Depression is a disorder that often comes along with strong impairments of social functioning. Until recently, researchers assumed that acute episodes of depression also impair empathy, an essential skill for successful social interactions and understanding others. However, previous research had been mostly carried out in groups of patients who were on antidepressant medication. Novel insights of an interdisciplinary collaboration involving social neuroscientists, neuroimaging experts, and psychiatrists from the University of Vienna and the Medical University of Vienna show that antidepressant treatment can lead to impaired empathy regarding perception of pain, and not just the state of depression itself. The results of this study have been published in the scientific journal Translational Psychiatry.
20 jun 2019--An interdisciplinary research team set out to disentangle effects of acute depressive episodes and antidepressant treatment on empathy. The researchers recruited unmedicated patients with acute depression, and tested their empathic responses to the pain of others twice: first, during an acute depressive episode, i.e., before they had received any medication. Second, after three months of psychopharmacological treatment with antidepressants (mostly selective serotonin reuptake inhibitors).
In both sessions, patients underwent functional magnetic resonance imaging while watching videos of people undergoing painful medical procedures. Their brain activity and self-reported empathy were compared to those of a group of healthy controls. Before treatment, patients and controls responded in a comparable way. After three months of antidepressant treatment, the research revealed relevant differences: patients reported their level of empathy to be lower, and brain activation was reduced in areas previously associated with empathy.
First author Markus Rütgen says that reduced empathic responses were not caused by a general dampening of negative emotions: "The lowered emotional impact of negative events in a social context possibly allows patients to recover more easily. Nevertheless, the actual impact of reduced empathy on patients' social behavior remains to be explored."
More information: Markus Rütgen et al. Antidepressant treatment, not depression, leads to reductions in behavioral and neural responses to pain empathy, Translational Psychiatry (2019). DOI: 10.1038/s41398-019-0496-4
Journal information: Translational Psychiatry
Provided by University of Vienna
Tuesday, June 18, 2019
Study shows 70% of patients lack advance directives before elective surgery
Only 30% of pre-op patients reported having some form of Advance Directive documenting their wishes regarding emergency medical care. Only 16% had one on file in their electronic medical record (EMR) where a clinician could access it at the time of surgery. When there is no record of care preferences, families must decide what kind of emergency care their loved one receives. Credit: Regenstrief Institute
The majority of people visiting preoperative testing clinics before an elective surgery do not have an advance directive (AD) in case of surgical complications. This can lead to situations where patients' families are forced to make tough decisions about their loved one's care.
18 jun 2019--A study from researchers at the Regenstrief Institute, Indiana University Health and Indiana University School of Medicine found that only 30% of the patients in the study reported having some form of AD documenting their wishes regarding emergencymedical care. However, only 16% had one on file in their electronic medical record (EMR) where a clinician could access it at the time of surgery. When there is no record of care preferences, families must decide what kind of emergency care their loved one receives.
An advance directive is a legal document stating the patient's wishes for care if he or she is incapacitated. These preferences can include whether or not the person wants to receive CPR or intubation or who is in charge of making care decisions on their behalf. If there is no AD, doctors turn to a priority list of people, reaching out to them, in order of priority, to make the decision.
The lead author of the study, Shilpee Sinha, M.D., is the service line lead for the Adult Academic Health Center for Palliative Care at IU Health in Indianapolis. She sees patients every day who are at an increased risk of surgical complications. "When a crisis does occur," Dr. Sinha said, "family members tend to project their own emotions into what they think is best for the patient, but their choices may not be what the patient actually wants."
Dr. Sinha and her colleagues looked at EMRs of 400 patients who underwent preoperative evaluation. They found only 16% of those people had some form of AD on file.
Dr. Sinha performed this research as part of The Advanced Scholars Program for Internists in Research and Education (ASPIRE). ASPIRE is a one-year program through the Division of General Internal Medicine and Geriatrics at IU School of Medicine and the Regenstrief Institute that provides physicians in clinical practicewith a chance to hone their skills in research.
"One of my goals for doing this study is to drive clinical change," said Dr. Sinha. "The discussion of advance care planning is not part of the established routine. I think we've achieved buy-in on the idea of having these conversations. Now we need actual logistical application."
Regenstrief researcher Alexia Torke, M.D., M.S., was Dr. Sinha's mentor through the ASPIRE program, and senior author of this paper. She has conducted extensive research in surrogate decision making.
"When an AD is not available in cases of emergency, it creates a complex situation for the care providers and surrogate decision makers. Emotions are often high, and family members may have difficulty navigating those emotions to make the best decision for their loved ones," said Dr. Torke. "Work like Dr. Sinha's is very important. These findings suggest there is a significant opportunity for improvement in advanced care planning in the clinical setting."
"Advance Care Planning in A Preoperative Clinic: A Retrospective Chart Review" was published in the Journal of General Internal Medicine. The study was funded through the ASPIRE program. Dr. Torke was supported by a Midcareer Investigator Award in Patient-Oriented Research (K24 AG053794) from the National Institute on Aging.
More information: Shilpee Sinha et al, Advance Care Planning in A Preoperative Clinic: A Retrospective Chart Review, Journal of General Internal Medicine (2019). DOI: 10.1007/s11606-018-4744-8
Journal information: Journal of General Internal Medicine
Provided by Regenstrief Institute
Sunday, June 16, 2019
Moral emotions, a diagnotic tool for frontotemporal dementia?
A study conducted by Marc Teichmann and Carole Azuar at the Brain and Spine Institute in Paris (France) and at the Pitié-Salpêtrière Hospital shows a particularly marked impairment of moral emotions in patients with frontotemporal dementia (FTD). The results, published in the Journal of Alzheimer's Disease, open a new approach for early, sensitive and specific diagnosis of FTD.
16 jun 201--Frontotemporal dementia is a cognitive and behavioral disease caused by degenerative alteration of anterior regions of the brain. The disease is characterized by behavioral disorders such as a progressive apathy, loss of interest, social withdrawal, loss of inhibition and the processing of emotions.
We have known for a long time that these patients demonstrate impairment of emotion recognition and of theory of mind i.e. the ability to figure out the mental states of others: what they think, what they feel, what they like... But does this emotional blunting also affect a specific kind of emotions called moral emotions, which are crucial for human interactions? " asks Marc Teichmann, coordinator of the study.
Moral emotions can be defined as « affective experiences promoting cooperation and group cohesion " including emotions such as admiration, shame or pity. They are distinct from other emotions in that they are strongly linked to the cultural context, moral rules and innate moral representations. In the context of FTD, which are primarily characterized by an impairment of behavior and social interactions, studying these particular set of emotions is a major issue to better understand the disease and to refine diagnostic accuracy.
In the present study, researchers and clinicians from the ICM—Brain and Spine Institute and the Pitié-Salpêtrière Hospital developed a test to assess moral emotions. It is composed of 42 scenarios for which the subject has to select, out of 4 response possibilities, the feeling s/he has in the scenario situation. La performance des patients FTD (N=22) are compared to the performance of 45 healthy subjects and to 15 patients with Alzheimer's disease. To evaluate the specificity of the impairment of moral emotions in FTD the researchers contrasted the 42 moral scenarios involving an inter-human context and eliciting moral emotions with scenarios eliciting similar emotions without any mral valence. For example, it is possible to feel admiration for both an altruistic act and the architecture of a building. In both cases, the emotion is identified as admiration but the context is entirely different (moral versus extra-moral).
The results show that moral emotions are much more impaired than emotions without moral valence. In contrast, patients with Alzheimer's disease had no impairment as compared to healthy subjects and they had similar performance with moral and extra-moral emotions.
Our findings confirm that emotions in general are impaired in FTD and they reveal a particularly profound alteration of moral emotions. Our novel test tool appears to provide an early, sensitive and specific marker for FTD diagnosis while reliably distinguishing FTD from Alzheimer's disease patients. It could also be a marker for other diseases involving the breakdown of moral emotions as for example in the case of psychopathic individuals. " concludes Marc Teichmann.
More information: Marc Teichmann et al, Moral Emotions in Frontotemporal Dementia, Journal of Alzheimer's Disease (2019). DOI: 10.3233/JAD-180991
Journal information: Journal of Alzheimer's Disease
Provided by IOS Press
Saturday, June 15, 2019
People with HIV are growing old—and society isn't ready for it
The good news is that people with HIV are living much longer than they used to; it's estimated that by 2020, 70 percent of people living with HIV in the United States will be age 50 and older, compared to 10 percent during the first 20 years of the epidemic. The bad news? With this longevity come challenges that our healthcare system isn't prepared to address.
15 jun 2019--"When I began my career as a nurse in the late 1980s, HIV was pretty much adeath sentence," says Michael Relf, a professor of nursing andglobal health. "People living with HIV were told, 'We'll keep you as healthy as possible, but you need to get your affairs in order.'"
But when combination antiretroviral therapy (ART) was introduced in the mid-1990s, the outlook for these individuals went from bleak to bright. And over time, as ART has become increasingly effective with fewer harmful side effects, the odds of longer survival continue to improve, necessitating a new focus on healthy aging for people living with HIV.
In 2014, the Joint United Nations Programme on HIV/AIDS established "90-90-90," a treatment target to end the HIV epidemic: by 2020, 90 percent of people living with HIV will know their HIV status, 90 percent of people diagnosed with HIV will receive ART, and 90 percent of people receiving ART will have viral suppression. Some HIV researchers, clinicians, and persons living with HIV refer to healthy aging with HIV as "the fourth 90," signifying the importance of addressing the particular challenges this population faces.
Many people living with HIV have higher rates of risk factors for cancer and chronic illnesses, such as cardiovascular disease and diabetes, than the general population. These factors include smoking, alcohol and drug use and poor nutrition, as well as other factors related directly to the disease and its treatment.
"The sustained inflammation from HIV over time, even when viral loads are suppressed, creates pathways in the body that increase the risk for cardiovascular disease, and some of the earlier antiretrovirals profoundly increased the risk for lipid disorders, insulin resistance and endocrine disorders," says Relf, who studies HIV and aging.
HIV also heightens the body's susceptibility to poor bone health. Conditions such as avascular necrosis—the death of bone tissue due to interruption of the blood supply—disproportionately affect people living with HIV and can lead to the need for a hip replacement.
And people living with HIV are prone to cognitive and neurological problems such as earlier onset of dementia. One study found that the epigenetic age of the brain of a person with HIV was more than seven years older than those who don't have HIV.
But the HIV-related challenges of aging extend beyond physical health. Loneliness, isolation, intersectional stigma and depressive symptoms are common among older adults living with HIV and can negatively impact their ability to access the health and social services they need. "Many people aging with HIV have been socially isolated from their families and communities," says Relf, who also studies HIV-related stigma. "Many older gay men, for example, lost a significant portion of their social network when their friends and partners died in the early days of the HIV epidemic."
In fact, insights Relf gleaned through his research on HIV stigma are what prompted him to delve deeper into HIV and aging. When he and his collaborators were studying internalized stigma among women in the southeastern United States, many of the participants reported experiencing different types and sources of stigma as they age. For example, one woman reported tearfully that her son—who had learned of her HIV status as a child and had been supportive of her throughout his childhood—doesn't allow her to use his dinner plates or go to the bathroom at his house out of fear that his children might contract HIV.
Unfortunately, Relf says, health systems in the U.S. and across the world aren't ready for the aging population in general, let alone older adults with these unique needs. He's among the proponents of a holistic approach to helping people living with HIV age successfully. Relf recently co-authored an update to a model that considers the interplay of biological, cognitive, mental and social factors in the aging process for people living with HIV. The model promotes a lifespan perspective that takes into account historical behaviors and lifestyle factors that affect one's aging process and quality of life as they get older. It also suggests that healthcare practitioners should screen patients with HIV for geriatric problems such as functional impairment and frailty at an earlier age because many of these symptoms occur prematurely in this population.
Relf also thinks healthcare professionals need to develop cross-disciplinary expertise. "HIV specialists need to be able to take care of the geriatric issues, gerontologists should be able to tackle HIV issues and primary care providers should be able to do both," he says. "In most places, we're not quite there yet."
Nurses, Relf says, are poised to play an important role in improving care for older adults with HIV—particularly in rural areas, where they're often the sole healthcare providers. "Because nurses who live and work in a community understand the community's norms, culture and values, they're well-positioned to help design and tailor effective prevention initiatives, testing and counseling programs, and treatment efforts," he says. "But often, they're functioning outside their skill set out of necessity, especially in the global setting."
Relf is working on changing that. As a member of an expert advisory panel of the Association of Nurses in AIDS Care, he's helping to create a series of professional development modules for nurses and nurse practitioners on issues associated with aging among people with HIV. The project is one of several funded by Gilead Sciences, Inc., a leading manufacturer of ART, to support innovative approaches to preparing healthcare and other systems to better serve older adults with HIV.
This "graying of the HIV epidemic" also calls for more sweeping changes in healthcare. In an editorial for a special issue of the Journal of the Association of Nurses in AIDS Care, Relf and his co-editors write, "individual-level interventions and redesigns of health care systems will be needed to meet the unique prevention, care, and treatment needs of older persons at risk of, living with, and/or affected by HIV."
In June 2021, the world will commemorate 40 years of the epidemic, and while significant challenges persist, Relf is hopeful. "Although there is still not a cure, it's tremendous progress that we're now focusing on the 'fourth 90' to help individuals living with HIV age successfully," he says.
More information: David E. Vance et al. Revisiting Successful Aging With HIV Through a Revised Biopsychosocial Model, Journal of the Association of Nurses in AIDS Care (2019). DOI: 10.1097/JNC.0000000000000029
Older adults who practice yoga are more likely to be in better mental and physical shape, research suggests.
11 jun 2019--Yoga improves physical function as well as mental wellbeing inhealthy adultsover the age of 60, the study found.
The physical benefits of yoga—an ancient practice that includes the use of postures and regulated breathing—were found to include better muscle strength, balance and flexibility.
Boosts to health
Boosts to mental health included improvement in the symptoms of depression, sleep quality and vitality in older adults.
Researchers at the University reviewed 22 studies that had investigated the effects of yoga on physical and mental wellbeing in older adults. The yoga programmes varied in length from one month to seven months, and duration of sessions ranged from 30 to 90 minutes.
Statistical analysis combined the results of the studies to see the effects of yoga compared with no activity, and compared to other activities such as walking and chair aerobics.
Physical improvements
The researchers found that people who practiced yoga had improved balance, flexibility, leg strength, depression, sleep quality, vitality and perceived mental and physical health—compared with no activity.
Compared with other activities yoga improved lower body strength, lower body flexibility and depression.
Researchers say the review improves understanding of the benefits yoga can offer an aging population. They say it provides evidence for promoting yoga in physical activity guidelines for older adults.
"A large proportion of older adults are inactive, and do not meet the balance and muscle strengthening recommendations set by government and international health organizations. Based on this study, we can conclude that yoga has great potential to improve important physical and psychological outcomes in older adults. Yoga is a gentle activity that can be modified to suit those with age-related conditions and diseases," says Divya Sivaramakrishnan of the Physical Activity for Health Research Centre.
More information: Divya Sivaramakrishnan et al. The effects of yoga compared to active and inactive controls on physical function and health related quality of life in older adults- systematic review and meta-analysis of randomised controlled trials, International Journal of Behavioral Nutrition and Physical Activity (2019). DOI: 10.1186/s12966-019-0789-2
Opioid analgesics were associated with a 30 percent increase in the risk of pneumonia in persons with Alzheimer's disease, a recent study from the University of Eastern Finland shows. The risk was most pronounced in the first two months of use. This is the first study to investigate the association between opioids and pneumonia in this population. The results were published in the Journal of Alzheimer's Disease.
10 jun 2019--The risk of pneumonia was highest among those using strong opioids, such as oxycodone or fentanyl, but the risk was also increased among those using buprenorphine, tramadol or codeine. Persons with active cancer were excluded from the study, and other diseases and drug use were accounted for in the analyses. Opioids impair the cough reflex and respiratory functions and cause sedation, possibly underlying the increased risk for pneumonia.
Pneumonia is a severe but relatively common complication among persons with Alzheimer's disease, and often leads to hospitalization and even death. Opioids are important in the treatment of severe acute pain, but treatment should be initiated at a low dose and regularly assessed for both benefit and harm. The diagnosis and assessment of pain is challenging among persons with Alzheimer's disease due to problems in communication.
The study is part of the MEDALZ cohort, which included 5,623 persons with Alzheimer's disease diagnosed in Finland during 2010-2011. Each person initiating opioid use was matched with a comparison person with Alzheimer's disease who did not initiate opioid use but had the same age, gender and year of Alzheimer's diagnosis. Data for the study were derived from Finnish nationwide registers.
More information: Aleksi Hamina et al. Hospital-Treated Pneumonia Associated with Opioid Use Among Community Dwellers with Alzheimer's Disease, Journal of Alzheimer's Disease (2019). DOI: 10.3233/JAD-181295
Intermittent fasting is a method of dieting that restricts the amount of time you are allowed to eat. The appeal of these diets is that you don't need to count calories or eat certain foods. But there are so many versions, it's hard to know which one is best. Here's what the research says.
The 5:2 diet
07 jun 2019--This is a popular version of intermittent fasting where you eat a very low calorie diet (about 500kcal) for two days each week (any two days). On the other five days, you eat as normal.
Research has shown that it's possible to lose weight with this diet; it also improves several markers of health, such as reducing levels of glucose and cholesterol in the blood. But the 5:2 diet is unlikely to be more effective for weight loss than traditional methods of dieting. This is because 5:2 reduces calorie intake to a similar extent as traditional dieting.
There is some evidence that conducting the two days of very low calorie intake on consecutive days can improve insulin sensitivity—a risk marker for type 2 diabetes—to a greater extent than traditional dieting. This approach also leads to decreases in blood lipids (fatty substances found in the blood) compared with traditional dieting.
An important extra benefit of 5:2 is that you can consume some food during the "fasting" period, providing an opportunity to take in vital nutrients. Dieting often leads to losses in muscle and bone mass, alongside fat mass because consuming a balanced diet while reducing calorie intake is difficult. This can compromise long-term weight loss efforts as muscle is more metabolically active (burns more calories) than fat. Eating enough protein can help to reduce the loss of muscle masswhile dieting, with a bonus of reducing appetite.
Alternate-day fasting
While 5:2 could be considered a "lifestyle intervention", alternate-day fasting (ADF) is more likely to be used to lose weight quickly. ADF is often referred to as the "every other day diet" and requires you to alternate daily between unrestricted eating and consuming a very low calorie diet.
Most research on ADF uses a similar approach to 5:2, allowing a small meal (usually about 500kcal) to be consumed on "fasting" days. Research has shown that ADF can lead to considerable weight loss in 8-12 weeks, but a big problem with ADF is that adherence tends to wane. Longer-term studies have shown that calorie intake on "fasting" days creeps up over time, which reduces the calorie deficit achieved and slows the rate of weight loss.
Randomised controlled trials (the gold standard of clinical research) show that ADF doesn't lead to more weight loss or improvements in health compared with traditional dieting when calorie intake is the same in both groups. Despite this, it is likely that ADF will result in a greater reduction in calorie intake compared with traditional methods of dieting, which should lead to greater weight loss, initially. But it's doubtful that many people will adhere to ADF in the long term.
Time-restricted eating
Time-restricted eating (TRE) involves complete fasting for long periods (16-20 hours) and consuming all calories within restricted hours, often referred to as "feeding windows".
The most common version of TRE uses a ratio between fasting and eating of 16:8 (16 hours of fasting and eight hours during which it is permissible to eat). Many people achieve this ratio by skipping breakfast thereby delaying their first meal until midday and consuming all food between midday and 8pm.
Research has shown that calorie intake over a 24-hour period is reduced when people skip breakfast. But the number of calories expended through physical activity is also reduced, which will partially or completely negate the calorie deficit achieved by skipping breakfast. So skipping breakfast is unlikely to lead to meaningful weight loss. Skipping breakfast also reduces the effectiveness of insulin to regulate blood glucose levels after lunch, indicating a negative effect on insulin sensitivity.
But an alternative approach to TRE has shown promise. A recent study found that fasting from 2pm improved insulin sensitivity in a group of pre-diabetic males. This could be due to an enhanced natural ability to regulate blood glucose levelseffectively in the morning, due to daily variations in metabolism. So, restricting food intake to a morning feeding window and fasting in the evening may be a healthier version of TRE.
And the winner is…
As with any diet, success will be dictated mostly by adherence. When it comes to weight loss, ADF is likely to lead to the most rapid success, but sustaining weight loss in the long term may be aided by the less intense 5:2 approach.
There is some evidence that adherence could be greater in TRE, as completely restricting food intake may be easier for some people than severely restricting it. In this sense, research suggests that skipping dinner may be better for health than skipping breakfast.
It's important to note that most research suggests that intermittent fasting is no better than traditional methods of dieting. But intermittent fasting regimens that have prolonged periods of fasting, such as TRE with shorter feeding windows and 5:2 with two consecutive very low calorie days, may provide additional health benefits.
Provided by The Conversation
Wednesday, June 05, 2019
Falls a 'major epidemic' for older Americans
Credit: CC0 Public Domain
From late-night tumbles on the way to the bathroom to accidents outdoors, more and more elderly Americans are dying after a fall, with the risk doubling since 2000, according to a study published Tuesday.
05 jun 2019--The figures confirm a trend that has also been observed in Europe.
In the United States, the absolute number of deaths among over 75s attributed to falling almost tripled from 2000 to 2016 (8,613 to 25,189).
While the population has grown since that time, it still represents a doubling in the rate of such deaths for men as well as women, according to a study published in the Journal of the American Medical Association(JAMA).
The research was led by Klaas Hartholt at the Reinier de Graaf Groep in the Netherlands.
"Approximately one in three persons aged 65 years or older falls every year," Marco Pahor, director of the Institute on Aging at the University of Florida, wrote in an editorial on the subject for the journal.
"Falling is a potentially catastrophic and life threatening event for older persons."
But the risk of death from head trauma and internal bleeding isn't where it ends. Fractures to hips, knees or ankles can mark the start of a vicious cycle: hospitalization, reduced independence, physical rehabilitation and long-lasting effects on morale and mental health.
One in five people who break their hips will never walk again, according to Atul Gawande, a doctor and the author of the book "Being Mortal."
In the US, the costs linked to falls is among the most expensive categories for hospital care.
"Falls represent a major emerging epidemic among older persons," Pahor told AFP.
Fewer pills
In the Netherlands, Spain, Australia and Canada where falls were also recently studied, the trend has been similar since 2000. In France, the problem is described as a "major public health issue."
The reasons for the spike have not been well studied, but geriatricians have some ideas.
It's possible that the elderly of today are more active than those of the past. Rising obesity levels could also play a role since it is linked to a weakening of the muscles.
Perhaps most of all, while modern medicine has done a good job in improving the treatment of chronic illnesses, it has neglected the quality of life that people can live in their old age.
That is according to George Taler, a geriatrician who heads the home visit program at the MedStar Washington Hospital Center in the US capital.
One of the methods he most favors for lowering the risk of falling is simple: "de-prescribing" medication that is no longer necessary.
Studies have shown that when the number of prescription drugs taken daily is four or more, disorientation and loss of balance rise significantly.
"We're very good at writing prescriptions for medications. We're not so good about taking them away, even when they're no longer helpful or necessary," he told AFP.
"I'll just give you a case today: this is an older woman who's had multiple falls, and she has swelling in her ankles.
"Well, if I gave her a prescription for a diuretic to get rid of the swelling, and all the fluid disappears, she is likely to have a fall from dehydration. So we need to adjust the medicine to her reality."
Another study published in JAMA led by Teresa Liu-Ambrose at the University of British Columbia found that physical exercise played a role in reducing falling.
In a relatively small experiment carried out in the Greater Vancouver area with around 300 septuagenarians, researchers tested the effectiveness of the Otago Exercise Program, a home-based program supervised by a physical therapist.
It involves numerous strength-building exercises for knees, hips and ankles as well as balance-training (including walking backwards, standing on a leg, etc), repeated three times a week with participants asked to also walk 30 minutes at least twice per week.
The physical therapist visited at various intervals to keep things on track, with their fifth and final visit six months after the program began.
The program "significantly reduced the rate of subsequent falls" compared to those in a control group, but the researchers cautioned that the results required replication in other clinical settings.
One thing that has intrigued researchers has been the positives associated with physical exercise even when it did not increase muscle mass.
"The very act of exercise just makes people more aware of their body, more aware of their space, feeling better about themselves," said Taler. "And even though we may not be able to measure that, it still has its measurable benefits in terms of falls."
"Cancer has a way of evolving and adapting," says Dr. Mariam Jamal-Hanjani, a cancer doctor and researcher at the Cancer Research UK Lung Cancer Centre of Excellence. "When tumours are under selection pressures, for example as a result of cancer treatment, they can develop new features that allow them to become resistant and, therefore, more aggressive."
02 jun 2019--Advanced cancers have often spread to other parts of the body. And it's these secondary tumours that reach and compromise vital organs like the brain or lungs that can ultimately lead to death.
To tackle aggressive cancers, scientists need to understand how they evolve, spread and become resistant to treatment. But as cancer progresses and patients become more unwell, it becomes increasingly difficult to study.
Doctors might ask a patient for permission to use tissue removed during surgery for research. But when cancer has spread to multiple locations, or to somewhere that might not be possible to operate on or obtain a biopsy from, it isn't possible to collect these gifts of precious tissue.
But now, thanks to an even greater gift to research, patients with advanced cancers are leaving a different type of legacy.
In new research, 10 patients with advanced breast cancer chose to donate their bodies after their death. Their gift allowed Cancer Research UK scientists in Cambridge to collect multiple samples of advanced cancer in all the places it had spread to—up to 37 tumours in a single patient. They analysed these samples to unravel how the cancers spread and developed treatment resistance, publishing their in-depth picture in the journal Cell Reports.
"It's really an unprecedented view of lethal cancers," says study lead Professor Carlos Caldas, from the Cancer Research UK Cambridge Institute.
Talking about death
Studies like this, and a larger national study called PEACE, involve collecting samples from patients after death and can sometimes require delicate conversations. For some patients the subject of death is a difficult one for many reasons, and patients are aware of the fact that their participation in studies like PEACE will not benefit themselves.
Despite how sensitive the topic is, patients often want to contribute to the research supported by PEACE, which is funded by Cancer Research UK. And they remain its biggest advocates.
"The truth is, even before PEACE existed I would often have patients ask me: "Is there anything I can do for science? Can I donate my body to research?"" recalls Jamal-Hanjani, who is the Principal Investigator for PEACE at the lead centre, UCL Cancer Institute.
"Our patients still want to give something of themselves to help cancer research, knowing that they won't benefit, but that future patients might. It's incredibly humbling."
In these circumstances, a strong doctor-patient relationship is key to an open and honest conversation. Understanding how the patient feels is the main steer for doctors in whether to discuss participating in PEACE.
Although it can be intimidating, Jamal-Hanjani believes this is something doctors need to become more comfortable with. "In treating patients with cancer especially, we as doctors have to overcome that stigma, because patients do think about death and we need to allow them to speak freely with us."
And these patients' contribution can be invaluable in helping those who come after them.
Decoding cancer spread
Cancer evolution has become one of the big topics in research. Studies are analysing tumours from when they are first discovered and throughout treatment.
Now, samples collected after death are helping to understand the hardest to treat stages of some cancers. Caldas and his team compared multiple tumours collected from patients who had died from breast cancer that had become resistant to treatment.
The results paint a more comprehensive picture of how closely related tumours can be, retracing the steps that led to these cancers growing and spreading. Caldas says the results are unexpected.
"Our work suggests something rather extraordinary: that cancer spread is not a continuous process. It seems to happen in waves," he says. Rather than new tumours appearing one after the other, each wave involves a group of cancer cells creating new tumours in several organs at the same time.
These could be cells breaking away from the primary tumour, or from elsewhere in the body where cancer cells can remain hidden and dormant for sometimes years.
"Even in patients who have a lot of secondary tumours," adds Caldas, "cancer appears to have spread in as few as two or three of these waves."
What triggers these waves? Could there be 'pauses' between them when cancer is unlikely to spread? Answers to these questions could change the way patients are monitored.
"This is just starting to open the book," Caldas says. "There is a lot more to be learned from studies like this."
The PEACE study is on a much larger scale: 150 patients have already volunteered in the first 2 years of the study. The research will focus on themes that scientists struggle to study without access to advanced cancer samples, like why certain cancers readily spread to specific organs but not others.
Coming together
Narrowing down the research questions to ensure these precious samples are used for the best possible research is an important aspect of PEACE.
A project of this scale also involves an element of unpredictability that represents a huge challenge for Jamal-Hanjani. Often, it's a patient's family who notifies the PEACE team that their loved one has died. An entire team must then come together very quickly, including researchers, laboratory staff, pathologists, mortuary technicians and clinical nurses.
"I would say that is far more challenging than talking to patients about death and about the PEACE study," Jamal-Hanjani says.
Yet she feels a sense of responsibility. "Ultimately, we make a promise to the patient when they are alive, and we want to fulfil the living wish of our patients," she says.
"We want our patients to know that even after they die, we will treat them with dignity and respect. We are very privileged to receive their samples and to be able to do the research we do."
Paying it forward
As we start to better understand the behaviour of advanced cancers, PEACE and other post-mortem studies continue to centre on the people affected. For those who take part, this is their legacy.
"The vast majority of patients want to help other patients," says Jamal-Hanjani. "I think that's just the nature of human beings."
That legacy will support many ongoing research projects focusing on several types of cancers, including lung, kidney, skin and breast, to name a few. Not only that, but samples will also be stored so that PEACE can contribute to future research projects. "It's about the research we can do now, but also the research we can offer future doctors and scientists," says Jamal-Hanjani.
More information: Leticia De Mattos-Arruda et al. The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer, Cell Reports (2019). DOI: 10.1016/j.celrep.2019.04.098
Cannabis use among older adults is growing faster than any other age group but many report barriers to getting medical marijuana, a lack of communication with their doctors and a lingering stigma attached to the drug, according to researchers.
01 jun 2019--The study, the first to look at how older Americans use cannabis and the outcomes they experience, was published this month in the journalDrugs & Aging.
"Older Americans are using cannabis for a lot of different reasons," said study co-author Hillary Lum, MD, Ph.D., assistant professor of medicine at the University of Colorado School of Medicine. "Some use it to manage pain while others use it for depression or anxiety."
The 2016 National Survey of Drug Use and Health showed a ten-fold increase in cannabis use among adults over age 65.
The researchers set out to understand how older people perceived cannabis, how they used it and the positive and negative outcomes associated with it.
They conducted 17 focus groups in in senior centers, health clinics and cannabis dispensaries in 13 Colorado counties that included more than 136 people over the age of 60. Some were cannabis users, others were not.
"We identified five major themes," Lum said.
These included: A lack of research and education about cannabis; A lack of provider communication about cannabis; A lack of access to medical cannabis; A lack of outcome information about cannabis use; A reluctance to discuss cannabis use.
Researchers found a general reluctance among some to ask their doctors for a red card to obtain medical marijuana. Instead, they chose to pay more for recreational cannabis.
Lum said this could be driven by feeling self-conscious about asking a doctor for cannabis. That, she said, points to a failure of communication between health care providers and their patients.
"I think [doctors can] be a lot more open to learning about it and discussing it with their patients," said one focus group respondent. "Because at this point I have told my primary care I was using it on my shoulder. And that was the end of the conversation. He didn't want to know why, he didn't want to know about effects, didn't want to know about side effects, didn't want to know anything."
Some said their doctors were unable or unwilling to provide a certificate, the document needed to obtain medical marijuana. They also said physicians need to educate themselves on the latest cannabis research.
Some older users reported positive outcomes when using cannabis for pain as opposed to taking highly addictive prescription opioids. They often differentiated between using cannabis for medical reasons and using it recreationally.
"Although study participants discussed recreational cannabis more negatively than medical cannabis, they felt it was more comparable to drinking alcohol, often asserting a preference for recreational cannabis over the negative effects of alcohol," the study said.
The researchers also found that despite the legalization of cannabis in Colorado and other states, some older people still felt a stigma attached to it.
"Some participants, for example, referred to the movie `Reefer Madness' (1936) and other anti-marijuana propaganda adverts that negatively framed cannabis as immoral and illegal," the researchers said.
The study adds to the growing literature on the diversity of marijuana use patterns in older adults, said co-author Sara Honn Qualls, Ph.D., ABPP, professor of psychology and director of the Gerontology Center at the University of Colorado Colorado Springs.
"Older adults who use marijuana are ingesting it in a variety of ways for multiple purposes," she said. "This and other papers from the same project show growing acceptance of marijuana use for medical purposes by older adults, and a clear desire to have their primary health providers involved in educating them about options and risks.
Lum agreed.
She said Colorado, the first state to legalize recreational marijuana, provides a unique laboratory to gauge public attitudes toward cannabis.
"From a physician's standpoint this study shows the need to talk to patients in a non-judgmental way about cannabis," she said. "Doctors should also educate themselves about the risks and benefits of cannabis and be able to communicate that effectively to patients."
More information: Julie Bobitt et al, Qualitative Analysis of Cannabis Use Among Older Adults in Colorado, Drugs & Aging (2019). DOI: 10.1007/s40266-019-00665-w
