Cite this: FDA Panel: Concerns Over PI3K Inhibitors in Blood Cancers - Medscape - Apr 22, 2022.

The continuing spread of SARS-CoV-2 remains a Public Health Emergency of International Concern. What physicians need to know about transmission, diagnosis, and treatment of Covid-19 is the subject of ongoing updates from infectious disease experts at the Journal.

In this audio interview conducted on March 29, 2022, the editors discuss a new study of vaccination in 5-to-18-year-olds and what may be a definitive study of ivermectin therapy for Covid-19.  Audio Interview  Effectiveness of Covid-19 Vaccination in Children (15:58) Download 
https://www.nejm.org/doi/full/10.1056/NEJMe2204268?query=featured_home

The number of available IV medications continues to expand. Many hospitals have experienced increases in patient acuity and a rise in the number of medications administered to each patient. This increases the likelihood that multiple IV medications will need to be administered concurrently. Separate IV access sites for drug administration are not always practical, and an increase in the number of sites can increase the risk for infectious complications.

These factors contribute to the escalating complexity of IV drug administration and have resulted in an ever-expanding number of possible incompatibilities.The potential for serious and life-threatening adverse drug events exists when incompatible medications are infused together. Therefore, it is important to verify drug compatibility before coadministration. A clear and concise compatibility chart can be a useful tool to help deliver safe, high-quality IV therapy to patients; in some settings, it is considered a preferred reference source due to ease of use.

A chance of incompatibility exists whenever any IV medication is combined with another. A change in pH is the primary characteristic involved in drug incompatibilities. However, compatibility depends on many factors including concentration, temperature, storage vehicle, order of mixing, and administration technique. Incompatibility also can be caused by excipients in a medication.

Three types of incompatibilities are commonly discussed: physical, chemical, and therapeutic. Physical incompatibilities are the most easily detected and are evidenced by visible changes, such as particulate formation, haze, precipitation, color change, and gas evolution. Chemical incompatibilities are those that result in decomposition of a drug. Loss of potency of greater than 10% over the defined testing period is considered chemical incompatibility. Most chemical incompatibilities can be detected only with a suitable analytical method. Therapeutic incompatibilities, in which a drug combination results in undesirable antagonistic or synergistic pharmacologic activity, are beyond the scope of most compatibility references.

The purpose of this chart is to provide concise, easily accessible, Y-site compatibility data. Although there are differing types of incompatibilities, the type of incompatibility or compatibility is not specified in this chart. A designation of “compatible” indicates that the combination evaluated appears to be compatible based on the tests performed, whether these tests measured physical, chemical, or both types of compatibility. All conditions that may affect compatibility cannot be included in such a format, and it is not possible to predict all incompatibilities that may arise, but it is hoped that the information provided may help clinicians minimize their occurrence. Continuing research adding to the existing body of knowledge on IV compatibilities is vital.

The FDA postponed the Feb. 15 meeting of the Vaccines and Related Biological Products Advisory Committee that was scheduled to discuss the authorization of Pfizer-BioNTech's COVID-19 vaccine for children 6 months through 4 years of age.

According to Peter Marks, MD, PhD, the director of the FDA Center for Biologics Evaluation and Research, the delay was requested by Pfizer-BioNTech, after the agency—which originally thought it could move forward with authorization of a two-dose schedule—requested more data about a third dose, he said.

“Since the early days of the pandemic, we've always followed the science in this ever-changing situation. Given the recent omicron surge and the notable increase in hospitalizations in the youngest children to their highest levels during the pandemic so far, we felt it was our responsibility as a public health agency to act with urgency and consider all available options, including requesting that the company Pfizer provide us with initial data on two doses from its ongoing study,” Dr. Marks said during a media briefing. 

“The goal was to understand if two doses would provide sufficient protection, to move forward with authorizing the use of the vaccine. But at this time, we believe additional information regarding the ongoing evaluation of a third dose should be considered,” he announced. “It makes sense for us to wait until we have the data from the evaluation of a third dose before taking action.”

The trial in children 6 months through 4 years of age is ongoing, and data on the first two 3-mcg doses in this age group are being shared with the FDA on a continuing basis, according to Pfizer. Cases continue to accumulate according to the study protocol, and more data are being generated because rates of infection and illness remain high in children of this age, especially due to the recent omicron surge.

Pfizer-BioNTech said a three-dose schedule may provide a higher level of protection in this age group. “This is also supported by recent observations of three-dose booster data in several other age groups that seems to meaningfully augment neutralizing antibody levels and real-world vaccine protection for omicron compared to the two-dose regimen. The companies expect to have three-dose protection data available in early April,” the companies said in a statement.

The phase 1/2/3 trial initially enrolled 4,500 children 6 months to 11 years of age in the United States, Finland, Poland and Spain at more than 90 clinical trial sites. Additional children have been enrolled in all age groups following study amendments and the trial currently includes approximately 8,300 children. 

The study was designed to evaluate the safety, tolerability and immunogenicity of the Pfizer-BioNTech vaccine in three groups: 

• ages 5 to 11 years; 
• ages 24 months to 4 years; and 
• ages 6 to 24 months. 

Based on the phase 1 dose escalation part of the trial, children ages 5 to 11 years received a two-dose schedule of 10 mcg each, while children younger than 5 years received a 3-mcg dose for each injection in the phase 2/3 study. The trial enrolled children with or without prior evidence of SARS-CoV-2 infection. On Dec. 17, 2021, Pfizer and BioNTech announced the companies would test a third 3-mcg dose given at least two months after the second dose in children under 5 years of age and a third dose of the 10-mcg formulation in children 5 to 11 years of age.

Dr. Marks said he hopes the decision to wait for more data is reassuring to parents and the public. “We take our responsibility for reviewing these vaccines very seriously because we're parents,” Dr. Marks said. “In looking over these data, I think parents can feel reassured that we have set the standard by which we feel that if something does not meet that standard, we can't proceed forward. 

“So, rather than having any issue causing anyone to question the process, I hope this reassures people that the process has a standard, that the process is one that we follow, and we follow the science in making sure that anything that we authorize has the safety and efficacy that people have come to [expect] from our regulatory review of medical product,” Dr. Marks said.

Although it is impossible to predict anything concerning COVID-19, Dr. Marks said, especially in light of recent surges involving more than three-quarters of a million cases per day, and a rise in pediatric cases and hospitalizations caused by omicron, he is hoping that waiting for this information will allow a more expeditious review.  

Dr. Marks added that he empathizes with parents who want the vaccine now for their children. “For the next few months while these additional data are gathered, parents will have to rely on what they've come to do well, which is their using masking procedures. They're making sure that they're vaccinated and taking those types of precautions with their youngest children. We will do our part, obviously, to move as fast as we can when we have the data, but for now we'll have to ask parents to help to continue to do what they've been doing.”

He added that he hopes that waiting will allow decisions to be made on clinical data about actual pediatric infections rather than immune-bridging analyses, which generalize clinical data based on using the vaccine in other age groups.

https://www.pharmacypracticenews.com/Covid-19/Article/02-22/FDA-Delays-Advisory-Meeting-for-COVID-19-Vaccine-for-Very-Young-Kids/66148

Omicron Significantly Different From Other Variants

Within only three weeks after the omicron variant was first identified in Houston Methodist patients, this variant rapidly took over and became the cause of a majority of new cases. By contrast, the delta variant took about three months to reach that same milestone after initial detection. Causing 98% of all new COVID-19 cases by the beginning of 2022, omicron had infected 4,468 of Houston Methodist’s patients by Jan. 5.

Compared with Houston Methodist patients infected with alpha or delta variants, the median age of omicron patients was 44.3 years versus 50 for alpha and 48.3 for delta; hospital length of stay was 3.2 days for omicron, 5.1 days for alpha and 5.4 days for delta; and omicron resulted in 55.4% of breakthrough cases in vaccinated patients, whereas 5.4% and 0.9% of vaccinated patients were infected with the alpha and delta variants, respectively.

As of mid-January, the researchers had also identified three patients with the BA.2 “stealth omicron” variant, which requires whole-genome sequencing to distinguish it from delta and the original BA.1 omicron strain. These were the first three “stealth omicron” cases discovered in Texas.

Houston Methodist has one of the largest, most comprehensive SARS-CoV-2 virus genome sequencing studies in the country, analyzing the genome of every positive COVID-19 sample identified throughout Houston Methodist’s hospital system. To get ahead of the virus and detect mutations that affect patient outcomes, such as causing more severe disease or impeding effectiveness of treatments and vaccines, Houston Methodist has sequenced nearly 80,000 SARS-CoV-2 virus genomes since the beginning of the pandemic.

Why Does COVID-19 Affect a Person’s Sense of Smell?

Infection with SARS-CoV-2 indirectly dials down the action of olfactory receptors, proteins on the surfaces of nerve cells in the nose that detect odors, leading to olfactory dysfunction (Cell 2022 Jan 26. doi:10.1016/j.cell.2022.01.024).

In most cases, the dysfunction lasts only a few weeks, but for more than 12% of COVID-19 patients, olfactory dysfunction persists in the form of ongoing reduction in hyposmia or changes in parosmia.

Led by researchers from NYU Grossman School of Medicine and Columbia University, the new study may also shed light on the effects of COVID-19 on other types of brain cells, and other lingering neurologic effects of COVID-19 like brain fog, headaches and depression.

Experiments showed the presence of the virus near neurons in olfactory tissue brought an inrushing of immune cells, microglia and T cells, which release cytokines that change the genetic activity of olfactory nerve cells, even though the virus does not infect them, the researchers said. Where immune cell activity would dissipate quickly in other scenarios, in the brain, immune signaling appears to persist in a way that reduces the activity of genes needed for the building of olfactory receptors.

To gain insight into COVID-19?induced loss of sense of smell, the researchers explored the molecular consequences of SARS-CoV-2 infection in golden hamsters and in olfactory tissue taken from 23 human autopsies. 

They confirmed that SARS-CoV-2 infection, and the immune reaction to it, decreases the ability of DNA chains in chromosomes that influence the formation of olfactory receptor building to be open and active, and to loop around to activate gene expression. In both hamster and human olfactory neuronal tissue, the team detected persistent and widespread downregulation of olfactory receptor building. Other work posted by the authors suggests that olfactory neurons are wired into sensitive brain regions, and that ongoing immune cell reactions in the nasal cavity could influence emotions and cognition consistent with long COVID.

Experiments in hamsters recorded over time revealed that downregulation of olfactory neuron receptors persisted after short-term changes that might affect the sense of smell had naturally recovered. This suggests COVID-19 causes longer-lasting disruption in chromosomal regulation of gene expression, representing a form of “nuclear memory” that could prevent the restoration of olfactory receptor transcription even after SARS-CoV-2 is cleared, they said.

“The realization that the sense of smell relies on ‘fragile’ genomic interactions between chromosomes has important implications,” said co-corresponding author Benjamin tenOever, PhD, a professor in the Department of Microbiology at NYU Langone Health, in New York City. 

“If olfactory gene expression ceases every time the immune system responds in certain ways that disrupts interchromosomal contacts, then the lost sense of smell may act as the ‘canary in the coal mine,’ providing any early signals that the COVID-19 virus is damaging brain tissue before other symptoms present, and suggesting new ways to treat it.”

How a SARS-CoV-2 infection Can Become Severe COVID-19

Severe courses of COVID-19 are marked not only by strong immune activation and inflammatory reactions, but also by a dysfunctional endothelium. If this barrier between blood flow and tissue is damaged, the patient’s condition deteriorates (Signal Transduct Target Ther 2021 Dec 10. doi:10.1038/s41392-021-00819-6).

Many clinical symptoms, such as the destruction of blood vessels in the lungs and acute respiratory distress syndrome, pointed to an impact on the endothelium, according to Christine Falk, PhD, a scientist at the Hanover Medical School and the German Center for Infection Research.

The endothelium is a thin layer of cells that line blood vessels, forming a barrier between blood flow and the surrounding tissues. Infection with SARS-CoV-2 appears to cause strong activation of immune and endothelial cells in the lungs, resulting in the release of various soluble plasma proteins. Severe COVID-19 cases are associated with a dysfunction of the endothelium wherein the barrier between the alveoli and the surrounding vessels is no longer intact.

The scientists studied 25 patients with severe COVID-19 and 17 recovered patients in the ICU. They found the severity of the disease is linked to disruption of the endothelial barrier and can be measured by looking at inflammatory and endothelial plasma proteins. A pattern of seven plasma proteins appears to be associated with a severe form of the disease, which is characterized by strong inflammatory processes and in which the endothelium is permanently damaged. Furthermore, recovery from severe COVID-19 seems to be related to the regeneration of this endothelial barrier.

The investigators found excessive activation of T-lymphocytes and natural killer cells as well as development of memory T-cells and strong proliferation of plasmablasts, which are cells that can produce large amounts of antibodies. Furthermore, ICU patients infected with SARS-CoV-2 had high titers of spike- and nucleocapsid-specific antibodies. 

The researchers found particularly interesting that the immune cell phenotype of these patients mainly changed over time and was less related to progressive severity of the disease. In contrast, the progression of COVID-19 was closely linked to increased levels of various soluble plasma proteins, namely certain inflammatory mediators and especially endothelial factors.

“We were able to demonstrate that ICU patients with COVID-19 can be divided into different groups based on their plasma protein profile, which are associated with disease severity,” explained lead author Louisa Ruhl, a PhD doctoral student at the Hanover Medical School. This could be a potential biomarker for severe COVID-19 courses, they said.  

COVID-19 Vaccination Protects Against Severe Disease Outcomes

Severe COVID-19 outcomes are rare among adults who have been vaccinated against SARS-CoV-2, according to data from 465 facilities (MMWR Morb Mortal Wkly Rep 2022;71[1]:19-25).

A total of 1,228,664 people who completed their primary vaccination series during December 2020 through October 2021 were included in the analysis. Severe disease outcomes were identified as diagnosis of acute respiratory failure, need for noninvasive ventilation, ICU admission or death.

After vaccination, 2,246 people contracted COVID-19, a rate of 18 per 10,000. Of these, 327 were hospitalized, 189 had a severe COVID-19 outcome, and 36 had a COVID-19–related death. All people who developed severe COVID-19 outcomes after vaccination had at least one of eight risk factors: age at least 65 years, being immunocompromised, diabetes mellitus, pulmonary disease, liver disease, chronic kidney disease, neurologic disease and cardiac disease.

“Our study confirms that vaccines are effective in lowering the risk of severe COVID-19,” said Christina Yek, MD, a clinical fellow in the Critical Care Medicine Department of the National Institutes of Health.

“These findings are also critical to help identify persons at continued risk of severe outcomes despite vaccination, who may benefit from targeted interventions including chronic disease management, exposure reduction, additional primary and booster vaccine doses, and effective pharmaceutical therapy, to reduce the risk for severe COVID-19 outcomes,” she added.

The study authors said the findings confirm the overwhelming benefit of COVID-19 vaccination and increasing COVID-19 vaccination coverage is a public health priority.

“Future studies,” Dr. Yek added, “should use contemporary data to describe risk factors for severe disease with the SARS-CoV-2 omicron variant and after booster vaccination.”

This Is Your Brain on COVID-19

The heart is not the only organ affected by COVID-19. A study from researchers at Columbia University Vagelos College of Physicians and Surgeons reports that the brains of a small sample of patients who died of COVID-19 display some of the same molecular changes found in the brains of people with Alzheimer's disease.

The findings could help explain the memory problems reported by sufferers of long COVID, although the researchers caution that the study is small—with data from only 10 patients—and needs to be replicated by others (Alzheimers Dement 2022 Feb 3. doi:10.1002/alz.12558)

Early reports of “brain fog” and persistent cardiac symptoms in COVID-19 survivors prompted the Columbia researchers to investigate how certain molecules, called ryanodine receptors, were affected by the disease.
Defective ryanodine receptors have been implicated in diverse pathogenic processes, ranging from heart and lung disease to the brain's response to stress and Alzheimer's disease, as reported in research led by Andrew Marks, MD, the chair of the Department of Physiology and Cellular Biophysics at the Vagelos College of Physicians and Surgeons, in New York City.

“What we found is really, I think, quite unexpected: Not only did we find defective ryanodine receptors in the hearts and lungs of deceased COVID patients, we also found them in their brains,” Dr. Marks said.

Inside neurons, defective ryanodine receptors have previously been linked to an increase in phosphorylated tau, a well-known hallmark protein of Alzheimer's.

In the new study, the Columbia researchers found high levels of phosphorylated tau in the brains of the COVID patients in addition to defective ryanodine receptors.

Phosphorylated tau was found in both areas where tau is typically located in Alzheimer's patientsand where it is not typically located in those patients. That suggests phosphorylated tau in the COVID-19 patients could be a sign of early-stage Alzheimer's and also contribute to other neurologic symptoms observed in COVID patients.

Increased levels of phosphorylated tau in the brain are believed to be associated with memory problems in Alzheimer's and could be causing similar issues in people with long COVID, Dr. Marks said.

Based on the findings, together with additional changes found in the brain, the investigators theorized that the immune response characteristic of severe COVID causes inflammation in the brain, which in turn leads to dysfunctional ryanodine receptors and then increases in phosphorylated tau. No changes in the pathways that lead to the formation of amyloid beta—another hallmark of Alzheimer's—were found. And perhaps, memory and neurologic impairments in long COVID can be traced to defective ryanodine receptors.

“One interpretation of these findings is that long COVID could be an atypical form of Alzheimer's and/or that patients who had severe COVID could be predisposed to developing Alzheimer's later in life,” Dr. Marks said, “but much more research needs to be done before we can make more definitive conclusions.”

https://www.pharmacypracticenews.com/Covid-19/Article/02-22/Omicron-s-Differences-Sense-of-Smell-Effects-on-the-Brain-and-Other-News/66059

The FDA revised the emergency use authorizations (EUAs) for two monoclonal antibody (mAb) treatments for COVID-19—bamlanivimab-etesevimab (Lilly) and casirivimab-imdevimab (Regen-COV, Regeneron)—to limit their use in areas where the omicron variant is widely circulating.

The treatments are highly unlikely to be active against the omicron variant, which is circulating throughout the country, the FDA said. Therefore, “these treatments are not authorized for use in any U.S. states, territories and jurisdictions at this time.” 

The National Institutes of Health COVID-19 Treatment Guidelines Panel recently recommended against using these mAbs. 

As of Jan. 15, the CDC estimated the omicron variant of SARS-CoV-2 accounts for more than 99% of cases in the United States. “Therefore, it’s highly unlikely that COVID-19 patients seeking care in

the U.S. at this time are infected with a variant other than omicron, and these treatments are not authorized to be used at this time. This avoids exposing patients to side effects, such as injection site reactions or allergic reactions, which can be potentially serious, from specific treatment agents that are not expected to provide benefit to patients who have been infected with or exposed to the omicron variant,” Patricia Cavazzoni, MD, the director of the FDA’s Center for Drug Evaluation and Research, said in a statement.

If the situation changes and a different variant is circulating that is susceptible, then use of these treatments may be authorized in these areas, the FDA said.

Regeneron said it was working to make a next-generation antibody that is active against omicron, delta and other variants of concern.

Monoclonal antibodies are laboratory-made proteins that mimic the immune system’s ability to fight off harmful pathogens. 

The FDA said several other therapies are still useful for outpatient management of COVID-19 during the omicron surge, including the mAb sotrovimab (GSK). The agency recently expanded the use of remdesivir (Veklury, Gilead) to outpatient use and issued EUAs for two oral medications, nirmatrelvir-ritonavir (Paxlovid, Pfizer) and molnupiravir (Merck). They are authorized to treat patients with mild to moderate COVID-19 who are at high risk for progression to severe disease, including hospitalization or death. 

COVID-19 daily case counts and hospitalizations are starting to go down, but deaths are starting to increase. Deaths usually lag behind case and hospitalization data. More than 864,203 people have died from COVID-19 in the United States.

https://www.pharmacypracticenews.com/Covid-19/Article/01-22/FDA-Limits-Use-of-Monoclonal-Antibodies-to-Treat-COVID-19-/65927

Exclusive: Eighty-seven per cent of UK pharmacies have had to contend with staff absences since the emergence of the Omicron wave, a new survey indicates.

The Pharmacy Magazine survey, which ran on January 7-8, reveals that just 13 per cent of respondents have had no absenteeism in their pharmacy as a result of Covid since Omicron took hold in Britain in December.  

Seventy-four per cent of respondents reported staff absences due to infection, while 60 per cent reported staff having to self-isolate because they had been a close contact of someone with Covid-19.

The survey, which had 220 responses from pharmacists and support staff members, suggests that the average pharmacy has had one pharmacist and two members of support staff off work because they were required to isolate.

Respondents working in independent pharmacies reported slightly higher infection rates, while those working in multiples had slightly higher rates of self-isolation as a result of being a close contact.

Workload and stress levels rising

Ninety per cent said these absences have had a significant impact on workload for remaining staff, while 89 per cent said this had led to increased stress levels among staff. Three-quarters said the level of service provided to patients had been compromised.

“Patients have to wait longer for prescriptions,” said one respondent, adding that some services such as NMS have been suspended.  

Discontented patients were a frequently cited issue, with one respondent noting that they “aren’t very understanding when it comes to staff sickness”.

One pharmacist summed up their experience: “Staff cuts during the pandemic have left us with no contingencies. This has created major safety and effectiveness risks”

An individual working at a multiple said it was “hard to keep up with targets from management,” adding that “not much support” had been offered by their company.

Meanwhile, 69 per cent of pharmacists said their pharmacy had faced significant difficulties sourcing locum cover to deal with these absences. One contractor accused locum pharmacists of “misusing the situation” by “texting the day before to cancel shifts and then working elsewhere for higher rates”.

Despite these difficulties, 69 per cent of respondents said their pharmacy was managing well overall, compared to 31 per cent who felt the business was struggling to cope or not coping at all.

One respondent said the current situation “has resulted in staff working many additional hours’ unpaid overtime out of professional pride to ensure patients receive their medicines”

Pharmacies ‘already operating on the edge’

Leyla Hannbeck, chief executive of the Association of Independent Multiple Pharmacies, told Pharmacy Network News: “We are being challenged by the impact on our staffing from Omicron infections daily. Our members have both business interruption and collapse down plans but each new day brings a new set of challenges.

“Pharmacies were already operating on the edge of their available capacity with no slack in the system, even as little as one or two absentees can have devastating effect on business as usual and many pharmacies have been forced to close under this regime of test and isolate.”

Pharmacists' Defence Association director Paul Day said: "Insufficient levels of suitably trained and competent staff seem to have been normalised at some pahrmacies and some pharmacists and their teams are already sacrificing their own wellbeing to keep pharmacies safe for patients. Covid-related absences will amplify those already challenging situations."

Mr Day claimed that some employers have forced PDA members to come to work even after testing positive, and that others have been told to use their annual leave to cover the isolation period. 

NPA: Investment needed

Helga Mangion, Policy Manager at the NPA commented: “The sector as a whole is currently under significant pressure with many pharmacies facing challenges in maintaining full services due to the current Omicron wave. 

“The overarching factor in England is the lack of NHS investment in community pharmacy services over the past six years.

“Our members have worked very hard to insulate patients from the effects of staff shortages, but the situation is not sustainable.

Company Chemists’ Association chief Malcolm Harrison said the Omicron wave was having a “significant impact, adding: “We are seeing this across all staff roles and, inevitably, in some cases this has forced closures.

“Unfortunately, this short-term crisis is exacerbating the longer term workforce shortage, making it harder and harder to avoid impacting patients. 

PSNC legal director Gordon Hockey told PNN: “We know that contractors are working tirelessly to keep their doors open through this latest wave, but the NHS needs to take a pragmatic and flexible approach to support pharmacies over the winter.

“PSNC will continue to monitor the situation but, in the meantime, contractors may still seek to use the emergency pandemic provisions to temporarily close or reduce their opening hours."

https://www.pharmacymagazine.co.uk/news/omicron-wave-9-in-10-pharmacies-struggling-with-staff-absences

Scientists at Scripps Research, University of Chicago and Icahn School of Medicine at Mount Sinai have identified a new Achilles' heel of influenza virus, making progress in the quest for a universal flu vaccine. Antibodies against a long-ignored section of the virus, which the team dubbed the anchor, have the potential to recognize a broad variety of flu strains, even as the virus mutates from year to year, they reported Dec. 23, 2021 in the journal Nature.

• Vitamin D, also known as the “sunshine” vitamin, is a fat-soluble vitamin that exists in two main forms: D-2 and D-3.
• As an essential micronutrient and one that is primarily derived from sunlight, vitamin D is important for the development of bones and teeth and the regular functioning of the immune system.
• Beyond these functions, previous studies suggest an association between low vitamin D levels and a higher likelihood of developing cardiovascular disease.
• In a new study, researchers have established that it is worthwhile to check vitamin D levels when assessing a person’s cardiovascular risk.

Worldwide, cardiovascular diseases (CVDs)Trusted Source are one of the leading causes of death. Every year, an estimated 17.9 million people around the world die as a result of complications from heart diseases. For context, this means that CVDs are responsible for 32% of all deaths globally.

Prior studiesTrusted Source show that various factors — such as several health conditions, age, family history, diet, and lifestyle — combine to influence the risk of developing CVD.

Using a novel analytical approach, researchers in Australia have discovered an additional factor that may increase a person’s likelihood of CVD.

Lead author Prof. Elina Hyppönen, director of the Australian Centre for Precision Health at the University of South Australia Cancer Research Institute, outlined the results of the study for Medical News Today,

“We found evidence that vitamin D deficiency can increase blood pressure and the risk of CVD.”

“However,” she added, “increasing vitamin D concentrations will only be helpful for those participants who ‘need it,’ and further benefits from elevating concentrations beyond the nutritional requirement are going to be modest, if they exist.”

The results from the study appear in the European Heart Journal.

The coronavirus that causes COVID-19 can spread to the heart and brain within days of infection and can survive for months in organs, according to a new study by the National Institutes of Health.

The virus can spread to almost every organ system in the body, which could contribute to the ongoing symptoms seen in "long COVID" patients, the study authors wrote. The study is considered one of the most comprehensive reviews of how the virus replicates in human cells and persists in the human body. It is under review for publication in the journal Nature.

"This is remarkably important work," Ziyad Al-Aly, MD, director of the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System in Missouri, told Bloomberg News. Al-Aly wasn't involved with this study but has researched the long-term effects of COVID-19.

"For a long time now, we have been scratching our heads and asking why long COVID seems to affect so many organ systems," he said. "This paper sheds some light and may help explain why long COVID can occur even in people who had mild or asymptomatic acute disease."

The NIH researchers sampled and analyzed tissues from autopsies on 44 patients who died after contracting the coronavirus during the first year of the pandemic. They found persistent virus particles in multiple parts of the body, including the heart and brain, for as long as 230 days after symptoms began. This could represent infection with defective virus particles, they said, which has also been seen in persistent infections among measles patients.

"We don't yet know what burden of chronic illness will result in years to come," Raina MacIntyre, PhD, a professor of global biosecurity at the University of New South Wales, told Bloomberg News.

"Will we see young-onset cardiac failure in survivors or early-onset dementia?" she said. "These are unanswered questions which call for a precautionary public health approach to mitigation of the spread of this virus."

Unlike other COVID-19 autopsy research, the NIH team had a more comprehensive post-mortem tissue collection process, which typically occurred within a day of the patient's death, Bloomberg News reported. The researchers also used a variety of ways to preserve tissue to figure out viral levels. They were able to grow the virus collected from several tissues, including the heart, lungs, small intestine, and adrenal glands.

"Our results collectively show that while the highest burden of SARS-CoV-2 is in the airways and lung, the virus can disseminate early during infection and infect cells throughout the entire body, including widely throughout the brain," the study authors wrote.

Cite this: Coronavirus Can Spread to Heart, Brain Days After Infection - Medscape - Dec 28, 2021.

The Food and Drug Administration has approved tralokinumab for the treatment of moderate to severe atopic dermatitis (AD) in adults whose disease is not well controlled with topical prescription therapies or when those therapies are not advisable.

Administered subcutaneously, tralokinumab is a fully human IgG4 monoclonal antibody that specifically binds to interleukin-13, a key driver of underlying inflammation in AD. The drug, which has been developed by LEO Pharma, comes as a single-dose (150 mg) prefilled syringe with needle guard.

In two pivotal phase 3 trials, ECZTRA 1 and ECZTRA 2, tralokinumab monotherapy was superior to placebo at week 16 for all primary and secondary endpoints. For example, at week 16, for the ECZTRA 1 and 2 monotherapy trials, respectively, 16% and 21% of patients treated with tralokinumab 300 mg every other week achieved clear or almost clear skin (IGA 0/1) versus 7% and 9% with placebo.

In addition, 25% and 33% of patients treated with tralokinumab 300 mg every other week achieved an improvement of 75% or more in the Eczema Area and Severity Index score (EASI-75) versus 13% and 10% with placebo. At 52 weeks, 51% and 60% of patients who responded at week 16 maintained IGA 0/1 response with tralokinumab 300 mg every other week in ECZTRA 1 and 2, respectively.

Trial offers first look at how tralokinumab-treated patients weather COVID-19

Finally, 60% and 57% of patients who responded at week 16 maintained EASI-75 response with tralokinumab 300 mg every other week.

In the drug's third pivotal trial, ECZTRA 3, researchers evaluated the efficacy and safety of tralokinumab 300 mg in combination with topical corticosteroids (TCS) as needed in adults with moderate to severe atopic dermatitis who are candidates for systemic therapy. At week 16, 38% of patients treated with tralokinumab 300 mg every other week plus TCS achieved clear or almost clear skin (IGA 0/1) versus 27% with placebo plus TCS. In addition, 56% of patients treated with tralokinumab 300 mg every other week plus TCS achieved an improvement of 75% or more in the EASI-75 versus 37% with placebo plus TCS. At 32 weeks, 89% and 92% of patients who responded at week 16 maintained response (IGA 0/1 and EASI-75, respectively) with tralokinumab 300 mg every other week.

Cite this: FDA Gives Nod to Tralokinumab for Adults With Moderate to Severe AD - Medscape - Dec 28, 2021.

Topline results from a phase 3 trial of P2B001, a fixed-dose combination of extended release (ER) formulations of pramipexole and rasagiline, showed it was superior to its individual components as a first-line treatment for early Parkinson's disease.

Study participants also reported less daytime sleepiness with P2B001, according to a statement from the drug's manufacturer.

The trial data "support our view that P2B001 can provide clinical benefits comparable to higher doses of commercially available dopamine agonists, while mitigating the side effects typically associated with this class of medicine such as somnolence, orthostatic hypotension, and hallucinations," Sheila Oren, MD, chief executive officer of Pharma Two B, said in a statement.

"This is important for PD patients of all ages and is critical for the elderly, who typically do not tolerate side effects of dopamine agonists," Oren added.

Promising Results

The 12-week, international, randomized, double-blind trial was designed to study the efficacy, safety, and tolerability of P2B001 compared to its individual components and to a calibration arm of pramipexole ER in 544 patients with early PD.

Participants received P2B001, a once-daily ER combination product composed of pramipexole 0.6 mg and rasagiline 0.75 mg; pramipexole ER capsule 0.6 mg once daily; rasagiline ER capsule 0.75 mg once daily; or the currently marketed product pramipexole ER capsules titrated to an optimal dose for each individual patient (1.5 to 4.5 mg).

The adjusted mean change from baseline in total Unified Parkinson's Disease Rating Scale (UPDRS) score was -2.66 points for P2B001 vs pramipexole (P = .0018) and -3.30 points for P2B001 vs rasagiline (P = .0001). There was no significant difference in UPRDRS scores between P2B001 and pramipexole ER.

The adjusted mean change from baseline in the Epworth Sleepiness Scale score for P2B001 vs pramipexole ER was -2.66 points (P < .0001).

Treatment-related adverse events were mostly mild or moderate and were similar among groups.

"The initiation of treatment of patients with Parkinson's disease represents an area of unmet need due to the side effects associated with current treatments," Warren Olanow, MD, professor emeritus of neurology and neuroscience at the Icahn School of Medicine at Mount Sinai in New York City, said in a statement from the manufacturer.

"Based on the data from this well-designed, rigorous, active-controlled study, P2B001 has the potential to become a leading treatment option for PD, particularly as first line therapy for early-stage patients of all ages," Olanow added.

The company plans to file a new drug application in 2022.

Cite this: Positive Phase 3 Topline Results for Early Parkinson's Drug - Medscape - Dec 27, 2021.

The oral Janus kinase 1 inhibitor abrocitinib has been approved in Europe for the treatment of moderate to severe atopic dermatitis (AD) in adults, who are candidates for systemic therapy, the manufacturer announced.

Approval by the European Commission was based on the results of studies that include four phase 3 clinical trials (JADE MONO-1, JADE-MONO-2, JADE COMPARE, JADE REGIMEN) and an ongoing open-label extension study (JADE EXTEND) in over 2,800 patients, according to the Pfizer press release announcing the approval. The approved doses are 100 and 200 mg a day; a 50-mg dose was approved for patients with moderate and severe renal impairment and "certain patients receiving treatment with inhibitors of cytochrome P450 (CYP) 2C19," the release said.

The approval follows a positive opinion by the Committee for Medicinal Products for Human Use of the European Medicines Agency supporting marketing authorization for treating AD, issued in October. It will be marketed as Cibinqo.

Abrocitinib is under review at the Food and Drug Administration. It was approved earlier in 2021 for treating AD in the United Kingdom, Japan, and Korea.
Abrocitinib Approved for Atopic Dermatitis in Europe - Medscape - Dec 13, 2021.

Most of the U.S. will see significant growth in COVID-19 cases during the next four weeks, according to the latest forecasting models by the PolicyLab at Children's Hospital of Philadelphia.

Large metropolitan areas, especially those in the Northeast, are already seeing a major increase in cases following Thanksgiving, and that trend is expected to continue.

"Why? Simply stated, the large amount of Thanksgiving travel and gatherings undermined the nation's pandemic footing and has elevated disease burden in areas of the country that were fortunate to have lower case rates before the holidays," the forecasters wrote.

Case numbers in New York City are expected to double throughout December, the forecasters said. Similar growth could happen across Boston, Philadelphia, and Baltimore.

Overall, COVID-19 cases, hospitalizations, and deaths are rising across the U.S. but remain below levels seen during the summer and last winter's surges, according to The New York Times. The increase is still being driven by the Delta variant, though it remains unclear how the Omicron variant, which has been detected in 27 states, could affect the trends in coming weeks.

During the past week, the U.S. has reported an average of more than 120,000 new cases each day, the newspaper reported, which is an increase of 38% from two weeks ago.

The daily average of COVID-19 hospitalizations is around 64,000, which marks an increase of 22% from two weeks ago. More than 1,300 deaths are being reported each day, which is up 26%.

Numerous states are reporting double the cases from two weeks ago, stretching across the country from states in the Northeast such as Connecticut and Rhode Island to southern states such as North Carolina and Texas and western states such as California.

The Great Lakes region and the Northeast are seeing some of the most severe increases, the newspaper reported. New Hampshire leads the U.S. in recent cases per capita, and Maine has reported more cases in the past week than in any other seven-day period during the pandemic.

Michigan has the country's highest hospitalization rate, and federal medical teams have been sent to the state to help with the surge in patients, according to The Detroit News. Michigan's top public health officials described the surge as a "critical" and "deeply concerning" situation on Friday, and they requested 200 more ventilators from the Strategic National Stockpile.

Indiana, Maine, and New York have also requested aid from the National Guard, according to USA Today. Health officials in those states urged residents to get vaccines or booster shots and wear masks in indoor public settings.

The Omicron variant can evade some vaccine protection, but booster shots can increase efficacy and offer more coverage, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said Sunday.

"If you want to be optimally protected, absolutely get a booster," he said on ABC's "This Week."

In addition, New York Gov. Kathy Hochul has announced a statewide mask mandate, which will take effect on Monday. Masks will be required in all indoor public spaces and businesses, unless the location implements a vaccine requirement instead, the news outlet reported.
Cite this: Major COVID-19 Case Growth Expected in Coming Weeks - Medscape - Dec 13, 2021.