Year: 2022

Categories : Respiratory DiseasesTags :

Mepolizumab Weans Severe Asthma Patients off Steroids

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Asthma inhaler
Source: PIxabay/CC0

In a real world study, patients taking oral corticosteroids for severe asthma, taking mepolizumab reduced the need for those steroids by 75%. These findings were presented at the annual meeting of the American Academy of Allergy, Asthma & Immunology.

By the end study, patients on a median 10 mg maintenance dose of oral corticosteroids at baseline reduced their intake to 2.5 mg, reported Mark Liu, MD, of Johns Hopkins Medicine, who presented the findings.

And those on a median 5 mg maintenance dose at the start of the trial reduced their use to 0.4 mg by study end, Dr Liu said.

In the high steroid dose group, 36% were able to be weaned off the drugs by the end of the study, he reported. In the lower dose group, 49% were able to discontinue steroid use.

Treatment with the interleukin-5 (IL-5) antagonist mepolizumab reduced clinically significant annual exacerbations from a mean of 4.3 in the 12 months prior to the trial to 1.5 with mepolizumab use. This reduction from baseline was seen across all patient groups, said Dr Liu, including those with high and low steroid use and those who were not taking steroids at baseline to control symptoms.

Dr Liu suggested that despite the limitation of being a single-arm study, the “clinically important real-world findings indicate that patients with severe asthma treated with mepolizumab can reduce their oral corticosteroid use, potentially reducing the risk of side effects associated with their use, while improving their asthma control.”

The co-moderator of the presentation session, William Anderson, MD, of Children’s Hospital Colorado, said the study was important – “especially for our adult patients who are on chronic steroids, because the side effects of chronic steroids are so profound and oftentimes can lead to equal if not worse effects than the underlying asthma itself.”

“The ability to use a biologic agent to decrease the dose of an oral steroid for our patients is certainly extraordinarily promising,” Dr Anderson said to MedPage Today. “Our ultimate goal is to get patients off oral steroids.”

For the year-long study, Dr Liu and colleagues enrolled 822 adults with asthma and a new prescription for mepolizumab with at least 12 months of previous medical records. Mepolizumab was given at the standard 100mg subcutaneous dose.

“Patients with severe asthma often rely on oral corticosteroids to control their symptoms despite a well-recognized risk of complications even at low daily doses,” Dr Liu explained. The goal of the study, he said, was to determine what happened in a real-world setting when these patients were treated with mepolizumab, stratified by steroid use. The researchers enrolled patients from December 2016 through October 2019.

About 10% of patients experienced adverse events, but serious adverse events occurred in less than 1%, Dr Liu noted.

Source: MedPage Today

Categories : COVIDTags :

Aspen to Locally Produce COVID Vaccine ‘Aspenovax’ for the African Continent

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Syringe withdrawing from vaccine vial
Photo by Mufid Majnun

In a news release, pharma giant Aspen has announced that it has concluded an agreement with Johnson & Johnson to manufacture an Aspen-branded COVID vaccine, Aspenovax, and to make it available throughout Africa.

This follows on from the November 2021 announcement of an agreement of terms between the two companies. This new agreement will expand the existing technical transfer and manufacturing agreements between the companies.

The agreement will grant Aspen’s South African subsidiary the rights to manufacture finished Aspenovax product from drug substance supplied by J&J. It will also make Aspenovax available to markets in Africa through transactions with designated multilateral organisations and with national governments of member states of the African Union.

Under the agreement, Aspen has secured the necessary intellectual property from Johnson & Johnson for production. There is also a good faith undertaking between the companies to expand the agreement to cover any new versions of the drug substance, such as those developed for new variants or a different formulation for administration as a booster.

The agreement will last through to the end of 2026.

Commenting on this agreement, Dr Matshidiso Moeti, World Health Organization Regional Director for Africa said: “This important agreement on sharing know-how and technologies for the production of COVID vaccines is a huge leap forward towards realising our shared vision for medicines and vaccines to be manufactured on the African soil for the African people. Vaccines are our best way out of this pandemic and local production is an essential recipe for our success.”

Stephen Saad, Aspen Group Chief Executive said: “Even with all the support in the world, none of this would be possible without the competence of our teams at Gqeberha. They knew the weight of a continent’s ambitions rested on their shoulders. They persevered and succeeded in becoming a significant supplier within the Johnson & Johnson network. Aspenovax has become a reality due to the confidence placed in their abilities. They are our African heroes.”

Categories : COVID GenderTags :

The Pandemic’s Negative Impact on Women in Academic Medicine

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Female scientist in laboratory
Photo by Gustavo Fring from Pexels

Like women in every other sector of the economy, the COVID pandemic has negatively impacted those working in academic medicine according to a commentary which appears in Nature Medicine.

Co-author Anne B. Curtis, MD, professor at the University at Buffalo, laid out the problem: “During the first year of the pandemic, when schools shut down and went to 100% remote learning, we saw that it affected women disproportionately, having to stay home and teach their children while their research languished.”

Even before the COVID pandemic, women in academic medicine were paid less than men in comparable positions, received lower startup funds for laboratory research and were promoted later.

Additionally, they wrote that, compared to men, women have fewer “conventional markers of achievement” in academia, such as principal investigator positions on research grants. Women write fewer grant applications; they have fewer grant renewals; they get lower funding amounts for initial grants; and are first or last author on fewer papers.

The reasons for these are well known, the authors wrote.

“Society expects women to assume the major portion of the burden for child rearing, and women themselves feel an obligation to put family above their own needs, to the detriment of their own career development,” she said. “There still isn’t the sharing of responsibilities in two-career families to mitigate these problems.”

The paper includes a detailed ‘menu’ of proposed solutions. These include providing financial support to hire technicians for two to three years to carry on lab research while women researchers focus on child care at home, or otherwise supporting child care at home so women can continue their lab research.

The paper also proposes slowing down tenure clocks, delaying the tenure decision by two to three years to make up for lost time while women give birth and care for young children.

In addition to such programs, the list includes a category of solutions termed “cultural,” described as creating the cultural expectation that gender equity is a shared responsibility and incorporating those expectations into bonuses and merit raises of institutional leaders. Also included is the need to engage university and hospital boards of trustees to support gender equity.

Prof Curtis said that the paper aims to highlight the persistence of these gender differences persist and that global phenomena like the pandemic only worsen them.

“As much as we would like to think that gender differences in career development no longer exist, they do, and they adversely affect women more than men,” she said. “Understanding these issues and implementing solutions are the best ways to minimise potentially adverse effects on women’s careers.”

As the pandemic and its associated restrictions ease, Prof Curtis warned, “The situation is improving now that schools are open, but the next pandemic may only be a mutation away.”

Source: Buffalo University

Categories : GastrointestinalTags :

A Touch-sensing Protein Helps the Gut to ‘Feel’

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Anatomy of the gut
Source: Pixabay CC0

New research published in the journal Gastroenterology has discovered that a touch-sensing protein is present in the gut, with its presence likely playing a key role in constipation. The protein, called Piezo2, was found using both human gut samples and mice is not just in our fingers, but also in our gut.

“Many people suffer from digestive issues on a daily basis, such as chronic constipation, however we still don’t understand the cause which underlies most of them,” said Lauren Jones, lead author and final year PhD student.

“Our research identified Piezo2 in cells that line the human digestive tract, allowing them to sense physical stimuli, such as touch or pressure, that would occur when food is present. The cells then respond by releasing serotonin to stimulate gut contractions and push the food along.”

Last year, international researchers Ardem Patapoutian and David Julius were awarded the Nobel Prize in Physiology or Medicine for their research on receptors responsible for the perception of touch and temperature, including the discovery of Piezo2, now known to be responsible for sensing light touch on our skin.

Of potential clinical importance, the Flinders research team also discovered that the levels of Piezo2 decrease in the gut with age, and found that if the protein was removed only from gut serotonin cells, gut motility slowed down in mice, causing constipation.

The authors say this could be a potential contributing factor to age-related constipation and provide a possible path to treatment.

Researchers discover a nuclear import mechanism essential for organ growth and development

“Age-related constipation affects 1 in 2 adults over the age of 80, whilst constipation generally affects almost everyone at some point throughout their life,” says Ms Jones.

“It’s therefore extremely important we increase our understanding of the underlying mechanisms, so that we can find targeted solutions to improve the quality of life of the many people who suffer daily from various gut disorders, including constipation.

“This research provides the building blocks for both further research and the development of highly specific treatments to reduce the impacts of constipation.”

The authors say that, though more studies are needed to firmly link Piezo2 to constipation, the research overall is an important advancement into our understanding of gut physiology, opening up new targets for the treatment of digestive issues.

The insights allow for reduced side effects, explained Ms Jones: “More specifically, we now have the potential to create treatments that are taken orally and only directly impact these cells that line the gut, therefore significantly reducing side effects typically seen with many of the current medications.”

Source: News-Medical.Net

Categories : AgeingTags :

Cells in Mice Partially Reset to More Youthful States

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Mouse
Photo by Kanasi on Unsplash

Scientists have shown that they can safely and effectively reverse the epigenetic markers of age in middle-aged and elderly mice by partially resetting their cells to more youthful states – reducing many signs of ageing as they do so.

As organisms age, their cells have different epigenetic markers on their DNA compared to younger ones. It is known that adding a mixture of reprogramming molecules, also known as ‘Yamanaka factors’, to cells can reset these epigenetic marks to their original patterns. This approach enables researchers to turn back the clock for adult cells, developmentally speaking, into stem cells.

“We are elated that we can use this approach across the life span to slow down aging in normal animals. The technique is both safe and effective in mice,” said Juan Carlos Izpisua Belmonte, co-corresponding author, professor at the Salk Institute. “In addition to tackling age-related diseases, this approach may provide the biomedical community with a new tool to restore tissue and organismal health by improving cell function and resilience in different disease situations, such as neurodegenerative diseases.”

The Salk Institute research lab reported in 2016 that, for the first time, they were able use the Yamanaka factors to counter the signs of aging and increase life span in mice with a premature ageing disease. More recently, the lab found that the Yamanaka factors can accelerate muscle regeneration even in younger mice. Building on these studies, other scientists have used the same approach to improve the function of other tissues like the heart, brain and optic nerve.

In the new study, the researchers tested variations of the cellular rejuvenation approach in healthy animals as they aged. One group of mice received regular doses of the Yamanaka factors from the time they were 15 months old until 22 months, approximately equivalent to age 50 through 70 in humans. Another group was treated from 12 through 22 months, approximately age 35 to 70 in humans. And a third group was treated for just one month at age 25 months, similar to age 80 in humans.

“What we really wanted to establish was that using this approach for a longer time span is safe,” said Pradeep Reddy, study co-first author. “Indeed, we did not see any negative effects on the health, behaviour or body weight of these animals.”

No blood cell alterations or neurological changes were seen in the mice treated with the Yamanaka factors compared to control mice. Additionally, no cancers were observed in any of the groups of animals.

In terms of normal signs of ageing, the treated mice resembled younger animals in a number of ways. In both the kidneys and skin, the epigenetics of treated animals more closely resembled epigenetic patterns seen in younger animals. When injured, the skin cells of treated animals had a greater ability to proliferate and were less likely to form permanent scars, unlike normal older animals. Metabolic molecules also did not reflect normal age-related changes.

This youthfulness was observed in the animals treated for seven or 10 months with the Yamanaka factors, but not the animals treated for just one month. What’s more, when the treated animals were analysed midway through their treatment, the effects were not yet as evident. This suggests that the treatment is not simply pausing aging, but actively turning it backwards–- although more research is needed to differentiate between the two.

The team is now planning future research to analyse how specific molecules and genes are changed by long-term treatment with the Yamanaka factors. They are also developing new ways of delivering the factors.

“At the end of the day, we want to bring resilience and function back to older cells so that they are more resistant to stress, injury and disease,” said Reddy. “This study shows that, at least in mice, there’s a path forward to achieving that.”

The study was published in Nature Aging.

Source: Salk Institute

Categories : HIV Medical IndustryTags :

Generic Options for HIV Prophylactic Cabotegravir Locked Out, MSF Warns

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Image of a syring for vaccination
Photo by Mika Baumeister on Unsplash

Médecins Sans Frontières (MSF) has warned that pharmaceutical company ViiV’s recent decision not to pursue voluntary licensing for the long-acting HIV prophylactic cabotegravir (CAB-LA) means that lower cost generic production in low- and middle-income countries (LMICs) is effectively locked out for countries like South Africa.

CAB-LA was approved for the prevention of HIV infection by the USFDA in December 2021, and ViiV currently charges $3700 (R55 000) per vial in the US ($22 200/R333 000 annually per person). The Clinton Health Access Initiative (CHAI) has shown that generic manufacturers could produce this drug for around $2.60 (R39) per vial (less than $20/R3000 per person per year). Although ViiV has publicly said they would provide CAB-LA for their at-cost price in many LMICs, they have yet to announce what that price is.

According to MSF, generic manufacturer prices are often much lower than the patented drug – and they can even produce complicated formulations like CAB-LA.  The generic equivalent [PDF] of ViiV’s paediatric formulation of the HIV drug dolutegravir costs 22 times less.

Amanda Banda, Infectious Diseases Policy and Advocacy Advisor of the MSF Access Campaign, said: “What good is HIV prevention if the people who need it can’t afford it? This is the most effective form of HIV prevention for vulnerable and marginalised communities and yet ViiV is delaying the ability of generic manufacturers to supply the drug, meaning that many people across low- and middle-income countries who would benefit from the medicine to prevent HIV infection won’t be able to access it. CAB-LA will need to be available at a price that is comparable to currently available oral PrEP if country treatment programs and donors are expected to scale up its use to the levels needed – and it’s hard to imagine that ViiV will make CAB-LA available at less than $40 (R600) per year.  ViiV needs to immediately sign a licensing deal with the Medicines Patent Pool so that more affordable generics can be produced, and more lives can be saved.”

Dr Tom Ellman, Head of MSF’s South African Medical Unit said: “We want to urgently make this drug available for people at high risk of HIV infection in our programs in sub-Saharan Africa – we don’t want a donation with many strings attached from the corporation; it is not the role of ViiV to control the use of a drug that is approved by the USFDA. We want ViiV to sell us this drug at an affordable price.”

Source: MSF

Categories : Injury & TraumaTags :

Over 70% of TBI Patients Report More Symptoms a Year On

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Source: Pixabay

More than 70% of patients with traumatic brain injury (TBI) reported at least one problematic symptom at one year of follow-up that was new or worse than before injury according to a study published in the Journal of Neurotrauma. Half of the patients reported three or more such symptoms after a year.

Joan Machamer, from the University of Washington, Harborview Medical Center, and colleagues representing the TRACK-TBI Investigators, compared the frequency and persistence of symptoms in patients with TBI to two control groups: patients with orthopedic trauma and friend controls. The groups were evaluated at 2 weeks, and 3, 6, and 12 months after injury.

Physical symptoms such as headache, fatigue, and dizziness tended to occur earlier, according to the researchers, with cognitive symptoms becoming dominant later. While physical symptoms declined noticeably over time, cognitive symptoms remained more constant over time.

“Clinicians should inquire about symptoms in patients who have had a TBI, reassure them that experiencing symptoms is common, and direct them to seek treatment for symptoms that are disrupting their lives,” the researchers said.

Commenting on the study, David L. Brody, MD, PhD, Editor-in-Chief of Journal of Neurotrauma noted that is remarkable for several reasons. “First, it is among the largest studies of its type, with over 2,000 participants. Second, it confirms what many of us who practice brain injury medicine have observed for many years– a wide variety of symptoms can be very persistent and very troubling to our patients even after so-called ‘mild’ TBI. Third, the investigators used the right controls; people with orthopedic injury as well as friends of the patients with TBI. Symptoms in patients with TBI were substantially more common and more severe than in both control groups.”

Source: Mary Ann Liebert, Inc.

Categories : COVIDTags :

COVID Battle not Over as Many Countries Continue to Struggle

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Image by Quicknews

Two years into the pandemic, and the COVID battle is not over for much of the world, warns the International Federation of Red Cross and Red Crescent Societies (IFRC). Many countries lack the capacities to transition to ‘a new normal’: high vaccination coverage, strong healthcare systems or testing capacities. The crisis will not be over until everyone has the same access to these tools, the IFRC says.

Francesco Rocca, IFRC President, said: “’Living with the virus’ is a privilege that many countries and communities around the world cannot enjoy. Ensuring equitable access to vaccines, diagnostics and treatments will not only save lives, but will also protect the world against the emergence of new and more dangerous variants. It is the only path to normalcy. None of us is safe until we all are.”

Red Cross Red Crescent staff and volunteers are constantly working to close the equity gap, ensuring that vaccines make it to the vulnerable individuals and communities that desperately need them. Their role is crucial, not only in vaccination but in informing communities, building trust, and dispelling COVID vaccine misinformation. They have now reached over 300 million people through immunisation activities.

In countries like Zambia, where health systems are fragile and rumours around vaccines are spreading fast, vaccine supply is just one of numerous obstacles. The Zambia Red Cross Society’s mobile COVID vaccination campaign takes vaccines directly to people in hard-to-access areas. Volunteers mobilise communities for vaccination, raise awareness about the mobile vaccination centres, provide information about vaccines and engage local leaders as advocates for healthy behaviour change.

Afghanistan’s health system is struggling as a new wave of COVID infections hits. Afghan Red Crescent is ramping up services at its health clinics across the country and its COVID hospital in Kabul, while supporting nationwide vaccination efforts and running information campaigns on preventing the spread of the virus.

A record surge of infections in the Pacific region is threatening to overwhelm hospitals and health systems which, until now, have largely avoided the worst of the pandemic. In countries like Fiji and Vanuatu, with more than 165 inhabited islands, Red Cross volunteers have been travelling by car, boat and foot to reach remote communities to increase awareness about COVID and get people vaccinated.

COVID not only thrives on inequality but deepens it. Women, urban communities and migrants have been disproportionately affected by the devastating socioeconomic impacts. More than 5 million children have also lost a parent or another caregiver to COVID. Psychosocial support has been at the centre of Red Cross Red Crescent work, and volunteers are seeing a significant rise in mental health support needs.

Source: International Federation of Red Cross and Red Crescent Societies (IFRC)

Categories : Medical Research & TechnologyTags :

Study Implicates High Leptin Levels in Androgen Deficiencies

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Source: National Cancer Institute on Unsplash

Researchers have uncovered new clues about the cellular processes that can lead to androgen deficiencies, in which high leptin levels appear to play a role. The findings are published in the journal Cell Death & Disease.

Symptoms of testosterone deficiency include low sex drive, erectile dysfunction, depression, and fatigue. TD afflicts approximately 30% of men aged 40-79 years, with an increase in prevalence strongly associated with ageing and common medical conditions including obesity, diabetes, and hypertension.

“Although testosterone deficiency may be present in one in five men 40 years or older, the driving factors remain largely unknown,” said Himanshu Arora, PhD, assistant professor of urology.

Dr Arora’s lab examined the effect of different concentrations of leptin on the microenvironment of the testes. The research builds on prior studies of how Sertoli and peritubular myoid cells (PMC) in the testicular microenvironment help drive Leydig stem cell differentiation via the cellular desert hedgehog signalling pathway, which transmits information to embryonic cells that guides proper cell differentiation.

The researchers extracted cellular samples from men undergoing testes biopsies for sperm retrieval. When the testes microenvironment secreted leptin in low doses, they found that Leydig stem cells differentiated into adult Leydig cells producing normal levels of testosterone. Higher doses of leptin were observed to depress testosterone levels.

“Our findings identify leptin as a key factor within the testes microenvironment,” said Dr Arora, adding that the insight “holds important implications for androgen deficiency and could have further application in prostate cancer research.”

Noting that leptin is already used in treating patients for obesity, “Preclinical studies could indicate whether adjusting levels of this hormone would be helpful in patients with testosterone deficiency,” said Ranjith Ramasamy, MD, study co-author and associate professor and director of the Miller School’s Reproductive Urology Program.

Source: University of Miami Health System, Miller School of Medicine

Categories : Environmental EffectsTags :

Climate Change Will Increase Deaths Linked to Extreme Temperatures

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Heat cracked earth
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The death rate linked to extreme temperatures will increase significantly under global warming of 2°C, with even steeper rises for each degree of warming, finds a report published in Environmental Research Letters.

With a warming scenario of just 2°C from pre-industrial levels, temperature-related mortality in England and Wales during the hottest days of the year will increase by 42%. This means an increase from present-day levels of around 117 deaths per day, averaged over the 10 hottest days of the year, to around 166 deaths per day. The findings underline the importance of keeping global warming levels to below 2°C.

At current global warming levels of around 1.21°C there would be a slight decrease in temperature-related mortality in winter and a minimal net effect in summer, meaning that overall, at this level of warming we see a slight decrease in temperature-related mortality rate.

The researchers assessed the impact of climate change on mortality rates England and Wales, specifically risk from heat in summer and cold in winter. They found that as the global mean temperature increases, temperature-related mortality in summer will increase at a much faster, non-linear rate.

The rate of increase particularly speeds up at 2°C of warming, with a much higher risk appearing beyond 2.5°C. The researchers say that 3°C warming could lead to a 75% increase in mortality risk during heatwaves.

The relationship between temperature and mortality on a graph is roughly U-shaped, meaning that at extremely high temperatures, mortality risk increases sharply for each degree rise of daily mean temperature.

The rate in winter will continue to decrease, although this leaves out extreme weather events such as storms.

Lead author Dr Katty Huang said: “The increase in mortality risk under current warming levels is mainly notable during heatwaves, but with further warming, we would see risk rise on average summer days in addition to escalating risks during heatwaves. What this means is that we shouldn’t expect past trends of impact per degree of warming to apply in the future. One degree of global warming beyond 2°C would have a much more severe impact on health in England and Wales than one degree warming from pre-industrial levels, with implications for how the NHS can cope.”

In England and Wales, temperature is associated with around 9% of total population mortality, meaning that 9% of all deaths during 2021 could be associated with the temperature. Most of those deaths are related to the side effects of cold weather.

The team analysed the 2018 UK Climate Projections (UKCP18) with data on present-day temperature and mortality in order to predict changes in temperature-related mortality relative to degrees of global warming.

In order to isolate the effects of global warming on mortality risk, the researchers looked at the potential impact for the current population, and not attempting to predict future age distributions and medical conditions.

Project lead Professor Andrew Charlton-Perez said: “As the Intergovernmental Panel on Climate Change impacts report recently showed, it is increasingly common to examine how different levels of mean global warming raise the risk of significant harm to people and society. Our study shows that because death rates will go up significantly if countries experience very high temperatures, limiting the average global rise in temperatures is likely to have substantial benefits for the overall health of the population.”

Source: University College London