Tag: 4/6/21

Olaparib Excels in Breast Cancer Trial

A clinical trial of olaparib has been shown to help keep certain early-stage, hard-to-treat breast cancers at bay after initial treatment in promising early findings.

The results were so promising they were published early, ahead of the American Society of Clinical Oncology’s annual meeting and published in the New England Journal of Medicine

Olaparib, sold under the name Lynparza, was found to help breast cancer patients with harmful mutations have a longer disease-free survival after their cancers had been treated with standard surgery and chemotherapy.

It was studied in patients with BRCA1 and BRCA2 gene mutations, which can not only predispose people to breast cancer if they don’t work properly, but who did not have a gene flaw that can be targeted by the drug Herceptin.

Most patients in the study also had tumours not fuelled by oestrogen or progesterone. Triple negative breast cancers are not fuelled by these two hormones nor by the gene Herceptin targets.

The new study tested Lynparza in 1836 women and men with early-stage disease who were given the drug or placebo pills for one year after surgery and chemotherapy. About 82% of participants had triple-negative breast cancer.

Independent monitors advised releasing the results after observing clear benefit from Lynparza. After three years, 86% of patients on it were alive without cancer recurrence compared to 77% in the placebo group.

The results suggest more patients should get their tumours tested for BRCA mutations to help guide treatment decisions, said ASCO president Dr Lori Pierce, a cancer radiation specialist at the University of Michigan.

Serious side effects were rare, and other less serious side effects included anaemia, fatigue and blood cell count abnormalities.

Lynparza, which is marketed by AstraZeneca and Merck, is already sold in the United States and elsewhere for treating metastatic breast cancers and for treating certain cancers of the ovaries, prostate and pancreas. It costs roughly US$14 000 per month, though what patients pay out of pocket varies depending on income, insurance and other factors.

Source: Medical Xpress

A COVID Vaccine Without the Jab

Photo by Webstacks on Unsplash

University of Queensland scientists used a ‘patch’ to deliver a US-developed COVID vaccine without the jab, and successfully protected mice from the virus.

The vaccine candidate from University of Texas Hexapro was delivered via the high-density microarray patch (HD-MAP) and provided protection against COVID disease with a single, painless ‘click’ from a handheld applicator.

Dr David Muller, from UQ’s School of Chemistry and Molecular Biosciences, said the vaccine patch produced strong immune responses that were shown to be effective when the mice were exposed to SARS-CoV-2.

“When the Hexapro vaccine is delivered via HD-MAP applicator – rather than a needle – it produces better and faster immune responses,” Dr Muller said.

“It also neutralises multiple variants, including the UK and South Africa variants.

“And it’s much more user-friendly than a needle – you simply ‘click’ an applicator on the skin, and 5000 microscopic projections almost-imperceptibly deliver vaccine into the skin.

“The UQ team, together with Vaxxas, hope to take the technology to the world and are looking for funding opportunities to accelerate to clinical trials as soon as possible.”
Dr Muller said that Hexapro, delivered by the high-density microarray patch, could dramatically assist global vaccine rollout effort, particularly for billions of vulnerable people in low- and middle-income countries.

“We’ve shown this vaccine, when dry-coated on a patch, is stable for at least 30 days at 25 degrees Celsius and one week at 40 degrees, so it doesn’t have the cold chain requirements of some of the current options.”

High-density microarray patch (HD-MAP)

Vaxxas was founded in 2011 with the help of University of Queensland. The company’s president and CEO, David L Hoey, said he was extremely excited about the findings.

“These results are extremely clear – vaccination by HD-MAP produces much stronger and more protective immune responses against COVID-19 in model systems than via needle or syringe,” he said.

“We thank and recognise our incredible research collaborators at UQ for these important findings.

“The prospect of having a single-dose vaccine, that could be easily distributed and self-administered, would greatly improve global pandemic vaccination capabilities,” said Hoey

The research is currently undergoing peer review and has been published in BioRxiv (DOI: 10.1101/2021.05.30.446357).

Source: The University of Queensland

Financial Feasibility of NHI Challenged

Photo by cottonbro from Pexels

Health groups are seeking detailed information on the workings of South Africa’s new National Health Insurance (NHI) scheme, particularly on its financial feasibility.

The Khayelitsha and Klipfonetin health forums said in a presentation to parliament that a proper analysis is necessary to see if South Africa can even afford to fund the NHI. This is a concern that has been echoed by experts. The analysis should also find out if the public trusts the government to be able to deliver an NHI that is fully inclusive of community participation, the forums said.

“There is a view that perhaps we need to be building our public healthcare system as a priority to ensure a successful transition to an NHI Fund,” it said.

The forums also raised concerns around what the NHI will mean for existing healthcare systems – including the future of the country’s medical aids.

“Clarity is needed with respect to how the NHI Bill will address the transition between private medical aids and a universal healthcare system for all.

“The gap between private and public healthcare needs to be bridged and how this is done is important.”

Other critics have also pointed out that the scheme does nothing to address the serious gaps and flaws in South Africa’s healthcare system.

The fate of medical aids

The NHI Bill currently states that when the system is “fully implemented”, services that are paid for by the NHI will not be covered by medical aids.

Discovery Health has said that while it is in general supportive of the structural changes being introduced through the NHI, medical aids should not be limited.

“Our strong view is that limiting the role of medical schemes would be counterproductive to the NHI because there are simply insufficient resources to meet the needs of all South Africans.

“Limiting people from purchasing the medical scheme coverage they seek will seriously curtail the healthcare they expect and demand. It poses the risks of eroding sentiment, and of denuding the country of critically needed skills, and is impacting negatively on local and international investor sentiment and business confidence.”

Crucially, by preventing those who can afford it from using their medical scheme cover, and forcing them into the NHI system, this approach will also have the effect of increasing the burden on the NHI and will drain the very resources that must be used for people in most need, the scheme said. Significantly, there is no indication by government as to how the NHI will be paid for, or whether it can even be afforded, with only mention made to payroll taxes and other revenue streams being tapped.

Source: BusinessTech

Diet Affects both Breast Microbiome and Breast Cancer Tumours

Breast cancer cells. Image source: National Cancer Institute on Unsplash

The breast has its own microbiome of bacteria, and new research has shown it can be influenced by diet, as can breast cancer tumours.

In 2018, scientists at Wake Forest School of Medicine, part of Wake Forest Baptist Health, showed that diet, just like the gut microbiome, can influence the breast microbiome.

Now, new research shows that diet, including fish oil supplements, can alter not only the breast microbiome, but also breast cancer tumours. The findings were published online in Cancer Research.

To untangle the relationship between microbiome, diet and cancer risk, researchers undertook a multi-pronged approach to study both animal models and breast cancer patients.

“Obesity, typically associated with a high-fat diet consumption, is a well-known risk factor in postmenopausal breast cancer,” said Katherine L. Cook, PhD, assistant professor in the surgery – hypertension and cancer biology departments at Wake Forest School of Medicine. “But there’s still a lot we don’t know about the obesity link to microbiomes and the impact on breast cancer and patient outcomes.”

In the first part of the study, mice susceptible to breast cancer were fed either a high-fat or a low-fat diet. Mice consuming the high-fat diet had more tumours, which were also larger and more aggressive than the tumours in the low-fat diet group.

Next, to study the microbiome, researchers performed faecal transplants. Mice consuming the low-fat diet received the high-fat diet microbiome transplant, and mice consuming the high-fat diet received the low-fat diet microbiome transplant. Unexpectedly, mice that consumed the low-fat diet and received a high-fat diet microbiome had just as many breast tumours as mice on the high-fat diet.

“Simply replacing the low-fat diet gut microbiome to the microbiome of high-fat diet consuming animals was enough to increase breast cancer risk in our models,” Cook said. “These results highlight the link between the microbiome and breast health.”

Researchers also conducted a double-blind placebo-controlled clinical trial with breast cancer patients, with patients either receiving placebo or fish oil supplements for two to four weeks before lumpectomy or mastectomy.

Results showed that fish oil supplementation significantly modified the breast microbiome in both non-cancerous and malignant breast tissue. For example, scientists found longer-term administration of fish oil supplements (four weeks) increased the proportional abundance of Lactobacillus in the breast tissue near the tumour. Lactobacillus is a genus of bacteria shown to decrease breast cancer tumour growth, suggesting potential anti-cancer properties of this intervention. Researchers also found decreased proportional abundance of Bacteroidales and Ruminococcus microbes in the breast tumours of patients taking the supplements, though the significance of this is not understood.

“This study provides additional evidence that diet plays a critical role in shaping the gut and breast microbiomes,” concluded Dr Cook. “Ultimately, our study highlights that potential dietary interventions might reduce breast cancer risk.”

Dr Cook’s team is also conducting further studies to see if probiotic supplements can affect microbiome populations in mammary glands and in breast tumours.

Source: Wake Forest Baptist Medical Center

Ventricular Assist Device Pulled from Market due to Failures

Photo from Olivier Collett on Unsplash
Photo from Olivier Collett on Unsplash

The HeartWare system, a left ventricular assist device (LVAD) for advanced heart failure patients, is being discontinued immediately, according to the Food and Drug Administration.

The manufacturer, Medtronic, is halting global distribution and sale of its HeartWare system in the wake of observational evidence of increased neurological adverse events and mortality for its LVAD compared with similar mechanical circulatory support (MCS) devices.

Last December, some HeartWare LVADs were recalled because of complaints that the pump may delay or fail to start. So far 100 of these complaints have been received, including 14 patient deaths and 13 cases where an explant was necessary, the FDA noted.

“We have been carefully monitoring the adverse events associated with this device and support its removal from the marketplace,” said Bram Zuckerman, MD, director of the Office of Cardiovascular Devices at the FDA’s Center for Devices and Radiological Health, in a statement.

Medtronic now advises physicians to immediately stop new implants of the HeartWare device, but does not recommend explants.

The company is working on a plan for ongoing support of the some 4000 patients around the world who currently have this LVAD. It received commercial approval for use in the US in November 2012.

The FDA named Abbott’s HeartMate 3 as one alternative LVAD for patients with end-stage heart failure. This device features a magnetic levitation system that keeps the rotor separate without mechanical contact.

“The FDA is working closely with both Medtronic and Abbott to ensure patient care is optimised during this transition period and that there is an adequate supply of devices available to provide this patient population with options for end-stage heart failure treatment,” said Dr Zuckerman.

In a separate press release, Abbott reassured the public that it has the ability to meet increased demand for MCS devices as a result of HeartWare withdrawal from clinical use.

Source: MedPage Today

Free Will not Undermined by Neuroscience

Image by Falkurian Design on Unsplash

A new article argues that recent research undermines the notion that free will is an illusion, due to the buildup of brain activity before conscious movement.

Experiments from the 1960s to 1980s measured brain signals, leading many neuroscientists to believe that our brains make decisions before we do — that human actions were initiated by electrical waves, and therefore did not reflect free, conscious thought.

However, a new article in Trends in Cognitive Science argues that recent research undermines this contention against free will.

Study co-author Adina Roskies, and Helman Family Distinguished Professor, Dartmouth College, said: “This new perspective on the data turns on its head the way well-known findings have been interpreted. The new interpretation accounts for the data while undermining all the reasons to think it challenges free will.”

The debate over free will is mostly built on 1980s research using electroencephalograms to study brain activity. The EEG-based research measured when electrical signals begin to build in the brain, relative to when a person is aware of their desire to initiate a movement. The averaged data showed a buildup before movement that became known as the ‘readiness potential‘ (RP).

That research, conducted by neurophysiologist Benjamin Libet, contended that if the RP was present before a person had a conscious thought about moving, free will therefore could not be responsible for either the buildup of electrical signals or the subsequent movement.

This part of Libet’s logic was based on a likely false premise, the researchers argue.

“Because the averaged readiness potential reliably precedes voluntary movement, people assumed that it reflected a process specifically directed at producing that movement. As it turns out, and as our model has shown, that is not necessarily the case,” explained co-author Aaron Schurger, an assistant professor of psychology at Chapman University.

The article notes new research using computational modeling that indicates that the RP’s standard interpretation should be reassessed, especially in relation to the question of free will.

The study highlights findings suggesting that the RP — the pre-movement buildup of activity — reflects the neural activity that underlies the formation of a decision to move, as opposed to the outcome of a decision to move.

“These new computational models account for the consistent finding of the readiness potential without positing anything like an RP in individual trials. The readiness potential itself is a kind of artifact or illusion, one which would be expected to appear just as it does give the experimental design, but doesn’t reflect a real brain signal that begins with the RP onset or is read out by other areas,” said Prof Roskies.

Numerous challenges exist to the idea that the RP causes humans to act: isolating RP from other electrical signals in the brain; RP presence in tasks where motor activity is not needed; and ‘noise’ in analyses trying to confirm that RP initiates movement.

False positives, where RP is observed but fails to initiate movement, and inconsistencies in the lag between brain wave buildup and movement also complicate the understanding of the connection between the electrical activity in the brain and free will. Finally, there are philosophical implications to attempting to explore free will with brain data.

Source: Medical Xpress

Journal information: Aaron Schurger et al, What Is the Readiness Potential?, Trends in Cognitive Sciences (2021). DOI: 10.1016/j.tics.2021.04.001