This Is A Very Interesting Theory Which Needs To Be Urgently Assessed As To Its Veracity!

This appeared last week:

New line of defence against dementia could lie in this routine vaccine

It makes sense to include routine adult vaccinations to our list of preventative measures, not only for prevention of common infections, but also for dementia prevention.

Magdalena Simonis

13 April, 2025

It makes sense to include routine adult vaccinations to our list of preventative measures, not only for prevention of common infections, but also for dementia prevention.

We are living at a time when the ageing population is increasing in size, and with age, comes a growing risk of all forms of dementia. Consequently, we are seeing the incidence of dementia double globally every 20 years. The condition puts a terrible burden on the sufferers, their families and caregivers, and most eventually require costly government support over many years.

In our efforts to understand what causes dementia and how to prevent it, observational studies have explored modifiable factors which include blood pressure, diabetes, lipid profile, heart disease, hearing, along with lifestyle, diet, exercise, social engagement, mental health, smoking, alcohol intake, and even geographic location, to name a few. These factors were found to impact the onset across different types of dementia, but what was also found was that having a combination of routine adult vaccinations seemed to be associated with a 35 per cent decrease in risk in all forms of dementia. This was an unexpected finding. In other words, we now know that we can influence the development of vascular dementia and even the expression of Alzheimer’s disease a fair bit through how we choose to live our life and how we treat our bodies over the course of time. Having your regular flu vaccine can also reduce your risk, and having the shingles vaccine reduces this risk even further.

Key points

• A 35 per cent decrease in all types of dementia is seen in people having a combination of routine adult vaccinations (influenza and shingles in particular)
• The shingles vaccination may prevent or delay dementia in up to twenty per cent of older people
• By 2030, the global population aged 65 and older is projected to surpass the youth population
• 1 in 12 people aged 65 and over are living with dementia in Australia

Shingles vaccine and dementia prevention

The shingles vaccination may prevent or delay dementia in up to 20 per cent of older people according to a study recently published in Nature journal. The Standford University researchers followed nearly 300,000 people in Wales over seven years and compared the outcomes of those who received the single-dose shingles vaccine with those who did not and found that the risk of developing dementia was significantly lower in the vaccinated group.

Although the shingles vaccine associated with this finding is the now discontinued single-dose Zostavax vaccine, it is assumed that the positive effect on dementia prevention is more likely due to the prevention of shingles, rather than the vaccine type itself.

Shingles is a painful rash-like reactivation to the chickenpox virus, also known as herpes zoster. It lies dormant in the nervous system following initial exposure, which usually occurs in childhood, and is part of the herpes virus family which includes the common cold sore virus (HVS1) and genital herpes (HSV2), glandular fever or Epstein Barr Virus (EBV), and Cytomegalovirus (CMV).

We have known for decades that there is a link between herpes viruses and dementia from as far back as 1975, and given current statistics are that one in three Australians will develop shingles at some stage, widespread vaccination of the older population could have a significant impact on the burden of dementia overall.

Just as this study showed, most prior studies that demonstrated the protective effect of the shingles vaccine were conducted on the live attenuated vaccine called Zostavax, which has since been discontinued due to its shorter length of efficacy and the risk of serious side-effects in immunocompromised people, such as people who take immunosuppressants for auto-immune disease, or those who are having treatment for cancer such as chemotherapy and radiation therapy. They also happen to be the people who need protection the most, and for longer periods.

Fortunately, we can now recommend the new recombinant shingles vaccine (no live particles), called Shingrix which is delivered in two doses, two to six months apart which is also freely available to anyone 65 in Australia. This newer recombinant version provides longer protection for up to 10 years.

For unknown reasons, the shingles vaccine appears to show a higher level of protection against dementia in women, but it protects men as well. This could just be because women generally mount a stronger immune system to vaccines due to biological sex differences. Either way, it makes sense to have a vaccine that can protect you from an awful disease which causes post-herpetic neuralgia (nerve pain) in up to 20 per cent of people, and which can linger in the form of electric shock-like pain for weeks, months and sometimes years, long after the rash resolves.

Influenza vaccinations and dementia prevention

Research has found that ‘people with more full vaccination types and more annual influenza vaccinations are less likely to develop dementia’. Picture: Getty Images

A large metanalysis of 9124 papers that were published in 2022 isolated 17 high-quality studies that compared the risk of dementia in those vaccinated against influenza virus versus unvaccinated populations, and found that the reduction in risk was as high as 49 per cent in those who had at least four annual influenza vaccinations.

The researchers then reviewed the other studies, looking at other vaccinations, and the findings were that there was a decreased incidence of dementia in people who receive routine adult vaccinations, with up to 35 per cent overall reduction, regardless of the type of dementia. This was equal across women and men.

The protective effect is cumulative and greater with those who have their annual influenza vaccinations, in other words, “people with more full vaccination types and more annual influenza vaccinations were less likely to develop dementia”.

The metanalysis included close to 1.8 million people from across the US, China, Israel, UK and Canada, and although there appears to be a stronger cumulative protective element with annual influenza vaccinations, they looked for any similar association with other vaccinations from the other remaining studies and found this is also evident in those with herpes zoster (shingles), tetanus and diphtheria and pertussis (Tdap), pneumonia, hepatitis A, hepatitis B, and polio vaccines, in declining order of impact. The exact mechanism of this is not well understood as there are numerous other risk factors for dementia. However, these findings are very exciting.

How do vaccines protect you from dementia?

The mechanism by which vaccines protect people from developing dementia is unclear, and there is no simple answer. With respect to Alzheimer’s disease, it is thought that the observed delay in expression of Alzheimer’s in vaccinated people is due to a combination of infection prevention, diminishing the severity of inflammation of the brain, and it is suggested that vaccines may even help the immune system remove amyloid plaques from the brain.

What about Covid-19 infection and RSV?

Covid-19 is an ongoing concern in the community, and we know that there is an association between Covid-19 infection and cognitive decline but this does not seem to be statistically higher than with other viral infections. Importantly, having the Covid-19 vaccine was not associated with an increased risk of developing Alzheimer’s disease. Respiratory syncytial virus has recently received a lot of attention with the introduction of a new vaccine, which has fortunately been approved for infants, children and pregnant women. The vaccine is also recommended for people over 75 years, and at 60 years for First Nations people and those who have other diseases or are immunocompromised. In older people, inflammation of the brain from RSV can cause acute confusion, and its connection with dementia is being investigated.

A new RSV vaccine has been approved for infants, children and pregnant women.

Vaccines are arguably the greatest medical invention of all time and despite what vaccine sceptics say, there are long-term benefits of being vaccinated, even in later life, so make it part of your annual overall health screens. From what the science is telling us, it is part of dementia prevention.

The current vaccinations recommended include:

• Influenza vaccine
• Covid-19 vaccine
• Pneumococcal vaccine
• Shingles vaccine
• Pertussis, tetanus, diphtheria vaccine (Tdap)
• RSV vaccine.

Magdalena Simonis is a GP, RACGP Red Book reviewer and clinical associate professor in the department of general practice, University of Melbourne.

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This column is published for information purposes only. It is not intended to be used as medical advice and should not be relied on as a substitute for independent professional advice about your personal health or a medical condition from your doctor or other qualified health professional.

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References:

• A natural experiment on the effect of herpes zoster vaccination on dementia
• Reduced dementia incidence after varicella zoster vaccination in Wales 2013–2020
• The recombinant shingles vaccine is associated with lower risk of dementia
• A potential association between COVID-19 vaccination and development of Alzheimer’s disease
• National Immunisation Guidelines
• Libíková H, Pogády J, Wiedermann V, Breier S. Search for herpetic antibodies in the cerebrospinal fluid in senile dementia and mental retardation. Acta Virologica. 1975 Nov; 19(6): 493-495. PMID: 1996.
• Wu X, Yang H, He S, Xia T, Chen D, Zhou Y, Liu J, Liu M, Sun Z. Adult Vaccination as a Protective Factor for Dementia: A Meta-Analysis and Systematic Review of Population-Based Observational Studies. Front Immunol. 2022 May 3;13:872542. doi: 10.3389/fimmu.2022.872542. PMID: 35592323; PMCID: PMC9110786.
• Pyne JD, Brickman AM. The Impact of the COVID-19 Pandemic on Dementia Risk: Potential Pathways to Cognitive Decline. Neurodegener Dis. 2021;21 (1-2): 1-23. doi: 10.1159/000518581. Epub 2021 Jul 28. PMID: 34348321; PMCID: PMC8678181.
• Libikova, H., Pogady, J., Wiedermann, V., & Breier, S. (1975). Search for herpetic antibodies in the cerebrospinal fluid in senile dementia and mental retardation. Acta virologica, 19(6), 493-495.

Here is the link:

https://www.theaustralian.com.au/health/medical/new-line-of-defence-against-dementia-could-lie-in-this-routine-vaccine/news-story/f4e197d2d861a8759f387e698628f82d

This would have to be a very good reason to get every vaccination going!

Will be interesting to see if it is confirmed over time!

David.

There Is A Rising Risk We Are About To Enter A Global Economic Recession.

This appeared a few days ago:

• The Wall Street Journal

World takes urgent steps to prepare for trade war downturn

Jason Douglas

13 April, 2025

Countries around the world are taking major steps to prop up their economies and prepare for a possible severe downturn as the US and China keep raising the stakes in an escalating global trade war.

Central banks are cutting interest rates, with India, New Zealand and the Philippines leading the way this week, and more expected to follow in the coming days. South Korea’s government has announced a multibillion-dollar package of emergency-support measures for the country’s auto sector, including subsidies for carmakers.

Several countries, including Australia, Spain and Canada are urging consumers to buy more locally, swapping imported foods and home furnishings for homegrown alternatives to support domestic companies facing tough times.

Canada is even planning to take funds raised through new duties it has imposed on the US to help pay auto workers affected by US tariffs.

The steps come as the US and China keep matching one another in a tit-for-tat battle to see who can inflict the most pain. In the latest move, China said it would raise its tariff on US goods to 125 per cent to match an earlier escalation by the White House, adding that it wouldn’t raise levies further and that any more American increases would be seen around the world as a “joke.”

President Trump rolled back a major portion of his tariff plan just hours after it went into effect, following a week of turbulence in the stock and bond markets. WSJ’s Gavin Bade explains how it unfolded and what happens next.

China is also stepping up support for its factories as US tariffs threaten to squeeze growth and hammer its exports. E-commerce company JD.com said it would purchase some $US27 billion ($about $43.2bn) of goods from Chinese firms in the coming year to help them shift purchases to Chinese consumers.

The People’s Bank of China has let China’s currency, the yuan, weaken against the dollar, aiding exports, while the government in Beijing is widely expected to borrow and spend more to counteract the drag from slowing trade. China “is not afraid of any unjust suppression,” its leader, Xi Jinping, said Friday.

The moves show how worries of a severe global economic downturn are intensifying. Financial market turmoil has added to the strain: The Bank of England postponed a planned sale of UK government bonds from its asset-purchase portfolio Thursday, blaming market volatility in bond markets ignited by a sell-off in US Treasurys.

The global economy is now widely expected to slow as tariffs begin to bite, and could even tip into recession if the brawl between the US and China intensifies or Trump revisits his plan for “reciprocal” tariffs on US trading partners. Economists at Capital Economics said in a report Friday that global growth could sink to 2.2 per cent in 2025, well short of the 2.5 per cent threshold that commonly signifies a global recession.

“Much hangs on the extent to which countries are able to do deals with the US to negotiate tariffs lower,” they said.

President Trump on Wednesday announced a 90-day pause on sweeping tariffs on imports unveiled on his self-proclaimed “Liberation Day” tariff bonanza on April 2. But a 10 per cent baseline tariff on virtually all imports arriving in the US has gone into effect as planned, and Trump has also raised tariff rates on cars, steel and aluminium.

Chinese imports, meanwhile, now face tariffs of around 145 per cent, according to the White House, after rounds of retaliation between Washington and Beijing pushed levies higher. In addition to raising its own tariffs, China is also targeting US companies and curbing access to rare-earth minerals.

More than 70 countries are engaged in high-speed efforts to negotiate ad hoc deals with Washington before the July deadline on higher reciprocal tariffs, The Wall Street Journal reported. Countries such as Vietnam have floated the ideas of buying more liquefied natural gas and agricultural products from the US, or lowering tariffs and dismantling regulatory barriers to imports in the hopes of avoiding higher duties that could crush their economies.

But with the outcome of negotiations still unclear, and some tariffs already in effect, governments are also looking for ways to stabilise their economies. Measures include targeted support for industries affected by tariffs as well as policy moves aimed at shoring up growth if trade and financial market disruptions worsen.

South Korea’s $US2 billion package, approved Tuesday, includes cheap loans, tax breaks and subsidies for carmakers, a key export sector. The government said it would also temporarily lower taxes on new-car purchases in South Korea and increase subsidies for electric-vehicle manufacturers to support auto sales at home.

In Spain, Prime Minister Pedro Sánchez in early April rolled out a government aid package to industry worth about $US16 billion to reduce the impact of Trump’s tariffs, including loans for companies, help for carmakers and funding for a buy-local campaign. Portugal’s development bank expanded trade credit and insurance aid to help exporters find new markets.

“Global trade is being transformed so we must go further and faster in reshaping our economy,” said UK Prime Minister Keir Starmer on April 6, announcing plans to give automakers some breathing room on environmental goals to help them manage tariffs. More help is on the way for other sectors, he said.

Canada has levied a 25 per cent counter tariff on roughly 67,000 US-made cars in retaliation for the 25 per cent levy the US imposed on foreign vehicles. Ottawa estimates it will collect roughly $US5.7 billion from the tariff, which it will use to pay auto workers and auto parts companies affected by the US tariff.

Canadian Prime Minister Mark Carney, currently campaigning in a federal election slated for April 28, has made it easier for laid-off workers to apply for employment insurance, deferred tax payments to corporations and asked Canada’s business development bank to lend more capital to companies in tariffed industries.

Carney warned this week that the risk of recession in the US has escalated, which will force the government to step in to help Canadians mitigate the economic fallout. His election rival, Conservative leader Pierre Poilievre, has also pledged financial support for workers in tariff-exposed sectors, and said he would also use the funds to cut taxes.

The European Central Bank meets Thursday and is expected to cut its key rate by a quarter-percentage point to help insulate the eurozone economy from tariffs. The Bank of England isn’t meeting until May, but is also expected to cut rates by a quarter point then. Partly reflecting a big rally in the Swiss franc as a result of trade and financial market gyrations, Switzerland’s central bank is now widely expected to cut rates to zero at its next meeting in June.

Reserve Bank of India Gov. Sanjay Malhotra, in a statement accompanying the central bank’s rate-cut decision Wednesday, said that as well as weaker exports, the uncertainty generated by trade frictions risks sapping investment and consumer spending, hurting overall economic growth.

The Reserve Bank of New Zealand was equally blunt: “Increases in global trade barriers weaken the outlook for global economic activity,” its rate-setting panel said, as it too, cut interest rates.

Indian officials are concerned that goods shut out from US markets could end up in India, undermining local producers. Piyush Goyal, India’s trade minister, in a speech on Monday urged Indian businesses to practice “economic nationalism” and favour domestic suppliers over tempting cheaper imports, highlighting another way governments are hoping their economies can weather the trade storm.

Dow Jones Newswires

Here is the link:

https://www.theaustralian.com.au/business/the-wall-street-journal/world-takes-urgent-steps-to-prepare-for-trade-war-downturn/news-story/626ef0c2729110ea5da1e46e0f6d07be

There is little doubt that the risk of an economic slowdown triggered by a worsening tariff war between the US and China is rising, and there is little doubt we will all be victims if that comes to reality. We must all hope this does not happen and do what we can to increase the diversity of our international trade and to ameliorate the level of risk.

Sadly I suspect we may all be the casualty of the global economic dance/war between the US and China and worryingly there is little we (essentially small Australia) can do about it!

We must all just “keep calm and carry-on”, and watch how things play out!

David.

AusHealthIT Poll Number 789 – Results – 13 April 2025.

Here are the results of the recent poll.

Are You Concerned About The Current Global Financial Instability Being Instigated By Donald Trump?

Yes                                                                19 (95%)

No                                                                   1 (5%)

I Have No Idea                                               1 (5%)

Total No. Of Votes: 20

It seems many are worried about how Trump is making the world more unsafe!

Any insights on the poll are welcome, as a comment, as usual!

Very poor voter turnout. 

1 of 20 who answered the poll admitted to not being sure about the answer to the question!

Again, many, many thanks to all those who voted! 

David.

This Has To Be The Closest To Immortality I Have Seen!

This appeared last week:

The Observer History

‘Peering into the eyes of the past’: reconstruction reveals face of woman who lived before Trojan war

Digital technology reveals ‘incredibly modern’ royal who lived 3,500 years ago in kingdom associated with Helen of Troy

Dalya Alberge

Sat 5 Apr 2025 21.35 AEDT

She lived around 3,500 years ago – but facial reconstruction technology has brought a woman from late bronze age Mycenae back to life.

The woman was in her mid-30s when she was buried in a royal cemetery between the 16th and 17th centuries BC. The site was uncovered in the 1950s on the Greek mainland at Mycenae, the legendary seat of Homer’s King Agamemnon.

Dr Emily Hauser, the historian who commissioned the digital reconstruction, told the Observer: “She’s incredibly modern. She took my breath away.

“For the first time, we are looking into the face of a woman from a kingdom associated with Helen of Troy – Helen’s sister, Clytemnestra, was queen of Mycenae in legend – and from where the poet Homer imagined the Greeks of the Trojan war setting out. Such digital reconstructions persuade us that these were real people.”

Hauser, a senior lecturer in classics and ancient history at the University of Exeter, said: “It is incredibly exciting to think that, for the first time since she was laid beneath the ground over 3,500 years ago, we are able to gaze into the actual face of a bronze age royal woman – and it truly is a face to launch a thousand ships.

“This woman died around the beginning of the late bronze age, several hundred years before the supposed date of the Trojan war.”

A digital artist, Juanjo Ortega G., has developed the lifelike face from a clay reconstruction of the same woman that was made in the 1980s by Manchester University, pioneers of one of the major methods in facial reconstruction.

Hauser, whose book Mythica: A New History of Homer’s World, Through the Women Written Out of It will be published next week, said that technical developments in forensic anthropology and DNA analysis, as well as radiocarbon dating and 3D digital printing, have led to dramatic improvements in reconstructions of the ancient world.

“We can – for the first time – peer back into the eyes of the past.”

The woman had been buried with an electrum face mask and a warrior kit of weapons – including three swords that were assumed to be associated with the man buried next to her, but are now thought to have belonged to her.

Hauser said: “The traditional story is that, if you have a woman next to a man, she must be his wife.” Facial similarities had previously been noted, but DNA has confirmed that these were brother and sister rather than husband and wife.

“This woman was buried there by virtue of her birth, not her marriage. That tells us a different story about how important she was … Data that is coming out is suggesting that far more of what archaeologists call warrior kits are associated with women than with men in these late bronze age burials, which is completely overturning our assumptions of how women are associated with war.”

She added that archaeological evidence and DNA analysis were allowing “the real women of ancient history to step out of the shadows”.

The condition of the woman’s bones suggests that she suffered from arthritis in her vertebrae and hands, perhaps “evidence of repeated weaving, a common and physically wearing activity among women, and one which we have seen Helen undertaking in the Iliad,” Hauser said.

“So this is such a wonderful way to connect real women’s experiences to the ancient myths and tales.”

Here is the link:

https://www.theguardian.com/education/2025/apr/05/peering-into-the-eyes-of-the-past-reconstruction-reveals-face-of-woman-who-lived-before-trojan-war

All I can say it is astonishing to have a face from so long ago that we believe is a real representation of how this young woman actually looked!

David.

If It Is Proven Really Effective And Safe, This Could Be Very Good News For Many With Acute Pain!

 This appeared last week:

The Observer Science

Painkillers without the addiction? The new wave of non-opioid pain relief

Pharma firms are developing drugs that avoid the brain’s opioid receptors to minimise the risks of dependence and overdoses, but not all experts are convinced

Ayisha Sharma

Sat 5 Apr 2025 23.00 AEDT

In January, the US Food and Drug Administration (FDA) approved the first new type of painkiller in more than two decades. The decision roused excitement across the healthcare sector for a key reason: the drug, which is called suzetrigine and sold under the brand name Journavx, is not an opioid.

Opioid painkillers such as oxycodone and morphine are still used to treat severe pain in the UK and US. But they come with an obvious downside: the risk of addiction.

Between 1999 and 2017, the number of overdose deaths in the US involving prescription opioids soared almost 400% from 3,442 to 17,029, according to the National Institute on Drug Abuse. In England and Wales the number of cases where opiates were mentioned on a death certificate rose from 1,332 in 1999 to 2,551 in 2023, according to the Office for National Statistics.

Pharma companies have been trying to develop safer painkillers since the start of the US opioid crisis. But these efforts have proven notoriously difficult, with a less than 1% chance that a novel pain drug will advance from phase 1 clinical trials to FDA approval.

One reason for this is that pain is not a purely physical phenomenon, but is also influenced by psychological factors.

The success of Journavx marks a welcome break from a long history of setbacks, but experts say it is just one piece of the puzzle. For starters, the medicine is only available for certain types of short-term pain, but there are many other kinds of pain that still need new treatments.

Further, the science behind some of those other types of pain is not clear, which makes designing treatments for them challenging. And pain relief is itself a rewarding experience. So opioid or not, is there even such a thing as a non-addictive painkiller?

What is pain?

When you think of pain, you might picture someone stubbing their toe. This type of pain – when something damages bodily tissue – is called nociceptive pain. Sensory neurons at the site of damage called nociceptors get activated, says Grégory Scherrer, associate professor at the University of North Carolina’s department of cell biology and physiology. The nociceptors send signals to the spinal cord, where other neurons process them.

Next, the signals travel through complex pathways into several parts of the brain. One of those parts, the cortex, is responsible for processing sensory information, says Anthony Dickenson, emeritus professor of neuroscience, physiology and pharmacology at University College London (UCL). It is only once this processing occurs that we “feel” the signal as pain.

A second type of pain – called neuropathic pain – happens as a result of damage to or disease of the nervous system outside the brain and spinal cord, Dickenson says. Damaged or defective neurons fire off signals that go through the same process. One example is diabetic peripheral neuropathy, where high blood sugar damages blood vessels that transport blood to the nerves, resulting in nerve damage and, potentially, death in the extremities.

One person could have a little wear and tear in their knees and feel significant pain, while another person with even more damage could feel no pain

In general, then, pain perception involves two systems. This first is a network of nerves running through the limbs, organs and other tissues, also known as the peripheral nervous system. Then there is the central nervous system, made up of the brain and spinal cord.

A third type of pain is less well understood. Nociplastic pain involves no obvious damage to tissues or neurons, but is thought to be driven by a problem with how the central nervous system processes signals. “Relatively normal stimuli produce pain when they shouldn’t,” Dickenson says. A key example is fibromyalgia, a disorder that mostly affects women.

Some researchers believe nociplastic pain is simply a more subtle form of nociceptive or neuropathic pain where the tissue or nerve damage is harder to detect, says Jeffrey Mogil, professor at McGill University’s department of psychology in Montreal.

In a medical setting, pain is treated according to how long it lasts, says Amanda Williams, professor of clinical health psychology at UCL. Pain that lasts for three months or less – after an injury or operation, for example – is generally classed as acute, while pain that lasts longer than three months is often considered chronic.

The amount of pain a person feels does not always correlate with physical signs of damage, Williams says. For instance, one person could have a little wear and tear in their knees and feel significant pain, while another person with even more damage could feel no pain.

Is pain relief addictive?

Regardless of the type and length, people are wired to dislike pain. Besides the cortex, pain signals also travel to another part of the brain called the limbic system, which is responsible for processing emotions, Dickenson says.

This triggers the feelings of fear, anxiety and depression that often accompany pain. Pain signals also switch off the release of dopamine, a neurotransmitter associated with feelings of reward, Dickenson adds. Relief from pain is “absolutely rewarding” in and of itself, says Mark Hutchinson, professor at the University of Adelaide’s school of biomedicine.

But there are many experiences that are rewarding without being addictive, from eating to seeing friends, Williams says. The “switch point”, at which a reward becomes an addiction, is defined by detriment to a person’s broader health and wellbeing, according to Hutchinson. Opioid painkillers can flip this switch because of how they work.

The resulting dopamine dump creates a feeling of reward or pleasure that can be over and above the inherently rewarding nature of pain relief

Opioids interrupt pain signalling by binding to and activating inhibitory opioid receptors in the brain and spinal cord. These receptors form part of the body’s endogenous opioid system, which helps regulate pain and mood. But one of the receptors – the μ-opioid receptor – can increase dopamine signalling between certain parts of the brain when activated.

The resulting dopamine dump creates a feeling of reward or pleasure that can be over and above the inherently rewarding nature of pain relief. The body can also build a tolerance to opioids over time, meaning that higher doses of the drugs may be required to experience the same feeling of pain relief or reward. This creates the basis for addiction.

But there are lots of painkillers that do not operate on the reward system, such as paracetamol and ibuprofen, says Christopher Eccleston, professor of psychology at the University of Bath. “Is pain relief always going to be addictive? I think the answer is no.”

What are the alternatives to opioids?

Journavx was developed by Vertex Pharmaceuticals and belongs to a class of drugs that block voltage-gated sodium channels (VGSCs).

VGSCs allow sodium ions to flow into certain cells of the body. Once inside the cells, the ions trigger electrical activity – or action potentials – that are responsible for a range of bodily functions, from heart beats to pain signalling.

Journavx selectively blocks a VGSC called Nav1.8 that is predominantly found in pain-sensing neurons in the peripheral nervous system, says David Altshuler, chief scientific officer of Vertex. The drug does not act on the brain the way opioids do and instead acts outside the brain, meaning there is no addiction risk.

Vertex has not applied for Journavx approval in the UK. In the US, the drug is only available for moderate to severe acute pain.

Some experts are sceptical about the need for a non-opioid in acute pain. It is relatively rare that someone taking an opioid for a few days after a surgery gets addicted to them, although it can happen, Scherrer says. There is also more communication about the risks of opioids these days and many patients request a minimal amount before switching to another medicine, he adds.

But Altshuler says the need is clear, citing estimates that 80,000 people a year in the US develop an opioid addiction just because they were given one for acute pain.

Experts agree that there is a significant need for non-opioid painkillers in chronic pain. There is little evidence of the effectiveness of opioids in treating chronic pain, according to the NHS, and using them long term only increases the risk of addiction.

Chronic pain is treated with much less success than acute pain, says David Andersson, professor of neuroscience at King’s College London. Each chronic pain condition has a different cause and in many cases, the cause is not well understood, he adds. To introduce a further layer of complication, placebos have been performing increasingly well in clinical trials of pain in recent decades, Mogil says, citing research published in 2015 on which he appeared as an author.

One potential explanation for this trend is the presence of a neural circuit in the brain that mediates people’s perception of pain based on their expectations of it, according to research co-written by Scherrer in 2024. People enrolled in clinical trials may expect to experience relief from pain. “When we’re expecting pain relief, we’re recruiting circuits in our brain that release endogenous opioids,” which itself suppresses pain, Scherrer explains.

In a study of patients with a chronic condition called lumbosacral radiculopathy, Journavx produced a level of pain reduction in the legs similar to that achieved by placebo. The drug did significantly reduce patients’ pain from their baseline level, which is what the trial was designed to show, according to Vertex. The company added that the placebo arm was included for “reference” and not for “statistical comparison”.

But experts largely remain unconvinced. The idea that Journavx works for lumbosacral radiculopathy seems “farcical” in the face of evidence that it does not work any better than placebo, Mogil says. Vertex said it plans to design future trials in a way that better controls placebo response.

Another new type of painkiller called cebranopadol is also angling for FDA approval after it succeeded in two late-stage clinical trials of acute pain after various surgeries. Cebranopadol activates the μ-opioid receptor, but also activates the nociceptin opioid receptor (NOP). The latter is structured very similarly to an opioid receptor but it behaves differently, says Scherrer.

Activating the NOP significantly reduces the effects of reward, tolerance and respiratory depression (slowness or shallowness of breathing) associated with μ-opioid receptor activation, according to Tris Pharma, the company behind cebranopadol. The result is a painkiller with similar effectiveness to an opioid but with much lower risk, the company said.

In what is known as a human abuse potential study, non-addicted recreational opioid users were given two types of opioids – oxycodone and tramadol – and cebranopadol to see which one they preferred. Cebranopadol was the least preferred of the three active drugs and only marginally preferred to placebo, says Tris’s chief executive, Ketan Mehta.

Another drug maker, Vertanical, recently reported phase 3 success for its non-opioid drug, VER-01, in patients with chronic back pain. The drug contains THC – the active ingredient in cannabis that causes a “high”. Patients in the trial did not experience intoxication because THC levels in their body were not high enough, the company said.

Despite all these new pharmaceutical approaches, most experts agree that there is no such thing as a magic bullet for pain. “We’re going to have to treat pain with multiple drugs that act in the peripheral nervous system, in the central nervous system, in the brain and on emotions and cognition, and not just on sensory systems,” Scherrer says. He adds that other types of treatments such as neurostimulation and cognitive behavioural therapy will also play a key role.

Here is the link:

https://www.theguardian.com/science/2025/apr/05/painkillers-without-the-addiction-the-new-wave-of-non-opioid-pain-relief

This sound like a really interesting break-through if it proves to be true in real world use!

David.

A Possible Explanation Of Why The USA Is So Keen On Tariffs!

 This appeared a few days ago

Return of the tariff man: why trade protection wins hearts and minds in America

Henry Ergas

12:19 PM April 05, 2025.

As the tariffs announced on Donald Trump’s “Liberation Day” send world markets reeling, the future of the international trading system seems more uncertain than ever. But it is important to remember that the crisis has been brewing for some time.

Its distant origins were set in the late 1970s and 80s when a sharp and prolonged tightening of monetary policy in the US, aimed at curbing inflation, provoked a steep rise in the value of the US dollar.

Compounding that increase were changes in global capital markets – and most notably in savings-abundant Japan – that made it easier for foreigners who had US dollars to use their dollars to purchase American financial assets, increasing the dollar’s attractiveness and further boosting its value.

As the dollar rose to spectacular heights, the competitiveness of US exports plummeted, while what had been a reasonably steady flow of manufactured imports became a flood.

At the same time, an attempt by the US to initiate a new round of global trade talks failed miserably, not least because the world economy was beset by both “stagflation” and the beginnings of a debt crisis in developing countries.

Faced with that failure, American policymakers concluded that only drastic unilateral action could reduce the obstacles and distortions that had built up in the world trading system.

Meanwhile, as imports surged, the protectionist pressures in congress became overwhelming, with 600 trade bills introduced in 1984 alone. And judging by the widespread support Richard Gephardt, a Democrat from Missouri, secured when he proposed that an immediate 25 per cent tariff surcharge be slapped on countries that ran “excessive” trade surpluses with the US, voters were plainly clamouring for more.

The result was a proliferation of unilateral measures. After rising from 8 per cent in 1975 to 12 per cent in 1980, the share of US imports covered by trade restrictions jumped to 21 per cent in 1984. Those restrictions took the form of quotas, which helped hide just how punitive the measures were: had the same protective effect been secured by tariffs, the tariff rate on the products affected would have been in the order of 50 per cent.

But although it undoubtedly imposed high economic costs, the wave of import restrictions induced a beneficial policy response.

In particular, James Baker, who became Treasury secretary after Ronald Reagan’s re-election in 1984, convinced Reagan that it would be far better to seek a reduction in the value of the dollar – which was plainly overvalued – than to strangle trade flows.

Other countries (whose exports would suffer if the US dollar depreciated) resisted strongly, as they had when Richard Nixon had tried to achieve the same outcome in 1971, but Baker had a trump card.

“Our leverage with them,” he later wrote, “was that if we didn’t act first, the protectionists in congress would throw up trade barriers.” With manufacturers “pounding the desks at the White House, Treasury and congress, demanding that something be done to save them from foreign competition”, the threat was all too credible; so that by late summer 1985, “top foreign economic officials had begun to see that we were serious”.

And in September 1985 the world’s leading economies signed the Plaza Accord, which helped effect a gradual decline in the US dollar to more sustainable levels.

Nor did the consequences of the protectionist episode end there. Rather, the initial wave of American unilateral restrictions, and the possibility of worse to come, were a crucial factor in the launch and success of the Uruguay Round of global trade negotiations. During what was by far the most ambitious and far-reaching multilateral trade negotiations ever held, the risk of American unilateralism weighed heavily on the negotiating parties.

The round’s results were spectacular. Tariffs, which had averaged 40 per cent in the early 50s, came down to a developed world average of about 5 per cent. Even more important, progress was made, for the very first time, in reducing a broad range of non-tariff barriers, including to trade in ser­vices, which would boom in the years ahead.

The impacts of those outcomes on US policymakers were as far-reaching as the outcomes themselves. Clearly, they concluded, multilateral negotiations could work; but, equally, occasionally wielding a big stick was not entirely counter-productive.

It was against that backdrop that the North American Free Trade Agreement was negotiated. The proposal had originated in Canada with Conservative prime minister Brian Mulroney inviting Reagan to initiate the process in October 1985. In February 1991, under the auspices of Baker, who had become secretary of state in the administration of George HW Bush, Canada, the US and Mexico announced their intention to proceed with what became NAFTA.

At first Bill Clinton, who took office in January 1993, was somewhat ambivalent; but in a speech he gave shortly after coming to office he argued that while globalisation brought new challenges, “open and competitive commerce will enrich us as a nation”.

“In the face of all the pressures to do the opposite,” he concluded, “we must compete, not retreat.”

What Clinton didn’t realise was that the politics of US trade policy were undergoing dramatic change.

In effect, the reaction to NAFTA verged on hysteria – on both sides of American politics.

On the left, the manufacturing unions, which had long been protectionist, found new, quite unexpected, allies in the environmental movement and, even more surprisingly, received strong support from consumer advocates including Ralph Nader. Equally opposed were leading civil rights activists, with Jesse Jackson declaring “NAFTA is a shafta, shifting our jobs out of the country”.

Nor was the reaction on the right any more favourable. Along with conservative leader Pat Buchanan, a serious campaign against NAFTA was launched in the 1992 election by Ross Perot, who famously warned that if NAFTA was approved, “you are going to hear a giant sucking sound of jobs being pulled out of this country”.

That Perot secured 19 per cent of the popular vote – an extraordinary success for a third-party candidate – signalled the depth of the change then under way.

It did not take long for the effects to become apparent in congress. From the late 50s through to NAFTA, both Democrats and Republicans were broadly in favour of trade liberalisation. With NAFTA, Democrat support for legislation liberalising trade collapsed, never to durably recover.

As a result, the Republicans (who had historically been protectionists) were left as trade liberalisation’s only reliable congressional supporters, greatly increasing their political vulnerability.

The split played itself out over the opening to China. The Clinton administration’s decision to support China’s accession to the World Trade Organisation had been announced in the most inauspicious circumstances imaginable – the riot-plagued WTO meeting held in Seattle in November 1999.

At that meeting, Charlene Barshefsky, the US trade representative, told the assembled parties that subject to congressional approval, the US would extend “permanent normal trade relations” to China.

China filed a World Trade Organization complaint on Wednesday against U.S. President Donald Trump's new 10% tariff on Chinese imports and his cancellation of a duty-free exemption for low-value packages, arguing the actions are "protectionist" and…

In theory, securing approval should have been straightforward: the economy was strong and the unemployment rate had fallen to 4 per cent. In practice, getting it through was no easy task.

In the end, the legislation was approved by the House of Representatives in May 2000, but two-thirds of the house Democrats voted against it. It passed only because of the support it received from 164 Republicans – though the fact 57 Republicans voted against was a sure sign of what was to come.

To make things worse, shortly after that, global trade liberalisation ground to a complete halt. Under US pressure, a new round of multilateral negotiations was launched at Doha in November 2001. But there was no enthusiasm for the round in developing countries, which believed the benefits they had been promised from the Uruguay Round had not materialised, nor from the EU, which was reluctant to liberalise its agricultural markets.

Moreover, by that time the WTO had become an incredibly unwieldy organisation: as the number of “contracting parties” rose from 42 in 1961 to 76 in 1967 and then 160 in 2015, reaching the consensus needed for agreements became virtually impossible.

By late 2015, the round was plainly making no progress and so was mercifully ended. For the first time, a round had failed; without fundamental change in the rules, it was hard to believe that any round aimed at multilateral liberalisation could ever again succeed.

Taken together, those two factors – the change in US domestic politics and the collapse of the multilateral rounds – would have been enough to eventually trigger a turn in American trade policy to unilateralism. However, their effect was compounded by the impacts of China’s entry into the global trading system.

Donald Trump is set to announce new tariffs this week in the hope of spurring American industry.

That American consumers benefited enormously is beyond question; but it is also beyond question that the job losses in US manufacturing were very substantial. There has been considerable controversy about their precise extent; however, the conclusion reached by Massachusetts Institute of Technology economics professor David Autor and his co-authors that imports from China caused 21 per cent of the decline in US manufacturing employment over the period 1990-2007 seems plausible.

Nor did the wider geopolitical benefits that Clinton had pointed to as an important justification for the opening to China eventuate. That opening, Clinton had said in March 2000, “represents the most significant opportunity that we have had to create positive change in China since the 1970s, when President Nixon first went there, and later in the decade when President Carter normalised relations”.

“In the new century,” he went on to claim, “liberty will spread by cell phone and cable modem” – and as China reduced its barriers to trade, those would become ever more affordable. Yes, China would try to “crack down on the internet”. But “that’s sort of like trying to nail Jello to the wall”. As those attempts failed, and as the middle class flourished, the pressures for democratisation, along with those for moving to a fully market-based economy, would become increasingly irresistible.

That those predictions haven’t been borne out hardly needs to be said. On the contrary, the communist regime has both raised the surveillance state to new heights and reasserted its control over the economy, imposing myriad restrictions on international trade.

Seen in that perspective, the impetus behind the Trump tariffs is not difficult to understand. They were, moreover, one of his fundamental election commitments, constantly proclaimed and promised during the campaign. It is therefore hard to see them as anything other than a core part of his compact with American voters.

But it is by no means obvious that by taking the world trading system to the brink of disaster, those tariffs will, like the quotas the Carter and Reagan administrations imposed, provoke a reaction that ultimately strengthens global trade.

That was certainly not the case with the unilateral tariffs championed in 1890 by William McKinley, whom Trump absolutely reveres.

Hailed by his admirers as “the Napoleon of protection”, McKinley claimed that those tariffs, which more than doubled US rates of protection, were justified by being linked to reciprocity: if the target countries reduced their tariffs, so would the US.

In reality, the completely arbitrary nature of the tariff increases, the sheer harshness of the US demands and the intransigence of the American negotiators induced a worldwide move to greater protection, slashing global economic growth.

Even in Australia, where the direct impacts were insignificant, the ramifications proved material.

There was, to begin with, the economic effect, notably on wool exports, as British textile exports to the US declined into insignificance.

President Donald Trump often cites the 25th President, William McKinley, as an inspiration. The ‘McKinley Tariffs’ were some of the largest hikes in U.S. history, but in his second term, McKinley changed his mind, and argued for more free trade.

“There is probably no country in the world with anything to export that is not affected by the McKinley tariff,” Perth’s Western Mail reported in January 1891, “and Australia is no exception to the rule. Her chief staple, wool, is as severely treated as can be imagined.”

But no less important were the political consequences as America’s shift to high tariffs emboldened protectionism’s Australian advocates, who had no difficulty caricaturing the free traders as babes in the wolf-infested woods of realpolitik.

Those claims were echoed by protectionists worldwide; and helping the protectionist cause was the immense boost the McKinley tariff gave to global anti-Americanism. In Canada, for example, there had been, until then, strong backing for some form of free trade with the US. But, Canadian politician George T. Denison said, the tariff was “a heavy blow struck alike at our home industries and at the prosperity and independence of the Dominion of Canada – an unprovoked aggression, an attempt at conquest by fiscal war”. Its inevitable consequence, said Denison, would be to rekindle “love for Queen, flag and country”.

Denison’s prediction was not far off the mark. With “American perfidy” causing an uproar, John Macdonald, Canada’s Conservative prime minister, transformed the elections of 1891 into a referendum on Canadian-American relations, changing the Conservatives’ likely defeat into a narrow victory over the partisans of continental free trade.

Convinced that “the great contest that is now going on will determine whether Canada is to remain British or become part of the United States” and that “we are in great danger”, Macdonald ensured Canadian protectionism would more than mirror its American counterpart, damaging economic relations between the two countries for a century.

Ultimately, McKinley came to regret the tariffs he had imposed, which contributed to the American recession of 1893 and durably soured relations between the US and its trading partners. But by then it was far too late.

There are, for sure, some economists, closely associated with the “Make America Great Again” movement, who believe that, far from stoking inflation and triggering a decline in economic activity, the Trump tariffs will revitalise American manufacturing and help unleash a new age of prosperity. And it is indeed true that if the tariffs remain in place, the protected industries will grow, as some part of the demand that was previously served by imports switches to domestic production.

But in an economy that now has low overall levels of unemployment, the growth of employment in traditional manufacturing must come at the expense of other industries – and the victims are almost certain to include the high-technology activities at which America excels. That those activities have – as the EU’s recent Draghi report on competitiveness clearly shows – both propelled economic growth in the US and cemented America’s geopolitical pre-eminence should lead Americans to think twice.

All the other inefficiencies that have always bedevilled protection, ranging from rampant rent-seeking to reductions in competition, make the likelihood of a renewed, tariff-induced, golden age all the dimmer.

Conversely, if the tariffs are merely an instrument to force greater openness in global markets and encourage an agreement along the lines of the Plaza Accord, they could, in the end, leave America and the world better off.

But that won’t happen automatically. It is often said that you can’t make an omelette without breaking a few eggs. But as anyone who has ever made an omelette knows, breaking the eggs is the easy part; transforming them into something worth eating requires real skill.

So too is it with the trading system: disrupting it is easy; putting it back together, in better shape than it originally was, requires both a clear political will and skills of the very highest order.

A great deal therefore rides on whether the Trump administration goes down the path McKinley and his successors took in the 1890s, provoking a dangerous spiral, or the path of co-ordinated global reform that Baker pursued a century later. With so much at stake, one can only hope that wisdom, along with a healthy dose of common sense, will prevail.

Here is the link:

https://www.theaustralian.com.au/inquirer/return-of-tariff-man-past-mistakes-should-make-us-think-twice-about-likelihood-of-renewed-golden-age/news-story/28333b5b27604cec8ff198824a10e030

Useful to have some background on that is going on. I dread to think where we will be by the time this appears!

I fear things may have got a lot worse by the time you read this, after it was written on Sunday!

David.