A recent analysis of published research found that more than half (59%) of cancer survivors and patients experience at least a moderate level of fear of cancer recurrence and that about one in five (19%) have a high level of fear. The findings, published in Psycho-Oncology, show women and younger people in particular have more fear of recurrence.
Cancer prevalence is increasing due to ageing populations, and more people are surviving cancer thanks to improved treatments. Managing fear of cancer recurrence (FCR) has been reported as one of the most important unmet needs for this growing group. FCR is defined as “fear, worry, or concern relating to the possibility that cancer will come back or progress”. Low levels of FCR can be helpful by promoting treatment compliance and healthy lifestyle adaptations. However, at clinical levels, FCR can limit quality of life and daily functioning and require professional help. Four features have been defined as key characteristics of clinical FCR: “(a) high levels of preoccupation; (b) high levels of worry; (c) that are persistent; and (d) hypervigilance to bodily symptoms”. It is important to address FCR, because FCR may also lead to increased healthcare costs14 and for most patients, it does not decrease over time without intervention.
The analysis, which is included 46 studies from 13 countries. Investigators found similar fear of cancer recurrence rates in survivors and patients. On average, younger people and women experienced more fear of cancer recurrence.
Additional research is needed to not only identify which patients desire support to address their fear of cancer recurrence but also to determine how to tailor interventions to different levels of fear and to individual needs and preferences.
“Knowing the prevalence and severity of fear of cancer recurrence for the general cancer population and for different subgroups is an important development, because it is essential for shaping healthcare provision, policy, and research on fear of cancer recurrence,” said lead author Yvonne Luigjes-Huizer, a PhD candidate at the Helen Dowling Institute and the University Medical Centre Utrecht, in the Netherlands.
Patient takes steps with the help of an assistant. Credit: Jmmy Ravier & NeuroRestore
A woman bedridden for over a year due to a debilitating neurodegenerative disease was able to get up and walk again, thanks to an innovative electrical stimulation system which was able to raise her blood pressure on standing and prevent her fainting. The system was developed by a team headed by Professors Jocelyne Bloch and Grégoire Courtine, and was detailed in The New England Journal of Medicine.
Their system includes electronics implanted directly on the spinal cord to reactivate the neurons that regulate blood pressure, thereby preventing the patient from losing consciousness every time she’s in an upright position. This type of implant was already in use for the treatment of low blood pressure in tetraplegic patients.
The female patient in the study suffers frommultiple system atrophy-parkinsonian type (MSA-P), a neurodegenerative disease that afflicts several parts of the nervous system, including the sympathetic nervous system.
MSA-P leads to the loss of sympathetic neurons regulating blood pressure, which results in orthostatic hypotension, a dramatic blood pressure drop when patients are in an upright position, which in some cases results in fainting. This increases fall risks, limits mobility, and can eventually shorten life expectancy. Having to remain in a reclined position to avoid passing out severely impacts patients’ quality of life.
The implant consists of a set of electrodes connected to an electrical-impulse generator typically used to treat chronic pain. After implanting their device directly on the patient’s spinal cord, the researchers found an improvement in the body’s capacity to regulate blood pressure, enabling the patient to remain conscious for longer periods in an upright position and to begin physical therapy to walk again. After being bedridden for 18 months, the patient is now able to walk as far as 250 metres.
For Jocelyne Bloch, this marks an important step toward the treatment of degenerative diseases: “We’ve already seen how this type of therapy can be applied to patients with a spinal-cord injury. But now, we can explore applications in treating deficiencies resulting from neurodegeneration. This is the first time we’ve been able to improve blood-pressure regulation in people suffering from MSA.”
Grégoire Courtine added that “this technology was initially intended for pain relief, not for this kind of application. Going forward, we and our company Onward Medical plan to develop a system targeted specifically to orthostatic hypotension that can help people around the world struggling with this disorder.”
A Danish cohort study published in Brain shows that people with epilepsy live 10-12 years fewer than those without the condition, with a slightly greater reduction for men than women. The study researchers also found that excess mortality is particularly pronounced among people with epilepsy and mental disorders.
One of the most frequently occurring neurological diseases, epilepsy affects 50 million people worldwide, and is known to increase the risk of early death by three times.
“The significantly reduced life expectancy is found both in people who develop epilepsy as a result of an underlying condition, such as brain cancer or stroke, and in those who develop epilepsy without an obvious underlying cause,” explained Julie Werenberg Dreier, one of the researchers behind the study.
The average reduction in life expectancy was 12 years for men with epilepsy and 11 years for women. Among people with epilepsy and mental disorders life expectancy was on average reduced by up to 16 years.
“We discovered that the reduced life expectancy for people with epilepsy was related to a wide range of causes of death which don’t just include the neurological, but also cardiovascular diseases, psychiatric disorders, alcohol related conditions, accidents and suicide,” said Jakob Christensen, one of the researchers behind the study.
Researchers used Danish healthcare register to follow almost six million Danes, including more than 130 000 people with epilepsy.
“The large study has enabled detailed analyses of a range of different causes of death and, for the first time, we’ve been able to estimate the number of years lost due to individual causes of death in people with epilepsy. This is important information as it can be used to target preventive efforts in order to reduce the mortality gap that we currently see in people with epilepsy,” said Julie Werenberg Dreier.
The mortality rate among people with epilepsy is due to a wide range of different conditions that cut across virtually all medical specialities, the researchers said. There is therefore a need for a collective effort to reduce mortality.
“The alarming results provide important knowledge for all healthcare professionals who, in one way or another, come into contact with people with epilepsy — also when prioritising and allocating resources in the healthcare system. The results clearly show how serious a disease epilepsy can be, and the findings of the study should be used in the prioritisation and planning of preventive measures,” said Jakob Christensen, emphasising that the results confirm the tendencies that have been shown in a few smaller studies which have estimated reduction in life expectancy in people with epilepsy.
“The study should be followed up by additional research, for example into the questions of how medical treatment and recurring seizures affect life expectancy.”
In a study on obese mice fed a high-fat diet, receiving prednisone once weekly improved their exercise endurance and strength, and their reduced weight. The study was published in the Journal of Experimental Medicine. A previous study had found that weekly prednisone was helpful in muscular dystrophy.
“These studies were done in mice. However, if these same pathways hold true in humans, then once-weekly prednisone could benefit obesity,” explained senior author Dr Elizabeth McNally.
“Daily prednisone is known to promote obesity and even metabolic syndrome – a disorder with elevated blood lipids and blood sugar and weight gain,” Dr McNally said. “So, these results, in which we intermittently ‘pulse’ the animals with once-weekly prednisone, are strikingly different. Obesity is a major problem, and the idea that once-weekly prednisone could promote nutrient uptake into muscle might be an approach to treating obesity.”
The once-weekly prednisone, a glucocorticoid steroid, promoted nutrient uptake into the muscles. The researchers also found these mice had increased adiponectin levels, an adipocyte-secreted hormone involved in protecting against diabetes and insulin resistance. Mice that were already obese from eating a high-fat diet were also found to benefit after once-weekly prednisone, experiencing increased strength, running capacity and lower blood glucose.
Most knowledge on steroids like prednisone is derived from studies of daily doses of prednisone
“We see a very different outcome when it is taken once a week,” Dr McNally said. “We need to fine tune dosing to figure out the right amount to make this work in humans, but knowing adiponectin might be one marker could provide a hint at determining what the right human dose is.”
Dr McNally described the weekly dose as “a bolus, or spike, of nutrients going into your muscle.”
“We think there is something special about promoting this spike of nutrients into muscle intermittently, and that it may be an efficient way to improve lean body mass,” she added.
“What is exciting to me about this work is the finding that a simple change in the dosing frequency can transform glucocorticoid drugs from inducers to preventers of obesity,” said corresponding author Mattia Quattrocelli. “Chronic once-daily intake of these drugs is known to promote obesity. Here we show that dosing the same type of drug intermittently – in this case, once weekly – reverses this effect, promotes muscle metabolism and energy expenditure, and curtails the metabolic stress induced by a fat-rich diet.”
Many patients take prednisone daily for different immune conditions, which has side effects including weight gain and even muscle atrophy with weakness. Investigators want to determine whether patients can get the same immune benefit with intermittent prednisone dosing, which could be much more beneficial to the muscle.
Dr McNally’s team previously found that intermittent prednisone administration was helpful for muscular dystrophy, showing once weekly prednisone improved strength, recently reporting that a pilot trial in humans with muscular dystrophy in which one weekly dose of prednisone improved lean mass.
McNally wants to identify biomarkers most critical to measure a beneficial response to prednisone.
“If we can determine how to choose the right dose of prednisone that minimises atrophy factors and maximises positive markers like adiponectin, then we can really personalise the dosing of prednisone,” she said.
The group also recently showed that weekly prednisone uses strikingly different molecular pathways to strengthening the muscle in male versus female mice, based on a new study just published in the Journal of Clinical Investigation by Isabella Salamone, a graduate student in Dr McNally’s lab.
The benefits of weekly prednisone are linked to circadian rhythms, according to another new study published in Science Advances. Human cortisol and steroid levels spike early in the morning before awakening.
“If you don’t give the drug at the right time of day, you don’t get the response,” Quattrocelli said. “In mice, we obtained good effects with intermittent prednisone in muscle mass and function when we dose them at the beginning of their daytime. Mice have a circadian rhythm inverted to us, as they generally sleep during the daytime and are active at night. This could mean that the optimal dosing time for humans during the day could be in the late afternoon/early evening, but this needs to be appropriately tested.”
Conducting these studies in mice is a major limitation, Dr McNally said.
“While we are encouraged by the pilot study in humans with muscular dystrophy, mouse muscles have more fast-twitch fibres than humans, and slow-twitch muscle could be different,” Dr McNally said. “More studies are needed to try to better understand whether these same mechanisms work in human muscles.”
A randomised controlled trial showed that people with heart failure receiving an annual flu shot had lower rates of pneumonia and hospitalisation on a year-round basis and a reduction in major cardiovascular events during peak flu season – but not year-round.
The study, presented at the American College of Cardiology’s 71st Annual Scientific Session, is the first randomised controlled trial to assess the benefits of the flu vaccine in people with heart failure, who face a high risk of cardiovascular events. It was conducted in countries across Asia, Africa and the Middle East where getting a flu shot is not commonplace.
Lead author Mark Loeb, MD, said: “Although our prespecified endpoints were not significant, our data suggest that there’s a clinical benefit [to getting a flu shot] given the clear reduction in pneumonia, moderate reduction in hospitalisation and reduction in vascular events and deaths during periods of peak influenza. When taken together with previous trials and observational studies, the collective data demonstrate there is a substantial benefit to receiving a flu vaccine for people with heart failure.”
Heart failure is a condition in which the heart becomes too weak or stiff to pump blood effectively. Previous studies have shown that people with heart disease or cardiovascular risk factors face an elevated risk of complications when they contract influenza, but there has been a lack of evidence on whether flu vaccines can help to mitigate this risk specifically in people with heart failure.
The trial enrolled 5129 patients with heart failure in 10 countries where flu vaccines are not common. Participants did not routinely get flu shots and had previously received a flu shot no more than once during the three years preceding the trial. Participants were randomised to receive a flu shot or a placebo annually for up to three years, though they could still get a flu shot outside of the trial. Researchers tracked health outcomes for a median of 2.9 years. The trial’s primary endpoint was a composite of death from cardiovascular causes, non-fatal heart attack or non-fatal stroke. Its co-primary endpoint included a composite of any of these events plus hospitalisation for heart failure.
Overall, the composite primary endpoint occurred in 691 participants and 1470 experienced the composite co-primary endpoint. When analysed on a year-round basis there was no significant difference in the rates of these events between those who had received a flu vaccine and those who had not.
Separate analyses of hospitalisation, pneumonia and other respiratory outcomes however found that rates of pneumonia were 42% lower and hospitalisations were down 15% among those who received a flu shot.
The flu vaccine arm showed a significant reduction in the first primary endpoint, as well as reductions in all-cause death and cardiovascular death, when the analysis was limited to periods of peak influenza circulation. When influenza circulation was low, no significant difference was seen.
The researchers accounted for the differences in influenza circulation seasons. Based on these results, researchers said the flu vaccine did help to protect patients from influenza complications, including cardiovascular events.
“Many of the effects we found during peak flu circulation disappeared outside of it,” Dr Loeb said. “There’s no biological explanation for that other than influenza infections.”
While the study was conducted in countries where the flu vaccine is either not widely available or not common to receive, Dr Loeb said the results could likely be generalisable even in countries where flu vaccine uptake is higher. Study participants were allowed to get a flu vaccine outside of the study, but Dr Loeb said that there was no impact on the findings as very few did so. He added that the study was stopped early in four countries due to the COVID pandemic.
Loeb said that additional trials and large-scale observational studies could further clarify the health benefits of influenza vaccination in people with cardiovascular disease.
“I think this study offers an important message about vaccines generally – that it is important to do randomised controlled trials in populations that historically haven’t had a very high uptake of vaccines,” Dr Loeb said. “These types of [research] gaps have to be filled.”
