Caitlin McNamee-Lamb

People who survive a first attempt at suicide by poisoning are 42 times more likely than the general population to kill themselves by poisoning eventually, say the authors of the world's largest suicide-risk study.

“The durable risk of suicide long after the first self-poisoning episode suggests that to save lives we may need ongoing sustained initiatives," said Associate Professor Yaron Finkelstein, lead author of the study. “Most individuals who eventually died by suicide used more violent methods on subsequent attempts, and only seven per cent of them reached hospital alive.”

Researchers at the University of Toronto, The Hospital for Sick Children (SickKids), the Institute for Clinical Evaluative Sciences (ICES) and Sunnybrook Health Sciences Centre, based the study on more than 65,000 people who survived a self-poisoning episode – including adults and children. The results were published in the April 1 online edition of JAMA Psychiatry.

Researchers tracked every person who presented to an emergency department in Ontario for self-poisoning between April 2002 and December 2010. They found that the risk of death from accidents was 10 times higher following self-poisoning.

This suggests that the first episode of deliberate self-poisoning is a strong predictor for subsequent suicide and premature death.

”The hope is that our findings can be used to target this high-risk group and that it may influence suicide-prevention strategies to include long-term follow-up and efforts,” said Dr. Finkelstein, an associate professor of paediatrics, pharmacology and toxicology at �Թϱ�� and staff physician in paediatric emergency medicine, and clinical pharmacology and toxicology, and associate scientist at SickKids.

In Canada, suicide is the second leading cause of death in individuals aged 15 to 35 years, yet prevention efforts have remained a challenge, because the long-term outcomes following suicide attempts have not been well characterized. The present study also identified population-level suicide risk factors, which include being male, having engaged in multiple self-poisonings, higher socioeconomic status, a diagnosis of depression and psychiatric care in the year preceding the first self-poisoning episode.

“Previous research has largely focused on short-term studies of patients with known psychiatric conditions in individual health-care centres,” said Finkelstein. “However, no one has looked at the entire population including both patients with diagnosed mental health conditions as well as everyone else in the community.

“Additionally, this is the first study to focus exclusively on individuals with a first presentation for self-poisoning. More research is required, and our multidisciplinary team is working hard to dig deeper, and is focusing on the vulnerable group of teenagers, as well as subsequent self-harm behaviours.”

Dr. David Juurlink, the study's senior author, is professor of medicine, pediatrics, and health policy, management, and evaluation at �Թϱ��, senior scientist at ICES, and head of the division of clinical pharmacology and toxicology at Sunnybrook Health Sciences Centre.

“It’s surprising how little we know about long-term outcomes after a first self-poisoning episode.” said Juurlink. “By following a very large group of patients over a long period of time, this study demonstrates that the risk of suicide remains elevated long after a first attempt. The implication of this is that suicide prevention efforts in these patients must also be sustained.”

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�Թϱ�� and SickKids first to grow lung cells using stem cell technology

sgupta — Mon, 27 Aug 2012 15:52:27 +0000

�Թϱ�� and SickKids first to grow lung cells using stem cell technology sgupta Mon, 08/27/2012 - 11:52

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Dr. Janet Rossant, a professor in the Departments of Molecular Genetics and Obstetrics and Gynaecology (photo courtesy of SickKids)

Caitlin McNamee-Lamb

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Novel research may advance individualized medicine for cystic fibrosis patients

Researchers at the University of Toronto and the Hospital for Sick Children (SickKids) are paving the way towards individualized medicine for patients with cystic fibrosis.

It is the first study to successfully use stem cells to produce mature lung cells that could potentially be used to study cystic fibrosis and test drugs.

“This study shows the major impact stem cell research can have on the field of individualized medicine,” says Dr. Janet Rossant, a professor in the Departments of Molecular Genetics and Obstetrics and Gynaecology, principal investigator of the study and chief of research at SickKids. “It is a promising move toward targeted therapy for patients with cystic fibrosis.”

Researchers were able to induce human embryonic stem cells to become mature lung cells, which contained the CFTR gene. The gene, discovered at SickKids in 1989, is responsible for cystic fibrosis when mutated.

To create the lung cells, researchers used an induced pluripotent stem cells (adult cells genetically induced to function like embryonic stem cells) derived from the skin of patients with cystic fibrosis. They prompted these stem cells to become lung cells, which contain mutations specific to the patients involved.

Once researchers found that they could create lung cells derived from individual patients they then used a compound that resembles an investigational drug that is currently being tested for cystic fibrosis to see if it would rescue the CFTR gene mutation.

If the lung cells of a particular patient can be generated then tests could also be done to evaluate the effectiveness of specific drugs on individual patient’s cells, says Rossant.

If the drug is effective in vitro, then the next step would be to see if it works on the patient.

Prior to this year, the only therapies available for patients with cystic fibrosis have targeted the symptoms (like infection and digestive disorders) rather than the CFTR gene mutation.

“More recently there has been a paradigm shift and now drugs are being developed to target the mutant CFTR specifically,” says Christine Bear, a co-investigator of the study, co-director of the SickKids Cystic Fibrosis Centre and senior scientist in Molecular Structure and Function at SickKids.

“However, every patient is unique, so one drug isn’t necessarily going to work on all patients with the same disease,” says Bear. “Take cancer as an example, each individual responds differently to each treatment. For some, a certain drug works, and for others it doesn’t. This tells us that we need to be prepared to find the best option for that individual patient.”

In this particular study, the compound used did not work in all of the derived cell lines. This finding further emphasizes the need for individualized medicine, says Bear.

Researchers say the next step is to perfect the method of generating epithelial lung cells, so that the process is more efficient and can be used to investigate other genetic diseases.

The study is published in the August 26 advance online edition of Nature Biotechnology.

This research was funded by an Emerging Team grant from the Canadian Institutes of Health Research, an Ontario Ministry of Economic Development and Innovation grant, and SickKids Foundation.

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Treating brain cancer in children

sgupta — Wed, 25 Jul 2012 11:57:38 +0000

Treating brain cancer in children sgupta Wed, 07/25/2012 - 07:57

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Researchers at �Թϱ�� and SickKids may spark a major shift in treating children with certain brain cancers (Bigstock photo)

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Study finds important differences between tumours

An international collaboration led by a team from the University of Toronto and The Hospital for Sick Kids (SickKids) may spark a major shift in treating children with certain brain cancers.

“This is exciting but also daunting,” says Dr. Eric Bouffet, professor in the Department of Paediatrics at the University of Toronto. “What we found suggests a huge shift in the way clinicians work and think about medulloblastoma.”

The most common malignant brain tumour in children, medulloblastoma affects 30 to 40 children in Canada each year. And with four different types of medulloblastoma, each case is even rarer – making it difficult for doctors to determine the best treatments for individual patients.

But that may change, thanks to Medulloblastoma Advanced Genomics International Consortium (MAGIC), which brought together scientists and physicians from 46 institutions across the globe to study more than 1,000 medulloblastoma tumours - an unprecedented number of samples.

Their findings are published in the July 25 advance online edition of Nature.

“By studying over 1,000 samples we now better understand the four groups and can therefore identify them faster and treat them more specifically,” says Dr. Michael Taylor, Associate Professor in the Departments of Surgery and Laboratory Medicine and Pathobiology at the University of Toronto.

Today, the standard treatment for medulloblastoma is the same for each patient. It includes nonspecific therapies such as surgery, radiation and aggressive chemotherapy. While the five-year survival rate is 70 to 85 per cent, the effects of such treatments on the developing brain mean children are often left with significant neurological, intellectual and physical disabilities.

“By learning more about each of the four types of medulloblastoma tumours, we’re moving into an era where we will be able to use targeted treatments that will hopefully kill the tumour and leave the normal developing brain unharmed,” says Taylor, Principal Investigator of the study, SickKids Neurosurgeon, Scientist in Developmental & Stem Cell Biology at SickKids Research Institute and at The Arthur and Sonia Labatt Brain Tumour Research Centre.

In the new study, researchers identified several clinical and genetic differences in each group which suggests that each group may require separate therapeutic strategies.

For example, the research suggests radiation may not be necessary in some medulloblastomas that arise in teenagers, says Bouffet, Director of the Paediatric Neuro-oncology program in the Division of Haematology/Oncology at SickKids, Senior Associate Scientist in Child Health Evaluative Sciences at SickKids Research Institute.

“Radiation has been part of the standard treatment for years, so eliminating radiation in this group of patients is a decision that will not be taken lightly,” Bouffet says. “We will need to lead this change with new innovative clinical strategies.”

Analysis of these tumours also revealed that, in some cases, the genetics of medulloblastoma are similar to some more common adult tumours, which means there may be potential “new” treatments already available.

“There are drugs that are currently being used to treat the adult tumours that could potentially be used to treat a specific group of paediatric patients with medulloblastoma,” says Taylor. “Developing new drugs can take upwards of 10 years, but if a drug already exists this would reduce the time significantly and enable patients to access it sooner.”

Additionally, a gene known to play a role in an adult condition, Parkinson’s disease, has now also been shown to be important in childhood medulloblastoma.

“If you have too little of this gene, you get Parkinson’s disease, if you have too much, you develop brain cancer (medulloblastoma),” explains Taylor.

The link between Parkinson’s disease and childhood brain cancer had not previously been identified.

These are just three examples of the many discoveries that were possible through international collaboration and major advancements in technology. Future research and clinical changes will also require this kind of collaboration.

“It seems more and more that not all medulloblastoma groups need the same intensity of treatment,” says Bouffet. “We have a unique opportunity to change the odds and move away from traditional treatment.

“We hope that these findings will enable us to identify and categorize medulloblastoma very quickly and then allocate a specific treatment for each individual patient.”

The study was supported by the Pediatric Brain Tumor Foundation and the National Institutes of Health; Genome Canada, Genome BC; the Terry Fox Research Institute; the Ontario Institute for Cancer Research; the Pediatric Oncology Group of Ontario; the Canadian Cancer Society; funds from ‘The Family of Kathleen Lorette’ and the Clark H. Smith Brain Tumour Centre; the Montreal Children’s Hospital Foundation; the Sonia and Arthur Labatt Brain Tumour Research Centre, Chief of Research Fund, Cancer Genetics Program, Garron Family Cancer Centre, b.r.a.i.n.child at SickKids; the Canadian Institutes of Health Research; the McLaughlin Centre at the University of Toronto; CIHR Institute of Cancer Research and C17 through the Advancing Technology Innovation through Discovery competition; and SickKids Foundation.

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