Day: February 16, 2021

Categories : Injury & Trauma Neurology Pain ManagementTags :

New Surgery Improves Prosthetic Use and Reduces Pain

On By ModernMedia

A new type of surgery that links muscles together may improve the precision of prosthetic use and also relieve pain.

In typical amputations, the muscle pairs (such as triceps and biceps) that work together to control the joints are severed. However, an MIT team has discovered that reconnecting these muscles that are in an agonistic-antagonistic (‘push-pull’) relationship improves the sensory feedback and thus precision of the affected limb.

“When one muscle contracts, the other one doesn’t have its antagonist activity, so the brain gets confusing signals,” explained Srinivasan, a former member of the Biomechatronics group now working at MIT’s Koch Institute for Integrative Cancer Research. “Even with state-of-the-art prostheses, people are constantly visually following the prosthesis to try to calibrate their brains to where the device is moving.”

The 15 patients who received the AMI surgery were able to flex their prosthetic ankle joint with more precision than those without it, who were only able to fully extend or flex their joint.

“Through surgical and regenerative techniques that restore natural agonist-antagonist muscle movements, our study shows that persons with an AMI amputation experience a greater phantom joint range of motion, a reduced level of pain, and an increased fidelity of prosthetic limb controllability,” says Hugh Herr, a professor of media arts and sciences, head of the Biomechatronics group in the Media Lab, and the senior author of the paper.

The surgery also had a completely unexpected benefit: the reduction of pain in the amputated area, which can be from neuromas or phantom limb pain. Phantom limb pain can occur in 80% of amputess. Six of the 15 AMI patients reported zero pain. This may be significant as in the five centuries since phantom limb pain was first described, there has not been much advancement in the understanding of it.

“Our study wasn’t specifically designed to achieve this, but it was a sentiment our subjects expressed over and over again. They had a much greater sensation of what their foot actually felt like and how it was moving in space,” Srinivasan says. “It became increasingly apparent that restoring the muscles to their normal physiology had benefits not only for prosthetic control, but also for their day-to-day mental well-being.”

To treat patients who had received the traditional amputation surgery, the team is also working on using muscle grafts to create a ‘regenerative AMI’ procedure that restores the effect of agonist and antagonist muscles.

Source: Medical Xpress

Journal information: Shriya S. Srinivasan el al., “Neural interfacing architecture enables enhanced motor control and residual limb functionality postamputation,” PNAS (2021). www.pnas.org/cgi/doi/10.1073/pnas.2019555118

Categories : Diseases, Syndromes and Conditions GeneticsTags :

Excessive False Positives from SNP Testing in Very Rare Diseases

On By ModernMedia

A widely-used genetic testing technology has a very high rate of false positives for extremely rare genetic diseases, a study has found.

Single nucleotide polymorphism (SNP) chips are DNA microarrays which test genetic variation at hundreds of thousands of specific genome locations. They were initially developed to study common genetic variations, and are excellent tools for tracing ancestry and aso detecting predisposition to common multifactorial diseases such as type 2 diabetes.

Prompted by accounts of women scheduling surgery because of wrongly being informed they had variations in the BRCA1 gene that could lead to very high risks of breast disease, a team from the University of Exeter set out to test the technology. Using data from 50 000 individuals, they found that the majority of rare disease detections were false.

“SNP chips are fantastic at detecting common genetic variants, yet we have to recognise that tests that perform well in one scenario are not necessarily applicable to others,” said senior author Caroline Wright, Professor in Genomic Medicine at the University of Exeter Medical School. “We’ve confirmed that SNP chips are extremely poor at detecting very rare disease-causing genetic variants, often giving false positive results that can have profound clinical impact. These false results had been used to schedule invasive medical procedures that were both unnecessary and unwarranted.”

The team compared data from the SNP chips to data from the UK Biobank which was sequenced with better technology, plus 21 volunteers sharing their consumer genetic data.

They found a false positive rate of 84% for variants that were 1 in 100 000. From the consumer data, 20 of the 21 had at least one false positive for a disease-causing variation.

Co-author Dr Leigh Jackson, Lecturer in Genomic Medicine at the University of Exeter, said the number of such false positives on SNP chips was “shockingly high.”

“To be clear: a very rare, disease-causing variant detected using a SNP chip is more likely to be wrong than right,” said Dr Jackson. “Although some consumer genomics companies perform sequencing to validate important results before releasing them to consumers, most consumers also download their ‘raw’ SNP chip data for secondary analysis, and this raw data still contain these incorrect results. The implications of our findings are very simple: SNP chips perform poorly for detecting very rare genetic variants and the results should never be used to guide a patient’s medical care, unless they have been validated.”

Source: Medical Xpress

Journal information: BMJ (2021). www.bmj.com/content/372/bmj.n214

Categories : COVIDTags :

Real-world Results for Pfizer Vaccine Match Trials

On By ModernMedia

Encouraging results have been reported from Israel, where the real-world efficacy of the Pfizer vaccine closely matches that seen in clinical trials.

Israel has engaged in the world’s most aggressive COVID immunisation schedule, with some 30% of its population vaccinated by late January with at least one dose.

Israeli health fund Clalit matched 600 000 vaccinated individuals to an equal number of unvaccinated individuals. Those who were vaccinated experienced a similar rate of positive COVID tests as was observed in clinical trial data, equating to a 94% effectiveness. Crucially, almost no severe cases of COVID were observed in vaccinated individuals. This pattern was also seen in the over-70s age group, which is generally underrepresented in trials.

Public health doctor Prof Hagai Levine said that high vaccination coverage of the most susceptible groups was key. However, he said that he could not give an answer as to what number needed to be vaccinated before containment measures could be eased. 

“We still don’t know what the impact is on transmission,” he said. But he added that “the vaccine is useful for personal protection”.

The greatest drop in cases was seen in the over 60s age group, and in areas which had been vaccinated, indicating that this was not the result of lockdown. However, many people still remain unvaccinated, resulting in tens of thousands of cases. Prof Segal noted that the fall in cases was not as rapid as had been hoped, due to the B.1.1.7 or UK strain becoming dominant in Israel.

“We still have to exit our lockdown very cautiously,” he warned, or else hospitalisations would spike again.

The fact that the same rate was observed in clinical trials is important news for other countries, which are watching to see the effects of Israel’s vaccination programme.

Source: BBC News

Categories : Mental Health Metabolic DisordersTags :

Why Antipsychotic Drugs Cause Weight Gain

On By ModernMedia

A University of Pittsburgh study has discovered that the reason antipsychotic medications have weight gain as side effects is because the pancreas also produces and responds to dopamine.

Dopamine is a neurotransmitter involved in mood regulation, pleasure and reward signalling. Many psychological disorders are thought to involve dopamine imbalances and are treated by medications designed to this end.
“There are dopamine theories of schizophrenia, drug addiction, depression and neurodegenerative disorders, and we are presenting a dopamine theory of metabolism,” said lead author Despoina Aslanoglou, PhD, at the University of Pittsburgh. “We’re seeing now that it is not only interesting to study dopamine in the brain, but it is equally interesting and important to study it in the periphery.”

Senior author Zachary Freyberg, MD, PhD, assistant professor of psychiatry and cell biology at Pitt, observed that the dopamine theory is not as simple or as well understood as we would like to think.

“We still don’t really understand how dopamine signals biologically,” said Dr Freyberg. “Even decades after dopamine receptors have been discovered and cloned, we still deploy this ‘magical thinking’ approach: something happens that’s good enough. We use drugs that work on dopamine receptors, but how they intersect with this ‘magical system’ is even less understood.”

The researchers found that dopamine is not only produced in the brain but also in the alpha and beta cells of the pancreas, which secrete glucagon and insulin, respectively.

Alpha cells can produce their own dopamine with no precursors in response to glucose levels, while beta cells require an L-DOPA precursor. It may be possible that alpha cells secrete dopamine for their own receptors, while also supplying it to beta cells to suppress the release of insulin.

Surprisingly, the researchers also discovered that pancreatic dopamine can affect other receptors, such as noradrenaline and adrenaline.
At low concentrations, dopamine binds to D2-like dopamine receptors, blocking the release of glucagon or insulin. At high concentrations, dopamine binds to beta-adrenergic receptors, becoming stimulatory and pushing up glucagon levels while inhibiting insulin levels by blocking alpha-adrenergic receptors.

The study revealed how blocking inhibitory dopamine receptors causes an unchecked release of insulin and glucagon, leading to metabolic disorders and eventually, obesity and diabetes. This finding will help to formulate better drugs that target the dopamine system, reducing the effect on the pancreas.

Source: News-Medical.Net

Categories : NeurologyTags :

Short Window for Recovery After Stroke

On By ModernMedia

Researchers have found that there is a short window for brain repair to be most effective after a stroke, which peaked at two weeks after the incident.

Brain scans conducted by the study showed that the brains of stroke survivors retained plasticity and an improved ability to rewire itself, the first time this had been observed in humans. The study took place in Adelaide and London.

The researchers regularly scanned the brains of 60 stroke survivors as they recovered over a period of 12 months. To assess neural plasticity, the researchers repeatedly activated the brain’s motor cortex using continuous transcranial magnetic stimulation (cTBS). The laboratory in London tested the non-damaged motor cortex, which is also important for stroke recovery while the one in Adelaide tested the damaged motor cortex. In the first few days following an ischaemic stroke, the brain had greater plasticity.

“Earlier animal studies suggested this was the case, but this is the first time we have conclusively demonstrated this phenomenon exists in humans,” Dr Hordacre said.

Only eight minutes of daily rehabilitation time after a stroke is spent on the upper limbs.

“Delivering more treatment within this brief window is needed to help people recover after a stroke,” Dr Hordacre said. “The next step is to identify techniques which prolong or even re-open a period of increased brain plasticity, so we can maximise recovery.”

Source: News-Medical.Net

Journal information: Hordacre, B., et al. (2021) Evidence for a Window of Enhanced Plasticity in the Human Motor Cortex Following Ischemic Stroke. doi.org/10.1177/1545968321992330.

Categories : COVID General InterestTags :

The Second Vaccine Dose Can Hit Hard

On By ModernMedia

The scuttlebut among healthcare workers is that the second dose of a COVID vaccine hits much harder than the first – unless you’ve had COVID, in which case the first is equally as bad.

TJ Maltese, DO, a neurologist in private practice on Long Island in New York state, was fine with the first dose of the Moderna vaccine but was flattened by the second one.

Dr Maltese got his second jab on a Friday at 4:30 pm. Within two hours his arm was sore. Overnight, he developed flu-like symptoms, and on Saturday experienced chills and body aches, with a lingering fever. He could have pushed through if he’d had to work, he said, but he rode out his symptoms on his couch with the help of the occasional painkiller.

By 9 pm on Saturday evening, Dr Maltese started to feel better, getting a good night’s sleep and on Sunday was fine again.

“I know plenty of people with minimal symptoms after the second dose, so it’s not definite you’ll feel side effects,” he wrote in a Facebook post. “But be prepared for the possibility.”

Immunology and the phase III clinical trial data from the vaccine backs up the view that the second dose is worse, and some hospitals have even altered their scheduling to allow time for recuperation after the second dose. Adverse reactions to the BCG vaccine in Brazilian school children, for example, have been reported to be common with the second dose, though still rare.  

Immunologists and infectious disease experts interviewed by MedPage Today and who shared their second-dose experiences said it’s not unexpected that second-dose reactions are more intense than the first. Typical reactions to the COVID vaccines include fever, headache and fatigue as the immune system responds to a vaccine’s antigens.

“The first time the immune system comes into contact with something, it’s getting primed,” said Purvi Parikh, MD, an immunologist at NYU Langone Health in New York City. “That goes for everything, from vaccines to allergies. It’s rare on the first time to have a strong reaction. After that, the immune system recognizes it, so you have a much stronger reaction.”

“We saw it in the trials, so it’s really not surprising,” Parikh added. “Now we’re seeing it in real time as the vaccines are being rolled out.”

More adverse effects were reported after the second dose in both Pfizer’s and Moderna’s phase III trial data. For Moderna, the rates were 54.9% versus 42.2% for placebo after the first dose and 79.4% versus 36.5% for placebo after the second dose.

Stanley Weiss, MD, an infectious disease specialist and epidemiologist at Rutgers New Jersey Medical School, told MedPage Today that because his institution served as a Moderna trial site, the primary investigator was able to give an early update on what to expect following vaccination.

“They said there was a very high rate of fatigue after the second dose, so we encouraged administrators … to figure that many healthcare workers getting the vaccine might not be well enough to work the day after the second dose,” Dr Weiss said.

Drs Weiss and Parikh both experienced a stronger response to the second COVID dose. 

Zubin Damania, MD, aka ZDoggMD, said he was knocked out by the second dose of Moderna vaccine, joking on his show that, “I couldn’t sleep, I had a fever, rigors, body aches, a headache — full-on man-flu.”

Paul Offit, MD, said that he also experienced fever and fatigue after taking the second dose of the Pfizer vaccine.

“That reaction is less common in people over 65, and I’m over 65, so I’m thinking I’m not going to suffer that, but I did,” Dr Offit said.

Older people are not expected to have as intense a reaction due to their weaker immune systems. According to Dr Parikh, “The idea is that their immune system is not as robust as a young person’s.”
The same immunological underpinnings of why reactions to the second dose are worse also apply to those who’ve had COVID.
Victoria Arthur, MD, of Lexington Pediatrics in Massachusetts, had suspected she had contracted COVID in March 2020 but could not prove it. When she received the Moderna vaccine, she felt much worse than her colleagues.

“How I felt was how everyone else was describing their second vaccine,” Dr Arthur told MedPage Today. Within three hours of her jab, she was suffering from a headache, neck pain, and cognitive fog. She awoke at 3am with nausea and stomach cramps, and spent the whole of the next day in bed. 

“I’m always grateful when I have a reaction, that means the body is doing its thing,” she said. “I’m very fortunate to have been given the vaccine, so any side effect is worth it.”

In spite of the side effects, these health care professionals all expressed gratitude at having been vaccinated.

Dr Weiss said that people shouldn’t be discouraged by the side effects from the second dose and not get vaccinated: “The benefits greatly overwhelm the risk of side effects. It’s not a reason to delay.”

Source: MedPage Today