Tag: 15/8/24

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Shingles Increases Risk of Cognitive Decline in Later Life

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The risk was higher for men who were carriers of a gene linked to dementia

Photo by Mari Lezhava on Unsplash

A new study led by investigators from Brigham and Women’s Hospital found that an episode of shingles is associated with about a 20 percent higher long-term risk of subjective cognitive decline. The study’s findings provide additional support for getting the shingles vaccine to decrease risk of developing shingles, according to the researchers. Their results are published in Alzheimer’s Research & Therapy.

“Our findings show long-term implications of shingles and highlight the importance of public health efforts to prevent and promote uptake of the shingles vaccine,” said corresponding author Sharon Curhan, MD, of the Channing Division for Network Medicine at Brigham and Women’s Hospital. “Given the growing number of Americans at risk for this painful and often disabling disease and the availability of a very effective vaccine, shingles vaccination could provide a valuable opportunity to reduce the burden of shingles and possibly reduce the burden of subsequent cognitive decline.”

Shingles, medically known as “herpes zoster,” is a viral infection that often causes a painful rash. Shingles is caused by the varicella zoster virus (VZV), the same virus that causes chickenpox. After a person has chickenpox, the virus stays in their body for the rest of their life. Most of the time, our immune system keeps the virus at bay. Years and even decades later, the virus may reactivate as shingles.

Almost all individuals in the US age 50 years and older have been infected with VZV and are therefore at risk for shingles. There’s a growing body of evidence that herpes viruses, including VZV, can influence cognitive decline. Subjective cognitive decline is an individual’s self-perceived experience of worsening or more frequent confusion or memory loss. It is a form of cognitive impairment and is one of the earliest noticeable symptoms of Alzheimer’s disease and related dementias.

Previous studies of shingles and dementia have been conflicting. Some research indicates that shingles increases the risk of dementia, while others indicate there’s no association or a negative association. In recent studies, the shingles vaccine was associated with a reduced risk of dementia.

To learn more about the link between shingles and cognitive decline, Curhan and her team used data from three large, well-characterized studies of men and women over long periods: The Nurses’ Health Study, the Nurses’ Health Study 2, and the Health Professionals Follow-Up Study. The study included 149,327 participants who completed health status surveys every two years, including questions about shingles episodes and cognitive decline. They compared those who had shingles with those who didn’t.

Curhan designed the study with first author Tian-Shin Yeh, formerly of the Harvard TH Chan School of Public Health. The researchers found that a history of shingles was significantly and independently associated with a higher risk – approximately 20% higher – of subjective cognitive decline in both women and men. That risk was higher among men who were carriers of the gene APOE4, which is linked to cognitive impairment and dementia. That same association wasn’t present in the women.

Researchers don’t know the mechanisms that link the virus to cognitive health, but there are several possible ways it may contribute to cognitive decline. There is growing evidence linking VZV to vascular disease, called VZV vasculopathy, in which the virus causes damage to blood vessels in the brain or body. Curhan’s group previously found that shingles was associated with higher long-term risk of stroke or heart disease.

Other mechanisms that may explain how the virus may lead to cognitive decline include causing inflammation in the brain, directly damaging the nerve and brain cells, and the activation of other herpesviruses.

The limitations of this research include that it was an observational study, information was based on self-report, and included a mostly white, highly educated population. In future studies, the researchers hope to learn more about preventing shingles and its complications.

“We’re evaluating to see if we can identify risk factors that could be modified to help reduce people’s risk of developing shingles,” Curhan said. “We also want to study whether the shingles vaccine can help reduce the risk of adverse health outcomes from shingles, such as cardiovascular disease and cognitive decline.” 

Source: Brigham and Women’s Hospital

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WHO Declares International Public Health Emergency over Mpox Outbreak

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Mpox (monkeypox) virus. Source: NIH

WHO Director-General Dr Tedros Adhanom Ghebreyesus has determined that the upsurge of mpox in the Democratic Republic of the Congo (DRC) and a growing number of countries in Africa constitutes a public health emergency of international concern (PHEIC) under the International Health Regulations (2005) (IHR).

Dr Tedros’s declaration came on the advice of an IHR Emergency Committee of independent experts who met earlier in the day to review data presented by experts from WHO and affected countries. The Committee informed the Director-General that it considers the upsurge of mpox to be a PHEIC, with potential to spread further across countries in Africa and possibly outside the continent.

The Director-General will share the report of the Committee’s meeting and, based on the advice of the Committee, issue temporary recommendations to countries.

In declaring the PHEIC, Dr Tedros said, “The emergence of a new clade of mpox, its rapid spread in eastern DRC, and the reporting of cases in several neighbouring countries are very worrying. On top of outbreaks of other mpox clades in DRC and other countries in Africa, it’s clear that a coordinated international response is needed to stop these outbreaks and save lives.”

WHO Regional Director for Africa Dr Matshidiso Moeti said, “Significant efforts are already underway in close collaboration with communities and governments, with our country teams working on the frontlines to help reinforce measures to curb mpox. With the growing spread of the virus, we’re scaling up further through coordinated international action to support countries bring the outbreaks to an end.”

Committee Chair Professor Dimie Ogoina said, “The current upsurge of mpox in parts of Africa, along with the spread of a new sexually transmissible strain of the monkeypox virus, is an emergency, not only for Africa, but for the entire globe. Mpox, originating in Africa, was neglected there, and later caused a global outbreak in 2022. It is time to act decisively to prevent history from repeating itself.”

This PHEIC determination is the second in two years relating to mpox. Caused by an Orthopoxvirus, mpox was first detected in humans in 1970, in the DRC. The disease is considered endemic to countries in central and west Africa.

In July 2022, the multi-country outbreak of mpox was declared a PHEIC as it spread rapidly via sexual contact across a range of countries where the virus had not been seen before. That PHEIC was declared over in May 2023 after there had been a sustained decline in global cases.

Mpox has been reported in the DRC for more than a decade, and the number of cases reported each year has increased steadily over that period. Last year, reported cases increased significantly, and already the number of cases reported so far this year has exceeded last year’s total, with more than 15 600 cases and 537 deaths.

The emergence last year and rapid spread of a new virus strain in DRC, clade 1b, which appears to be spreading mainly through sexual networks, and its detection in countries neighbouring the DRC is especially concerning, and one of the main reasons for the declaration of the PHEIC.

In the past month, over 100 laboratory-confirmed cases of clade 1b have been reported in four countries neighbouring the DRC that have not reported mpox before: Burundi, Kenya, Rwanda and Uganda. Experts believe the true number of cases to be higher as a large proportion of clinically compatible cases have not been tested.

Several outbreaks of different clades of mpox have occurred in different countries, with different modes of transmission and different levels of risk.

The two vaccines currently in use for mpox are recommended by WHO’s Strategic Advisory Group of Experts on Immunization, and are also approved by WHO-listed national regulatory authorities, as well as by individual countries including Nigeria and the DRC.

Last week, the Director-General triggered the process for Emergency Use Listing for mpox vaccines, which will accelerate vaccine access for lower-income countries which have not yet issued their own national regulatory approval. Emergency Use Listing also enables partners including Gavi and UNICEF to procure vaccines for distribution.

WHO is working with countries and vaccine manufacturers on potential vaccine donations, and coordinating with partners through the interim Medical Countermeasures Network to facilitate equitable access to vaccines, therapeutics, diagnostics and other tools.

WHO anticipates an immediate funding requirement of an initial US$ 15 million to support surveillance, preparedness and response activities. A needs assessment is being undertaken across the three levels of the Organization.

To allow for an immediate scale up, WHO has released US$ 1.45 million from the WHO Contingency Fund for Emergencies and may need to release more in the coming days. The Organization appeals to donors to fund the full extent of needs of the mpox response.

Source: WHO

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Sanofi Commits to Affordable Insulin Pens for Diabetic Patients

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Novolog insulin pen. Photo by Dennis Klicker on Unsplash

Over the past few years, there has been a notable shift towards the use of insulin pens in the public sector, replacing traditional vials. This transition has been driven by the advantages insulin pens offer, including improved dosing accuracy, ease of use for patients, greater convenience, and better adherence to treatment.1

The move to basal insulin is in line with the National Strategic Plan for the Prevention and Control of Non-Communicable Diseases 2022-2027, which outlines specific targets for managing diabetes. This plan aims to improve early detection and treatment of diabetes by ensuring that 90% of people over 18 know their blood pressure and blood sugar levels. It also aims for 60% of those with high levels to receive treatment, and 50% of those treated to have their levels under control. These measures are designed to improve the management and outcomes of diabetes in the population.2

Since May 2023, the Department of Health has faced insulin pen rationing as the previous sole supplier opted not to tender. Nearly 50% of the insulin required for patients was expected to come in pen sets. To mitigate the impact, the health department has sourced a limited supply of insulin pens and analogues for vulnerable groups like the elderly, young children, and visually impaired individuals, despite the higher cost of insulin analogues, which offer more convenient and effective blood sugar management.3

In 2021, long-acting analogue insulins were added to the WHO Model List of Essential Medicines (EML) and have significantly reduced aligning with those of human insulin.3 Recognising this need, Sanofi has adjusted the price of its basal insulin to the cost of human insulin in South Africa.

Sanofi has been engaging with the National Department of Health to meet the needs of vulnerable patient groups,” says Dr Asafika Mbangata, Medical Advisor for Diabetes and Established Products, Sanofi. “A circular has been released by the department, identifying patient groups that would benefit from analogue insulins. This includes vulnerable groups like the elderly, young children, and visually impaired individuals. Sanofi is committed to ensuring that patients have access to treatment which will help control the disease by achieving adequate glycaemic control and eventually, prevention of complications in South Africa.”

Long-acting insulin analogues offer significant clinical benefits over human insulin, including prolonged duration of action,4 more stable glucose control with less hypoglycaemia, and reduced need for multiple daily doses.5 These benefits are particularly crucial for patients experiencing dangerously low blood glucose levels with human insulin.5 In addition, reductions in HbA1c (a key blood sugar indicator) are greater with all basal insulin analogues compared to human basal insulins.6

Diabetes Type 1

It’s estimated that more than 31 000 people in South Africa live with Type 1 diabetes and require full insulin replacement therapy, with multiple daily injections. Among them, 5000 are children.7

“Insulin pens, which are more accurate, user-friendly, and associated with less pain when used with short and fine needles, significantly enhance their quality of life,” says Dr. Mbangata. “This is particularly important for children, who are more likely to adhere to their treatment schedules with the easier-to-use and less painful pens.”

Diabetes Type 2

According to the International Diabetes Federation (IDF), 4.2 million South African adults are living with diabetes, primarily type 2.7 Of these, 84% access diabetes care in the public sector. Diabetes is the second leading cause of death in South Africa, following tuberculosis, and the leading cause of death among females.8

More than 9% of the South African population is 60 or older.9 Around 600 000 elderly individuals are living with diabetes, with approximately 500 000 of them accessing public sector healthcare.10

Treating diabetes in the elderly often requires a multidrug regimen, including insulin therapy. However, due to comorbidities such as dementia, vision loss, neuropathies, poor mobility, and manual dexterity issues, elderly patients are at increased risk of hypoglycaemia and dosing errors associated with insulin administration. Insulin pen devices have been shown to provide more reliable, accurate, and simplified dosing, making them a safer and more acceptable method of insulin delivery for the elderly population.11

Impaired vision

Diabetic retinopathy (impaired vision) is the third most common cause of blindness in South Africa, following cataracts and glaucoma​​.12 A pilot project screening for diabetic retinopathy in primary care at three Cape Town community healthcare centres assessed 400 patients living with diabetes. Over 80% had significantly reduced visual acuity, and 63% had retinopathy.12 These visually impaired patients would greatly benefit from using insulin pens, which make a clicking sound when the dial is turned, indicating the dose.

“Against the backdrop of these statistics, Sanofi continues in its efforts to make insulin pens more affordable and accessible, and our aim is to improve the quality of life and healthcare outcomes for South Africa’s diabetic population,” says Prudence Selani, External Affairs Head, Sanofi.

References

  1. Diabetes Spectr 2012;25(2):117–122
  2. Health Policy Watch. New WHO Essential Medicines List Includes Controversial Insulin Analogues. Available from: https://healthpolicy-watch.news/who-essential-medicines-insulin-analogues/
  3. Brunetti VC et al. Diabetes ObesMetab. 2022;1–13
  4. Sims EK et al. Nat Med. 2021;27:1154-64
  5. MannucciE et al. Endocrine. 2021;74:508-17
  6. IDF Diabetes Atlas 10th edition 2021
  7. Report-03-08-012018 (www.statssa.gov.za)
  8. StatsSA report: Marginalised Groups Series VI: The Social Profile of Older Persons, 2017–2021
  9. Werfalli M, Kassanjee R, Kalula S, Kowal P, Phaswana-Mafuya N, Levitt NS. Diabetes in South African older adults: prevalence and impact on quality of life and functional disability – as assessed using SAGE Wave 1 data. Glob Health Action. 2018;11(1):1449924. doi: 10.1080/16549716.2018.1449924. PMID: 29699475; PMCID: PMC5933282.
  10. Wright BM, Bellone JM, McCoy EK. A review of insulin pen devices and use in the elderly diabetic population. Clin Med Insights Endocrinol Diabetes. 2010;3:53-63. doi: 10.4137/CMED.S5534. Epub 2010 Nov 22. PMID: 22879787; PMCID: PMC3411523.
  11. Bertram MY, Jaswal AV, Van Wyk VP, Levitt NS, Hofman KJ. The non-fatal disease burden caused by type 2 diabetes in South Africa, 2009. Glob Health Action 2013;6:12944. [http://dx.doi.org/10.3402/gha.v6i0.19244]
  12. Cairncross JP, Steinberg WJ, Labuschagne MJ. Prevalence of eye pathology in a group of diabetic patients at National District Hospital Outpatient Department in Bloemfontein, South Africa. Afr J Prim Health Care Fam Med. 2017 Sep 27;9(1):e1-e7. doi: 10.4102/phcfm.v9i1.1440. PMID: 29041796; PMCID: PMC5645559.
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The Ageing Process Makes Big Jumps in Our 40s and 60s

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Photo by LOGAN WEAVER | @LGNWVR on Unsplash

If it’s ever felt like everything in your body is breaking down at once, that might not be your imagination. A new Stanford Medicine study shows that many of our molecules and microorganisms dramatically rise or fall in number during our 40s and 60s.

Researchers assessed many thousands of different molecules in people from age 25 to 75, as well as their microbiomes – the bacteria, viruses and fungi that live inside us and on our skin – and found that the abundance of most molecules and microbes do not shift in a gradual, chronological fashion. Rather, we undergo two periods of rapid change during our life span, averaging around age 44 and age 60. A paper describing these findings was published in the journal Nature Aging.

“We’re not just changing gradually over time; there are some really dramatic changes,” said Michael Snyder, PhD, professor of genetics and the study’s senior author. “It turns out the mid-40s is a time of dramatic change, as is the early 60s. And that’s true no matter what class of molecules you look at.”

Xiaotao Shen, PhD, a former Stanford Medicine postdoctoral scholar, was the first author of the study. Shen is now an assistant professor at Nanyang Technological University Singapore.

These big changes likely impact our health – the number of molecules related to cardiovascular disease showed significant changes at both time points, and those related to immune function changed in people in their early 60s.

Abrupt changes in number

Snyder, the Stanford W. Ascherman, MD, FACS Professor in Genetics, and his colleagues were inspired to look at the rate of molecular and microbial shifts by the observation that the risk of developing many age-linked diseases does not rise incrementally along with years. For example, risks for Alzheimer’s disease and cardiovascular disease rise sharply in older age, compared with a gradual increase in risk for those under 60.

The researchers used data from 108 people they’ve been following to better understand the biology of aging. Past insights from this same group of study volunteers include the discovery of four distinct “ageotypes,” showing that people’s kidneys, livers, metabolism and immune system age at different rates in different people.

The new study analysed participants who donated blood and other biological samples every few months over the span of several years; the scientists tracked many different kinds of molecules in these samples, including RNA, proteins and metabolites, as well as shifts in the participants’ microbiomes. The researchers tracked age-related changes in more than 135 000 different molecules and microbes, for a total of nearly 250 billion distinct data points.

They found that thousands of molecules and microbes undergo shifts in their abundance, either increasing or decreasing – around 81% of all the molecules they studied showed non-linear fluctuations in number, meaning that they changed more at certain ages than other times. When they looked for clusters of molecules with the largest changes in amount, they found these transformations occurred the most in two time periods: when people were in their mid-40s, and when they were in their early 60s.

Although much research has focused on how different molecules increase or decrease as we age and how biological age may differ from chronological age, very few have looked at the rate of biological aging. That so many dramatic changes happen in the early 60s is perhaps not surprising, Snyder said, as many age-related disease risks and other age-related phenomena are known to increase at that point in life.

The large cluster of changes in the mid-40s was somewhat surprising to the scientists. At first, they assumed that menopause or perimenopause was driving large changes in the women in their study, skewing the whole group. But when they broke out the study group by sex, they found the shift was happening in men in their mid-40s, too.

“This suggests that while menopause or perimenopause may contribute to the changes observed in women in their mid-40s, there are likely other, more significant factors influencing these changes in both men and women. Identifying and studying these factors should be a priority for future research,” Shen said.

Changes may influence health and disease risk

In people in their 40s, significant changes were seen in the number of molecules related to alcohol, caffeine and lipid metabolism; cardiovascular disease; and skin and muscle. In those in their 60s, changes were related to carbohydrate and caffeine metabolism, immune regulation, kidney function, cardiovascular disease, and skin and muscle.

It’s possible some of these changes could be tied to lifestyle or behavioural factors that cluster at these age groups, rather than being driven by biological factors, Snyder said. For example, dysfunction in alcohol metabolism could result from an uptick in alcohol consumption in people’s mid-40s, often a stressful period of life.

The team plans to explore the drivers of these clusters of change. But whatever their causes, the existence of these clusters points to the need for people to pay attention to their health, especially in their 40s and 60s, the researchers said. That could look like increasing exercise to protect your heart and maintain muscle mass at both ages or decreasing alcohol consumption in your 40s as your ability to metabolise alcohol slows.

“I’m a big believer that we should try to adjust our lifestyles while we’re still healthy,” Snyder said.

Source: Stanford Medicine

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New, Inexpensive Medical Computers that Run on Air

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Closeup of the pneumatic logic sensing device. (William Grover/UCR)

Medical engineers have developed a new, air-powered computer sets off alarms when certain medical devices fail. The invention is a more reliable and lower-cost way to help prevent blood clots and strokes – all without electronic sensors. 

Described in a paper in the journal Device, the computer not only runs on air, but also uses air to issue warnings. It immediately blows a whistle when it detects a problem with the lifesaving compression machine it is designed to monitor.

Intermittent pneumatic compression (IPC) devices are pneumatic leg sleeves that periodically squeeze a patient’s legs to increase blood flow. This prevents clots that lead to blocked blood vessels, strokes, or death. Typically, these machines are powered and monitored by electronics.

“IPC devices can save lives, but all the electronics in them make them expensive. So, we wanted to develop a pneumatic device that gets rid of some of the electronics, to make these devices cheaper and safer,” said William Grover, associate professor of bioengineering at UC Riverside and corresponding paper author.

Pneumatics move compressed air from place to place. Emergency brakes on freight trains operate this way, as do bicycle pumps, tire pressure gauges, respirators, and IPC devices. It made sense to Grover and his colleagues to use one pneumatic logic device to control another and make it safer.

This type of device operates in a similar way to electronic circuits, by making parity bit calculations. “Let’s say I want to send a message in ones and zeroes, like 1-0-1, three bits,” Grover said. “Decades ago, people realized they could send these three bits with one additional piece of information to make sure the recipient got the right message.” 

That extra piece of information is called a parity bit. The bit is a number – 1 if the message contains an odd number of ones, and 0 if the message contains an even number of ones. Should the number one appear at the end of a message with an even number of bits, then it is clear the message was flawed. Many electronic computers send messages this way. 

An air-powered computer uses differences in air pressure flowing through 21 tiny valves to count the number of ones and zeroes. If no error in counting has occurred, then the whistle doesn’t blow. 

If it does blow, that’s a sign the machine requires repairs. Grover and his students, in a video demonstrating the air computer, are shown damaging an IPC device with a knife, rendering it unusable. Seconds later, the whistle blows.

“This device is about the size of a box of matches. It replaces a handful of sensors as well as a computer,” Grover said. “So, we can reduce costs while still detecting problems in a device. And it could also be used in high humidity or high temperature environments that aren’t ideal for electronics.”

The IPC device monitoring is only one application for air computing. For his next project, Grover would like to design a device that could eliminate the need for a job that kills people every year: moving around grain at the top of tall silos. 

Tall buildings full of corn or wheat, grain silos are a common sight in the Midwest. Often times, a human has to go inside with a shovel to break up the grains and even out the piles inside. 

“A remarkable number of deaths occur because the grain shifts and the person gets trapped. A robot could do this job instead of a person. However, these silos are explosive, and a single electric spark could blow a silo apart, so an electronic robot may not be the best choice,” Grover said. “I want to make an air-powered robot that could work in this explosive environment, not generate any sparks, and take humans out of danger.” 

Air-powered computing is an idea that has been around for at least a century. People used to make air-powered pianos that could play music from punched rolls of paper. After the rise of modern computing, engineers lost interest in pneumatic circuits.

“Once a new technology becomes dominant, we lose awareness of other solutions to problems,” Grover said. “One thing I like about this research is that it can show the world that there are situations today when 100-plus-year-old ideas can still be useful.”

Source: University of California Riverside