A new study has helped researchers understand the experiences of people who withdraw from clinical cancer trials.
Cancer clinical trials (CCTs) provide patients with an opportunity to receive experimental drugs, tests, and/or procedures that may lead to remissions. Such opportunities can be a great benefit for those who took part, but there is little known of the experiences of participants who withdraw from CCTs.
To address this, a first-of-its-kind study from the University of Pennsylvania School of Nursing (Penn Nursing) was conducted to better understand the post-trial needs of these patients and define responsible transitions when patients exit CCTs.
“Understanding the post-trial needs of patients with cancer and their families represents a measure of ethical respect of the many contributions that patients with cancer make to advancing our scientific knowledge and finding treatments that save lives,” said the study’s lead researcher, Connie M Ulrich, the Lillian S Brunner Chair in Medical and Surgical Nursing, professor of nursing, professor of medical ethics and health policy.
The study revealed three important areas:
Patients exiting CCTs feel intense symptoms, emotions, and awareness that their life spans are short and options seem limited.
The limited discussions with patients who are exiting on their immediate post-trial care needs can result in many feeling that there is no clear path forward.
Good communication that deliberately includes attention to post-trial needs throughout the CCT is needed to help scared and disappointed patients navigate their next steps.
The study is set for publication on the JAMA Network.
Medical students who experienced mistreatment during medical school were more likely to become exhausted or disengaged, have less empathy, and have career regret, a new study has revealed.
Among a large national sample of trainees, the 22.9% of respondents who reported mistreatment on the Association of American Medical Colleges’ Medical School Year 2 Questionnaire (Y2Q) had higher exhaustion and disengagement scores on the Graduation Questionnaire (GQ) 2 years later, reported Liselotte Dyrbye, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues writing in JAMA Network Open.
Furthermore, of those who had experienced mistreatment, 18.8% reported career regret on the GQ.
Conversely, medical students who experienced a better environment more likely to:
Have lower exhaustion scores: for each 1-point increase on the Y2Q, there was a 0.05 reduction in exhaustion score Report lower disengagement scores on the GQ: for each 1-point increase on the Y2Q, there was a 0.04 reduction in disengagement score Further, reports of having positive interactions with faculty on the Y2Q were associated with higher empathy scores on the GQ. For each 1-point increase, there was a rise of 0.02 in empathy score. Positive student-to-student interactions were linked to having lower odds of career regret during the last year of medical school.
“The potential protective effect of positive experiences within the learning environment may provide insight into strengths that organizations can amplify to mitigate burnout, decline in empathy, and career choice regret among their students,” wrote Dyrbye and colleagues.
The team noted the opportunity for potential interventions. “Although the most effective approaches to addressing mistreatment of learners remain elusive, the frequency of mistreatment varies between educational programs, suggesting there are likely to be levers within the control of the organisation that adequate commitment, leadership, infrastructure, resources, and accountability can lead to a meaningful reduction in mistreatment.”
Average age of the respondents was 28 years, 52% were women, 72.8% were single, and 91% reported having no dependents. The study also found that older medical students reported higher disengagement scores, and that women reported lower exhaustion (by 0.27 points) and disengagement (by 0.47 points) scores on the GQ.
However, women and older medical students had higher empathy scores compared with their male peers (0.74 points and 0.05 points, respectively).
The researchers observed that conflicting findings on burnout among women in medicine have been reported. For example, a longitudinal cohort study of resident physicians across specialties in the US found that female residents were “more likely to develop burnout and have worsening in the severity of their emotional exhaustion between the second and third year of training compared with male residents, even after controlling for various forms of mistreatment.”
Limitations of their own study, the researchers noted, included unestablished differences between the exhaustion, disengagement, and empathy scale measures that were used in the questionnaires; and the varying response rates between questionnaires: 55.5% for the Y2Q and 81.5% for the GQ.
A US study showed that adults with atopic dermatitis (AD) had a higher burden of disease than those with other chronic diseases. Even mild dermatitis can negatively affect quality of life (QoL), increasing risk of anxiety, depression, and suicide.
Persistent itching and skin pain can disrupt sleep, leading to poor work or study performance. In moderate to severe disease, oozing, crusting lesions can lead to stigmatisation social isolation. More adults are affected than previously thought, with some 16.5 million adults in the US estimated to have AD.
In a study of 1278 patients using the US web-based Growth from Knowledge (GfK) panel, 60.1% had mild disease, 28.9% had moderate AD, and 11% had severe AD. Patients with more severe disease had higher scores on the dermatology life quality index and on the hospital anxiety and depression scale (HADS) when compared with controls.
This indicates “a worse impact on quality of life and an increased likelihood of anxiety or depression,” the researchers wrote in the Journal of Investigative Dermatology. “Our study confirms the high prevalence and disease burden of atopic dermatitis in this population.”
Quality of life threatened A pair of studies in patients from the GfK panel reinforce these findings. The first, with 602 patients, showed that AD carried a “profound” disease burden, based on a comparison of patient-oriented AD measures between patients with and without AD. Those with moderate and severe AD had lower mean mental health scores compared with those who had mild disease, and lower QoL compared with patients with other chronic disorders.
“We recommend that clinicians incorporate QoL assessments in clinical practice to determine disease burden, identify patients requiring step-up treatment of their skin disease, and potentially screen for patients with mental health disturbance,” wrote Jonathan I Silverberg, MD, PhD, MPH, of George Washington University, and colleagues in the Annals of Allergy, Asthma and Immunology.
A subsequent study in 2137 patients from the GfK Knowledge Panel found that 40% of patients with AD had a higher prevalence of anxiety or depression in the previous 12 months compared with 17.5% of adults without AD. The researchers concluded that anxiety and depression were driven primarily by disease severity, and were heavily underdiagnosed.
Breaking the ‘vicious cycle’ AD can be life-threatening in some patients, warned the authors of a systematic review and meta-analysis of AD studies. The combination of pruritus, visible skin lesions, social isolation, depression, and anxiety likely sets up a “vicious cycle,” according to the authors.
The investigators found a positive and significant association between AD in adulthood and depression, anxiety, and suicidal ideation, regardless of where the patients lived. And while only a few studies examined the risk of completed suicide, the majority showed a positive association, the authors said. A positive association between AD and depression in children was also identified.
They advised that “depression, anxiety, and suicidal ideation should be considered by doctors when treating patients with AD,” adding: “Because AD disease improvement appears to reduce these risks, this should be a priority.”
Better systemic and topical AD therapies are improving the QoL of patients. “It is important to recognise that improvement of AD often results in improvements in symptoms of depression and anxiety, as these mental health symptoms are caused or worsened by the AD,” Dr Silverberg told MedPage Today. “We already have data for dupilumab and the JAK inhibitors that show improvements of HADS scores and other patient-reported outcome measures of mental health.”
Robert Sidbury, MD, MPH, of the University of Washington School of Medicine in Seattle said, “relatively recent literature suggests screening for depression is particularly important for kids with AD, especially those with severe disease.”
AD affects children of all ages, including the very young, and more than 50% of children with AD are diagnosed by age 1 year, he noted.”Dupilumab has been the most effective new available therapy to date by far,” Dr Sidbury told MedPage Today. “Pipeline drugs, particularly the JAK inhibitors like upadacitinib show tremendous promise.”
Giving the means to quit smoking to patients with depression could save as many as 125 000 lives over the next 80 years, researchers estimate. This number could be as high as 203 000 if people with depression who are not yet in mental health care settings are included.
The study, led by the Yale School of Public Health, shows the potential benefits that smoking cessation could have in a population suffering disproportionately from tobacco-related disease and death. Smokers with depression already find it harder to quit, and experience more negative withdrawal symptoms if they do, including increased depression. The study is also the first to estimate the population health effects of integrating smoking cessation treatments with standard mental health care. Using more than a decade of data from the National Survey on Drug Use and Health, the researchers made a model to project the effectiveness of smoking-cessation treatments into the future. They assessed how the benefits varied based on different rates of treatment adoption over the next 80 years.
Simulating the health benefits reveals that, at least 32 000 deaths could be prevented by 2100 if a significant number of patients with depression adopted any kind of cessation treatment. Assuming 100% mental health service utilisation and pharmacological cessation treatment, the number of potential lives saved could rise to 203 000.
“We’ve known for a long time that people with depression smoke more than the general population, and that mental health care settings often don’t have cessation treatment as part of standard care. Our study asks: what is that missed opportunity? What do we have to gain when mental health care and smoking cessation treatment are fully integrated,” said lead author and assistant professor Jamie Tam, PhD. The findings are published in the American Journal of Preventive Medicine.
Such high benefits would be a best-case scenario, the researchers cautioned. Even so, the model’s results match public health experts’ long-standing predictions of the results of smoking-cessation treatment becoming a routine part of mental health care. The findings show that even less-optimal cessation treatments would greatly impact both quality and length of life for patients living with depression.
“Beyond reducing the risk of early death, smoking cessation improves quality of life and increases productivity,” Tam added. “Decision makers should remove barriers to mental health care and smoking cessation treatments for people with mental health conditions.”
The researchers concluded that while existing treatments, such as nicotine replacement therapy, varenicline, and bupropion, can raise cessation rates by nearly 60%, in the future there would be even larger health gains if there were better cessation treatments.
Employee wellbeing in healthcare is reflected in patient satisfaction, and a new study found that a heavy workload, even positive challenges such as learning new things are experienced as increased stress.
Researchers from the Department of Psychology at the University of Jyväskylä in Finland explored how the staff of a healthcare district experienced increasing job demands, and how wellbeing at work was linked to these demands. The study also clarified whether the demands on employees were reflected in patient satisfaction.
More than a thousand employees took part in the study and evaluated their experiences in a survey measuring intensified job demands, work exhaustion, and work engagement. Additionally, nearly a thousand patients of the healthcare district evaluated their treatment by the healthcare staff.
In line with expectations, healthcare staff’s experiences of greater time pressure and workload were associated with greater exhaustion. An especially high risk of exhaustion was seen in those working in emergency care and nurses.
Additionally, experience of increased job planning demands shared by the working community was associated with greater exhaustion and lower customer satisfaction. This was particularly evident in the staff of leadership services.
“A surprising observation was that none of the intensification demands was positively connected with work engagement,” said Senior Lecturer Mari Huhtala. “In the light of previous studies, employees may find some demands such as learning new things positive challenges, especially when the demands are reasonable. However, this was not the case with the studied healthcare employees. It is possible the general workload in healthcare has led to these positive challenges being experienced as additional stress as well.”
Research data for the study were collected using an electronic survey in the third quarter of 2019. The study will continue in the third quarter of 2021 with the collection of follow-up data.
Journal information: Huhtala, M., et al. (2021) Intensified job demands in healthcare and their consequences for employee well‐being and patient satisfaction: A multilevel approach. Journal of Advanced Nursing. doi.org/10.1111/jan.14861.
A team of researchers has found that workers using their smartphone to take short breaks do not find reductions in boredom or fatigue.
Smartphones have had an inescapable impact on society, and allow users to engage with a variety of apps. Anecdotal evidence also suggests that people use their phones in other ways as well, such as to alleviate boredom or to reduce stress. The researchers noted that many people use their smartphones to take short breaks from their work—and they wondered if doing so actually helped with boredom or reduced stress.
To find out, researchers at Radboud University’s Behavioural Science Institute in The Netherlands recruited 83 PhD candidates, each of whom were asked to report their level of boredom and fatigue every hour while they were working. They also received a smartphone app that logged its usage.
In comparing phone usage with self-reported levels of boredom and fatigue, the researchers were able to track the volunteers’ use of their phones to deal with boredom or fatigue. They found that not only did using their phones in such a manner not alleviate boredom or fatigue, in many cases it in fact made things worse. Volunteers who described themselves as more bored or more fatigued than others in the study did not take longer smartphone breaks than those feeling less bored or fatigued.
The researchers acknowledged that their study was small but their results suggest that workers might consider fatigue or boredom reducing alternatives. They noted also that some prior research has shown that boredom can sometimes be alleviated by engaging in activities that bring some degree of joy. They suggest that rather than mindlessly scrolling, they find ways to use their phones to bring them joy, such as by looking at pictures of loved ones.
Journal information: Jonas Dora et al, Fatigue, boredom and objectively measured smartphone use at work, Royal Society Open Science (2021). DOI: 10.1098/rsos.201915
In a new study, researchers have shown that a single dose of psilocybin, a psychedelic compound with potential applications for depression, prompted long-lasting increase in connections between neurons in mice.
For some people, psilocybin, an active compound in ‘magic mushrooms’, can produce a profound mystical experience. The psychedelic was a staple of religious ceremonies among indigenous populations of the Americas and is also a popular recreational drug. It has been the subject of some interest in treating depression. But exactly how it works in the brain and how long beneficial results might last is still unclear. “We not only saw a 10% increase in the number of neuronal connections, but also they were on average about 10% larger, so the connections were stronger as well,” reported senior author Alex Kwan, associate professor of psychiatry and of neuroscience at Yale.
Earlier work had found promising evidence that psilocybin, as well as the anaesthetic ketamine, could decrease depression. This new study found that these compounds increase the density of dendritic spines, which are small protrusions found on nerve cells which aid in the transmission of information between neurons. The number of these neuronal connections are known to be reduced by chronic stress and depression.
Prof Kwan and first author Ling-Xiao Shao, a postdoctoral associate, imaged dendritic spines in high resolution with a laser-scanning microscope, and tracked them for multiple days in living mice. They found increases in the number of dendritic spines and in their size within 24 hours of administration of psilocybin. These changes were still evident a month later. Also, mice subjected to stress showed behavioural improvements and increased neurotransmitter activity after being given psilocybin.
It may be the novel psychological effects of psilocybin itself that spurs the growth of neuronal connections, Kwan said.
“It was a real surprise to see such enduring changes from just one dose of psilocybin,” he said. “These new connections may be the structural changes the brain uses to store new experiences.”
Scientists have found that significant amounts of THC and CBD, the two main components of cannabis enter the embryonic brain of mice in utero and impair the mice’s ability as adults to respond to fluoxetine (Prozac).
The study suggests that when the developing brain is exposed to THC or CBD, normal interactions between endocannabinoid and serotonin signaling may be diminished as exposed individuals become adults.
“Hemp-derived CBD is a legal substance in the US, and we are in a time of increasing state-level legalisation of cannabis. Therefore, use of cannabis components have increased across most levels of society, including among pregnant women. The study marks the beginning of an effort to understand the effects of THC and CBD on the endogenous cannabinoid system (ECS) in the developing brain and body,” explained Hui-Chen Lu, director of the Linda and Jack Gill Center and professor in the Department of Psychological and Brain Sciences in the IU Bloomington College of Arts and Sciences.
Researchers studied four groups of pregnant mice. Some received daily moderate doses of either THC, CBD, or a combination of equal parts THC and CBD; a control group had placebo injections throughout pregnancy. Using mass spectrometry, IU psychological and brain sciences professor Heather Bradshaw tested embryos and found that CBD and THC both could cross the placenta and reach the embryonic brain.
“The surprising part is that maternal exposure to CBD alone — a drug that is often considered as safe and harmless and is a popular ‘natural’ therapy for morning sickness — resulted in a lasting impact on adult mice offspring,” Lu said. “Both prenatal THC and CBD exposure impaired the adult’s ability to respond to fluoxetine. The results suggest taking a cautious approach to using CBD during pregnancy.”
There is however some evidence for CBD’s effectiveness in treating chronic pain and anxiety, though currently the only FDA-approved indication for CBD is the treatment of severe seizure disorders.
“We still know very little about the effects of CBD on the developing brain,” Prof Lu said.
The new paper is one of the first studies to see the potential negative impact of CBD on the developing brain and later behaviours. However observational studies in the 1980s saw increased anxiety and depression in offspring of mothers who used the lower-strength cannabis available at the time. Since women may take cannabis products for nausea and vomiting, this has relevance for public health awareness.
Study co-author Ken Mackie, Gill Chair of Neuroscience at IU Bloomington, said researchers know that prenatal cannabis exposure may increase the risk for anxiety and depression, so it is important to evaluate the response to a class of drug used to treat anxiety and depression.
Though normal mouse behaviours were seen in many tests, one test — to determine their response to stress — had a strongly atypical result. In all groups, the mice responded normally to a stressful situation. As expected, fluoxetine increased stress resilience in mice whose mothers had received the placebo. However, the drug was ineffective in mice whose mothers had received THC, CBD or their combination.
Fluoxetine works by increasing the amount of serotonin available at brain synapses, an effect known to require the endocannabinoid system. This internal system of receptors, enzymes and molecules both mediates the effects of cannabis and plays a role in regulating various bodily systems, such as appetite, mood, stress and chronic pain.
To test if maternal exposure to THC and/or CBD impaired endocannabinoid signaling in the adult offspring, the researchers tested whether boosting the ECS with a drug would restore fluoxetine’s effectiveness. They found that the ECS boosting restored normal fluoxetine responses in mice that had received THC or CBD while their brains were developing.
Journal reference: de Sousa Maciel, I., et al. (2021) Perinatal CBD or THC Exposure Results in Lasting Resistance to Fluoxetine in the Forced Swim Test: Reversal by Fatty Acid Amide Hydrolase Inhibition. Cannabis and Cannabinoid Research. doi.org/10.1089/can.2021.0015.
Scientists have uncovered an unexpected link between a synapse protein that has been implicated in neuropsychiatric disorders and the endocannabinoid pathway.
These findings suggest a role for the endocannabinoid system in conditions including bipolar disorder, according to Peter Penzes, PhD, the Ruth and Evelyn Dunbar Professor of Psychiatry and Behavioral Sciences, professor of Physiology and Pharmacology, and senior author of the study.
“The endocannabinoid system could be disrupted in patients with bipolar disease, or it could be the opposite: medical marijuana could have therapeutic potential for these patients,” said Prof Penzes, who is also director of the Center for Autism and Neurodevelopment. “These are the questions that need to be answered.”
Cannabis mimics naturally occurring endocannabinoids in the brain, which is how it produces its effect in humans. Since the specific function of endocannabinoids is still not fully understood, the legalisation of marijuana in many US states has prompted more investigation into its biological pathways, Prof Penzes said. The endocannabinoid system is a widespread neuromodulatory system that plays important roles in central nervous system (CNS) development, synaptic plasticity, and the response to endogenous and environmental insults.
Endocannabinoids are produced by an enzyme known as diacylglycerol lipase alpha (DAGLA), which is concentrated in synapses. Endocannabinoids dampen synaptic strength, which is why marijuana has calming effects.
Prof Penzes and colleagues have previously studied ankyrin-G, another synapse protein which regulates transmission speed across synapses. Aberrant over- or under-expression of ankyrin-G has been associated with disorders such as bipolar disorder, schizophrenia and autism.
Studying mice with ankyrin-G genetically deleted, they made a surprising discovery: Ankyrin-G seemed to stabilise DAGLA at synapses, increasing the efficiency of DAGLA.
“It’s a delicate mechanism that regulates dendritic spine morphology,” said lead author Sehyoun Yoon, PhD, research assistant professor of Physiology.
These findings comport with another recent study, led by investigators at Icahn School of Medicine at Mount Sinai and published in Nature Genetics. The study showed that both DAGLA and ankyrin-G (ANK3) are risk genes for bipolar disorder in a genome analysis of over 40,000 patients.
“It’s almost like somebody who is leading a double life, Dr. Jekyll and Mr. Hyde,” Prof Penzes said. “Ankyrin-G has this entire separate function.”
The convergence of ankyrin-G with the endocannabinoid pathway opens up an entire new world of possibilities, both for investigating disease risk and possible therapies.
“Cannabis may contribute to increased risk for mental disorders, which has actually been shown in schizophrenia,” Prof Penzes said. “Conversely, cannabis could be beneficial in some brain disorders, which prompted trials of medical marijuana in patients with autism.”
Prof Penzes said in future he plans to examine the downstream effects of this biological pathway, both in normal subjects and in disease.
According to a new study from the University of Toronto, 63% of Canadians who suffer from migraine headaches are able to flourish, despite the painful condition.
“This research provides a very hopeful message for individuals struggling with migraines, their families and health professionals. The findings of our study have contributed to a major paradigm shift for me. There are important lessons to be learned from those who are flourishing,” said lead author Esme Fuller-Thomson, Professor at both the Factor-Inwentash Faculty of Social Work and the Department of Family & Community Medicine, University of Toronto.
Over the past decade, Prof Fuller-Thomson has published on negative mental health outcomes associated with migraines, including suicide attempts, anxiety disorders and depression.
Migraine is a complex, genetically influenced disorder characterised by episodes of moderate-to-severe headache, usually unilateral and associated with nausea and increased sensitivity to light and sound. A migraine headache is the seventh most disabling disorder in the world. However, there is little research investigating factors associated with mental health and well-being among sufferers.
The University of Toronto study investigated optimal mental health in a nationally representative sample of 2186 Canadian adults diagnosed with migraines. The data were drawn from Statistics Canada’s Canadian Community Health Survey-Mental Health. To be defined in excellent mental health, respondents had to achieve three things: 1) almost daily happiness or life satisfaction in the past month, 2) high levels of social and psychological well-being in the past month, and 3) freedom from generalised anxiety disorder and depressive disorders, suicidal thoughts and substance dependence for at least the preceding full year.
“We were so encouraged to learn that more than three in every five migraineurs were in excellent mental health and had very high levels of well-being,” said Prof Fuller-Thomson.
Those experiencing migraines who had at least one person they could confide in were four times more likely to be in excellent mental health than those without. Additionally, those using religious or spiritual beliefs to cope with everyday difficulties had 86% higher odds of excellent mental health than those who did not use spiritual coping. Poor physical health, functional limitations, and a history of depression were also found to inhibit excellent mental health among those with migraines.
“Health professionals who are treating individuals with migraines need to consider their patients’ physical health needs and possible social isolation in their treatment plans” said co-author Marta Sadkowski, a recent nursing graduate from the University of Toronto.
Journal reference: Fuller-Thomson, E & Sadkowski, M., (2021) Flourishing Despite Migraines: A Nationally Representative Portrait of Resilience and Mental Health among Canadians. Annals of Headache Medicine. doi.org/10.30756/ahmj.2021.05.02.
