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New focused ultrasound effective for treating Parkinson’s – study

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In a new study researchers show that a new focused ultrasound treatment improved dyskinesia and motor impairment in patients with Parkinson’s disease.

Parkinson’s disease is a common neurological disorder characterised by the loss of dopamine neurons in the brain. Patients with Parkinson’s disease can be effectively treated with medications such as levodopa. 

However, some patients develop dyskinesia – involuntary movements – and motor impairment. Dyskinesia is an involuntary movement of any region of the body that can occur with long-term use of levodopa. 

At the same time, motor impairment is characterised by the return of debilitating Parkinsonian symptoms as medication effectiveness declines.

The new research, published in the New England Journal of Medicine, is co-authored by Vibhor Krishna, MD, associate professor of neurosurgery at the UNC School of Medicine.

“Focused ultrasound is an exciting new treatment for patients with certain neurological disorders,” said Krishna, who also is vice chair of inpatient operations in the UNC Department of Neurosurgery. 

“The procedure is incisionless, eliminating the risks associated with surgery. Using focused ultrasound, we can target a specific area of the brain and safely ablate the diseased tissue.”

Patients who receive focused ultrasound treatment can go home the same day after surgery. This treatment was FDA-approved for patients with essential tremor in 2016, and now this pivotal trial has led to FDA-approval of focused ultrasound ablation to treat dyskinesia and motor impairment in Parkinson’ disease.

“Almost twice as many patients achieved improved motor function or reduced dyskinesia in the focused ultrasound group than those who underwent a sham procedure,” Krishna said. 

“In addition, we observed that 75 per cent of patients in the focused ultrasound group maintained their results for up to one year after the treatment.”

For this pivotal trial, the researchers randomly assigned 94 Parkinson’s disease patients with dyskinesias or motor impairment to undergo either focused ultrasound ablation or a “sham” procedure. 

The primary outcome was a response to therapy at three months, defined as a decrease of at least three points from baseline either in the score on the Movement Disorders Society–Unified Parkinson’s Disease Rating Scale, part III (off medication state), or in the score on the Unified Dyskinesia Rating Scale (on medication state). 

Secondary outcomes included changes from baseline to month three in the scores on various parts of the Movement Disorders Society–Unified Parkinson’s Disease Rating Scale.

Sixty-nine patients were assigned to undergo ultrasound ablation, and 25 underwent the sham (control) procedure. In the focused ultrasound group, 65 patients completed the primary-outcome assessment, while 22 in the control group completed the study. In the focused ultrasound group, 45 patients (69 per cent) had a response, as compared with seven (32 per cent) in the control group.

The adverse effects related to ablation of the globus pallidus were infrequent and included speech difficulty, visual disturbance, and gait difficulty – in one patient each. There was one serious adverse event documented one week after the treatment in one patient.

Krishna added: “Our research aims to optimise focused ultrasound treatment to minimise risks and maximise improvements,” 

“We observed that clinical outcomes after focused ultrasound ablation can be site-specific. Specifically, we observed two distinct hotspots in the globus pallidus that correlated with improvements in dyskinesia and motor impairment respectively. 

“In the future, we aim to investigate whether these findings can lead to a personalised approach to treating Parkinson’s disease with focused ultrasound.”

 

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Sitting still for long periods increases mortality risk, says study

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Sitting for long hours without breaks can increase risk mortality risk in older women, a new study shows.

The research, published in the Journal of the American Heart Association (JAHA), has data showing that older women who sat for 11.7 hours or more per day increased their risk of death by 30 percent, regardless of whether they exercised vigorously.

The study examined measurements of sitting and daily activity collected from hip devices worn for up to seven days by 6,489 women, aged 63 to 99, who were followed for eight years for mortality outcomes.

This data was collected  as part of a long-term national project known as the Women’s Health Initiative (WHI), which began in 1991 and is ongoing, led by Andrea LaCroix, Ph.D., M.P.H., Distinguished Professor at the Herbert Wertheim School of Public Health.

The paper is the first to apply a novel and validated machine-learned algorithm called CHAP to examine total sitting time and length of sitting bouts in relation to the risk of death.

Study co-author Steve Nguyen, PhD., M.P.H., a postdoctoral fellow at the University of California San Diego Herbert Wertheim School of Public Health and Human Longevity Science, said: “Sedentary behaviour is defined as any waking behaviour involving sitting or reclining with low energy expenditure.

“Previous techniques for calculating sedentary behaviour used cut points that identified low or absent movement. The CHAP algorithm was developed using machine-learning, a type of artificial intelligence, that enhanced its ability to accurately distinguish between standing and sitting.”

Fine-tuning “sitting” enabled Nguyen to parse total sitting time and usual sitting bout durations.

Sedentary behaviour is a health risk because it reduces muscle contractions, blood flow and glucose metabolism.

Exercise cannot undo these negative effects, according to the study, whether women participated in low or high amounts of moderate-to-vigorous intensity physical activity, they showed the same heightened risk if they sat for long hours.

LaCroix explained: “When you’re sitting, the blood flow throughout your body slows down, decreasing glucose uptake. Your muscles aren’t contracting as much, so anything that requires oxygen consumption to move the muscles diminishes, and your pulse rate is low.

“If I take a brisk long walk for an hour but sit the rest of the day, I’m still accruing all the negative effects on my metabolism.”

Based on the research, LaCroix makes the following recommendation: “The risk starts climbing when you’re sitting about 11 hours per day, combined with the longer you sit in a single session. For example, sitting more than 30 minutes at a time is associated with higher risk than sitting only 10 minutes at a time. Most people aren’t going to get up six times an hour, but maybe people could get up once an hour, or every 20 minutes or so. They don’t have to go anywhere, they can just stand for a little while.”

However, Nguyen points out that not all sitting is the same.

“Looking beyond conditions like cardiovascular disease, we start thinking about cognitive outcomes, including dementia,” he said.

“There are cognitively stimulating activities that can result in sedentary behavior, like sitting while studying a new language. Is sedentary behavior in that context overall bad for a person? I think it’s hard to say.” Nguyen has recently received a National Institute of General Medical Sciences K99 award for 12 months of mentored research to look at protein signatures of physical activity and how they relate to dementia.

LaCroix added: “We’ve created this world in which it’s so fascinating to sit and do things. You can be engrossed by TV or scroll on your Instagram for hours. But sitting all the time isn’t the way we were meant to be as humans, and we could reverse all of that culturally just by not being so attracted to all the things that we do while sitting.”

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High risk of hospital readmission after surgery among older Americans

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A study finds an increased risk of hospital readmission for older Americans within 180 days of undergoing major surgery — a risk that is particularly acute for individuals who are frail or have dementia.

The findings from researchers at the University of Yale, were published in the journal JAMA Network Open.

Previous research by the same team demonstrated that major surgery is a common event for older Americans and also demonstrated a heightened mortality risk within one year of major surgery for people who are age 65 and older.

The new study is the first to describe both the short-term risk (within 30 days) and longer-term risk (within 180 days) of hospital readmission for older Americans who have recently had major surgery.

The study looked at hospital readmission among a nationally representative sample of 1,477 older Americans, not living in nursing homes, who had at least one major surgery between 2011 and 2018. More than one in four (27.6 per cent) had a readmission to the hospital within 180 days after major surgery; nearly one in eight (11.6 per cent) were readmitted within just 30 days.

Dr. Robert D. Becher, associate professor of surgery at Yale School of Medicine and co-senior author of the study, commented: “Prior to now, data on longer-term readmissions after major surgery in older persons have been lacking. This is problematic, as older persons undergoing major surgery represent a large and growing population.

“These readmission rates are high. And this study adds to our understanding of what it means to recover from major surgery as an older person.”

The numbers are even higher for those with geriatric-specific conditions such as frailty and dementia. Frail patients were readmitted within 180 days at a rate of 36.9 per cent; patients with probable dementia were readmitted at a rate of 39 per cent; and patients 90 years old and older were readmitted at a rate of 36.8 per cent.

Dr. Thomas M. Gill, the Humana Foundation Professor of Geriatric Medicine at Yale and co-senior author of the study, said: “These findings reenforce the importance of enhanced preoperative recognition of frailty and dementia in older persons and may inform patient and family expectations — and surgical decision making — about postoperative trajectories in the setting of these geriatric conditions.”

The issue of hospital readmission looms large in the USS health care system for a variety of reasons.

In 2018 alone, readmission costs totalled more than $50 billion, the researchers said. This was driven, in part, by the nearly 3.8 million 30-day hospital readmissions that year. The vast majority of those patients are Medicare beneficiaries aged 65 and older.

“From a patient perspective, the most important outcome among older persons with multiple conditions is maintaining independence and function. And we know that being readmitted to the hospital after major surgery can negatively impact that independence and function,” Becher said.

“So these new data put into perspective just how common hospital readmissions, and their negative downstream consequences, are to older persons.”

The researchers said the next steps in their examination of the issue will be to further understand why vulnerable older persons have such high readmission rates and suggest meaningful ways to minimise the risk of readmission.

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Risk factors for frailty in old age different in men and women, finds study

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A study conducted by researchers at the Federal University of São Carlos (UFSCar) in Brazil and University College London (UCL), found the factors that increase the risk of frailty in old age to be different in men and women.

The study, which was funded by FAPESP, is published in the journal Archives of Gerontology and Geriatrics.

According to the results, osteoporosis, low weight, heart disease, and poor hearing increased the risk of frailty in men, while a high level of fibrinogen (a marker of cardiovascular disease) in the blood, diabetes and stroke were associated with a higher risk of frailty in women.

The findings were based on an analysis of data from 1,747 participants in the English Longitudinal Study of Ageing (ELSA), an ongoing population survey that explores the dynamic relationships between health, functioning, social networks and economic status in people aged 50 and over who reside in England. ELSA began in 2002. These participants were interviewed and assessed every four years between 2004 and 2016.

The researchers selected participants aged 60 or more who initially did not have frailty syndrome and were not classified as pre-frailty (with only one or two of the above factors).

Frailty syndrome is characterised by the presence of three or more of the following factors: involuntary weight loss, fatigue, muscle weakness, slow gait, and a low level of physical activity. It is more common in women than men, partly because of women’s greater life expectancy.

Tiago da Silva Alexandre, last author of the article and a professor in UFSCar’s Department of Gerontology, explained: “Frailty syndrome serves as a warning sign of the possibility of a negative outcome in an older person. We used to think of frailty as having a single pathway in the elderly, but our study shows there are several routes. The differences between men and women in this regard are important for policymakers to take into account. They should influence primary health care and could result in more gender-specific action plans and intervention for older people.”

Frailty syndrome has a phenotype, he explained – a set of easily identifiable signs and symptoms designed to identify older people with a heightened risk of falls, hospitalisations, incapacitation, and early death.

“Our study went back a few steps before this process begins to find out which characteristics may lead to frailty during the lives of these older people. When we think about aging and the quality of life in old age, it’s very important to identify the main risk factors so as to be able to foresee problems and formulate public policy for men and women,” he added.

According to Dayane Capra de Oliveira, first author of the article, although frailty as a tool is based on biology, sex-related differences in risk factors for development of the syndrome are mainly associated with the different social roles of men and women, and with their different degrees of access to resources during their lives.

“Another key aspect is that frailty is a multifactorial condition. While socioeconomic factors, skeletal muscle disorders, heart disease and low weight appear to underlie frailty in men, in women the process appears to be driven mainly by cardiovascular and neuroendocrine disturbances,” Oliveira said.

Differences and similarities

According to the researchers, while some risk factors for frailty are the same for men and women – including old age, low educational attainment, sedentarism and depression, for example – differences in body composition and fat deposition throughout life and especially in old age may lead directly or indirectly to the appearance of components of frailty, such as metabolic alterations that culminate in the development of diseases, which in turn increase the risk of frailty.

Alexandre said: “Our study is based on data for people now aged 60 or more and living in England. We don’t know how these sex-based differences will play out in future generations. However, the fact is that the men in the cohort we studied were more exposed to several kinds of working conditions considered risk factors for diseases. Their diet was less healthy. They didn’t go to the doctor as much as the women [so that there was less early diagnosis]. They drank more and were more exposed to other substances that increased the risk of cardiovascular disease and heart attack.”

Women are more affected by chronic diseases, which are not as lethal but can be incapacitating.

He added: “The sex-based differences are a lifelong backdrop and culminate in different ageing processes, different causes of death or disability, and different kinds of frailty in men and women.”

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