Year: 2021

Bacteria in Cystic Fibrosis Use Slimy Shield to Ward off Drugs

Research has revealed that a common bacteria found in the lungs of those with cystic fibrosis produces a slime that acts as a defence against a variety of therapeutic drugs.

Dr Laura Jennings, a research assistant professor in UM’s Division of Biological Sciences and an affiliate with the University’s Center for Translational Medicine, headed the research.

A life threatening-condition caused by a genetic mutation, cystic fibrosis causes persistent lung infections and gradually reduces a person’s breathing capacity. A common strain of bacteria, Pseudomonas aeruginosa, often thrives in the lungs of people with cystic fibrosis,  and when a P. aeruginosa infection is established, it can be extremely hard to remove.
The research showed that stubborn bacteria dwelling in the lungs of cystic fibrosis patients produce a carbohydrate slime, which both shields them against antibiotics and also mucus-reducing drugs.

“We found the first direct evidence that these carbohydrates are produced at the sites of infection,” Dr Jennings said. “We showed that one of the carbohydrates, called Pel, sticks to extracellular DNA, which is abundant in the thick mucus secretions prominent in cystic fibrosis lungs.

“This interaction makes a slimy protective layer around the bacteria, making them harder to kill,” she said. “As such, it reduces the pathogen’s susceptibility to antibiotics and drugs aimed at reducing the thickness of airway mucus by digesting DNA.”

She explained that the research supports a theory that these carbohydrates also support the aggregation of these bacteria in the lungs of cystic fibrosis patients.

“This is important because we know that physically breaking up bacterial aggregates can restore bacterial susceptibility to killing with antibiotics and cells of the immune system,” Jennings said. “Therefore, understanding the mechanisms that promote bacterial aggregation may facilitate new therapeutic approaches aimed at digesting the carbohydrates holding bacterial cells together.”

Source: Medical Xpress

Journal information: Laura K. Jennings et al. Pseudomonas aeruginosa aggregates in cystic fibrosis sputum produce exopolysaccharides that likely impede current therapies, Cell Reports (2021). DOI: 10.1016/j.celrep.2021.108782

Only Smaller ‘Good’ Cholesterol Particles Reduce Heart Risk

New research on cholesterol shows that ‘good cholesterol’ is not all good for the heart – only smaller particles reduce heart risk.

Higher levels of ‘good cholesterol’ or high-density lipoprotein cholesterol (HDL-c ) have been associated with better cardiovascular outcomes. In contrast, ‘bad cholesterol’ or low-density lipoprotein cholesterol (LDL-c ), deposits cholesterol on artery walls, increasing the risk of cardiovascular disease.

Medications that lowers LDL-c  also reduce cardiovascular risk, but medication that increases HDL-c does not decrease cardiovascular risk. This paradox calls into question the assumption that HDL-c is protective against cardiovascular risk.

Researchers analysed the size of HDL-c particles, which is determined by genetic characteristics, and compared this to the risk of myocardial infarction. The results showed that genetic characteristics for having large HDL-c particles were associated with increased heart attack risk. Characteristics for smaller HDL-c particles were linked to reduced heart attack risk.

“There is a positive causal relationship between the size of HDL cholesterol particles and the risk of heart attack, so although we have to increase the levels of good cholesterol in the blood, they must always be small particles,” explains the study’s principal investigator, Dr Robert Elosua, a researcher at the Hospital del Mar-IMIM, CIBERCV, and the University of Vic-Central University of Catalonia.

The HDL-c particles are more effective in transferring cholesterol to the liver for subsequent elimination. “If we need to do something in relation to HDL, it is to increase the number of small particles, which are those that adequately perform the function of eliminating cholesterol, those that really move it to the liver for removal, and do not allow it to accumulate in the arteries and cause cardiovascular disease,” said Dr Álvaro Hernáez.
There are currently no drugs that increase HDL-c and also reduce cardiovascular risk. “This study highlights new and potential therapeutic targets in the field of cardiovascular diseases, including several genes related to the qualitative aspects of HDL particles, which may contribute to cardiovascular prevention,” concluded first author Dr Albert Prats.

Source: Medical Xpress

Journal information: Albert Prats-Uribe et al, High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization study, Metabolism (2020). DOI: 10.1016/j.metabol.2020.154351

US Rollout of Johnson & Johnson Vaccine As It Gets FDA Approval

Johnson & Johnson’s single shot COVID vaccine is set to roll out in the US after its approval, but concerns linger as to the public’s perception of its relative effectiveness.

The vaccine received an emergency use authorisation (EUA) on Saturday from the FDA, and received approval from the CDC the following day. On Sunday night White House officials stated that distribution of 3.9 million doses of the J&J vaccine would begin immediately, with J&J expecting to deliver some 16 million more doses by the end of March. These vaccines will be allocated proportionally, as per the procedure for Pfizer/BioNTech and Moderna vaccines.

At a Saturday media briefing, acting FDA Commissioner Janet Woodcock, MD, reiterated issues raised by the FDA advisory committee, that the J&J product’s lower efficacy number (70% vs 95%) may cause people to think it is less effective than the alternatives. She said that wasn’t necessarily so, urging Americans to “take the vaccine they are able to access.”

“All these vaccines meet our standards for effectiveness. They were not studied in head-to-head trials, so [they’re] difficult to compare … due to differences in development programs,” she said. (Preventing moderate-to-severe COVID illness was the J&J endpoint, whereas in the Pfizer and Moderna studies the endpoint was all symptomatic COVID.)

“We need to be clear on our messaging regarding comparisons with other vaccines,” said Jason Goldman, MD, of the American College of Physicians. “As a primary care physician, many of us are eager to vaccinate” patients and this vaccine will be “helpful in achieving that goal.”

Macaya Douoguih, MD, of J&J’s Janssen unit where the vaccine was developed, talked about the potential advantages of a one-dose vaccine, referencing the company experience with the Ebola vaccine

“For an outbreak setting, a single dose has a tremendous advantage in terms of being able to rapidly roll out mass vaccination” without the complexity of following up for a second dose, she said.

Dr Douoguih addressed the company’s planned two-dose study, saying that while a two-dose regimen might be “more immunogenic and lead to durable efficacy,” she thought there was room for both options. The two-dose option would be preferable in an ‘everyday’ COVID setting. The company was trying to enroll 16-17 year olds for additional data in a study starting next week, Dr Douoguih said.

The CDC researchers discussed preliminary data on asymptomatic infection, which assessed seroconversion between days 29 and 71. Those data showed vaccine efficacy against seroconversion was 74% (95% CI 48%-87%), but the CDC urged caution as the data was only preliminary.

“Our level of confidence in asymptomatic infection is tempered by low numbers and that is important for us to remember,” said Advisory Committee on Immunization Practices committee member Sarah Long, MD, of Drexel University College of Medicine in Philadelphia. “I appreciate the workgroup concluding the confidence is not that high.”

Source: MedPage Today

New Care Review Process Helps Cut Preventable Deaths

At a Los Angeles hospital, a new in-person multidisciplinary rapid mortality review (RMR) process successfully helped identification of critical patient care areas, according to a new study.

This novel approach assisted front-line healthcare workers in understanding key individual- and systems-level issues which increase mortality. The aim is to produce more effective, optimised patient care. Though efforts have been made since the Institute of Medicine’s 1999 report on preventable patient mortality, reducing the number of these deaths has been difficult, and in many cases, elusive.

The study looked at five years of the RMR process that reviewed patient deaths that took place in the 24-bed medical intensive care unit (ICU) at Ronald Reagan University of California Los Angeles (UCLA) Medical Center. Not only immediate concerns were picked up, but also valuable insights into preventable patient deaths.

“Our findings suggest that these short and timely in-person meetings can be a powerful tool for efforts to both improve quality and prevent mortality in the ICU,” said first author Kristin Schwab, MD. “Bringing members of the multidisciplinary care team together for regular face-to-face discussions provided a forum that revealed concerns and solicited tangible ideas for solutions.”

Retrospective case reviews, provider surveys, and structured morbidity and mortality conferences are common tactics, but unlikely to provide an efficient and practical means of reviewing all patient deaths. The RMR process started in 2013 as pilot, using data on a subset of patients who had died in the medical ICU during the week before. The subset gradually increased in size and by 2017, the team tried to review every death that occurred in the unit that week. Over the five-year period, the RMR team reviewed a total 542 deaths, over 80% of all those that occurred in the unit.

For each patient death, a facilitator led a semistructured interview with the care team after reviewing the patient’s chart, and added a brief report to a database. The quality team reviewed the data from each meeting, referring action items to the relevant department.

Only 7% of deaths were determined by the treatment team, RMR facilitator or both to be possibly preventable. However, in more than 40% of the deaths the treatment team thought care could have been improved, while the facilitator identified areas for improvement in over half the cases.

Cases in which the patient required resuscitation after an in-hospital cardiac arrest or those in which the patient did not get comfort care at the time of death were more likely to result in an action item.

Issues included concerns with communication or teamwork, advance care planning, care delays, medical errors, procedural complications and hospital-acquired infections. The systems-related action items were lack of protocols, resource availability and throughput. Among the action items, over 10% led to substantive systemic change, with 29 discrete changes occurring over the study period. Action items included making a standardised checklist for inbound patient transfers, and modifying the electronic health record to separate one-time orders from continuing orders.

Source: News-Medical.Net

Journal information: Schwab, K.E., et al. (2021) Rapid Mortality Review in the Intensive Care Unit: An In-Person, Multidisciplinary Improvement Initiative. American Journal of Critical Care. doi.org/10.4037/ajcc2021829.

Gratitude for Engineer’s ‘Hack’ Website for Vaccination Appointments

Frustrated with the difficulties faced in scheduling a vaccination appointment, a New York software engineer developed a website to make it easier for his fellow New Yorkers to schedule an appointment.

Huge Ma was trying to get a COVID vaccination appointment for his mother. “You had to basically open three tabs, one for each major government vaccine portal, and then refresh all day until you got an appointment,” the 31-year-old told The Guardian. This experience inspired him to create a website, Turbovax, that helped people to book their appointments more easily. After taking a “look under the hood” in January and doing two weeks of coding, he unveiled his website – essentially a bot that trawls relevant New York sites for appointments and shares them on Twitter and on a website.

Almost immediately, the website took off, with one million page views a day, with tens of thousand of people having booked appointments using the bot, Mr Ma estimated. People have even asked him to bring TurboVax to their cities.

“The response has been incredibly overwhelming,” he said. “There’s been so much gratitude. Hundreds, thousands of emails from people who have gotten appointments through TurboVax, which is honestly kind of just mind-blowing, and humbling as well.” 

He was unprepared for the reaction. “I would never have thought that I could have built something that has such tangible impact on other people’s lives.” 

However, running the site is difficult as Mr Ma has to balance this with his day job working at Airbnb, and the Google Docs-based site is buckling under the demand.

“Technically it’s kind of a hack. It’s not built in the way that modern websites are supposed to be built,” said Ma. “These are the shortcuts that we take to put something in the world that we think is useful and I think that’s a trade-off that I would still make.”

Though it is free, Mr Ma accepts donations and has gathered $35 000 so far. TurboVax is one of a number of citizen-led services that have popped up to help Americans deal with the difficulties of vaccine appointment bookings, such as NYC Vaccine List in New York and VaccinateCA in California.

Mr Ma shut down the website over the weekend in protest against a spate of hate crimes targetting Asian Americans, tweeting, “Anti-Asian hate crimes are out of control. I am taking a stand because I fear for my friends and family.” However, local law enforcements said there is no sign that a number of recent assaults against Asian Americans were racially motivated.

Since far more white people have received vaccinations than black or Latino people, Mr Ma said the technology can “help level the playing field”.

“Not everyone has the ability to sit in front of a computer and refresh all day,” he explained. “That said, I know that no system is perfect. This tech can help but it can’t solve other inequities in the system.”

Source: The Guardian

Social Cues Impacts on Human Decision-making in Emergencies

Man at the wheel of a car. Photo by why kei on Unsplash.

A study showed that, when participants in a simulated crash of an autonomous vehicle were told that others had chosen to crash into a wall to save pedestrians, their own willingness to do so went up by two-thirds.

As autonomous vehicles become more commonplace, and the need to program them for safety emerges, a better understanding of how humans react in such situations is needed. Study author Jonathan Gratch, the principal investigator for this project, and a computer scientist at the USC Institute for Creative Technologies, said that current models for humans in life-or-death situations, humans think differently to how they do in reality. There are no moral absolutes, rather ” it is more nuanced”.

Seeking to understand how humans make decisions in life-or-death situations and how to apply them to the programming of autonomous vehicles and robots, researchers presented a modified trolley problem to participants using a modified ‘trolley problem’.

The trolley problem is a classic hypothetical scenario psychologists use to investigate human decision-making. Essentially, it involves the decision to divert a tram to hit one person or to leave it on its track and hit five, and it has a number of variations. In one medical variation of the trolley problem, one person could be killed and their organs harvested to save five terminally ill patients — a choice that is overwhelmingly rejected.  

In three of four simulations presented to them, the participants had to choose whether to tell their autonomous vehicle to hit a wall, risking harm to themselves, or hit five pedestrians. The higher the likelihood of injury to pedestrians, the more likely the participants were to choose hitting the wall and risking self harm. The authors showed that in so doing, people balance the risk of injury to self against the potential of injury to others as a guideline.

In the fourth scenario, a social element was added, where participants were told that their peers had chosen to save the pedestrians. In this case, the proportion of participants electing to save the pedestrian went up from 30% to 50%.

However, Gratch there is a reverse as well: “Technically there are two forces at work. When people realize their peers don’t care, this pulls people down to selfishness. When they realize they care, this pulls them up.”

The researchers showed that using the trolley problem as a basis for decision-making is insufficient, as it fails to capture the complexity of human decision-making. The researchers also concluded that transparency in the programming of autonomous machines was important for the public, as well as human operators assuming control in the event of an emergency.

Source: News-Medical.Net

Journal information: de Melo, C. M., et al. (2021) Risk of Injury in Moral Dilemmas With Autonomous Vehicles. Frontiers in Robotics and AI. doi.org/10.3389/frobt.2020.572529.

SA Medical Aid Schemes May Not Have to Pay for Public’s Vaccines

Medical aid scheme executives have pointed out that the latest budget means that medical aid schemes may no longer need to contribute for the vaccination of the South African population without medical insurance. 

South Africa’s medical insurance schemes had been in discussions on funding at least part of the government’s vaccine rollout for uninsured members of the public.

The R9 billion allocated in the budget may be enough to cover the vaccine costs of the entire country, said executives from the two leading medical aid schemes.

About 7 million people are covered by medical aid schemes, about a quarter of the country’s population. Discovery Health, Medscheme and Momentum together administer some 80% of private sector medical aid plans.

“I think the government is looking at this and saying this is our role,” said Damian McHugh, executive head of sales and marketing at Momentum Health Solutions. He agreed with the idea that the budget figure implied that schemes may not have to help cover vaccinations for non-members, although it did not remove the discussion of subsidies.

McHugh went on to explain that the costs would depend on which vaccines were procured, and schemes would still have to contribute in case booster shots or new vaccination rounds became necessary.

However, given record additions to their reserves last year due to medical services not being taken or postponed, along with not having to contribute to the vaccination of non-members, medical aid schemes stand to reap even greater benefits.

Source: Reuters

Siemens COVID Antigen Test Kit Receives German Approval

Siemens Healthineers announced on Wednesday that their antigen self-test kit, which uses samples from a nasal swab, has received limited special approval from the Federal Office for Drugs and Medical Devices (BfArM) for self-use by laypeople in Germany. The regular conformity assessment procedure for the standardised ‘CE‘ mark was also initiated for personal use by laypeople.

“With the provision of the COVID-19 antigen rapid test for possible use by laypeople in Germany, we are breaking new ground and are thus continuing to fulfill our social responsibility to support a return to normal social life,” said Bernd Ohnesorge, Head of Europe, Middle East, and Africa Regions, Siemens Healthineers

The practicability of the kit was confirmed by a study in which 50 participants without medical training personally carried out the test by following the instructions for use. The test already has a CE mark for use by specialist groups for taking samples in the nose.

“The CLINITEST COVID-19 Antigen Self-Test offers users a high degree of flexibility in performing the test with very good quality results,” said Christoph Pedain, Head of Point of Care Diagnostics at Siemens Healthineers.

Siemens’ COVID-19 Antigen Self-Test takes 15 minutes to give a result, using samples taken from both nostrils using a swab. The swab is then washed out in a reagent, which detaches a specific protein from the surface of the virus. The resulting liquid is dripped into a recess in the test cassette.

The test liquid migrates into the field of view of the cassette within 15 minutes, becoming visible as a line. The position and number of lines indicate as to whether there is a positive or negative test result, or whether there was a problem, necessitating a repeat of the test.

In the instructions, the tester is shown the steps to achieve a test result, including instructions on how to proceed according to the test result. A negative test result does not exempt the user from any local COVID regulations. Currently, the test kit is also available in the UK.

Source: Siemens

Discovering Antibodies That Are Safe And Effective Against Zika

The Zika outbreak of 2015 and 2016 left lasting consequences for children who were in the womb when their mothers were infected with the virus, and now researchers are investigating a safe vaccine that will not negatively interact with certain other viruses.

Zika is a flavivirus, a family which includes dengue, West Nile, and yellow fever virus. In order to protect against these and other pathogens, “we have the ability to make a huge diversity of antibodies, and if we get infected or vaccinated, those antibodies recognise the pathogen,” explained first author Shannon Esswein, a graduate student at the California Institute of Technology.

However, when getting sick with a virus a second time, the body’s own immune response can worsen the situation. Known as antibody-dependent enhancement (ADE), this is when the antibodies stick to the outside of the virus but not neutralising its ability to lock onto cells. This can inadvertently help the virus to infect more cells by letting it enter cells the antibodies are sticking to. A recent study sought to investigate whether this could happen with monoclonal antibody treatments for COVID.

In order to prevent ADE when creating a vaccine, knowing how antibodies adhere to a specific virus is crucial for scientists. In the case flaviviruses, this is especially important as antibodies that protect against one flavivirus may also stick to, but not protect against other flaviviruses, raising the risk of ADE. Antibodies generated in response to a Zika virus vaccine could trigger ADE, if that person is exposed to other flaviviruses such as dengue.

To understand this, the researchers looked at a portion of the flavivirus called the envelope domain III protein, which has been shown to be an important target for protective antibodies fighting flavivirus infections. They studied how those antibodies changed over time as they matured and became better able to adhere to the Zika virus. They also looked at how the antibodies cross-reacted with other flaviviruses, including the four dengue virus types. Their results showed that the Zika antibodies also tightly stick to and defend against dengue type 1, but only weakly stick to West Nile and dengue types 2 and 4. “The weak cross-reactivity of these antibodies doesn’t seem to defend against those flaviviruses, but also doesn’t induce ADE,” Esswein said. These results suggest that the envelope domain III could be a useful basis for a safe vaccine. They also described structures demonstrating how two antibodies recognise Zika and West Nile envelope domain III.

The study results demonstrate how the body mounts “a potent immune response to Zika virus,” said Esswein. Insights gained on the antibodies involved in this immune response will aid the development of new vaccines.

Source: Medical Xpress

Journal information: Shannon R. Esswein et al. Structural basis for Zika envelope domain III recognition by a germline version of a recurrent neutralizing antibody, Proceedings of the National Academy of Sciences (2020). DOI: 10.1073/pnas.1919269117

Global COVID Recovery Needs to Address Oxygen Shortages

At the virtual launch of Global Citizen’s Recover Better Together Campaign, access to vaccines and medical resources was highlighted as a key area to address.

“Covid-19 has threatened the lives and livelihoods of everyone on the planet. To respond, we must take several urgent actions. The only way that we will be able to recover better, together is by defeating the virus everywhere through universal access of vaccines, diagnostics, and therapeutics,” said World Health Organization Director-General Dr Tedros Adhanom Ghebreyesus.

To this end, the Recover Better Together Campaign, an initiative organised by the Global Citizen, the European Commission and the WHO, aims to create momentum for global COVID pandemic recovery, with a return to the implementation of global goals.

“To fight the pandemic, we need to pool resources, capabilities, knowledge and intellectual property. That is why we continue to call on world leaders to support the COVAX facility to ensure rapid and equitable access to Covid-19 vaccines for all countries. Another important step is to enable the transfer of medical technology for the duration of the pandemic,” said President Cyril Ramaphosa.

One of key medical resource is oxygen, which is in short supply in many low- and middle-income countries, which have to provide enough for up to half a million COVID patients. WHO data shows that 1.1 million cylinders are needed daily in developing countries, with Africa seeing the biggest surge in demand. Hospitals in Nigeria have reported running out of oxygen, leading to preventable deaths.

According to the WHO, public hospitals across 41 African countries have fewer than 2000 working ventilators. In comparison, the United States has more than 170 000 ventilators. The South African private sector has about 4000 ventilators, and around 2000 in the public sector. The WHO said the launch of the Covid Tools Accelerator Therapeutics pillar, co-led by Unitaid and Wellcome, has improved access to oxygen. On 25 February the Covid-19 Oxygen Emergency Taskforce was also launched by the WHO.

Unitaid Executive Director Dr Philippe Duneton said the Taskforce now needs an additional $90 million US for delivery of oxygen in up to 20 countries including Malawi, Nigeria and Afghanistan.

“This is a global emergency that needs a truly global response, both from international organisations and donors. Many of the countries seeing this demand struggled before the pandemic to meet their daily oxygen needs,” said Duneton. “Now it’s more vital than ever that we come together to build on the work that has already been done, with a firm commitment to helping the worst-affected countries as quickly as possible.”

Source: Health-e News