disease Management, 5(2), 87 – 94. Ng, T., Niti, M., Tan, W., Cao, Z., Ong, K., & Eng, P. (2007). “Depressive Symptoms and Chronic Obstructive Pulmonary Disease”. Archives of Internal Medicine, 167(1), 60 – 67.
Ontario Ministry of Health and Long-Term Care. (2005). “Guide to Chronic Disease Management and Prevention”. Retrieved March 9, 2008 from http://www.health.gov.on.ca/transformation/fht/guides/fht_chronic_disease.pdf Ontario Telemedicine Network. (2007). “Ontario Telehomecare Strategy Phase One Program”. Retrieved March 9, 2008 from http://www.otn.ca/telehomecare/files/Telehomecare%20 Fact%20Sheet%20FINAL%20Sept192007.pdf Public Health Agency of Canada. (2002). “Economic Burden of Illness in Canada”. Statistics Canada. Retrieved March 9, 2008 from http://www.phac-aspc.gc.ca/publicat/ebic-femc98/pdf/ ebic1998.pdf Stachura, M., & Khasanshina, E. (2007). “Telehomecare and Remote Monitoring: An Outcomes Overview”. The Advanced Medical Technology Association. Retrieved March 9, 2008 from http://www.advamed.org/NR/rdonlyres/2250724C5005-45CD-A3C9-0EC0CD3132A1/0/TelehomecarereportFNL103107.pdf Statistics Canada. (2003). “Canadian Community Health Survey”. Retrieved March 9, 2008 from http://www.statcan.ca/english/ sdds/document/3226_D37_T9_V2_E.pdf van Manen, J., Bindels, P., Dekker, F., Ijzermans, C., van der Zee, J., & Schade, E. (2002). “Risk of depression in patients with chronic obstructive pulmonary disease and its determinants”. Thorax, 57, 412 – 416. Wong, J., Gilbert, J., & Kilburn, L. (2004). “Seeking Program Sustainability in Chronic Disease Management: The Ontario Experience”. The Change Foundation. Young, N., Barden, W., Lefort, S., Nijssen-Jordan, C., Daniels, C., Booth, M., Dick, P., & the Tele-Homecare Team. (2004). “Telehomecare: A Comparison of Three Canadian Models”. Telemedicine Journal and e-Health, 10(1), 45 – 52.
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The Quarantine Conundrum: An Investigation into Public Health Measures to Control the Spread of Infectious Diseases With the recent outbreaks of infectious diseases such as SARS and TB, health authorities in Canada have had to rely on the practice of quarantine for the protection of public health. The use of quarantine, however, has spurred ethical debates about the suitability of the restrictive conditions of quarantine in a
Alexandra Perri
democratic society.
This article discusses some of the questions surrounding
the practice of quarantine and provides a framework for its use on the basis of a set of ethical considerations.
Brief History
Q
uarantine, the segregation of the diseased from the healthy, is a practice that has been in use for many years in an effort to control the spread of communicable diseases. Evidence of the first use of quarantine dates back as early as the writing of the Old Testament, when rules existed for the isolation of individuals infected with leprosy (Nova, 2004). Not until the outbreak of the Black Death in the 14th century, were the first forms of institutionalized quarantine established. Innovations in systems of quarantine were first pioneered in Venice where ships were required to lay at anchor for 40 days before docking. The term quarantine itself is derived from the Venetian words quaranta giorni, meaning 40 day period (CDC, 2007). The Venetian system of quarantine was the common practice until the discovery that microbes are the cause of disease in the late 1800s. After this discovery, public health authorities began to tailor quarantine protocols to particular disease-causing microbes (Figure 1) (Nova, 2004). The development of antibiotics and the routine administration of vaccinations in the 20th century rendered the Venetian method obsolete. Today, however, emerging infectious diseases such as tuberculosis, SARS, and HIV/ AIDS currently threaten to cause the reinstitution of this practice (Mandavalli, 2003). Quarantine programs have been established by agencies such as the Centers for Disease
Figure 1 This photograph, taken in 1930, demonstrates how individuals placed under quarantine are often treated as criminals of the law. In this photo, a man is immediately segregated at the Immigration Station on New York’s Ellis Island after demonstrating symptoms of a communicable disease. If diagnosis confirmed the suspicion, individuals were placed in quarantine until they were no longer contagious (Nova, 2004).
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ASK THE EXPERT
Dr. Lisa Schwartz
To discuss the extent of public health measures that should be taken to control the spread of highly contagious diseases, Alexandra Perri of the McMaster Meducator has consulted an expert in the field, Dr. Lisa Schwartz, the Arnold L. Johnson Chair in Health Care Ethics at McMaster University.
Q: To what extent should public health agencies and officials go to contain individuals with highly infectious and communicable diseases? A: It is hard to say how far we ought to permit public health measures to restrict the personal liberty of individuals. What is important is that we recognize that no matter how far we are prepared to go, movement toward limiting individual liberty for public good needs to be done with caution, and incrementally to prevent any one person being left with excessive burden or limitation. All limits need to be justifiable, and reciprocation and appeals are essential. Q: In forcibly confining individuals with infectious diseases, are we doing the right thing? A: Quarantine should only be employed in very extreme cases where the person will not co-operate and harm to others is clear and imminent. Here again, the notion of reciprocation is very important because there may be strong social reasons that would prevent a person from willingly being quarantined. I suspect that if we examined what it is that makes quarantine appear to be a threat to the person involved, we could go a long way to gaining cooperation and enforced restrictions would not be needed. We must also bear in mind that the broader effect of enforced quarantine may be to make others reluctant to self-report or seek treatment, thereby further endangering the wider public. It seems, then, that enforced quarantine can effectively undo its own efforts. Q: Do public health authorities have the right to forcibly confine individuals infected with infectious diseases? Public health authorities do have the right to forcibly confine individuals infected with infectious diseases. However, this right should only be employed in rare circumstances where the infected individual may pose harm to the public and only within Public Health guidelines. Q: How important is the discussion of the issue of quarantine for the upcoming months and years? Where should future research on the issue of quarantine be directed? A: Quarantine is an important area for discussion. Only if we are aware of the concerns and potential challenges it presents will we be properly prepared to avoid the worst case scenarios, such as a loss of trust in the system and unwillingness to cooperate with proactive measures to control disease. In the case of potential pandemics, quarantine will no longer be an issue and we will be faced with more difficult ethical problems. Future research on the issue of quarantine should perhaps look at public attitudes and should engage public upon their concerns or intuitions on justice in terms of restrictive measures for disease control. It is important that the public is better educated around this issue of quarantine.
Control and Prevention (CDC) in hopes of protecting the public from infected persons or those at risk of infection (CDC, 2008).
Threat Posed by Infectious Diseases The 2003 SARS epidemic was the first time in several generations that health authorities in Canada were required to implement quarantine to prevent public contamination (Figure 2) (Mitka, 2003). In addition to the SARS epidemic, the emergence of highly infectious, incurable diseases is increasing at an alarming rate around the world. The CDC of the United States recently released a publication reporting that more than 90 000 Americans are infected with a potentially deadly methicillin-resistant strain of Staphylococcus aureus. This “superbug� is now the most frequent cause of skin and soft tissue infections reported in emergency departments across the United States (Klevens et al., 2007). Additionally, more than 25 000 to 30 000 people carry extensively drug-resistant tuberculosis (XDRTB) worldwide (Figure 3) (WHO, 2006). Given the increasing threat and severity of newly emergent infectious diseases, it is clear that the control of communicable diseases must be addressed.
Defining Conditions of Quarantine and Isolation Isolation and quarantine are both public health practices aimed at controlling the spread of infectious diseases, but a stark difference exists between the two. Isolation is used to separate infected persons who have a communicable disease from those who are healthy. Isolation restricts the movement of the ill in order to impede the spread of certain diseases (CDC, 2007). For example, patients with infectious tuberculosis are isolated in hospitals during remediation. Conversely, quarantine is used to separate and restrict the movement of asymptomatic persons who may have been exposed to a communicable disease. The separation of exposed individuals and the restriction of their movements slows the spread of disease, should symptoms develop (CDC, 2007).
When Should Public S afety O verride Personal Freedom? The decision to quarantine an individual is complicated by ethical debates about the extreme conditions of quarantine in a democratic society. In many
April 2008 cases, patients are reluctant to be placed in quarantine and may be forced to assume these restrictions against their will (Svoboda et al., 2004). This begs the question: when should concerns over public safety supersede our individual rights to liberty? Due to growing rates of highly communicable diseasesahh, this question is often asked by public health officials. The decision to place an individual in quarantine is based on a few considerations. Public health officials first need to consider whether medications are still effective in mitigating the proliferation of disease (Thompson et al., 2006). Contagious diseases are often treated with a first line of standard drugs, followed by Direct Observed Therapy (DOT) in which a trained nurse oversees all therapy given
25
“In addition to the SARS epidemic, the emergence of highly infectious, incurable diseases is increasing at an alarming rate around the world.� to the patient. If faced with a situation where no suitable course of treatment exists, quarantine may be considered an option to ensure protection of the health of the communities (Bensimon & Uphsur, 2007).
Upon placing an individual under quarantine, there are other ethical considerations. First, given the understanding that a mitigation of disease requires some degree of isolation, there is a need for a quarantine policy that enforces harsher limitations when lighter restrictions have been exhausted. Second, conditions of reciprocity must be put in place. This means that if public health has asked an individual to give up their mobility rights for the public and common good, then it is incumbent upon the public health authorities to make things as livable as possible for the person who relinquishes their liberties. Therefore, quarantined individuals should be provided with financial and social support to minimize the burden. Third, transparency is essential. The
Figure 2 A SARS patient receives treatment at a hospital in China during the 2003 SARS outbreak. Public health authorities ultimately credit quarantine, especially in Canada, with helping to mitigate the total number of individuals infected with SARS (Nova, 2004).
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decision to quarantine and the extent of the loss of liberties must be available for public observation, while quarantined persons should have free access to legal counsel and appeal (Schwartz & Upshur, 2007).
Quarantine for the Future Quarantine is a highly charged topic of health debate because of its direct and serious implications on the lives of those quarantined and on public health. Some see the practice of quarantine as a fundamental tool in infectious disease control, whereas others believe that the use of quarantine is an excessive measure that degrades one’s rights in a democratic and liberal society. How we choose to treat individuals in these circumstances reflects the values of our society (Ruderman et al., 2006). Given the escalating incidence of communicable diseases, it is becoming increasingly important to understand effective decision-making and to discuss any ethical concerns and promote research regarding the practice of quarantine.
Figure 3 Electron micrograph of a highly pathogenic strain of bacteria, Myobacterium tuberculosis. An individual may be forcibly placed in quarantine according to the Centers for Disease Control and Prevention (Image provided by the Public Health Image Library of the Centers for Disease Control and Prevention, #4428).
References Attaran A, Wilson K. (2008). Legal and epidemiological justifiÂŹcation for federal authority in public health emergencies. McGill Law Journal, 52(2), 381. Bensimon, C.M., Upshur R. (2007). Evidence and effectiveness in decision-making for quarantine. American Journal of Public Health, 97 (S1), S44-S48. Department of Health and Human Services: Centers for Disease Control and Prevention. (2007). Global Migration and Quarantine: History of Quarantine. Retrieved November 23, 2007, from http://www.cdc.gov/NCIDOD/DQ/history.html Department of Health and Human Services: Centers for Disease Control and Prevention. (2007). Fact Sheet: Legal Authorities for Isolation and Quarantine. Retrieved November 23, 2007, from http://www.cdc.gov/ncidod/dq/pdf/legal_authorities_ isolation_quarantine.pdf Klevens, R. M., Morrison, M.A., Nadle, J., Petit, S., Gershman, Ken., Ray, S., Harrison, L.H., Lynfield, R., Dumyati, G., Townes, J.M., Craig, A.D., Zell, E.R., Fosheim, G.E., McDougal, L.K., Carey, R.B., and Fridkin, S.K. (2007). Invasive Methicillin-Resistant Staphylococcus aureus Infections in the United States, Journal of the American Medical Association, JAMA, 298 (15), 1763-1771. Mandavalli, A. (2003). SARS epidemic unmasks age-old quarantine conundrum. Nature Medicine, 9(5), 487.
Mitka, M. (2003). SARS Thrusts Quarantine Into the Limelight. Journal of the American Medical Association, 290, 1696-1698. Nova: Science Programming On Air and Online. (2004) History of Quarantine. Retrieved November 23, 2007, from http://www. pbs.org/wgbh/nova/typhoid/quarantine.html Ruderman, C., Tracy, C.S., Bensimon, C.M., Shaul, R.DZ., Hawryluck, L., Bernstein, M., Upshur, R.E.G. (2006). On pandemics and the duty to care: Whose Duty? Who cares? BMC Medical Ethics, 7(1), 5. Schwartz, L., Upshur R. (2007) The Current. Toronto, ON: CBC Radio One Thompson, A.K., Faith, K., Gibson, J.L., Upshur, R.E. (2006). Pandemic influenza preparedness: an ethical framework to guide decision-making. BMC Medical Ethics, 7(12), 1-12. Svoboda,T., Henry, B., Shulman, L., Kennedy, E., Rea, E., Ng, Wil., Wallington, T., Yaffe, B., Gournis, E., Vicencio, E., Basrur, S., Glazier, R.H. (2004). Public Health Measures to Control the Spread of the Severe Acute Respiratory Syndrome during the Outbreak in Toronto. New England Journal of Medicine, 350(23), 2352-2361. The World Health Organization. (2006). The World Health Report. Retrieved November 23, 2007, from http://www.who.int/ whr/2006/en/index.html
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Have you read all the articles? Test yourself and see how well you understood the articles by answering the questions below.
5. Individuals with HIV are legally obligated to disclose their HIVpositive status when: a) They undergo any medical or surgical procedure b) They engage in risky sexual behaviour c) They apply for a job d) They have no legal obligation to disclose their status
2. The idea of quarantine was first developed in: a) China b) South America c) Venice 3. What is one of the most frequent cause of skin and tissue infections in U.S., as discussed in the article a) Staphylococcus aureus b) Stanierella latercula c) E.coli 4. Which of the following would be the more persuasive precedent for the ruling of a case: a) A decision made twenty years ago in Canada b) A 2007 ruling made in the Ontario provincial court c) A 2007 case in the Supreme Court in Canada d) A ruling from a recent American case
6. What purpose do daily doses of aspirin serve in children suffering from progeria? a) To encourage blood clot forrmation b) To prevent complications such a stroke or heart attack c) To reduce the body’s absorption of dietary fats d) To increase the patient’s blood pressure e) To help maintain the subcutaneous adipose tissue 7. Why are RNA viruses better than DNA viruses for oncolytic therapy? a) RNA viruses are larger, therefore they encode more proteins independently. b) RNA viruses are not dependent on host proteins in the nucleus. c) RNA viruses are bullet-shaped and enter cancer cells more efficiently. d) RNA viruses pack more genetic material
Answers: b, c, a, c, b, b, b
1. Which of the following challenges a patient’s self-efficacy in their ability to manage their disease? a) Language barriers b) Depression c) Fear surrounding confidentiality
MedQuiz
MedQuiz
Meducator Staff
McMaster’s Medical Research and Health
Ethics Student Journal
Phase One The Ontario Telehomecare Strategy: Also in this issue: Progeria: the Fight against Time Curing Cancer with Viruses HIV in the context of Science and the Law
The Quarantine Conundrum McMaster’s Medical Research and Health Ethics Student Journal
Should doctors be allowed to refuse treatment? Also in this issue:
Innovation and Implementation Debate on Canada’s health care
Issue 12 | April 2008
Alzheimer’s drug www.meducator.org may prevent breast cancer relapse Loneliness & cardiovascular disease Chaperones & protein folding
From Proteins to Patients Issue 11 | Nov 2007
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Back Row (Left to Right): Andrew Yuen, Ran Ran, Randall Lau, Harman Chaudhry Third Row: Jeannette So, Veronica Chan, Alexandra Perri, Fanyu Yang, Simone Liang, Jonathan Liu Second Row: Navpreet Rana, Stephanie Low, Siddhi Mathur, Jacqueline Ho, Sarah Mullen Front Row: Crystal Chung, Tyler Law Absent: Harjot Atwal, Avinash Ramsaroop
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