Robert Califf has cleared another stage on his return journey to the top job at the FDA, after the influential Senate committee on Health, Education, Labour and Pensions (HELP) voted by 13 to eight to support his nomination by President Joe Biden.
Califf was nominated by Biden as FDA commissioner last November, ending a search for a permanent replacement for current acting commissioner Janet Woodcock after almost a full year of the new administration.
He led the FDA under the Obama administration in 2016 and garnered a reputation for cracking down on manufacturing and safety, and pushed for the modernisation of the regulator before Donald Trump’s election win saw his time come to an end just 11 months later.
If he makes it over the line, Califf will lead an agency having to make difficult decisions over the future handling of the pandemic, affected by a lack of permanent leadership and facing scrutiny over its handling of the opioid epidemic.
The dissenting votes – from Vermont independent Bernie Saunders, Democrats Maggie Hassan and Edward Markey, and a clutch of Republican senators – suggest that the full Senate vote on Califf’s appointment may not be a foregone conclusion.
Sanders reiterated his concerns about Califf’s consultancy work with pharma companies and the “revolving door” between the FDA and industry, while Hassan and Markey are both from US states (New Hampshire and Massachusetts, respectively) that have been hard hit by the opioid crisis.
Hassan said in a statement that she did not believe Califf would take the action needed to address the FDA’s “inaction…to address opioid misuse and the failure to address issues of labelling guidance for prescriptions.”
Califf has said he will review FDA decision-making on opioid drugs, and he will face other challenges as well.
An advocate of reform of the clinical trial framework, Califf will have to tackle the issue of approving drugs based on preliminary data while a confirmatory trial is carried out – brought to the fore last year when the FDA approved Biogen and Eisai’s Alzheimer’s drug Aduhelm (aducanumab). It’s now facing an investigation into that by the Office of the Inspector General (OIG).
There have been concerns that for many years the industry dragged its heels on those follow-up studies, and the DA failed to take a tough stance on tardy companies. There are signs of change with various cancer drugs losing indications last year, but pressure from within and outside the agency to do more.
After so long without a permanent commissioner, however, market observers think that the odds are in favour of Califf returning to the role.
“As a former FDA commissioner, Dr Califf is an experienced pick to lead this important agency, and today the committee advanced his nomination in a bipartisan manner,” said HELP chair, Washington Democrat Patty Murray.
“As our nation continues to fight the COVID-19 pandemic, the scientists and experts at the Food and Drug Administration who are working diligently to ensure we have safe and effective vaccines, tests, treatments, and more, deserve a strong leader who will make sure science always comes first,” she added.
A date for the full Senate vote has not yet been set.
Over 30,000 cases of monkeypox have been reported in more than 80 countries worldwide in 2022. Most are in countries that have never previously reported monkeypox. While monkeypox is not as transmissible as many respiratory infections (such as COVID-19), it’s still important to curb the spread.
There are a number of reasons why we are seeing shortages of the vaccine used to protect against monkeypox. Broadly, it’s due to chronic weaknesses in our global vaccine manufacturing and distribution systems, which make it especially difficult to supply the vaccines needed to protect against new infections and outbreaks.
The vaccine currently being used to protect against monkeypox is the smallpox vaccine, which works because the monkeypox virus is so closely related to smallpox.
Until now, the smallpox vaccine has been a niche product because it’s not been needed since smallpox was eradicated in 1980. Pharmaceutical companies can’t afford to manufacture vast numbers of doses just in case, and few governments can justify buying a vaccine that isn’t used. This means the vaccines currently being administered are from emergency stockpiles that were created to respond to an accidental (or deliberate) release of smallpox.
As such, there are limited stocks and production capacity globally, so demand is rapidly outstripping supply. Even the US, with one of the largest smallpox vaccine stockpiles, recently ordered 2.5 million additional doses in response to the monkeypox outbreak. But there are reports that the factory in Denmark which makes the world’s only smallpox vaccine approved for monkeypox is temporarily closed, which may further impact the world’s ability to source more vaccine doses. And unfortunately, transferring production to other facilities is not straightforward.
One particular problem for vaccine manufacturers is that it’s hard to predict when or where big outbreaks of infections may happen. Of course, there are some infections that we know consistently require a regular supply of vaccines – such as the influenza virus. But while 1 billion influenza vaccines are produced globally each year, it still takes approximately six months from picking the most important new strains to manufacturing and rolling out jabs.
So even with vaccines in high demand, it isn’t simple to manufacture more doses. This is why we are still striving to innovate ways to rapidly produce new vaccines affordably and at a very large scale.
Vaccines are inherently complicated to make. Because they are made from relatively fragile and complex biological materials (such as a virus), the product has to be exactly right every time. If the formula changes even slightly, it might not work as well – or even increase the risk of side-effects.
Adding to this challenge is the fact that different vaccine products may be manufactured by different methods. For example, the equipment needed to produce a viral vaccine (such as the smallpox vaccine used against monkeypox) will be very different to that used to make COVID-19 RNA vaccines. It’s also slow and expensive to test any necessary modifications or improvements that may be needed to make a vaccine safer and more effective.
Surprisingly, even some simple processes common to all vaccines and other medicines – such as filling doses into vials for distribution to patients – still have a mismatch of capacity. Vaccines are usually manufactured in different locations to packaging facilities, raising logistical hurdles (such as strictly controlled refrigeration requirements) that can further delay distribution. These facilities are used for many different medicines and are usually fully booked years in advance; schedules that are still recovering from COVID-19 disruptions may now be experiencing urgent changes to package the smallpox vaccine from stockpiles.
It also isn’t just a case of developing new monkeypox vaccines that are easier to manufacture. Even with major recent scientific progress, it would take many months to develop a safe and effective new vaccine. For monkeypox, it’s far quicker and simpler to use the existing smallpox vaccine.
What can be done?
Smallpox vaccine production is likely to be increased to meet demand. But until this happens, many countries will have to make best use of what supplies they can access, and rely on other strategies to help curb the virus’s spread.
The most effective way to prevent monkeypox causing further harm is by using an integrated, locally led public health response – vaccines are just one part of this. Testing and contact tracing is vital. If enough infected people in a region can be identified and supported to isolate while they’re infectious, transmission can be blocked.
Given the vaccine shortages, we expect that people don’t need two vaccine doses to be protected against monkeypox. This is why vaccinating the most at-risk groups with one dose now, paired with other public health measures, is the most effective strategy for curbing the spread of monkeypox – especially while vaccine supplies are limited. Second doses can be administered to maximise immunity when supplies do become available.
The current monkeypox outbreak is yet another reminder of the importance of investing in global health, and ensuring there’s more equal access to vaccines and other medical interventions that can help prevent the spread of harmful diseases.
Alexander Edwards does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.
Ivana Trump, the first wife of Donald Trump, was recently found dead in her Manhattan residence. She was 73.
Known throughout her life as a dynamo socialite and dealmaker in heels, her death from a blunt trauma from a fall down the stairs in her multi-story townhome, was a shock to residents who perceived her as vibrant and full of life. So, her passing got me thinking about Ivana Trump’s money lessons for older Americans.
Listen, it’s tough to age, but don’t let the process get you down. It’s too hard to get back up! Get it?
Seriously, a great challenge is an acceptance of growing older. Aging can be a tough pill to swallow. Especially for those who are known for the travails of their younger days. I have friends who explain as they age, they ‘disappear.’ I hate to hear this.
Personally, I’m living my best self and wouldn’t change a thing. However, Ageism is a real societal challenge. Based on numerous surveys, white papers, and reports from health organizations, those who are 60 and older are subject to negative stereotyping and discrimination in the workplace. Also, to younger generations, they do disappear in a manner of speaking.
But I have news for you. I think that’s about to change for you ‘seasoned’ folks.
During the pandemic, the Labor Force Participation Rate collapsed and has yet to recover. For those who need a reminder, the LFPR represents the people age 16 and older employed or seeking employment. Older Americans decided to accelerate retirement. Younger cohorts decided to go out on their own or sit back – satiated by government stimulus.
I think many older Americans will seek to unravel their retirement decision and return to the workforce. Also, I believe they’ll be welcomed with open arms by employers eager for a generation that is timely, responsible, and willing to work!
Let’s kick Ageism where it hurts. Right in the work ethic!
One money lesson I’ve learned from Ivana Trump about older Americans is that the entire world is wrinkling.
According to Peter Zeihan in his latest book – The End of The World is just the Beginning, population, and spending shrinkages are realities the entire globe must embrace. Demographics outline that mass-consumption-driven economies have already peaked.
By 2030, the world will be populated with twice as many retirees. Therefore, we all better internalize the fact that we’re getting older and financially and emotionally prepare accordingly. Long-term, poor demographics are deflationary.
In my opinion, Ivana Trump refused to accept aging. Thus, I consider Ivana Trump’s money lessons for older Americans applicable to all of us.
Regardless of her immense wealth, she must have encountered anguish when it comes to getting older. Sure having money doesn’t hurt. Suffering in luxury isn’t bad. However, aging doesn’t care about a net worth statement.
Denial of aging is real and one of Ivana Trump’s best money lessons for older Americans.
Who needs comprehensive studies to understand that denial of getting older is a reality? I see it in myself as I dramatically changed my diet and amped up my physical workouts years ago to fight or slow the inevitable.
Frankly, my graying hairline stresses me out.
I engage with people regularly who aren’t ready to deal with how someday they may move slower, forget things often and work through periodic illness or injury. Older clients and their adult children have a tough time facing that mom and dad are grayer, smaller, and frailer than they used to be.
Per a July 2022 analysis from the Center for Retirement Research, older Americans and retirees poorly assess the risks they face in retirement. Health and longevity risks (the risk of living longer than expected and exhausting financial resources) are underestimated.
Per the study: Perceived longevity risk and health risk rank lower because retirees are pessimistic about their survival probabilities and often underestimate their health costs in late life.
I cannot tell you how many clients inform me how sure they are about dying early. How do they know? So, I always ask the following question –
“What if you don’t?”
Ivana Trump’s friends were concerned about her home’s beautiful but dangerous staircase. They were worried about her falling. She had an elevator and rarely used it. The stairs at her home were steep, the carpet was worn. Although she had trouble walking, she regularly took the stairs. She had the money to remove or replace the carpet; the elevator would have been perfect, but she rarely used it.
In her halcyon days, Ivana was New York royalty. Young, vibrant. She could accomplish anything. How can someone like that stare into the mirror and face vincibility? How can you? Can I? Acceptance is the first step to a rich life as we age, to feel comfortable in different but richer skins.
That acceptance opens the door to preparation – eating right, exercising regularly, and preparing for the risks of aging through comprehensive planning and open communication with family and friends.
If I deny aging, then I’ll force everyone around me to deny it too. Or, at the least, family members and friends will discuss issues concerning me behind my back. Who wants that? Older Americans must be open to listening.
This leads to my next financial lesson for older Americans from Ivana Trump.
Communication. Another one of the money lessons Ivana Trump has for older Americans.
I wonder how many times Ivana was advised (perhaps delicately) by Ivanka and the other kids to update her place for aging, move to a one-story, or take the damn elevator. Whatever it is, would Ivana listen or just carry on like it was the 1980s? In her mind, it may have been decades ago, but her aging body lived in the here and now.
There’s a nuance and empathy to communicating with older loved ones.
Remember, they were young like you once. Listen to your special older Americans. Never be condescending. A good idea may be to bring in an objective third party such as your financial advisor to assist with the discussions. I’ve witnessed adult children infantilize their parents, and that never works. Imagine approaching Ivana with that tone! Not good!
Remember, even mild cognitive impairment can drive a communication wedge between you, and your aging loved one. However, don’t give up sparking conversation. I work with clients who consistently need to nuance their speech with their parents. They get their points across eventually. Impaired older relatives eventually take action, but the process is like chipping away at an iceberg with a butter knife.
Don’t give up!
Genworth, a leader in long-term care insurance and research, maintains an impactful Conversation Starters page with helpful tips about what to talk about and how to maintain a dialogue. Check it out.
Use your financial plan to motivate others.
How can you discuss long-term care issues with loved ones if you’re personally in denial about aging? A risk mitigation plan as part of a comprehensive financial strategy validates your commitment to preparation. Actions forge your conversations with credibility.
According to AARP’s most recent Home and Community Preference Survey, 77% of adults 50 and older want to remain in their homes or age in place. The number has been consistent for over a decade. Aging in place requires planning – whether it’s to eventually downsize to a one-story home, renovate kitchen and baths or install easy access ramps for items of mobility such as wheelchairs. It would be worth practicing financial openness and sharing this information with aging parents. In other words, if you’re preparing for these expenses, they should be too.
Don’t forget long-term care insurance as one of Ivana Trump’s money lessons for older Americans.
Ivana didn’t need long-term care insurance. You probably need to consider it.
Unfortunately, nearly half of individuals who apply for traditional long-term care insurance after age 70 have their applications declined by an insurer, according to Jesse Slome, director of the American Association for Long-Term Care Insurance. However, loved ones in good health in their 50s and 60s can still consider long-term care insurance. The sweet spot for looking into long-term care coverage is generally between ages 55 and 65, per Jesse Slome.
Three out of every five financial plans I create reflect deficiencies in meeting long-term care expenses. Medical insurance like Medicare does not cover long-term care expenses – a common misperception. Nearly 60% of people surveyed in various studies falsely believe that Medicare covers long-term care expenses.
Genworth’s results assume an annual 3% inflation rate. In today’s dollars, a home-health aide who assists with cleaning, cooking, and other responsibilities for those who seek to age in place or require temporary assistance with daily living activities can cost over $54,912 a year in the Houston area. We use a 4.25-4.5% inflation rate for financial planning purposes to reflect recent median annual costs for assisted living and nursing home care. Candidly, I fear that I’ll need to increase this inflation rate in 2023.
As I examine long-term care policies issued recently vs. those 10 years or later, it’s glaringly obvious that coverage isn’t as comprehensive, and costs are more prohibitive.
One option is to consider a reverse mortgage, specifically a home equity conversion mortgage. The horror stories about these products are overblown. The most astute planners and academics understand how incorporating the equity from a primary residence in a retirement income strategy can help with the burden of long-term care costs. Those who talk down these products are speaking out of lack of knowledge and falling easily for pervasive false narratives.
Reverse mortgages have several layers of costs (nothing like they were in the past), and it pays for consumers to shop around for the best deals. Also, to qualify for a reverse mortgage, the homeowner must be 62, the home must be a primary residence, and the debt limited to mortgage debt. There are several ways to receive payouts.
One of the smartest strategies is to establish a reverse mortgage line of credit at age 62, leave it untapped, and allow it to grow along with the home’s value.
The line may be tapped for long-term care expenses if needed or to mitigate the sequence of poor return risk in portfolios. Simply, in years where portfolios are down, the reverse mortgage line is used for income while portfolios recover. Once assets recover, rebalancing proceeds or gains may be used to repay the reverse mortgage loan, restoring the line of credit.
RIA’s approach to helping older Americans age comfortably in place.
Our planning software allows our team to consider a reverse mortgage in the analysis. Those plans have a high probability of success. We explain that income is as necessary as water regarding retirement. For many retirees, converting the glacier of a home into the water of income using a reverse mortgage will be required for retirement survival and especially long-term care expenses.
Ivana Trump’s money lessons for older Americans are lessons for us all, regardless of age.
Planning to age gracefully and healthfully will lead to a prosperous retirement attitude.
As George Burns said: You can’t help getting older, but you don’t have to get old.
The longer I live, the more I realize how true that quote is.
An analysis of millions of SARS-CoV-2 genomes finds that recombination of the virus is uncommon, but when it occurs, it is most often in the spike protein region, the area which allows the virus to attach to and infect host cells.
Credit: Centers for Disease Control and Protection
An analysis of millions of SARS-CoV-2 genomes finds that recombination of the virus is uncommon, but when it occurs, it is most often in the spike protein region, the area which allows the virus to attach to and infect host cells.
The study, led by scientists at UC Santa Cruz, was published August 11 in the journal Nature. It details a new software created by the researchers to search the COVID-19 phylogenetic tree, a diagram of the virus’s evolutionary history, for instances of recombination. This software is open source, allowing public health officials to use it to track instances of recombination within their communities.
Recombination occurs when two genetically distinct forms of the virus hybridize. This study focused on detectable recombination, when the hybridization results in a sequence that is genetically new, and not on instances where two sequences combine to form a sequence identical to an already existing one.
“It’s really important for reconstructing the virus’s evolutionary history,” said Russell Corbett-Detig, senior author on the study and an associate professor of biomolecular engineering at the Baskin School of Engineering. “When there’s recombination it’s not one tree, it’s many trees, and being able to trace that accurately is really crucial for understanding evolution of the virus.”
Findings on recombination
The researchers analyzed 1.6 million samples of COVID-19 and found 589 recombination events, which indicates that only about 2.7% of sequenced genomes result from recombination. These sequences were sourced from the UC Santa Cruz SARS-CoV-2 Browser, a repository for COVID-19 genomic data, which is now the largest collection of genomic sequences of a single species ever assembled, currently at nearly 12 million sequences.
While results show that recombination occurs more frequently in the spike protein region, it is not yet known why this is. This could potentially be the result of a mechanistic bias, indicating it is the natural tendency of all coronaviruses to recombine toward the three-prime region of the viral genome, which contains the spike protein, or that positive natural selection for COVID-19 is favoring recombinants that occur in this region.
While recombination does occur, there is no evidence that the resulting strains are more likely to be epidemiologically important. In fact, most recombinant variants die out, as do most of the thousands of mutated variants of COVID-19.
A new software, written primarily by UC San Diego Assistant Professor Yatish Turakhia during his postdoctoral training in Corbett-Detig’s lab, enabled the computational feat required for the analysis of millions of genomes. The software, called Recombination Inference using Phylogenetic PLacEmentS (RIPPLES), can efficiently search a massive phylogenetic tree of COVID-19 genomes to find instances where a new sequence appears to be a combination of two distinct sections of the tree. The COVID-19 phylogenetic tree, called UShER, was created by UCSC researchers and is the primary tool used by health officials worldwide to track the spread of variants in their community.
The researchers found recombination most often shows up on the COVID-19 phylogenetic tree in the form of “long branches,” making it appear that several mutations happened sequentially, which is quite rare.
“In a tree of millions of sequences, you find these long branches, which reduce the possible instances of detectable recombination down to only about 10’s of thousands of branches,” Turakhia said. “These long branches make recombination much easier to spot on the tree, which enables the efficient performance of the new software.”
Turakhia and his team aim to continue to improve RIPPLES’ speed and performance and to create visual tools to make it more accessible for a wider audience.
Use for public health
Knowing when recombination occurs is crucial for understanding the evolutionary lineage of a sequence of the virus. Recombination can complicate the process of tracing back the phylogenetic tree of a particular sequence because its genetic material is a result of two joining areas of the overall COVID-19 family tree.
This can help public officials understand when a lineage of COVID-19 which appears to be novel is truly an independent mutation introduced for the first time, or rather just a combination of two lineages that already existed in the community. Understanding when recombination occurs is also important from a public health perspective as it can potentially make the virus more adept at evading immunity.
Furthermore, the RIPPLES software’s availability and ease of use has positive implications for genomics experts and public health officials alike, who can efficiently search a set of COVID-19 genomic samples for recombination in just minutes.
This reflects a larger theme of the work of scalable translation of pathogen genomics data at Corbett-Detig’s lab and the UCSC Genomics Institute. Researchers are focused on creating tools that enable public health officials to automate and translate the questions they want to ask, and receive answers that are easy to act on and dependable.
“A big part of the success of our work has been that the software is extremely accessible and computationally cheap in the grand scheme of things,” Corbett-Detig said. “Anybody could take their hundred new SARS-CoV-2 genome sequences and figure out if there were potentially recombinant samples in just minutes on a basic laptop. Global public health needs to be democratized, to the point that anyone can do it, even if they’re not a super wealthy lab with giant servers.”
Pandemic-Scale Phylogenomics Reveals The SARS-CoV-2 Recombination Landscape