Year: 2021

Categories : CancerTags :

Common Chemical in Medical Products Linked to Breast Cancer

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Researchers in Japan have found that widely used chemicals called photoinitiators cause breast tumours to accelerate in mice. 

Photoinitiators, which release reactive molecules in response to UV radiation,  are used in a wide range of products, including plastics, paints, inks, and adhesives. Photoinitiators are present in common objects as well as in medical products and instruments such as dental fillers and containers.

Recent studies have demonstrated several health hazards associated with photoinitiators, raising safety concerns. In particular, the presence of these compounds in clinical instruments, routinely used for treating high-risk individuals such as cancer patients, has become a major cause for concern. Previous research has shown that three photoinitiators commonly found in plastics and paints 1-HCHPK, MBB, and MTMP show oestrogen-like effects on cultured breast cancer cells, increasing their proliferation. Found in marketed injection solutions, the clear link between oestrogen activity and breast cancer made determining their effect a priority.

In a study published in Current Research in Toxicology, lead researcher Dr Yoichi Kawasaki and Prof Toshiaki Sendo from Okayama University examined how exposure to 1-HCHPK, MBB, and MTMP affected the growth of transplanted breast cancer tumours in mice. They found that all three compounds caused a faster increase in the growth of breast tumors, within 13 weeks of treatment. “This study extends our previous findings and shows that in addition to promoting the proliferation of breast cancer cells in culture, these photoinitiators also increase the growth of breast tumours in live animals. This implies that they could also potentially hasten disease progression in breast cancer patients,” explained Dr Kawasaki.    

The study results show that 1-HCHPK, MBB, and MTMP have oestrogen-like activity and could thus act as hormonal disruptions. Given oestrogen’s role in regulating reproductive function in both men and women, such disruptions could affect not only patients with breast cancer, but also healthy individuals. While the researchers intend to explore the effects of photoinitiators on reproduction in future research, the present study informs breast cancer management, as well as making urgent call-to-action to eliminate toxic materials from medical equipment.

“Photoinitiators have helped us improve the quality of several commonly used products. But it is time we reconsider whether their benefits outweigh their risks, and our findings are an important milestone in encouraging this conversation. We hope that it will prompt more intensive research and stricter regulations on what materials can be adopted for commonly used products, especially those with medical applications,” said Dr Kawasaki.

Source: EurekAlert!

Categories : Medical Research & TechnologyTags :

New Effort to Improve Diversity in Clinical Trials

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Columbia University and Pfizer Inc. have established the Columbia-Pfizer Clinical Trials Diversity Initiative, which aims to reduce health disparities by increasing the number of minorities in clinical trials and making clinical researchers more diverse.

In the United States, 12% of the population is Black and 18% is Hispanic or Latino but in 2020, only 8% were Black and 11% were Hispanic among the 32 000 patients who participated in clinical trials that led to FDA approval of new drugs. For example, a review of clinical trials between 1999 and 2015 for cystic fibrosis only had a representation of 2.0% for Latinos, 1.0% for Black individuals, and 0.1% for Asians.

“People of different ethnicities can have different responses to the same medicine or treatment, so a lack of diversity among clinical trial participants means doctors cannot know if the treatment will be effective in all the patients they treat,” said Anil K Rustgi, MD, Interim Executive Vice President and Dean of the Faculties of Health Sciences and Medicine at Columbia University and director of the Herbert Irving Comprehensive Cancer Center. “Increasing diversity in trials will improve the treatment of patients from underrepresented groups and is a moral imperative as well as a fundamental medical issue.”

Rod MacKenzie, PhD, Executive Vice President and Chief Development Officer at Pfizer, said, “Diversity of representation in clinical trials is a matter of equity, which is a core Pfizer value. We are deeply committed to ensuring our clinical trials reflect the diversity of the communities like New York in which they are conducted. We look forward to working with Columbia University both to offer any willing individual, regardless of background, the opportunity to participate in and contribute to clinical research, and to expand the roster of diverse clinical researchers who are helping us conduct studies.”

Pfizer will provide a three-year, $10 million grant to Columbia to help establish and expand the Initiative, which will improve the diversity of participants in clinical trials by looking at the barriers that prevent participation by marginalised individuals. The Initiative will expand Columbia’s Community Health Workers Program network to connect with underserved populations and create culturally sensitive engagement tools. The efforts will include researching new ways to increase the accessibility of clinical trials through telemedicine, wearable technology, and home visits.

The Initiative also aims to improve diversity among clinical research faculty and staff. Columbia will help build an additional pipeline of diverse clinical investigators through a new National Diversity Clinical Trials Leadership Program to increase the number of faculty and staff from underrepresented groups as well.

“A diverse research staff not only helps to improve trust in clinical trials among participants from underserved groups but improves the entire clinical trial enterprise by bringing different questions, experience, and perspective to the table,” Dr Rustgi said.

Source: Columbia University Irving Medical Center

Categories : PaediatricsTags :

Glasses Boosts Academic Performance for Students Who Need Them

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Students receiving eyeglasses through a school-based initiative scored higher on reading and math tests, found in the largest clinical study of the impact of glasses on education ever conducted in the US. Students struggling the most academically showed the greatest improvement.

The study by Johns Hopkins researchers from the Wilmer Eye Institute and School of Education is published in JAMA Ophthalmology.

“We rigorously demonstrated that giving kids the glasses they need helps them succeed in school,” said senior author Megan Collins, a paediatric ophthalmologist at the Wilmer Eye Institute. “This collaborative project with Johns Hopkins, Baltimore City and its partners has major implications for advancing health and educational equity all across the country.”

The team studied students who received eye examinations and glasses through the Vision for Baltimore program. The effort was launched in 2016 after an acute need for vision care among the city’s public school students was identified: as many as 15 000 of the city’s 60 000 pre-K (age 2 to 4) through 8th-grade (age 13 to 14) students likely needed glasses though many were unaware or were unable to get them.

Over five years, Vision for Baltimore has tested the vision of more than 64 000 students and distributed more than 8000 pairs of glasses. The Johns Hopkins study represents the most robust work thus far evaluating whether having glasses affects a child’s performance in school.

The three-year randomised clinical trial, conducted from 2016 to 2019, analysed the performance of 2304 students in grades 3 to 7 who received screenings, eye examinations and eyeglasses from Vision for Baltimore. The team looked at their scores on standardised reading and math tests, measuring both 1-year and 2-year impact.

After one year, reading scores increased significantly for students who got glasses, compared to those getting glasses later. There was also significant improvement in maths for students in primary grades.

There were particularly striking improvements for girls, special education students, and students who had been among the lowest performing.

Megan Collins, senior author said, “The glasses offered the biggest benefit to the very kids who needed it the most – the ones who were really struggling in school.”

The gains were about the same as two to four months of extra education compared to students with glasses, said lead author Amanda J Neitzel, deputy director of evidence research at the Johns Hopkins Center for Research and Reform in Education. For students performing in the lowest quartile and students in special education, wearing glasses equated to four to six months of additional learning.

“This is how you close gaps,” Neitzel said.

However, the academic improvements seen after one year were not sustained over two years. Researchers suspect this could be a result of students starting to wear their glasses less, perhaps from loss or breakage.

To keep up the academic achievement boost, the researchers recommend that school-based vision initiatives should also try to ensure children are wearing the glasses and to replace them if needed.

Source: Johns Hopkins University

Categories : Cancer Ethics and LawTags :

Many Lung Cancer Patients Choose Euthanasia Without Exploring Treatment

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A Canadian study of lung cancer patients who opted for “medical assistance in dying” often proceeded without consultation with their radiation oncologist or medical oncologist.

In a Canadian study of 45 individuals diagnosed with lung cancer who used medical assistance in dying (also known as physician-assisted suicide), about 20% did not have a radiation oncologist involved when making the decision and 22% did not have a consultation with a medical oncologist, said Sara Moore, MD, of Ottawa Hospital Research Institute of the University of Ottawa.

Since 2016, about 60% of those seeking to end their life through legal means introduced in Canada had been diagnosed with cancer, Dr Moore explained in a presentation at the virtual World Conference on Lung Cancer.

Driven by loss of autonomy, control and dignity
The designated discussant, Monica Malec, MD, a geriatric and palliative care physician at the University of Chicago, said this was the first study to evaluate medical assistance in dying in patients with lung cancer, oncologists’ involvement, and treatment history.

“The demand for medical assistance in dying is increasing and is becoming more readily available to patients,” Dr Malec said. “Patients are seeking this option despite the availability of more effective and more tolerable treatment options. Existing literature suggests that loss of autonomy, control, and dignity are the primary drivers for seeking medical assistance in dying rather than uncontrolled symptoms, and the decision to pursue medical assistance in dying may occur pre-illness.”

Moore noted that while lung cancer accounts for 20%-25% of all cancer deaths overall, in the current study 17.5% of the patients had lung cancer diagnoses. “Lung cancer comprises slightly fewer medical assistance in dying cases than expected compared to lung cancer death rates,” she said.

Improved treatments disregarded
“Biomarker-driven targeted therapy and immunotherapy offer effective and tolerable new treatments, but a subset of patients undergo medical assistance in dying without accessing — or, in some cases, without being assessed for — these treatment options,” Dr Moore continued. “Most patients were assessed by an oncology specialist, though less than half received systemic therapy.”

“Given the growing number of efficacious and well-tolerated treatment options in lung cancer, consultation with an oncologist may be reasonable to consider for all patients with lung cancer who request medical assistance in dying,” she said.

The researchers screened data from the Ottawa region, and identified 256 patients with a cancer diagnosis who had used medical assistance in dying. Of these, 45 patients had a lung cancer diagnosis.About 85% had a history of tobacco smoking, and 36% were current smokers at the time they sought medical assistance in dying, Moore reported. Thirteen of these patients had no biopsy confirmation of their disease, but almost all (91%) opting for medical assistance in dying were diagnosed with metastatic disease. Average age was 72 years, and 64% (29 of 45 patients) were women, even though men are more often diagnosed with lung cancer, Dr Moore noted. 
Limitations included being limited to only a single region, and a lack of information on patients’ decision-making process.

Source: MedPage Today

Categories : New Compounds and Treatments Pain ManagementTags :

Breakthrough Could Lead to New Opioid Alternatives

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Monash University researchers have made a breakthrough discovery that might lead to new non-opioid analgesics to treat neuropathic pain safely and effectively, without the risk of opioid addictions.

Neuropathic pain occurs when nerves are damaged or dysfunctional, and can be caused by injury, virus infection or cancer treatment, or it can be a symptom or complication of conditions such as multiple sclerosis and diabetes.

The new study, published in Nature, has shown a new mode of targeting the adenosine A1 receptor protein, which had long been a promising therapeutic target for non-opioid painkillers to treat neuropathic pain. However, development of analgesics using it had failed due to a lack of sufficient on-target selectivity, as well as undesirable adverse effects.

In the study, Monash researchers used electrophysiology and preclinical pain models to show that a particular class of molecule, called a ‘positive allosteric modulator’ (PAM), can enhance the targeting of the A1 receptor by binding to a different region of the protein.

Another breakthrough in the study was observing the high-resolution structure of the A1 receptor bound to both its natural activator, adenosine, and an analgesic PAM, which was facilitated by the application of cryo electron microscopy (cryoEM), providing the first atomic level snapshot of the drug binding location.

Chronic pain remains a widespread global health burden. A lack of treatment options has led to over-reliance on opioid painkillers, which provide only limited relief in patients with chronic (particularly neuropathic) pain, while having severe adverse effects, such as respiratory depression and addiction. In 2016, 42 000 deaths related to opioid misuse were recorded in the US, while 25 million Americans suffer from chronic pain.

This new discovery opens the door to the development of non-opioid drugs that lack such side effects.

Co-corresponding author of the study and Dean of the Faculty of Pharmacy and Pharmaceutical Sciences, Professor Arthur Christopoulos said: “The world is in the grip of a global opioid crisis and there is an urgent need for non-opioid drugs that are both safe and effective.”

Source: Monash University

Categories : COVIDTags :

Platelet Signalling Implicated in COVID Organ Damage

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New research finds that one cause of organ damage in COVID patients is abnormal crosstalk between blood platelets and cells lining blood vessels.

The study published in Science Advances, revealed the protein signals released by platelets cause inflammation, abnormal clotting, and damage to vessels when exposed to SARS-CoV-2.

The work identified two related genes, S1000A8 and S1000A9, which are turned up in the platelets of COVID patients, causing them to make more of myeloid-related proteins (MRP) 8 and 14. Higher levels of the dual proteins were linked in the study to higher levels of clotting and inflammation in vessels and worse outcomes.

In support of the theory that platelets are at the core of blood vessel damage in COVID, the research team also presented evidence that approved medications known to block platelet activation via the platelet surface protein P2Y12 (clopidogrel or ticagrelor) reduced COVID-related inflammation in vessels. The study also found that COVID-exposed platelets change cells lining blood vessels (endothelial cells) largely through a protein called p-selectin, which makes platelets stickier and more likely to form clots.

“Our findings reveal a new role for platelets in COVID blood vessel damage, and may explain in large part what makes the COVID virus so much more deadly than its relatives that cause the common cold,” said corresponding author Tessa Barrett, PhD,.

Abnormal, body-wide inflammation and blood clotting were identified early in the pandemic as central features of severe COVID-19, with the two thought to be interrelated, say the study authors. As blood components that react to injuries in vessels by triggering inflammation, and by becoming sticky to clump together in clots, platelets are a possible culprit. Increasing evidence shows that interplay between platelets and endothelial cells may be important to these disease mechanisms.

For the current study, endothelial cells from small blood vessels were exposed to fluid released from the platelets of either COVID patients or healthy controls. RNA was then sequenced, In the presence of COVID-activated platelets, changes were observed in the activity of the exposed endothelial cells. Genes expressed differently in COVID-19 were linked to clotting, inflammation, and the weakening of junctions between endothelial cells, which lets blood serum seep into tissue to cause the pulmonary oedema seen in severe cases, where patients’ lungs fill with fluid.

The large list was narrowed down to S100A8 and S100A9, which coded for the building of MRP 8 and 14. COVID in patients was found to increase the amount of MRP8/14 produced by platelets and other cells by 166 percent compared to controls. Higher levels of these proteins were linked to abnormal thrombosis, inflammation, and critical illness among hospitalised COVID patients. Curiously S100A8/A9 were not upregulated after exposure of platelets to a coronavirus relative, CoV-OC43, which causes the common cold.

Additionally, damage and abnormal clotting could arise from p-selectin, which promotes platelet clumping and immune-boosting signals. The researchers also found that the anti-clotting P2Y12 inhibitors reduced the expression of S100A8 and S100A9 in platelets by 18 percent over four weeks, and in lab tests prevented COVID platelets from inducing blood vessel damage.

“The current study supports the theory that platelets are activating endothelial cells through P-selectin, and that both p-selectin and MRP8/14 contribute to vessel damage and an increased risk of dying,” said senior study author Jeffrey S. Berger, MD. “As our team also leads ACTIV4a, a large, ongoing NIH-funded, anti-clotting trial in COVID, we are currently testing in patients whether P2Y12 inhibitors can better prevent severe disease, with the results to be presented at the American Heart Association annual meeting in November.”

Source: NYU Langone Health

Categories : CancerTags :

Bone Marrow Cell Mutations That Protect Against Cancers

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Source: NIH

People with shortened telomeres caused by rare disorders may be more likely to have blood cancers such as leukaemia or myelodyplastic syndrome (MS). Now researchers have discovered several “self-correcting” genetic mutations in bone marrow that may protect such patients from these cancers.

In a study published in the Journal of Clinical Investigation, these mutations can serve as biomarkers to indicate if patients with short telomere syndromes (STS) are likely to develop blood cancers.

“These are the most common cancers we see in patients with short telomere syndromes,” said Mary Armanios, MD, director of the Telomere Center and professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. “We know that at a certain point, the cells of patients with shortened telomeres either become cancerous or stay healthy.”

Dr Armanios and her team suspected that a self-correcting mechanism in areas of the body with high cell turnover, such as bone marrow, was allowing normal cells to turn malignant. Instead, it appears this mechanism protects against cells from becoming cancerous.

As over 300 billion blood cells are produced in the bone marrow daily, the researchers suspected they could find evidence of cellular self-correction in this area of the body, especially amid the spongey interior of bones, where quick adaptation is crucial for high-volume cell production.
The researchers tested the bone marrow and blood cells of 84 study participants divided into three groups: Those with STS and MS or leukaemia; those with short telomere syndromes and no MS or leukemia; and those in the control group without short telomere syndromes or any cancers.

Using ultra-deep genetic sequencing which picks up hard-to-detect mutations, Armanios and her team observed genetic mutations and self-correction in several telomere-associated genes. Nearly a quarter of patients with STS had these mutations, some even showing multiple mutations.

One such mutation in a gene called TERT enables the production of crucial parts of telomerase, which stabilises telomeres. By boosting telomerase production and overwriting faulty copies of the TERT gene, the researchers found that bone marrow cells seemed to self-correct to avoid becoming cancerous.

“Our findings speak to the versatility of the bone marrow and other areas with high cell turnover in the body,” says Armanios. “Such advantageous mutations provide the body with a better chance to protect itself. These findings may be important in the screening process of shortened telomere patients so that we can predict who may be protected from cancer.”

Source: John Hopkins Medicine

Categories : COVID Diet and NutritionTags :

Healthy Diets Reduce COVID Risk

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A study based on self-reported app data showed that people who eat a high quality, gut friendly diet are less likely to develop COVID-19 or become severely ill. Those eating poorer quality diets are more at risk, especially if they live in a more socioeconomically deprived area.

The study, presented in GUT, analysed data from almost 600 000 ZOE COVID Study app contributors. Participants completed a survey about the food they ate before the pandemic, in February 2020, making it the largest study in this space. 19% of these contributors contracted COVID-19.

People with the highest quality diet were around 10% less likely to develop COVID than those with the lowest quality diet, and 40% less likely to fall severely ill.

This is the first longitudinal study of diet and COVID and the first to show that a healthy diet cuts the chances of developing the disease in the first place.

Instead of looking at specific foods, the survey aimed to broadly capture people’s diets. A ‘diet quality score’ reflected the overall merit of each person’s diet. Diets with high quality scores were found to contain plant-based foods such as fruits, vegetables and whole grains, as well as oily fish, less processed foods and refined carbohydrates. A low diet quality score is associated with diets high in ultra processed foods and low amounts of plant based foods.

The researchers found that people who ate the highest quality diet were around 10% less likely to develop COVID-19 than those with the least nutritious diet and 40% less likely to become severely ill if they developed COVID.

The link between diet quality and COVID risk persisted after accounting for all potential confounding factors such as age and BMI. Mask-wearing habits and population density were also considered.

The effect of diet was amplified by individual life situations, with people living in low-income neighbourhoods with the lowest quality diet being around 25% more at risk from COVID than people in more affluent communities eating the same kind of diet.

Based on these results, the researchers estimate that nearly a quarter of COVID cases could have been prevented if these differences in diet quality and socioeconomic status had not existed. The study also showed that improved access to better food is an important public health consideration.

Dr Sarah Berry, study co-lead and Reader in nutritional sciences at the School of Life Course Sciences said: “For the first time we’ve been able to show that a healthier diet can cut the chances of developing COVID, especially for people living in the more deprived areas. Access to healthier food is important to everyone in society, but our findings tell us that helping those living in more deprived areas to eat more healthily could have the biggest public health benefits.”

Professor Tim Spector, professor of genetic epidemiology at the School of Life Course Sciences, said: “These findings chime with recent results from our landmark PREDICT study, showing that people who eat higher quality diets (with low levels of ultra-processed foods) have a healthier collection of microbes in their guts, which is linked to better health. You don’t have to go vegan, but getting more diverse plants on your plate is a great way to boost the health of your gut microbiome, improve your immunity and overall health, and potentially reduce your risk from COVID.”

Source: Kings College London

Categories : Diseases, Syndromes and Conditions Medical IndustryTags :

Review Looks at The Evidence for Cannabis in Paediatric Epilepsies

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A review published in Developmental Medicine & Child Neurology investigates the knowledge base of cannabis-based medicinal products in paediatric epilepsies, highlighting areas in need of additional research.

Following reports in the media of children with epilepsies apparently deriving benefits from medical marijuana (or cannabis-based medicinal products) accessed abroad, the UK government allowed clinicians to prescribe these products. A previous review found that there was some benefit in certain drug-resistant epilepsies in children.

In the review, the authors also looked at the prescribing environment surrounding these products. They found that the major obstacle to prescribing is a lack of quality evidence for efficacy and safety.
The authors stress that unlicensed cannabis-based medicinal products should not circumvent the usual regulatory requirements before being prescribed. They are also concerned that children with epilepsy are at risk of being exploited as a “Trojan horse” for the cannabis industry, with widespread acceptance of medicinal cannabis accelerating the wider legalisation of marijuana and opening up a highly lucrative commercial market.

Source: News-Medical.Net

Categories : Ethics and Law Medical Research & TechnologyTags :

Fraud Trial of Theranos Boss Begins

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On Wednesday, the trial of Elizabeth Holmes, founder of medical technology company Theranos, began. Prosecutors alleged she “lied and cheated” for money and fame.

Ms Holmes faces 12 fraud charges over her role at the failed company which was once worth $9bn, facing up to 20 years in prison if found guilty.

She is accused of deceiving patients and investors about the company’s testing technology, which was claimed to diagnose basic illnesses from a few drops of blood. Her defence team argues that she was naive and her company simply failed.

“Failure is not a crime. Trying your hardest and coming up short is not a crime,” said defence lawyer Lance Wade in his opening statement on Wednesday.

Former Theranos executive Ramesh “Sunny” Balwani faces the same charges next year. He was romantically involved with Ms Holmes.

Ms Holmes, who founded Theranos in 2003 aged 19, was dubbed the world’s youngest self-made female billionaire and hailed as the “next Steve Jobs”.

In 2015 and 2016, investigations by the Wall Street Journal revealed Theranos’ blood-testing devices did not work and the company was doing most of its testing on commercially available machines made by other manufacturers. She initially denied these reports.

Prosecutor Robert Leach alleges that, after running out of funds, Ms Holmes and Mr Balwani turned to fraud in 2009, lying about the tests and exaggerating the firm’s performance. Mr Leach said this included falsely claiming the tests were vetted by Pfizer and being used by the US military.

The case will probably take months and Ms Holmes will likely take the stand — a necessary gamble in the face of overwhelming evidence that the technology did not work.

Ms Holmes “dazzled” Walgreens into using the company’s services, and the company brought her fame.

“She had become, as she sought, one of the most celebrated CEOs in Silicon Valley and the world. But under the facade of Theranos’ success there were significant problems brewing.”

 The defence’s Mr Wade said Ms Holmes “naively underestimated” the business challenges but did not attempt to defraud investors. Ms Holmes has also alleged years of emotional and psychological abuse by Mr Balwani, who has denied the allegations. She is likely to testify as to how this affected her.

Source: BBC News