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A new study from ICES, Lawson Health Research Institute and Western University suggests that injection drug users prescribed controlled-release hydromorphone are three times more likely to develop endocarditis, a serious bacterial heart infection, when compared to those prescribed other opioids. The findings build on growing evidence that some controlled-release opioids may lead to higher risk of infectious disease among persons who inject drugs. 

The researchers looked at de-identified Ontario health data for hospital admissions related to injection drug use between 2006 and 2015. Of 60,529 admissions, 733 patients had infective endocarditis. The team found that regions with high hydromorphone prescription rates had more than double the cases of infective endocarditis (254 cases) when compared to regions with low prescription rates (113 cases).

The study also analyzed individual prescription records and found that among persons who inject drugs, those prescribed controlled-release hydromorphone were three times more likely to develop infective endocarditis when compared to those prescribed any other opioid. There was no increased risk for those prescribed the immediate-release form of hydromorphone.

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Above: Dr. Matthew Weir

“Added to the existing data, these findings make a compelling argument for the role of controlled-release hydromorphone in the growing risk of infective endocarditis among persons who inject drugs,” says Dr. Matthew Weir, Adjunct Scientist at ICES, Associate Scientist at Lawson and Assistant Professor at Western’s Schulich School of Medicine & Dentistry. 

Opioids are often manufactured as controlled-release or ‘slow-release’ capsules to prevent rapid absorption of the drug. Properties in the capsules help to spread pain relief over a longer period of time.

This is the latest in a series of studies from the research team that suggest some controlled-release opioids may be leading to increased risk of infectious disease among persons who inject drugs. 

In one study, they demonstrated that polymer-coated beads used to provide the slow-release property make controlled-release hydromorphone difficult to dissolve. They found equipment used to dissolve the drug retains up to 45 per cent of the initial dose, leading injection drugs users to save and reuse equipment.

With frequent re-handling of equipment, there are multiple opportunities for bacterial and viral contamination. The team found that HIV and a dangerous bacterium called Staphylococcus aureus are more likely to survive in equipment used to prepare controlled-release hydromorphone since added chemicals that make the drug slow-release promote survival of bacteria and viruses. 

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Above: Dr. Michael Silverman

“There’s been a global increase in infectious diseases among persons who inject drugs and our research suggests that controlled-release prescription opioids may be a major culprit,” says Dr. Michael Silverman, Associate Scientist at Lawson and Associate Professor at Schulich Medicine & Dentistry. “We now have evidence that suggests the injection of controlled-release hydromorphone is increasing the spread of HIV, hepatitis C and endocarditis in Canada.” 

The team believes these findings could also explain the increase in infectious complications in the USA and other countries where controlled-release hydromorphone is not on the market.  There are other controlled-release opioids, such as controlled-release morphine, that use a similar slow-release mechanism and may carry similar risks. 

“It’s important that people are aware of the infectious risks of injecting opioids and, if necessary, practice harm reduction techniques,” says Dr. Silverman. “We’ve found you can use a cigarette lighter to destroy bacteria and viruses by heating the cooker used to prepare the drug for about 10 seconds or until the mixture bubbles. We’ve termed the technique ‘cook your wash.’” 

The study, "Hydromorphone and the risk of infective endocarditis among people who inject drugs: a population-based, retrospective cohort study," was published in The Lancet Infectious Diseases.

The legalization of cannabis in Canada in October 2018 created an important concern for the health of mothers and babies during pregnancy and beyond. Studies from 2002 – 2014 indicate that one in five pregnant women between the ages of 18 and 25 use cannabis, as the  perception is common that it will reduce anxiety and pregnancy-induced nausea. 

Although there is a large body of evidence detailing the mode of action of the main component of cannabis (Δ9-tetrahydrocannabinol (THC)) in adults, little research has focused on understanding how it may impact development of the fetus. This is a critical knowledge gap considering that fetal growth deficits are accompanied with an increased risk of developing chronic metabolic disease later in life.

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Dr. Edith Arany, Scientist at Lawson, is studying the implications of cannabis use during pregnancy on the offspring’s pancreas development “in utero” and its effects on glucose control in adulthood. 

With the increased epidemic of Type 2 diabetes due to environmental factors, her research in cannabis consumption might bring to light another contributor to this burden. 

Dr. Arany’s study is being funded through Lawson’s Internal Research Fund (IRF).

“I’m extremely grateful for this IRF award as it will help me open up a new direction in my research program.” Dr. Arany states.  “These IRF grants are crucial to basic scientists to get preliminary data to support future grant applications. Without this support, it is difficult to test novel directions of research and to maintain research programs.”

Lawson’s IRF is designed to provide Lawson scientists the opportunity to obtain start-up funds for new projects with the potential to obtain larger funding, be published in a high-impact journal, or provide a clinical benefit to patients. Funding is provided by the clinical departments of London Health Sciences Centre and St. Joseph’s Health Care London, as well as the hospital foundations (London Health Sciences Foundation and St. Joseph’s Health Care Foundation).
 

A multidisciplinary team at Lawson Health Research Institute is exploring whether fecal transplants can improve outcomes in melanoma patients treated with immunotherapy.

Immunotherapy drugs stimulate a person’s immune system to attack and destroy cancer. While they can significantly improve survival outcomes in those with melanoma, they are only effective in 40 to 50 per cent of patients. Preliminary research has suggested that the human microbiome – the diverse collection of microbes in our body – may play a role in whether or not a patient responds.

“The gut microbiome helps establish immunity from an early age. It makes sense that a healthy gut could improve response to immunotherapy,” explains Dr. Jeremy Burton, a Lawson Scientist who specializes in human microbiome research. “This led us to consider the potential of fecal transplants.”

Fecal transplants involve collecting stool from a healthy donor, preparing it in a lab and transplanting it to the patient. The goal is to transplant the donor’s microbiome so that healthy bacteria will colonize in the patient’s gut.

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Above (from left): Drs. Michael Silverman and Jeremy Burton

In a phase I clinical trial, the research team is the first in Canada to study the use of fecal transplants to alter a cancer patient’s microbiome and improve their response to anti-PD1 immunotherapy drugs.

Research participants will be 20 melanoma patients recruited from the London Regional Cancer Program (LRCP) at London Health Sciences Centre (LHSC). They will undergo a fecal transplant at St. Joseph’s Hospital, a part of St. Joseph’s Health Care London, followed by immunotherapy at LRCP. The transplant will consist of taking a number of specially-prepared oral capsules. 

Patients will be assessed over time for any changes to their cancer, microbiome, immune system and overall health. The primary goal of the study is to evaluate safety of the novel treatment combination, but researchers will also evaluate patient outcomes.

“Melanoma is the least common skin cancer but it is the most deadly and rates are going up,” says Dr. John Lenehan, Associate Scientist at Lawson and Oncologist at LHSC. “Anti-PD1 immunotherapy drugs can be extremely effective but we want to help more patients respond. That’s our goal.”

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Above (from left): Drs. Saman Maleki and John Lenehan

While the team is studying the combination of fecal transplants and immunotherapy for melanoma, they see potential for other cancers as well.  

“We’re one of the first in the world to study fecal transplants in cancer patients. This study is as cutting-edge as it gets with potential applications for multiple disease sites,” notes Dr. Saman Maleki, a Lawson Associate Scientist who specializes in cancer immunology. “With experts in microbiology, infectious disease, cancer and immunology, our institute is well-positioned to carry this forward.”

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Dr. Michael Silverman, Lawson Associate Scientist and Chief of Infectious Disease at St. Joseph’s and LHSC, is a pioneer in the field of fecal transplants. St. Joseph’s is a leading centre for the procedure, performing them for Clostridium difficile (C. diff) patients across the province. 

“Fecal transplants have saved the lives of countless patients with recurrent C. diff,” says Dr. Silverman. “We’re now starting to see its potential for the treatment of other diseases.”

Lawson researchers are planning fecal transplant studies for multiple other conditions including non-alcoholic fatty liver disease, multiple sclerosis (MS) and cancer treatment toxicity.“But in order to conduct this research, we need stool donors,” notes Dr. Silverman.

Check out media coverage of this research:

• CTV News: Why fecal transplants could be the next frontier in fighting skin cancer
• Forbes: Could poop be the next treatment for cancer?
• London Free Press: Researchers seeking poop donors for skin cancer treatment study
• Daily Mirror: How human poo 'transplants' could help doctors treat deadliest form of skin cancer
• CBC: London cancer researchers make number 2 their number 1 priority

A $125,000 grant from the Canadian Cancer Society will help create a database of PET/CT (positron emission tomography/computed tomography) and PET/MR (magnetic resonance) images of prostate cancer. The hope is that this database will be used to help improve diagnosis and treatment of men with prostate cancer.

The scans use radiopharmaceuticals to target prostate specific membrane antigen (PSMA), a transmembrane protein commonly found on prostate cancer cells.

 “The idea behind this grant is to put together a database of PSMA PET/CT and PET/MR scans with annotated findings so medical professionals can scroll through cases and see the sites of prostate cancer. Our hope is this will help clinicians learn how to interpret these scans and ultimately help them to make informed treatment decisions for their patients,” says Dr. Katherine Zukotynski, Adjunct Scientist at Lawson Health Research Institute and lead researcher on the project.

The use of PSMA PET/CT and PET/MR scans in clinical practice is relatively new and currently only accessible through clinical trials. In fact, the first PSMA PET/MR scan in Canada was performed at St. Joseph’s Health Care London in 2016 by Dr. Glenn Bauman, Lawson Scientist and Radiation Oncologist at the London Regional Cancer Program at London Health Sciences Centre. Dr. Bauman is also part of this database project.

Studies have found these scans more accurately detect sites of prostate cancer than earlier imaging techniques, which then helps inform treatment decisions.

Dr. Zukotynski explains, “If you have an idea of the amount of disease and where it is located, and you can correlate it with prognosis, this could be very helpful. It might also allow physicians to compare current patients with patients who have similar findings, which may help determine the best therapies to try.”

There is hope that eventually this same database could lead to the use of artificial intelligence (AI) to assist in diagnosis and treatment planning.

“PSMA PET/CT and PET/MR may be tools helpful to categorize the total burden of disease, and then establish how that disease changes with therapy. Our first step down this path is to assemble a database that can be used both for research and educational purposes.”

The database will include data from centres across Canada, with a number of researchers contributing to the project funded by the Canadian Cancer Society.

Other principal investigators include: Dr. Bauman; Dr. François Bénard of the BC Cancer Research Institute; Dr. Vincent Gaudet, University of Waterloo; Dr. Phil Kuo, University of Arizona; Dr. Cynthia Ménard, Centre Hospitalier Universitaire de Montreal; and Dr. Ur Metser of the Princess Margaret Hospital. Dr. Carlos Uribe of the BC Cancer Research Centre and Dr. Aaron Ward of Lawson are co-applicants for the grant.

This is the part three of a three-part series on PSMA PET imaging research. Check out part one and two.