Month: January 2021

Categories : AgeingTags :

For Older IBD Patients, Vedolizumab is a Safer Option

On By ModernMedia

Vedolizumab appeared to be safer than tumour necrosis factor (TNF) inhibitors in older adults with inflammatory bowel disease (IBD), according to the results of a large retrospective study.

Vedolizumab is a fully humanised monoclonal antibody which targets α4β7 integrin, and prevents leukocyte movement from the blood into inflamed gut tissue.

At the virtual Crohn’s and Colitis Congress, Bharati Kochar, MD, of Massachusetts General Hospital in Boston, presented data showing that all-cause hospitalisation during the 12 months after initiating biologic treatment was lower in new users of vedolizumab than in those starting TNF inhibitors, with a hazard ratio of 0.81 (95% CI 0.68-0.96)

“The American population is rapidly aging, and the number of Americans 65 and older in 2060 will be more than double what it was in 2014,” Dr Kochar said. “The combination of increasing IBD incidence, improvements in disease treatment-related knowledge, and decreasing IBD mortality is resulting in a high prevalence of older adults with IBD,” she added.

It is estimated that a quarter of Americans over 65 have IBD, yet are less likely to receive adequate immunosuppression. Over 65s are underrepresented in IBD clinical trials, creating a lack of understanding over what medications work or not in this age group.

To answer this question, Dr Kochar and her team analysed a 20% sample of Medicare claims database. Patients were included if they were diagnosed with Crohn’s disease or ulcerative colitis and if they initiated treatment with vedolizumab, infliximab, adalimumab, golimumab, or certolizumab from 2014 to 2018 after being on Medicare for 12 months while not receiving any of those medications.

There were 488 new users of vedolizumab and 2213 initiators of TNF inhibitors in the analysis group, with an average age of 71. More than half were women and most were white, 44% had ulcerative colitis and over half of patients had Carlson Comorbidity Index scores of 2 or higher.

There was otherwise no significant difference between vedolizumab and TNF for IBD-related hospitalisation (HR 0.77, 95% Ci 0.53-1.12), IBD-related surgery: (HR 0.78, 95% CI 0.49-1.22), or new steroid prescription within 60 days of starting the biologic (HR 1.01, 95% CI 0.86-1.18).

In the 6-month period prior to biologic initiation, nearly one-third had a prescription for budesonide, 58% had a prescription for a systemic corticosteroid, and nearly one-third were being prescribed immunomodulators.

“In conclusion, I think it’s important to use your clinical judgment to treat the patient in front of you, and these data should simply help contextualise risk for older IBD patients newly initiating vedolizumab or TNF inhibitors,” said Dr Kochar.

“There is a vast need for additional large and robust comparative effectiveness and safety studies for older adults with IBD, with the rapid proliferation of new IBD medications,” she concluded.

Source: MedPage Today

Presentation information: Kochar B, et al “Comparative effectiveness and safety of vedolizumab and anti-tumor necrosis factor agents in older adults with inflammatory bowel diseases in Medicare administrative claims database” CCC 2021

Categories : COVID Immune SystemTags :

NSAIDs Suppress Antibodies in COVID Infections

On By ModernMedia

A new study has found that non-steroidal anti-inflammatory drugs (NSAIDs) suppress antibody counts as well as inflammatory levels in mice infected with the SARS-CoV-2 virus.

NSAIDs inhibit the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), which are needed for prostaglandin generation – lipid molecules involved in homeostasis and inflammation. The study used ibuprofen and meloxicam in mice infected with SARS-CoV-2. The researchers aimed to observe: viral infection through modified expression of angiotensin-converting enzyme 2 (ACE2), the cell entry receptor for SARS-CoV-2, effects on viral replication and modulated response of the immune system. However, they did not observe altered viral infection or replication.

“NSAIDs are arguably the most commonly used anti-inflammatory medications,” said principal investigator Craig B Wilen, Assistant Professor of Laboratory Medicine and Immunology, Yale University School of Medicine.

As well as taking NSAIDs for chronic conditions, eg arthritis, people take them “for shorter periods of time during infections, and [during] acute inflammation as experienced with COVID-19, and for side effects from vaccination, such as soreness, fever, and malaise,” Dr Wilen explained.

“Our work suggests that the NSAID meloxicam dampens the immune response to SARS-CoV-2 infection. Taking NSAIDs during COVID-19 could be harmful or beneficial, depending on the timing of administration,” said Dr Wilen. Dexamethasone, a potent anti-inflammatory but not an NSAID, is detrimental when administered at early stages of COVID but beneficial at later stages. NSAIDs may similarly be detrimental at the early stage because they counteract beneficial inflammation.

An antibody reduction by NSAIDs might not be harmful, but it could also reduce the immune system’s ability to mount a defence early on, or even reduce the length or magnitude of immunity or vaccination protection, Dr Wilen said. Antipyretics such as paracetamol have also been observed to blunt immune system response to vaccination.  

According to Dr Wilen, the original motivation from the study “was a twitter thread, suggesting NSAIDs should not be used during COVID-19. This seemed suspicious to us, so we wanted to investigate.”

Dr Wilen and his team believed there would be no effect of NSAIDs on viral infection, which turned out to be correct. However, they also thought there would be no effect on antibody response.

“In fact, we initially didn’t even carefully look at the antibody response, because we didn’t expect it to be altered by NSAIDs. This turned out to be wrong,” commented Dr Wilen.

Source: Medical Xpress

Journal information: Jennifer S. Chen et al. Non-steroidal anti-inflammatory drugs dampen the cytokine and antibody response to SARS-CoV-2 infection, Journal of Virology (2021). DOI: 10.1128/JVI.00014-21

Categories : Expert Opinion Medical IndustryTags :

Like 60s Cars, Brand Drugs Have no Price Competition

On By ModernMedia

Brand name drugs, like American cars in the 1960s, are subject to broadly rising prices with little evidence of competing on cost.

Before the oil embargo by Arab countries in 1973 allowed competition from more affordable, fuel efficient cars that we take for granted today, the Big Three car manufacturers, Ford, Chrysler and General Motors, would annually announce price increases at about the same time. Any adjustment by one manufacturer, for example, in size, was quickly matched by competitors.New research analysed the prices for five classes of drugs, and found them to be increasing in lock-step from 2015 to 2020. These classes are direct-acting oral anticoagulants (DOACs), P2Y12 inhibitors, glucagon-like peptide-1 (GLP-1) agonists, dipeptidyl dipeptidase-4 (DPP-4) inhibitors, and sodium-glucose transport protein-2 (SGLT-2) inhibitors.

The study had limitations due to not taking into account measures such as rebates, which would affect the price for the patient. However, even if these were taken into consideration, the researchers believe the overall prices would still increase and have to be borne by some patients who would not benefit from certain rebates. “Rebates, list prices, and net prices have been growing for brand-name medications, and rebate growth has been shown to positively correlate with list price growth, thereby impacting costs faced by patients paying a percentage of (or the full) list price,” the researchers noted. “Therefore, the lock-step price increases of brand-name medications, without evidence of price competition, raise concerns and would be expected to adversely affect patient adherence to medications and thus clinical outcomes.”

Unlike the oil crisis which broke open the automobile market to foreign competitors, the solution with “Big Pharma” is less clear. The researchers recommend policies which would limit such lock-step price increases, reduced patent exclusivity periods, and quicker introduction of generic equivalents.

Source: MedPage Today

Journal information: Liu P, et al “Trends in Within-Class Changes in US Average Wholesale Prices for Brand-Name Medications for Common Conditions From 2015 to 2020” JAMA Netw Open 2021; DOI: 10.1001/jamanetworkopen.2020.35064.

Categories : Uncategorized

Exercise can Block Muscle Wasting from Chronic Inflammation

On By ModernMedia

In yet another discovery pointing to the benefits of physical activity, human muscle has been shown to stave off the destructive effects of chronic inflammation through exercise.

“Lots of processes are taking place throughout the human body during exercise, and it is difficult to tease apart which systems and cells are doing what inside an active person,” said Nenad Bursac, professor of biomedical engineering at Duke. “Our engineered muscle platform is modular, meaning we can mix and match various types of cells and tissue components if we want to. But in this case, we discovered that the muscle cells were capable of taking anti-inflammatory actions all on their own.”

Inflammation can be beneficial, such as a low-level response which clears out debris and helps regeneration, or it can be detrimental, such as the lethal COVID cytokine storms. Chronic inflammation as in arthritis or sarcopenia can be damaging as it takes away the ability of muscle to contract, resulting in weakening.

One inflammatory molecule in particular, interferon gamma, has been shown to be associated in many different types of muscular wasting. Interferon gamma is primarily produced by T lymphocytes and natural killer (NK) cells.

“We know that chronic inflammatory diseases induce muscle atrophy, but we wanted to see if the same thing would happen to our engineered human muscles grown in a Petri dish,” said Zhaowei Chen, a postdoctoral researcher in Bursac’s laboratory and first author of the paper. “Not only did we confirm that interferon gamma primarily works through a specific signaling pathway, we showed that exercising muscle cells can directly counter this pro-inflammatory signaling independent of the presence of other cell types or tissues.”

To determine if interferon gamma was the true culprit, Berac and Chen grew contractile human muscle tissue in vitro, then flooded it with interferon gamma over seven days. As predicted, the muscle shrank and lost strength,

They then applied interferon gamma again, but this time electrically stimulating the muscle to contract. They expected the simulated exercise to result in some muscle regrowth as seen in their previous studies, but to their surprise, the muscle suffered almost no effect from the chronic inflammation.They demonstrated that exercise blocked a particular molecular pathway as used in a pair of drugs to treat rheumatoid arthritis, tofacitinib and baricitinib, which produce the same anti-inflammatory effect.

“When exercising, the muscle cells themselves were directly opposing the pro-inflammatory signal induced by interferon gamma, which we did not expect to happen,” Bursac said. “These results show just how valuable lab-grown human muscles might be in discovering new mechanisms of disease and potential treatments. There are notions out there that optimal levels and regimes of exercise could fight chronic inflammation while not overstressing the cells. Maybe with our engineered muscle, we can help find out if such notions are true,” Bursac concluded.

Source: Medical Xpress

Journal information: Z. Chen el al., “Exercise mimetics and JAK inhibition attenuate IFN-γ-induced wasting in engineered human skeletal muscle,” Science Advances (2020). advances.sciencemag.org/lookup … .1126/sciadv.abd9502

Categories : COVID Immune SystemTags :

New “Double Antibodies” can Treat COVID Variants

On By ModernMedia

A new generation of “double antibodies” has been developed which can protect against all SARS-CoV-2 variants, as well as inhibiting mutations against the antibodies.

These “bispecific”  antibodies were created by the Institute for Research in Biomedicine (IRB; Bellinzona, Switzerland), which is affiliated to the Università della Svizzera italiana (USI).

While traditional antibody-based immunisation is able to offer protection against SARS-CoV-2, there is still a need to protect against variants which may achieve “vaccine escape”, as well as inhibiting mutations which give rise to resistance, as with antibiotic resistance in bacteria.

The researchers overcame these difficulties by splicing together a pair of antibodies to make a “bispecific” antibody that simultaneously targets two viral sites. The bispecific antibody treatment has proved effective in mouse models, which maintained body weight when infected with SARS-CoV-2, compared to infected controls, which lost 20-30% body weight before humane euthanisation. The paper is available on the bioRxiv preprint server.

Study author Luca Varani of USI explained: “We exploited our knowledge of the molecular structure and biochemical traits of the virus to fuse together two human antibodies, obtaining a single bispecific molecule simultaneously attacking the virus in two independent sites critical for infectivity. Supercomputing simulations allowed us to refine and validate the bispecific antibody design, which was later produced and tested in the laboratory. Although the virus can mutate and escape from the attack of a single first-generation antibody, we have shown that it cannot do so against the double action of the bispecific.

“A single injection of the bispecific antibody provides instantaneous protection against the disease in pre-clinical trials. The antibody effectively reduces viral burden in the lungs and mitigates inflammation typical of COVID-19”, said Daniel Ruzek from the Czech Academy of Sciences who led the antibody pre-clinical testing.

The effectiveness of the bispecific antibodies holds promise for human clinical trials, with the prospect of being both an effective prevention and treatment of COVID.

Source: News-Medical.Net

Journal information: Gasparo, R D., et al. (2020) Bispecific antibody prevents SARS-CoV-2 escape and protects mice from disease. bioRxiv.doi.org/10.1101/2021.01.22.427567.

Categories : Ageing CancerTags :

Aspirin Protects against Colorectal Cancer

On By ModernMedia

Aspirin is known to reduce the risk of colorectal cancer in middle-aged adults and up until age 70, but has some risky side effects, such as colorectal bleeding. 

It was not known at what stage it was still worth it to start taking aspirin. Indeed, the recent Aspirin in Reducing Events in the Elderly (ASPREE) trial reported that participants taking a daily dose of aspirin (100mg) after the age of 70 for five years had a 30% increased risk of cancer mortality.
It is also currently recommended by the US Preventive Services Task Force that people aged 50-59 years with specific cardiovascular risk profiles take aspirin for its protective effect against heart disease.

To answer the question of whether aspirin was beneficial or harmful after age 70, Andrew T Chan MD, MPH, a gastroenterologist and chief of the Clinical and Translational Epidemiology Unit at Massachusetts General Hospital (MGH), led a team of researchers that analysed a pair of large cohort studies.These were The Nurses’ Health Study (January 1980 – June 2014) and the Health Professionals Follow-up Study (January 1986 – January 2014), giving them a total of 94 500 participants over 35 years.

Their findings showed that aspirin could indeed protect adults over 70 from colorectal cancer – with the caveat that the protection only applied if they started taking aspirin before the age of 70.”There is considerable evidence that aspirin can prevent colorectal cancer in adults between 50 and 70 years old,” commented Chan. “But it has not been clear whether the effect is similar in older adults.”

The researchers concluded that their results “strongly suggest that there is a potential biological difference in the effect of aspirin at older ages which requires further research.”

Source: News-Medical.Net

Categories : UncategorizedTags :

Fatal Netcare Helicopter Crash to Be Investigated

On By ModernMedia

The Civil Aviation Authority has dispatched investigators to the crash site  of a Netcare helicopter on Thursday, in which five people including four health care professionals lost their lives.

The ECMO-equipped air ambulance, Netcare 1, was en route to Hillcrest in KZN to pick up a critically ill patient for transfer back to Milpark Hospital in Johannesburg. The helicopter went down near Bergville..

Netcare on Thursday released the names of those aboard:
Dr Kgopotso Rudolf Mononyane, an anaesthetist. Dr Mononyane had delayed the flight in order to try help to save the life of Jackson Mthembu, who unfortunately passed away from a COVID-related illness.
Curnick Siyabonga Mahlangu, a cardiothoracic surgeon.Mpho Xaba, a specialist theatre nurse for cardiothoracic and transplant.
The above three were all from Netcare Milpark Hospital.
Sinjin Joshua Farrance, an advanced life support paramedic at Netcare 911, Mark Stroxreiter, a helicopter pilot who worked for the National Airways Corporation.

Health Minister Zwile Mkhize said: “We’d like to convey our very sincere condolences to the families of all those doctors and pilot who lost their lives. We know their dedication, their hard work and their effort to try to save lives all the time.”

Dr Richard Friedland, chief executive officer of Netcare said: “We are shocked beyond words at the tragic loss of these healthcare heroes. The whole of Netcare falls silent as we bow our heads in tribute, respect, love and memory of our fallen colleagues and frontline heroes who have died in the line of duty.”

No cause for the accident has yet been identified, although videos from the scene show that wreckage was spread in a wide area. Unconfirmed reports from witnesses recounted a mid-air explosion, whilst a voice note circulating on social media claimed that the helicopter fell to the ground and exploded.

Source: IOL News

Categories : COVID T-cellsTags :

Severe COVID May Lead to Stronger Immunity

On By ModernMedia

Researchers from La Jolla Institute for Immunology (LJI), The University of Liverpool and the University of Southampton have discovered that the degree of COVID severity appears to be linked to how long-lasting and strong the subsequent immunity is. 

“The data from this study suggest people with severe COVID-19 cases may have stronger long-term immunity,” said study co-leader LJI Professor Pandurangan Vijayanand, MD, PhD.

The research examines T-cells from COVID infections in unprecedently high detail.

“This study highlights the enormous variability in how human beings react to a viral challenge,” added co-leader Christian Ottensmeier, MD, PhD, FRCP, a professor at the University of Liverpool and adjunct professor at LJI.

Vijayanand and Ottensmeier have been studying how antibodies and the different subsets of T-cells control COVID disease severity. In this study, they examined CD8+ T-cells, which are the T-cells responsible for destroying virus-infected cells, and “memory” CD8+ T-cells are also important for guarding the body against reinfections of the same virus. These memory T-cells are poised to rapidly proliferate and engage their cell-destroying functions on subsequent antigen encounters. They can reside in peripheral organs and their memory can also be shaped by infection history.

Utilising a new technique called single-cell transcriptomics analysis, they were able to study expressions of individual genes of 80 000 CD8+ T-cells drawn from 39 COVID patients and from 10 non-exposed donors, whose blood samples had been taken before the pandemic. Of the COVID patients, 17 cases were mild and non-hospitalised, 13 were hospitalised and 9 had required ICU care.

Surprisingly, the researchers found that the strongest CD8+ T-cell responses were from those with the more severe form of the disease, and not the milder cases.”There is an inverse link between how poorly T cells work and how bad the infection is,” observed Ottensmeier. “I think that was quite unexpected.” A stronger response would be expected from CD8+ T-cells in mild cases due to having the resources of a better functioning immune system. However, the mild group of CD8+ T-cells showed signs of “exhaustion”, which happens when the immune system overloads the T-cells, causing them to lose effectiveness.

The researchers believe that it will be beneficial to study whether this phenomenon may hinder the ability to build long-term immunity.

“People who have severe disease are likely to end up with a good number of memory cells,” said Vijayanand. “People with milder disease have memory cells, but they seem exhausted and dysfunctional—so they might not be effective for long enough.

“What the researchers would like to look at next is to look at T-cells from lung tissue as opposed to blood samples, because that is where the infection hits hardest.

“This study is very much a first step in understanding the spectrum of immune responses against infectious agents,” said Ottensmeier. The researchers will also look at T-cells in cancer patients who are also infected with COVID.

Source: Medical Xpress

Journal information: Anthony Kusnadi et al, Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8+ T cells, Science Immunology  21 Jan 2021: Vol. 6, Issue 55, eabe4782 DOI: 10.1126/sciimmunol.abe4782

Categories : New Compounds and TreatmentsTags :

Paralysed Mice Walk Again with ‘Designer’ Cytokines

On By ModernMedia

Scientists have sought a means to regenerate spinal cord injuries which leaves patients paraplegic or quadriplegic – and now a breakthrough by researchers at Ruhr-University Bochum, Germany, may see that dream realised.

By the time humans reach adulthood, after an injury they can no longer regenerate the axons which transfer nerve impulses from brain to muscles. In 2013, the researchers discovered that a cytokine called interleukin-6 (IL-6) promoted the regeneration of optic axon fibres in vitro. IL-6 was known to be involved in nerve regeneration as well as in neuropathic pain from peripheral nerve injuries. As promising as this experiment was, delivery of the cytokine to the injury location deep in the body was an obstacles, as was the fact that it had a fairly weak effect on stimulating nerve tissue regrowth.

The team subsequently developed hyper-IL-6, an artificial variant of IL-6 that was far more potent than its natural counterpart. However, the “designer” cytokine still could not be delivered to the injured tissue where it was needed. To get around this, the researchers turned to a somewhat novel delivery method: gene therapy. A few motor neurons in the brain’s sensorimotor cortex are altered via engineered viruses to produce hyper-IL-6, which is then distributed along the axon’s length to the injury site.

“Thus, gene therapy treatment of only a few nerve cells stimulated the axonal regeneration of various nerve cells in the brain and several motor tracts in the spinal cord simultaneously,” explained senior author Dr Dietmar Fischer.

After a single injection of the engineered virus and its hyper-IL-6 payload, mice with severed spinal cords were able to walk again after two to three weeks.

“This came as a great surprise to us at the beginning, as it had never been shown to be possible before after full paraplegia,” said Dr. Fischer.
Following the success of these experiments, Dr. Fischer’s team is looking at combining the engineered cytokine treatment to other promising applications, such as tissue grafts. Additionally, they are investigating whether the hyper-IL-6 treatment can regenerate spinal cord damage that occurred weeks beforehand.

“This aspect would be particularly relevant for application in humans. We are now breaking new scientific ground. These further experiments will show, among other things, whether it will be possible to transfer these new approaches to humans in the future.”

However, adapting this designer cytokine treatment to be one that is safe for humans will take several years.

Source: Medical News Today

Categories : COVIDTags :

Biden’s Promise to “Manage the Hell” out of COVID

On By ModernMedia

Almost immediately upon assuming office, the newly sworn-in President Joe Biden started to deliver on his promise to tackle the COVID pandemic raging in the United States.

On Wednesday, shortly after being sworn in, he wrote to both the United Nations Secretary General and the WHO Director General to notify them of the United States’ return to the WHO – a move no doubt welcomed around the world. He also began to sign a raft of orders related to the COVID pandemic.

Following up on his promise to “manage the hell” out of the COVID pandemic, President Biden signed a directive which “seeks to support the international health and humanitarian response to the COVID-19 pandemic and its secondary impacts, global health security and diplomacy, and better biopreparedness and resilience for emerging and future biological threats.”

His actions and executive orders include:– Increased equipment procurement. Using the Defense Production Act (DPA) to accelerate manufacturing and meet shortfalls in COVID-related equipment and supplies.
– Increased COVID testing. Another order establishes a testing board to help expand the supply of tests and testing equipment, as well as supporting the public healthcare force.
– Increasing studies on COVID-19 treatments. More studies requested on COVID, as well as on COVID in diverse populations. Also requests more healthcare workers.
– Speeding up vaccinations. Federal Emergency Management Agency (FEMA) is directed to begin deploying vaccination centres, aiming toward a goal of 100 in the next month.
– Reopening schools and businesses. The Departments of Education and Health and Human Services (HHS) are directed to provide guidance on safe reopening and operating for education institutions and child care providers.
– Improving protections for workers. Clear guidance for employers to keep employees safe from COVID exposure.
– Increasing travel safety. Masks are to be worn in federal buildings, and mask requirements are extended to interstate travel, including on planes, trains, and buses. People flying into the US from another country will need to test negative for COVID prior to departure and quarantine upon arrival.

President Biden’s plan and the full texts of the executive orders were detailed in a 200 page document which was made available on Thursday.

At a White House signing ceremony, he affirmed his commitment to “following the science” on COVID, saying: “We will make sure that scientists and public health experts will speak directly to you — not the president, but real, genuine experts and scientists.” He added that they will work free of political interference.

He also warned Americans of a “dark winter” ahead, and the nation was in a national emergency and that “we should treat it like one.”

Source: MedPage Today