Month: June 2022

Categories : Ethics and Law Medical Research & TechnologyTags :

Scientists Sound Alarm on Badly Run Medical Studies

On By ModernMedia
Woman using lab equipment
Source: NCI on Unsplash

A new research paper has signalled a crisis in medical research: “over 60% of trials are so methodologically flawed we cannot believe their results”. Researchers estimate that 88% of trial spending is wasted.

Dodgy research design and bad statistical methodology mean that most randomised trials are a waste of time, money and effort, and of no or dubious scientific value, say Stefania Pirosca, Frances Shiely, Mike Clarke and Shaun Treweek, in a new paper published in the journal Trials in early June.

Their paper examined 1659 randomised trials, involving 400,000 participants, that took place between May 2020 and April 2021 in 84 countries as well as 193 multinational trials. 

The majority of trials (62%) showed a high risk of bias. More than half of trial participants were in these high risk of bias trials. Trials where the risk of bias was unclear accounted for 30% of those reviewed, while trials with a low risk of bias – those that can be trusted – accounted for just 8% of the total.

Bad trials – ones where we have little confidence in the results – are not just common, they represent the majority of trials in all countries and across most clinical areas. For instance, all trials looking at drugs and alcohol exhibited a high risk of bias. The most reliable field was anaesthesia, with 60% of trials exhibiting a low risk of bias.

The research team drew trial data from 96 reviews from 49 of the 53 clinical Cochrane Review Groups. Cochrane is an international organisation that helps to gather and propagate the results of medical research to better guide medical decision-making. This is done by experts compiling and evaluating research trials and results in “standardised, high-quality systematic reviews”.

Bad science was common everywhere. “No patient or member of the public should be in a bad trial and ethical committees, like funders, have a duty to stop this happening,” the paper’s authors write.

South Africa was bad, but Spain and Germany may be worse

In the seven trials reviewed that took place in South Africa, four had a high risk of bias, two had an unclear bias risk, and one trial was “good science”. This share of bad science is roughly similar to those found in the clinical trials done in the UK and USA. The most reliable health research science was done in multinational trials – with these, 23% of trials were a low risk of bias. (The authors didn’t identify the trials.)

The least reliable science, in countries that conducted 20 or more RCTs, was done in Spain and Germany, with 86% and 83% of the trials exhibiting a high risk of bias.

While results from just one year were interrogated, the paper’s authors found that their results map to similar studies, and that bad science can be expected to be the norm, over time.

This amounts to a massive waste of money and effort.

Statisticians and research method experts have been sounding the alarm on biased research for years, since Doug Altman’s 1994 paper in the British Medical Journal, “The scandal of poor medical research”.

Doctors want to know if they can rely on a particular treatment to produce a desired outcome, and need research that confers a degree of confidence. One way to do that – the most popular – is randomised control trials.

Randomised trials are great – but you need statisticians

Randomised control trials, also known as randomised trials, or RCTs, are for many (though not all), the gold standard for achieving scientific knowledge about a medical intervention – whether a drug or another type of therapy. The way that RCTs are conducted is crucial, as it is adherence to the method that gives people relying on the research confidence that the results produce scientific knowledge. See this explainer video for more: How do we know vaccines work?

But, if there is a high risk that the results were biased by errors in how they were conducted and how results were achieved, they should not be relied on. Pirosca and colleagues did not examine the type (or domain) of bias in the studies, arguing that having a high risk in one type of bias is sufficient to undermine the trial’s results.

In short, for Pirosca and colleagues, health research in randomised trials is bad when there is an identifiable risk of bias in the way that the results were obtained.

The large number of high risk of bias trials appears to be due to “a lack of input from methodologists and statisticians at the trial planning stage combined with insufficient knowledge of research methods among the trial teams”. You would not, they say by analogy, think it appropriate that a statistician conduct surgery, just because they are doing work in a surgical domain.

Bad science during COVID

Recent medical scandals in the headlines have highlighted the risks of bad science in medicine. The Covid pandemic has brought a boom in medical research, and popular attention to the results of medical research. This environment has produced some remarkable science, but it has also created scientific fiascos, like the one that surrounded ivermectin.

As GroundUp has previously reported, a review of studies investigating ivermectin as a possible therapy for Covid initially suggested that the deworming drug led to better outcomes in those that used it. On the face of it, the small studies that supported this conclusion seemed to provide promise for a low-cost, life-saving Covid intervention. But once the methodology and statistics were looked at closely, many of these papers were deemed unscientific – for instance, patients were excluded from analysis for no good reason. And once these trials were excluded from the review, the drug’s promise as a Covid treatment vanished.

Medical research watchdog Retraction Watch currently lists 12 papers purporting to investigate ivermectin that were subsequently withdrawn or for which concerns have been expressed. According to their records, 235 Covid papers have been withdrawn to date.

But the crisis is not insurmountable. Pirosca and colleagues say that relatively simple fixes would dramatically reduce the amount of untrustworthy health research – by ensuring that methodological principles that underlie RCTs are not compromised.

More expenditure on statistical expertise will save money

A 2015 review examined 142 trials that exhibited a high risk of bias. The authors found that in half of the high risk trials, the methodological adjustments required to reduce the risk of bias would have been low or zero cost. Easy adjustments at the design stage would have made important improvements to 42% of trials that exhibited high risk of bias.

Pirosca and colleagues propose that no medical RCT should be funded or given ethical approval if it cannot prove that the team conducting the trial has a member that has methodological and statistical expertise. Every RCT should, in its design, use risk of bias tools to make sure that results are not compromised.

The expertise that could restore the worth to medical research is in short supply.

More methodologists and statisticians are needed, and money should be invested in training people with this expertise, and investing in applied methodology research and supporting infrastructure. The authors call for 10% of a funder’s budget.

This might seem like a lot of money, but, argue Pirosca and co, it would be a fraction of the cost of the wasted research in the year under review – estimated to be billions of rands.

The task is urgent: “Randomised trials have the potential to improve health and wellbeing, change lives for the better and support economies through healthier populations … Society will only see the potential benefits of randomised trials if these studies are good, and, at the moment, most are not.”

Written by James Stent

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Source: GroundUp

Categories : Metabolic DisordersTags :

Researchers Successfully Restore Pancreatic Beta Cells in Type 1 Diabetes

On By ModernMedia
Image depicting diabetes
Image by Nataliya Vaitkevich on Pexels

Scientists have successfully treated type 1 diabetes in mice using pancreatic beta-cell, target-specific, chimeric antigen-receptor (CAR) regulatory T cells (Tregs), showing the feasibility of replicating this in humans according to data presented at ENDO 2022, the Endocrine Society’s annual meeting.

The study was led by Professor Juan Carlos Jaume, MD, at the University of Toledo.

Adoptive cell transfer therapies with CAR cytotoxic T cells have proven effective for the treatment of haematologic malignancies. Prof Jaume and colleagues attempted to replicate an equally effective experimental treatment for type 1 diabetes using instead non-cytotoxic, anti-inflammatory Tregs.

“The purpose of this study was to determine if pancreatic beta-cell, target-specific, human CAR Tregs could also identify human pancreatic beta cells and home to human pancreatic islets in culture as they do in mice undergoing CAR Treg treatment for T1D,” Prof Jaume said.

The researchers drew blood one to two weeks prior to pancreas surgery, followed by a collection of a a 5cc wedge of the pancreas after the pancreas was removed for a clinically indicated reason, either cancer or pancreatitis.

The researchers isolated Tregs from the blood samples and expanded them in vitro. Those cells were genetically modified to express a beta-cell, target-specific CAR combined with a green fluorescence protein (GFP) marker.

The next step was to process the pancreas tissue for islet separation. Following this, they co-cultured the human pancreatic islets combined with the beta-cell, target-specific CAR Tregs.

Within 24 hours, confocal microscopy demonstrated the successful migration of the GFP positive, CAR Tregs onto the pancreatic islets. What’s more, the CAR Tregs significantly proliferated while in physical contact with the pancreatic islets in the subsequent 72 hours.

“Ours is the first successful, pancreatic beta-cell, target-specific CAR-Treg treatment of T1D in a humanized mouse model that closely resembles the human disease. Based on our mice and human in-vitro data, we believe treatment with pancreatic beta-cell, target-specific, CAR-Tregs will allow for recovery and reconstitution of beta cells in human T1D patients as well,” Prof Jaume said.

Source: EurekAlert!

Categories : Hospitals Lab Tests and ImagingTags :

Amid Shortage, Suggested Ways to Conserve Contrast Agent

On By ModernMedia
Technician and patient with MRI machine
Source: Mart Production on Pexels

Amid an ongoing worldwide shortage of contrast agent for medical imaging, a new UC San Francisco research letter in JAMA described strategies that can be used to safely reduce contrast agent use in computed tomography (CT) by up to 83%.

The three conservation strategies are weight-based (rather than fixed) dosing, reducing contrast dose while reducing tube voltage on scanners, and replacing contrast-enhanced CT with nonenhanced CT when it will minimally affect diagnostic accuracy.

That third strategy – not using the contrast agent in certain CT scans where there is only a small improvement in accuracy – yielded the most dramatic reduction of contrast agent use: 78%.

“Contrast is essential in any situation where we need to assess the blood vessels – for example, for some trauma patients or those with a suspected acute gastrointestinal bleed – and it is also needed for evaluation of certain cancers, such as in the liver or pancreas,” said senior study author Rebecca Smith-Bindman, MD, professor at UCSF.

“However, most CT scans are done for less specific indications such as abdominal pain in a patient with suspected appendicitis,” Prof Smith-Bindman added. “These can and should be done without contrast during the shortage, because the loss of information in these patients will be acceptable for most patients.”

The global shortage of contrast agent started in April with a COVID-related supply chain disruption of GE Healthcare in Shanghai and is expected to last at least several more weeks. More than 54 million diagnostic imaging exams using contrast agents are done every year in the US, a majority being CT scans, and these conservation methods could continue past the current shortage to reduce the use of contrast agent in general, the authors noted.

Referring clinicians are key to conservation
Researchers modelled the three strategies individually and in combination using a sample of 1.04 million CT exams in the UCSF International CT Dose Registry from January 2015 to March 2021.

On its own, weight-based dosing for abdomen, chest, cardiac, spine and extremity imaging reduced contrast agent use by 10%; reducing the tube voltage in appropriate patients allowed a contrast agent reduction of 25%. These two measures combined with using non-contrast CT when possible led to a total reduction of 83%.

Following all three strategies at once may not be possible for some facilities, but each can help conserve supply, Prof Smith-Bindman said. And it is not just radiologists who need to know about them.

“Given the acute shortage, it’s important that clinicians who order imaging exams coordinate with radiology to cancel scans that aren’t absolutely necessary, postpone exams that can be safely delayed, replace CT with MRI and ultrasound where possible, and order an unenhanced scan where possible. Further, clinicians should communicate with their patients about why this is necessary. It is crucial that contrast be conserved for clinical situations where its use is essential for accurate diagnosis,” said Prof Smith-Bindman.

After the shortage ends, medical facilities should consider continuing some of these practices that conserve contrast agent, she added. For example, reducing the tube voltage not only reduces the contrast agent used but also lowers the radiation dose. Tailoring doses weight allows lower dosing volumes for many patients.

In addition, Prof Smith-Bindman noted that this analysis highlights the large amount of contrast agent that is wasted when single-dose vials are used Hospitals and imaging centres that routinely use single-dose contrast agent vials should consider using larger multi-dose vials, which allows for exact dosing and obviates the need to discard unused portions, she said.

“By carrying some of these practices forward, we can mitigate future supply-chain risk and reduce overall waste,” said Smith-Bindman.

Source: University of California – San Francisco

Categories : Medical Research & Technology UncategorizedTags :

Bacteriophage Therapy over 50% Successful against Mycobacterium Infections

On By ModernMedia
A bacteriophage. Credit: Wikimedia CC0

Using bacteriophages, viruses which prey on bacteria, is an emerging alternative to antibiotic use but with limited evidence. Now, with a new paper published in Clinical Infectious Diseases, collaborators report 20 new case studies on the use of the experimental treatment in Mycobacterium infections, with successes in more than half of the patients.

This is the largest ever set of published case studies for bacteriophage (or ‘phage’) therapy, giving unprecedented detail on their use to treat dire infections while laying the groundwork for a future clinical trial.

“Some of those are spectacular outcomes, and others are complicated,” said Professor Graham Hatfull at the University of Pittsburgh. “But when we do 20 cases, it becomes much more compelling that the phages are contributing to favourable outcomes – and in patients who have no other alternatives.”

The patients in the study had an infection from one or more strains of Mycobacterium, a group of bacteria that can cause deadly, treatment-resistant infections in those with compromised immune systems or cystic fibrosis. In 2019, Prof Hatfull led a team showing the first successful use of phages to treat one of these infections.

“For clinicians, these are really a nightmare: They’re not as common as some other types of infections, but they’re amongst some of the most difficult to treat with antibiotics,” said Prof Hatfull. “And especially when you take these antibiotics over extended periods of time, they’re toxic or not very well-tolerated.”

Since 2019, Prof Hatfull and his lab have fielded requests from more than 200 clinicians looking for treatments for their patients, working with them to find phages that could be effective against the particular strain of bacteria infecting each patient.

This newest paper, with collaborators from 20 institutions, dramatically expands the body of published evidence on the effectiveness of the therapy.

“These are incredibly brave physicians, jumping off the ledge to do an experimental therapy to try to help patients who have no other options,” said Prof Hatfull. “And each of these collaborations represents a marker that can move the field forward.”

Going on patient health and presence of Mycobacterium in samples, the team found that the therapy was successful in 11 out of 20 cases. No patients showed any adverse reactions to the treatment.

In another five patients the results of the therapy were inconclusive, and four patients showed no improvement. According to Prof Hatfull, even these apparent failures are key to making the therapy available to more patients. “In some ways, those are the most interesting cases,” he said. “Understanding why they didn’t work is going to be important.”

Several unexpected patterns emerged from the case studies. In 11 cases, researchers were unable to find more than one kind of phage that could kill the patient’s infection, even though standard practice would be to inject a cocktail of different viruses so the bacteria would be less likely to evolve resistance.

“If you’d asked me whether that was a good idea three years ago, I would have had a fit,” Prof Hatfull said. “But we just didn’t observe resistance, and we didn’t see a failure of treatment from resistance even when using only a single phage.”

Additionally, the team saw that some patients’ immune systems attacked the viruses, but only in a few cases did that render the virus ineffective. And in some instances, the treatment was still successful despite such an immune reaction. The study paints an encouraging picture for the therapy, said Prof Hatfull, opening up the possibility for new phage regimens that clinicians could use to maximise the treatment’s chance of success.

Along with the study’s significance to patients facing Mycobacterium infections, it also represents a substantial advance for the wider field of phage therapy. One concern is that researchers may be only publishing case studies of successful phage therapy.

“A series of consecutive case studies, where we’re not cherry-picking, is a much more transparent way of looking to see what works and what doesn’t,” said Prof Hatfull. “This adds considerable weight to the sense that the therapy is safe.”

This is still a very early stage in the development of phage therapy, and phages have not even begun to be tailored for treatment, Prof Hatfull said.

Source: University of Pittsburgh

Categories : HospitalsTags :

Soothing Tunes: Music Reduces Anxiety in the ICU

On By ModernMedia

Music session interventions were found to reduce anxiety among patients admitted to the intensive care unit (ICU), according to a systematic review and meta-analysis in the Journal of Clinical Nursing.

Reviewing 25 studies, music was found to significantly reduce anxiety scores overall, regardless of the system of measurement, reported Öznur Erbay Dalli, RN, MSc, PhD, of Bursa Uludag University in Turkey, and colleagues.

Music also significantly reduced anxiety scores versus standard care, including prescribed drugs or care protocol as part of usual treatment. This was comparable to noise-reducing methods. In the ICU, noise is an important driver of stress, the authors explained.

Throughout history, music has been used as one of the “proven non-pharmacological tools” to reduce anxiety, depression, and pain and to increase patient comfort, they added.

Dr Dalli told MedPage Today that ICU nurses and other healthcare workers may complement their daily routine care with music to reduce the anxiety of ICU patients and to avoid the side effects of medications, which are commonly used for treating anxiety.

No effect on diastolic blood pressure, respiration rate, or heart rate due to the music was seen. Subgroup analysis showed that multiple sessions produced better outcomes.

The researchers searched for studies published up to January 2022. All of the 25 included studies were randomised controlled trials or controlled clinical trials in 9 different countries with 1751 participants in total. Average age was 59 and 57% were male.

Of the anxiety assessment tools, the State-Trait Anxiety Inventory was the most commonly used tool (9 studies), followed by the Fear, Anxiety, and Stress Scale (4 studies) and the Visual Analogue Scale for Anxiety (2 studies).

Music interventions were mostly recorded music, although one study included a harp being played live. Music was used during rest times in most studies, though in four studies, music was used during specific procedures, like catheterisation or endotracheal suctioning.

No side effects were reported in the studies examined, but some patients objected to the choice of music, something which could be addressed by consultation with family members.

Limitations to the study included the fact that it was “difficult or impossible” to blind participants and other healthcare personnel involved in the study due to the nature of the intervention, which could lead to a “high risk of performance bias,” the authors noted. Additionally, the range of protocols and evaluation techniques used among the studies resulted in high heterogeneity.

Publication bias was possible due certain studies having small sample sizes, and a lack of available data.

Source: MedPage Today

Categories : AgeingTags :

In Women, an Optimistic Outlook Leads to Longer Lifespan

On By ModernMedia
Photo by Loren Joseph on Unsplash

In a study published in the Journal of the American Geriatrics Society with 159 255 female participants from a variety of racial and ethnic backgrounds, higher levels of optimism were associated with longer lifespans and a greater likelihood of living past 90 years of age. 

Investigators found that the link between optimism and longevity was evident across racial and ethnic groups, and that lifestyle factors accounted for nearly one-quarter of the optimism-lifespan association. 

“Although optimism itself may be patterned by social structural factors, our findings suggest that the benefits of optimism for longevity may hold across racial and ethnic groups,” said lead author Hayami K. Koga, of the Harvard T.H. Chan School of Public Health. “Optimism may be an important target of intervention for longevity across diverse groups.”  

Source: Wiley

Categories : General Interest Hospitals UncategorizedTags : 1 Comment

Whistle-blowing Paediatrician at Rahima Moosa Suspended

On By ModernMedia
Photo by Christian Bowen on Unsplash

The whistle-blowing paediatrician Dr Tim de Maayer who spoke out about appalling conditions at Rahima Moosa Mother and Child Hospital (RMMCH) was suspended yesterday, apparently in a retaliatory move.

In the widely-read open letter appearing on the Daily Maverick, he spoke of the preventable tragedy of babies dying due to lack of resources. This came shortly after a viral video showed pregnant mothers sleeping on the floor.

Presciently, the Daily Maverick, which broke the story, stated that there were two options: act to change the situation for the better, or “shoot the messenger”. As the newspaper wryly noted as it broke the news on Friday, 10 June, the option of shooting the messenger has been taken.

Although there appeared to be an initial positive response, Dr Maayer gave notice on Thursday evening that he was not able to come into work on Friday as he was being placed on suspension. RMMCH doctors then contacted the Daily Maverick.

His suspension leaves the hospital without its only paediatric gastroenterologist, according to an anxious doctor who got in touch with the Daily Maverick late Thursday night. The news has spread like wildfire across social media, with other doctors quick to come to Dr de Maayer’s defence.

A petition on Change.org to reinstate the paediatrician is being circulated by ordinary citizens and clinicians including Professor Shabir Madhi, who has been vocal in his support of Dr de Maayer.

Guy Richards, critical-care professor at Wits University tweeted that it was a “shocking response”.

The Progressive Health Forum (PHF) called for the suspension of Dr de Maayer to be overturned.

“Dr de Maayer has been suspended on the grounds that he has a voice, a conscience and a professional ethic and being a committed public health clinician. This pattern of victimisation has been repeatedly applied to clinicians who dare call out inadequacies of the administration and negative impact on clinicians and on the lives of patients,” the PHF said in a statement.

Source: Daily Maverick

Categories : UncategorizedTags :

Secrets of Pregnant Mothers’ ‘Super Antibodies’ Revealed

On By ModernMedia
Pregnant with ultrasound image
Source: Pixabay

Pregnant mothers have the ability to confer greater immunity to the vulnerable developing foetus with ‘super antibodies’. Now, a far-reaching study published in Nature provides a surprising explanation of how this actually works, and what it could mean for preventing death and disability from a wide range of infectious diseases.

The findings suggest the amped-up antibodies that expecting mothers produce could be mimicked to create new drugs to treat diseases as well as improved vaccines to prevent them.

“For many years, scientists believed that antibodies cannot get inside cells. They don’t have the necessary machinery. And so, infections caused by pathogens that live exclusively inside cells were thought to be invisible to antibody-based therapies,” said Sing Sing Way, MD. “Our findings show that pregnancy changes the structure of certain sugars attached to the antibodies, which allows them to protect babies from infection by a much wider range of pathogens.”

“The maternal-infant dyad is so special. It’s the intimate connection between a mother and her baby,” says John Erickson, MD, PhD, first-author of the study.

Drs Way and Erickson are both part of Cincinnati Children’s Center for Inflammation and Tolerance and the Perinatal Institute, which strives to improve outcomes for all pregnant women and their newborns.

Erickson continues, “This special connection starts when babies are in the womb and continues after birth. I love seeing the closeness between mothers and their babies in our newborn care units. This discovery paves the way for pioneering new therapies that can specifically target infections in pregnant mothers and newborns babies. I believe these findings also will have far-reaching implications for antibody-based therapies in other fields.”

How mothers make super antibodies
The new study identifies the specific change in the sugar. During pregnancy, the “acetylated” form of sialic acid (one of the sugars attached to antibodies) shifts to the “deacetylated” form. This subtle molecular shift lets immunoglobulin G (IgG) take on an expanded protective role by stimulating immunity through receptors that respond specifically to deacetylated sugars.

“This change is the light switch that allows maternal antibodies to protect babies against infection inside cells,” Dr Way said.

“Mothers always seem to know best,” Dr Erickson added.

Revved-up antibodies can be produced in the lab
The research team pinned down the key biochemical differences between antibodies in virgin mice compared to pregnant ones. They also identified the enzyme naturally expressed during pregnancy responsible for driving this transformation.

Further, the team successfully restored lost immune protection by supplying lab-grown supplies of the antibodies from healthy pregnant mice to pups born to mothers that were gene-edited to lack the ability to remove acetylation from antibodies to enhance protection.

Hundreds of monoclonal antibodies have been produced as potential treatments for various disorders, including COVID, with a variety of results.

Dr Way said this molecular alteration can be replicated to change how antibodies stimulate the immune system to fine-tune their effects. This potentially could lead to improved treatments for infections caused by other intracellular pathogens including HIV and respiratory syncytial virus (RSV), a common virus that poses serious risks to infants.

Another reason to accelerate vaccine development
“We’ve known for years the many far-reaching benefits of breastfeeding,” Dr Erickson said. “One major factor is the transfer of antibodies in breastmilk.”

The study shows that nursing mothers retain the molecular switch, passing through the antibodies to their newborns.

Additionally, Dr Way says the findings underscore the importance of receiving all available vaccines for women of reproductive age – as well as the need for researchers to develop even more vaccines against infections that which are especially prominent in women during pregnancy or in newborn babies.

“The immunity needs to exist within the mother for it to be transferred to her child,” Dr Way said. “Without natural exposures or immunity primed by vaccination, when that light switch flips during pregnancy, there’s no electricity behind it.”

Source: Cincinnati Children’s Hospital Medical Center

Categories : COVID VaccinesTags :

New Vaccines Could Focus on T Cell Response – Without Antibodies

On By ModernMedia
T cell
Scanning Electron Micrograph image of a human T cell. Credit: NIH/NIAID

In a groundbreaking new study, scientists report training T cells to protect against SARS-CoV-2 even without an antibody response. This could open the way to more broadly effective vaccines.

The study’s findings appear in the Proceedings of the National Academy of Sciences.

Current vaccines prompt the creation of antibodies and immune cells that recognise the spike protein. However, these vaccines were developed using the spike protein from an older variant of SARS-CoV-2, reducing their effectiveness against newer variants. Researchers have found that immune cells called T cells tend to recognise parts of SARS-CoV-2 that don’t mutate rapidly. T cells coordinate the immune system’s response and kill cells that have been infected by the SARS-CoV-2 virus.

A vaccine that prompted the body to create more T cells against SARS-CoV-2 could help prevent disease caused by a wide range of variants. To explore this approach, a research team led by Dr Marulasiddappa Suresh from the University of Wisconsin studied two experimental vaccines that included compounds to specifically provoke a strong T-cell response in mice.

The team tested the vaccines’ ability to control infection and prevent severe disease caused by an earlier strain of SARS-CoV-2 as well as by the Beta variant, which is relatively resistant to antibodies raised against earlier strains.

When the researchers vaccinated the mice either either nasally or by injection, the animals developed T cells that could recognise the early SARS-CoV-2 strain and the Beta variant. The vaccines also caused the mice to develop antibodies that could neutralise the early strain. However, they failed to create antibodies that neutralised the Beta variant.

The mice were exposed to SARS-CoV-2 around 3 to 5 months after vaccination. Compared to the controls, vaccinated mice had very low levels of virus in their lungs and were protected against severe illness, which was true of infection with the Beta variant too. This showed that the vaccine provided protection against the Beta variant despite failing to produce effective antibodies against it.

To understand which T cells were providing this protection, the researchers selectively removed different types of T cells in vaccinated mice prior to infection. When they removed CD8 (killer) T cells, vaccinated mice remained well protected against the early strain, although not against the Beta variant. When they blocked CD4 T (helper) cells, levels of both the early strain and Beta variant in the lungs and severity of disease were substantially higher than in vaccinated mice that didn’t have their T cells removed.

These results suggest important roles for CD8 and CD4 T cells in controlling SARS-CoV-2 infection. Current mRNA vaccines do produce some T cells that recognize multiple variants. This may help account for part of the observed protection against severe disease from the Omicron variant. Future vaccines might be designed to specifically enhance this T cell response.

“I see the next generation of vaccines being able to provide immunity to current and future COVID variants by stimulating both broadly-neutralising antibodies and T cell immunity,” Dr Suresh predicted.

Source: National Institutes of Health

Categories : Addiction Healthcare Politics and RegulationsTags :

Up in Smoke: The Tobacco Wars and Lessons for Vaccination Efforts

On By ModernMedia
Tobacco companies waged a massive disinformation campaign to keep people consuming their products. There are parallels with today’s antivaxx movement. Even before the 1964 US Surgeon General’s report on tobacco, the tobacco industry was deflecting health concerns by featuring doctors in their advertising and actively courting the medical industry. This advert is from 1930.

In a perspective piece published in the New England Journal of Medicine, authors find a parallel between the tactics used in the ‘tobacco wars’ and vaccination efforts. In a seeming repeat of history, anti-vaccination groups are using the same tactics the tobacco industry used to defend their products and undermine trust in science, but the successful anti-tobacco campaign holds important lessons for turning the tide against misinformation and normalising vaccination.

In late 2020 when the first COVID vaccines became available, the authors note that surveys indicated that about a third of US adults were keen to be vaccinated, 15% expressed strong resistance to vaccination (a proportion that has stayed fairly constant), and the remainder didn’t harbour strong ideological resistance. Now, about 27% of US adults now remain unvaccinated – and reaching this remainder is an important public health challenge.

The authors believe that the ‘tobacco wars’ can provide perspective. The tobacco industry fuelled preventable deaths by glamourising smoking, with almost 50% of US adults smoking cigarettes in the 1960s.

The current rate of about 12.5% is the result of decades of public health efforts to make tobacco use less socially acceptable. The first US Surgeon General’s report on smoking and health in 1964 was attacked by the tobacco industry. It was only until C. Everett Koop’s overwhelming report in 1986 that cemented tobacco use as a major preventable cause of cancer and death and highlighted the dangers of second-hand smoking.

Koop and others were vilified by the tobacco industry, which mounted a sustained campaign that cast doubts on the science, publicised misinformation, emphasised tobacco’s economic importance, and warned against restricting individual freedom. Industry leaders directly lied about knowing that nicotine was addictive and the lethal dangers of tobacco use. Indeed, from the 1920s to 1950s, in response to growing health concerns, the tobacco industry had actively courted doctors and influenced medical journals, widely reporting positive findings of studies that were deeply flawed. This may have only played into the hands of antivaxxers, creating a historical example of distrust in the medical system.

A 1940s advert showing how ‘doctors’ (probably actors) enjoyed Camel brand cigarettes. With the 1950 publication of studies showing the connection between cancer and tobacco, the public began to be suspicious and such campaigns featuring doctors ended by 1954.

While the focus of the debate was initially on smoking as an individual choice, two 1981 studies on nonsmoking wives of smokers vs nonsmokers revealed the dangers of secondhand smoke and shifted the discourse.

The US Congress has never enacted a federal smoking ban, but did grant the FDA limited authority to regulate tobacco in 2009, enabling restrictions on youth sales.

However, the broad-based effort from all levels of society that were important, discouraging smoking in public settings. This was supplemented by messaging from celebrities, taxation, and even a 1998 legal battle against the tobacco industry.

Efforts undertaken by the antivaccination movement, which is hardly new but is thriving during the COVID pandemic, bear many similarities to strategies used during the tobacco wars. Although not driven by a single industry but a collection of celebrities and social media groups, it sows mistrust in science and promotes conspiracy theories. Misinformation tactics are used that are strikingly similar to the tobacco industry’s, and this time Dr Antony Fauci is vilified instead of Koop.

There are big differences between tobacco control and vaccination; such as taking a long time for smoking interventions to reduce chronic diseases, whereas vaccinations usually reduce hospitalisations and severe illness within days or weeks.

The authors believe that success against antivaccination movement can draw on the tobacco wars’ lessons, illustrating COVID’s harm and the power of vaccines. Getting vaccinated and boosted should be the accepted social norm during a pandemic, they stress.

Drawing on similar efforts for anti-tobacco campaigns, vaccination campaigns using real patients in ICU who express regret over not being vaccinated. Unvaccinated people often assume they can be cared for if they get sick, so messages could also be included from healthcare works talking about the strain of the pandemic.

“There is an opportunity to mount a serious effort to provide accurate vaccination information using the same media channels on which people currently consume misinformation,” they wrote.

They also consider vaccine mandates which make being vaccinated a social norm such as wearing a seatbelt, and other regulations at the community and business level may be more effective.

They note that personal physicians play a key role, being the best way to transmit health information. But many people at risk of remaining unvaccinated have had negative experiences with health care, compounded by doctors spreading misinformation.

The authors note that the dangers of tobacco use were known to public health practitioners for years, but it took a well-funded concerted effort that emphasised the impact on others to achieve a change in behaviour. This is something that needs to be repeated for vaccinations.

“Freedom of choice remains; people can still smoke cigarettes and decline vaccinations. But the roadmap drawn by tobacco-control efforts shows that the public mindset can be tilted toward public health and social good. With vaccination, this work shouldn’t take decades; it needs to begin immediately.”

Source: New England Journal of Medicine