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Friday, December 25, 2020

India likely to approve AstraZeneca vaccine by next week

 India is likely to approve Oxford/AstraZeneca’s coronavirus vaccine for emergency use by next week after its local manufacturer submitted additional data sought by authorities, two sources with knowledge of the matter told Reuters on Tuesday.

This could be the first country to give the regulatory green light for the British drugmaker’s vaccine as the British medicine regulator continues to examine data from the trials.

India, the world’s biggest vaccine-making country, wants to start inoculating its citizens next month and is also considering emergency use authorisation applications for vaccines made by Pfizer Inc and local company Bharat Biotech.

Getting vaccines to the world’s second-most populous country with one of the highest infection rates will also be a big step in the battle against the pandemic.

The AstraZeneca-Oxford shot is considered vital for lower-income countries and those in hot climates because it is cheaper, easier to transport and can be stored for long periods at normal fridge temperatures.

The Indian regulator is only considering the two full-dose regimen of the shot despite it showing a lower success rate, the sources said.

“Serum is ready,” said one of the sources. “Initially, we may get around 50 million to 60 million doses.”

The sources declined to be named as deliberations were ongoing and the timeline could change.

CDSCO chief V.G. Somani did not immediately respond to a request for comment. Bharat Biotech and Pfizer declined to comment, while SII did not immediately respond to an email seeking comment.

India has not yet signed a vaccine supply deal with any company, but SII has already stockpiled more than 50 million doses of the AstraZeneca shot and plans to make a total of 400 million doses by July.

https://www.reuters.com/article/uk-health-coronavirus-india-vaccine-excl/exclusive-india-likely-to-approve-astrazeneca-vaccine-by-next-week-sources-idUSKBN28W27I

Moderna COVID vax causes swelling, inflammation with cosmetic facial fillers

 The FDA advisory committee reviewing the new Moderna vaccine has noted a specific side effect involving several trial participants who have cosmetic facial fillers.


Local board certified dermatologist Dr. Shirley Chi explains what the FDA committee noted.

"In these cases the patients all had swelling and inflammation in the area that was given the filler. A couple of the patients had cheek filler six months prior to their vaccine and one patient had lip filler done two days after the vaccine. All were treated with steroids and anti-histamines and all of their reactions resolved," she said.

Millions of people have physician administered cosmetic facial fillers to smooth out fine lines, wrinkles and to enhance cheeks and lips. Chi says the reaction to the vaccine is immunological.

"Your immune system which causes inflammation is revved up when you get a vaccine, that's how it's supposed to work. So it makes sense that you would see an immune response in certain areas where they see some substance that is not a naturally occurring substance in your body" says Chi.

Chi also says to not let this stop you from getting the vaccine when your turn comes up and that all the derma fillers reactions were easily treated by medical personnel.

Don't Cancel Christmas

 The holidays are almost here, and one gift has come early. Two effective vaccines against SARS-CoV-2, and perhaps more to come. However, it is important to remember that merely approving a vaccine does not immediately end a pandemic, and the coming months will remain crucial.

Pre-Thanksgiving, one of us argued that an unyielding "Just Don't Do It" message is unlikely to be persuasive. Public polls and TSA screening numbers suggested that people were desperate and longing for social connections with their families. Christmas and New Year's are on track to be similar based on early TSA reports.

We continue to believe that abstinence-only messaging is misguided and may not be successful. Instead of what not to do; we wish to offer ideas and suggestions about what to do.

Beyond Cancellation

"Cancel everything" has become reflexive in efforts to control a pandemic, and in recent weeks targets have included playgrounds, social gatherings, and outdoor youth athletic activities. Restrictions on social and recreational outlets represent a convenient solution for leaders short on resources and even shorter on public support for renewed lockdowns. The problem is that these measures undermine the best available tools to combat pandemic fatigue and thwart low-risk ways to satisfy the understandable desire for social connection. We instead need to pair public health restrictions on the highest risk activities with a massive scale-up of safer social and recreational activities.

Planning recreational activities at the height of a pandemic may seem misguided and perhaps disrespectful toward the hundreds of thousands of lives lost. But, the reality is pandemic-fatigued Americans are already seeking outlets to satisfy their need for social connection and recreation. Playground outings with friends shift to indoor household play. Video games among teenagers may replace youth sports. Dinners at shuttered outside restaurants become backyard gatherings that move indoors as night falls. Cancellation may paradoxically lead to riskier behavior. How can we balance the need for social and recreational activity while minimizing the risk of transmission this holiday season?

Enable and Organize Holiday Fun

We should reject the urge to postpone social and recreational activities until the spring and instead actively create and incentivize opportunities for social and recreational activities. We can encourage these activities by reopening safer outdoor spaces, distributing discounted and free gear, and providing access to passes and recreational fees.

Cities can open public parks, open spaces, and golf courses for walking and play. Colder climates might open sledding hills and expand ice-skating rinks (a straightforward task when the temperature is below freezing). Warmer climates may reopen kayak rentals for local lakes and streams. Municipalities can organize outdoor games and activities for kids and adults -- with food trucks and hot chocolate stations for parents (no-refills). These efforts may even modestly stimulate spending if done right.

Outdoor athletics and organized activities for kids are vital to a sense of purpose for families and can be done safely. We need to think creatively about the activities that can happen safely -- soccer, skating, skiing, football -- and then work to make these activities organized and enjoyable. Indeed, much of the disease transmission that has happened in athletics may have occurred off the playing fields -- in locker rooms, carpools, and team social activities -- and be reduced with good mitigation strategies.

Guidance for Home Activities

Most public health efforts have centered on America's main street -- schools, businesses, and healthcare settings -- and yet, disease transmission also occurs in its living rooms and backyard gatherings. With the holidays arriving, Americans need enabling guidance and support for their private lives that can help them to identify the highest risk activities and structure safer ones. In short, they need both clear instructions to enjoy fun more safely as well as the resources to do so. Access to warm winter clothing, fire pits, or bonfire materials can enable this. Encouraging folks to move their holiday (and winter) gatherings from the living room to a backyard bonfire can lower the risk of holiday celebrations that are likely to occur either way.

A Holiday Tailgate

Even on the coldest days, college football tailgating shows how when organized and motivated, people can enjoy hours together braving the elements. Municipalities can designate space, and provide water, trash, and grill access for folks to set up tailgate stations. Streets can be closed off, and picnic tables deployed, to facilitate outdoor gatherings. Free food and drink can be provided. Outdoor sporting events can be organized.

It's Not Over Yet

News of vaccines offers much-needed hope, and we share the excitement, but we still need to sustain a public health response over several months, which may be the darkest yet.

Pandemic fatigue and stress are high, and the need for social connections is as real as our thirst for water. Americans are a fiercely independent society, but the holidays mark an important time where we crave, seek, and need to spend time with others. We can celebrate this season by coming together in ways that minimize risk, but still satisfy the real and understandable desire of social connection.

Vinay Prasad, MD, MPH, is a hematologist-oncologist and associate professor of medicine at the University of California San Francisco, and author of Malignant: How Bad Policy and Bad Evidence Harm People With Cancer.

Anne N. Sosin, MPH, is the program director for the Center for Global Health Equity at Dartmouth College and the co-lead on Dartmouth research on COVID-19 and rural health equity in Northern New England.

https://www.medpagetoday.com/blogs/vinay-prasad/90368

Parkinson's Motor Symptoms Improve With Focused Ultrasound

 Focused ultrasound in one brain hemisphere improved motor function on the opposite side of the body in people with Parkinson's disease, but led to frequent, persistent adverse events, a small sham-controlled trial showed.

In a select group of patients with markedly asymmetric Parkinson's signs, focused ultrasound subthalamotomy led to a significant improvement in Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor scores (MDS-UPDRS III) at 4 months compared with sham treatment, with a between-group difference of 8.1 points (95% CI 6.0-10.3, P<0.001), reported Raul Martinez-Fernandez, MD, PhD, of CEU San Pablo University in Mostoles, Spain, and co-authors.

"This randomized, sham-controlled trial showed that focused ultrasound subthalamotomy performed in one hemisphere improved the motor features of Parkinson's disease on the more affected side at 4 months," they wrote in the New England Journal of Medicine.

"Adverse events such as dyskinesias, motor weakness, and gait and speech disturbances were frequent and persisted in several patients," Martinez-Fernandez and colleagues noted. "These results are similar to outcomes in uncontrolled series of stereotactic radiofrequency subthalamotomy for the treatment of Parkinson's disease."

Changes from baseline MDS-UPDRS motor scores for the more affected side varied, ranging from 5% to 95%, and were more apparent for tremor and rigidity reduction than bradykinesia.

Among 27 patients treated with focused ultrasound subthalamotomy, adverse events included:

  • Dyskinesia in the off-medication state in six patients and on-medication state in six patients, which persisted in three patients and one patient, respectively, at 4 months
  • Weakness on the treated side in five patients, which persisted in two patients at 4 months
  • Speech disturbance in 15 patients, which persisted in three patients at 4 months
  • Facial weakness in three patients, which persisted in one patient at 4 months
  • Gait disturbance in 13 patients, which persisted in two patients at 4 months
  • Some of these deficits were present in six patients at 12 months.

Deep-brain stimulation (DBS) to treat Parkinson's disease predominantly has targeted the subthalamic nucleus or the internal segment of the globus pallidus, but some patients are wary of DBS surgery and hardware, noted Joel Perlmutter, MD, and Mwiza Ushe, MD, both of Washington University in St. Louis, in an accompanying editorial. Focused ultrasound, which has been approved to treat intractable essential tremor, "has the advantage of producing lesions without the need for craniotomy," they observed.

But in this small trial, patients who had focused ultrasound subthalamotomy had almost five times as many adverse events as those who had the sham procedure, Perlmutter and Ushe pointed out.

"These adverse events in a group of relatively young patients and the lack of ability to modulate treatment over time to treat prominent tremor raise questions about the appropriate implementation of focused ultrasound-produced lesions for the treatment of Parkinson's disease," they wrote.

The trial included 40 adults with markedly asymmetric Parkinson's disease who had motor signs not fully controlled by medication or who were ineligible for DBS surgery. In total, 27 patients (mean age 56.6, 59% men) had focused ultrasound subthalamotomy on the side opposite their main motor signs and 13 had a sham procedure (mean age 58.1, 77% men).

At 4 months, mean MDS-UPDRS motor scores for the more affected side decreased from 19.9 at baseline to 9.9 in the treated group (least-squares mean difference 9.8 points, 95% CI 8.6-11.1) and from 18.7 to 17.1 in the sham group (least-squares mean difference 1.7 points, 95% CI 0.0-3.5).

"Side effects such as dysarthria may limit application to focused ultrasound-produced lesions in one hemisphere because the frequency of dysarthria is likely to be greater with procedures that are conducted in both hemispheres," Perlmutter and Ushe wrote. But "limiting the treatment to one side of the brain by ultrasound-produced lesioning constrains the application, since most patients with Parkinson's disease have progression of symptoms on both sides of the body," they added.

The trial had several limitations, including its small sample size, the researchers noted. Almost all patients were enrolled at one of the two trial sites, making it in effect a single-center trial. In addition, both patients and assessors correctly guessed trial group assignments, erasing the intended effect of blinding.

Disclosures

This study was sponsored by device manufacturer INSIGHTEC and was supported by the Focused Ultrasound Foundation, Fundación MAPFRE, Fundación Hospitales de Madrid, and the University of Virginia Center of Excellence.

Martinez-Fernandez reported relationships with BIAL Biotech, Boston Scientific, Focused Ultrasound Foundation, INSIGHTEC Ltd., and Zambon. Co-authors reported numerous relationships with industry and others.

Perlmutter had no disclosures. Ushe reported non-financial support from Abbott.

Thursday, December 24, 2020

NYC orders international visitors to quarantine

 New York City has introduced quarantine rules for international travellers following emergence of new Covid variants in countries like the UK.

Mayor Bill de Blasio said all visitors would be ordered to stay for 14 days at the address they provided on arrival.

He said anyone arriving from the UK would be visited by sheriff's deputies to ensure they abide by the rules.

Those who breach them will be fined $1,000 (£737) a day, Mr de Blasio warned.

About 18.4m coronavirus cases and more than 326,000 deaths have been recorded across the US, according to Johns Hopkins University.

New York City was at the epicentre of America's coronavirus outbreak earlier this year, and has again become one of the country's worst-affected states.


In a statement, Mayor de Blasio said all inbound international travellers must provide their contact details.

"We are really serious about the fact that if you violate quarantine you're creating a danger for everyone else," said Mr de Blasio.

"We are in the final battle here, all we have to do is get through these holidays," he added.


https://www.bbc.com/news/world-us-canada-55432977

Lilly’s monoclonal antibody fails in NIH-sponsored ACTIV-3 trial

 The US National Institutes of Health (NIH) has announced that preliminary results from a Phase III clinical trial of Eli Lilly and Company’s investigational monoclonal antibody, LY-CoV555, showed it failed to provide clinical benefit in hospitalised Covid-19 patients.

The US National Institutes of Health (NIH) has announced that preliminary results from a Phase III clinical trial of Eli Lilly and Company’s investigational monoclonal antibody, LY-CoV555, showed it failed to provide clinical benefit in hospitalised Covid-19 patients.

Discovered by AbCellera Biologics and the National Institute of Allergy and Infectious Diseases (NIAID)’s Vaccine Research Center, LY-CoV555 is developed and manufactured by Eli Lilly and Company, in collaboration with AbCellera.

In October, the trial halted new enrolment after an independent Data and Safety Monitoring Board (DSMB) recommended so.

The trial, which is part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) programme, is sponsored by NIH unit NIAID.

The randomised, placebo-controlled ACTIV-3 trial used a master protocol, which would aid in analysing various investigational agents versus placebo in hospitalised adult patients with Covid-19.

In the trial, participants randomly received either an experimental agent or a matched placebo along with the standard of care, including the antiviral remdesivir.

The LY-CoV555 sub-study enrolled 326 participants. Around 314 subjects randomly received either LY-CoV555 or placebo.

NIH noted that after five days, 50% of those received LY-CoV555 and 54% of placebo recipients were in one of the two most favourable outcome categories.

The investigators concluded that LY-CoV555 did not expedite clinical improvement versus placebo at day five in hospitalised Covid-19 patients without end-stage organ failure.

In addition, no difference in time to hospital discharge or the primary outcome of sustained recovery, back at home for 14 days were observed among those who received the treatment as compared with placebo.

In November, the US Food and Drug Administration granted emergency use authorisation (EUA) to LY-CoV555 to treat non-hospitalised adolescents and adults with mild to moderate Covid-19 symptoms who are at the risk of progressing to severe Covid-19.

In August, the NIH initiated a Phase III ACTIV-3 trial to evaluate various types of monoclonal antibodies as potential treatments for hospitalised Covid-19 patients.

Separately, three global trials, notably REMAP-CAP, ACTIV-4 and ATTACC, analysing the effects of full doses of anticoagulants (blood thinners) in Covid-19 patients have paused the enrolment for critically ill Covid-19 patients requiring intensive care unit (ICU) support.

https://www.clinicaltrialsarena.com/news/lilly-antibody-nih-trial/

Hospital Readmission Common Among COVID-19 Survivors

 Bridget M. Kuehn, MSJ

JAMA. 2020;324(24):2477. doi:10.1001/jama.2020.23910

Nearly 1 in 10 patients who were discharged after receiving inpatient care for coronavirus disease 2019 (COVID-19) earlier this year were readmitted within 2 months, according to a recent study.

Image description not available.

To help fill the knowledge gap about posthospitalization COVID-19 outcomes, CDC investigators analyzed hospital records and administrative data for 126 137 patients with COVID-19 who were admitted between March and July. They found that 15% of the patients died during their initial hospitalization. Among survivors, 9% were readmitted to the same hospital within 2 months of discharge and 1.6% were readmitted more than once. Fifteen percent of patients discharged to nursing home care were readmitted to a hospital, as were 12% who were discharged to home health care and 7% who didn’t need professional care at home. Fewer than 0.1% of readmitted patients died. Diseases of the circulatory, respiratory, or digestive systems were readmitted patients’ most common discharge diagnoses.

Having preexisting pulmonary disease, heart failure, diabetes, or chronic kidney disease increased patients’ odds of readmission. Patients discharged to home-based or self-care were less likely to be readmitted, but two-thirds of those who were had 1 or more of those chronic conditions. Although Black and Hispanic patients were overrepresented among the hospitalized patients, they were less likely than White patients to be readmitted.

The data add new urgency to the need to curb surging US COVID-19 infections—particularly among high-risk populations—as hospitals across the country become overwhelmed. The findings may also help physicians determine the best discharge plans for inpatients.

“Continued public health messaging and interventions to prevent COVID-19 among older persons and those with underlying medical conditions is essential,” the authors wrote.

https://jamanetwork.com/journals/jama/fullarticle/2774420