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Verve Therapeutics now has the formal FDA documentation specifying what the regulator wants to see before it allows the company to begin human testing of its gene-editing therapy for an inherited form of high cholesterol.
VERVE-101 is designed to turn off PCSK9, a gene that produces a liver protein that makes it more difficult for the body to clear low-density lipoprotein, the “bad” form of cholesterol. Patients have already been dosed in a clinical program underway in New Zealand and the U.K. Last month, the FDA placed a clinical hold on the Boston-based company’s new drug application for a U.S. trial.
The FDA wants to see more preclinical data regarding potency differences between human and non-human cells as well as additional data about the risks that the changes made by the therapy can be inherited by a patient’s children, Verve said in a Monday regulatory filing. The FDA asked that Verve modify the clinical trial protocol in the U.S. to incorporate additional contraceptive measures and to increase the length of time between the dosing of patients.
The FDA also has concerns about off-target effects. The filing states the agency asked the company to provide analyses of data showing whether the therapy’s effects reach cell types beyond liver cells. Furthermore, the FDA has asked to see the available data from New Zealand and U.K. so far. Those data were not part of the initial submission filed with the FDA. Verve said enrollment is continuing in those regions and the company plans to report initial safety and pharmacodynamic data from the dose-escalation part of the trial in the second half of 2023. Without specifying a timeline, the company said it plans to submit a response to the FDA’s information requests “as expeditiously as possible.”
The lifting of a clinical hold on another experimental genetic medicine was among the other recent regulatory news from the past week, which included two drug approvals and one rejection. Here’s a roundup of those developments:
—The FDA lifted a clinical hold on the investigational new drug application for a Beam Therapeutics gene-edited cell therapy for acute lymphoblastic leukemia. The FDA placed the hold on the program, BEAM-201, in August. With the hold lifted, the Cambridge, Massachusetts-based biotech is now cleared to proceed with tests in humans. BEAM-201 is an off-the-shelf cell therapy that employs four edits made with base-editing technology. Beam said it will provide details for the program’s next steps in 2023.
—The FDA has approved the first fecal microbiota treatment for preventing the recurrence of Clostridioides difficile (C. diff) infection in adults. The regulatory decision covers those who have finished a course of antibiotics for the potentially deadly infection. The Ferring Pharmaceuticals product, named Rebyota, is made from stool provided by qualified donors. This rectally administered live biotherapeutic is intended to restore the gut microbiome, which in turn prevents episodes of C. diff infection.
—A Rigel Pharmaceuticals drug won FDA approval for treating acute myeloid leukemia (AML) with a particular genetic signature. The South San Francisco-based biotech will commercialize the drug, olutasidenib, under the name Rezlidhia. The small molecule is designed to target mutated isocitrate dehydrogenase-1 (IDH1), an enzyme found in cancerous cells. Blocking this enzyme is intended to restore normal differentiation of myeloid cells. The regulatory decision for Rezlidhia covers the treatment of adults whose AML has the IDH1 mutation as detected by an FDA-approved test.
—The FDA turned down Y-mAbs Therapeutics application seeking approval for its drug to treat a rare pediatric brain cancer. The drug, omburtamab, was developed to address leptomeningeal metastases, which is the spread of neuroblastoma from the brain to the membranes surrounding the brain and spinal cord. The negative regulatory decision came a little more than a month after an independent advisory committee to the FDA voted unanimously that New York-based Y-mAbs had not provided enough evidence to show that the clinical program, which compared omburtamab to a historical control group, improved overall survival in patients.
—Eli Lilly’s Covid-19 drug bebtelovimab is no longer authorized for use anywhere in the U.S. According to the FDA, the change was made because the antibody is not expected to work against the omicron subvariants BQ.1 and BQ.1.1., which together account for 57% of all cases nationally. Revocation of the Lilly drug’s emergency use authorization removes from the market the last remaining monoclonal antibody drug for Covid-19.
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About two weeks ago, California Nurses Association reached a tentative agreement with Kaiser Permanente, averting what would have been the biggest private sector nurses strike in American history. On Monday, the union announced that its nurses voted to ratify a new four-year contract — one that includes provisions for a significant wage increase, improved staffing and more.
California Nurses Association represents about 22,000 nurses at 22 Kaiser facilities. 
The averted strike would have involved about 21,000 nurses and nurse practitioners at 21 Kaiser Permanente facilities in Northern California. These nurses had been in negotiations since June. The strike would have also involved about 1,000 nurses at Kaiser’s medical center in Los Angeles. They joined their Northern California nurse colleagues in September.
The new contract’s provisions to retain experienced nurses and hire new ones is expected to provide much-needed relief for nurses amid staffing shortages, according to Cathy Kennedy, who is the president of the California Nurses Association and a nurse in the neonatal intensive care unit at Kaiser’s medical center in Roseville. 
“We are so happy that this contract adds more than 2,000 positions across our Northern California facilities,” she said in a statement sent to MedCity News. “That is amazing and will improve staffing greatly.”
In an interview last month, Kennedy called the contract a “huge win” for Kaiser’s nurses. 
Under the contract, Kaiser is increasing wages for its Northern California nurses by 22.5% over four years. This wage growth “is driven by the changing economy, including inflation, significant changes in the marketplace and our commitment to providing our employees with excellent pay and benefits to attract and retain the best nurses,” according to the health system.
Kaiser also agreed to increase tuition reimbursement for nurses’ continuing education, maintain a three-month stockpile of personal protective equipment, and scale workplace violence prevention plans to all facilities.
The contract’s patient-first language and provisions for equity are significant as well.
The ratified contract asserts that healthcare is a human right, Kennedy pointed out. It also states that the U.S. healthcare system must eliminate racial and ethnic disparities in patient outcomes, promote culturally competent care delivery, and expand the diversity of its workforce.
Kaiser has promised to create a new regional committee for equity, diversity and inclusion at each facility. These committees will be composed of two nurses from each facility, and they will “bring nurses to the table” to address systematic racism within the healthcare system, Kennedy explained.
When the new contract was put on the table last week, Kaiser said it was “proud of the work our nurses do and we are making sure Kaiser Permanente continues to be the best place to work for our valued nurses.”
Nurses at Kaiser’s Los Angeles medical center ratified a new contract on November 22. For the Northern California nurses, voting began on November 22 and concluded on December 2.
The contract’s ratification comes about six weeks after another swath of Kaiser’s Northern California employees approved a four-year contract of their own — that time, it was about 1,600 mental health workers. Their approval followed a 10-week strike.
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As the world enters a possible recession and healthcare costs rise, affordability will be a key concern for employers in 2023, according to the Business Group on Health. Other top health trends for employers next year will be continued support of wellbeing programs and health equity.
“None of these are new issues, but they’re magnified and a bit nuanced in light of current events and where the macroeconomic environment is,” Ellen Kelsay, president and CEO of Business Group on Health, said in an interview. “That’s why we’ve really pulled them forward as things that we’re keeping a sharp eye on as we head into 2023.”
The Business Group on Health is a nonprofit organization that represents large employers on health and benefits policy.
Here are the top three trends the organization is watching for employers in 2023:

Healthcare costs

Employers will likely see higher healthcare costs in 2023, partially due to an increase in demand for care after people put off services during the beginning of the pandemic. A recent Business Group on Health survey of 135 large employers found that 43% have already seen a rise in medical services because of delayed care from Covid-19, and another 39% expect to in the future.
Additionally, cancer is now the top condition driving healthcare costs, surpassing musculoskeletal conditions, another Business Group on Health Survey found. This is because cancers are now being identified at later stages.
“During the pandemic, there were a lot of preventive visits and cancer screenings that didn’t occur,” Kelsay said. “So there’s a backlog of services that now people are going to get treated for and we might see some more late stage cancers being diagnosed, which are going to be more expensive and challenging to treat.”
In response, many employers are absorbing the increases in healthcare costs, rather than putting the burden on employees, Kelsay said. They’re also moving away from fee-for-service payment models to more value-based arrangements, and looking at their vendors to see if they have any duplication of services. 

More focus on health and wellbeing programs

Despite this increase in healthcare costs, the Business Group on Health doesn’t anticipate health and wellbeing programs going away for employees, Kelsay said. In fact, 65% view health and wellbeing as an integral role in their workforce strategy, up from 27% five years ago, the nonprofit found.
“We’ve had some folks say, ‘Well, gosh, maybe in a time of uncertain economic situations, employers might start to retract some of those efforts,’” Kelsay said. “We don’t see that happening at all. In fact, for a number of years when we’ve surveyed our employer members, they take a long-term view of their health and wellbeing offerings and really view them as … part of a strategic component of their overall workforce strategy.”
To continue offering these wellbeing programs, employers will be searching for partnerships that can provide high quality solutions and improve patient outcomes, Kelsay said. Many employers are focusing on programs for mental health, financial wellbeing and caregiver support, she added.

Efforts to battle health inequities

There are several key areas employers are looking to reduce health inequities within their organization, though it depends on the company. These areas include housing, food, maternal health, transgender care and care for neurodiverse populations, Kelsay said. Some employers are also looking to help workers living in rural communities.
“Different employers and different workforces might have different areas of inequity that they might be addressing,” Kelsay said. “But they’re very keen to make sure that all of their employees of any type of population or however they might identify have equal access to health and wellbeing services to treat their particular needs.”
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Health information exchanges (HIEs) ensure the secure mobilization of electronic health information across organizations within a region. Each state in the country has an HIE, and some even have more than one.
HIEs, which can be public or private, are meant to enable more effective care that better meets patients’ unique needs. They have been around for a couple decades, but results are mixed when it comes to their success. The next generation of HIEs must think beyond the transfer of information and explore how they can use real-time health data to improve population health outcomes, according to Jamie Bland, the president and CEO of CyncHealth.
CyncHealth is Nebraska’s designated statewide HIE and prescription monitoring program. The nonprofit became a statewide HIE in 2012, Bland said in an interview.
“If you think about how people access healthcare, as well as the differences in electronic health records and how they have evolved over the past 20 years, what we’re really trying to do is connect data to the person,” she declared.
With CyncHealth, a person’s health information follows them throughout their healthcare journey. When it’s appropriate for a provider to seek their information (perhaps for treatment or a check-in), their data is available as a health history. CyncHealth also provides citizens with their longitudinal health information, according to Bland.
“Having data follow the person is important for patient safety outcomes, care coordination and just really looking at population health overall,” she said.
A key way that CyncHealth is seeking to improve population health outcomes is through a program it launched six months ago in Omaha to improve health and equity in maternal and postpartum care. Under the program, CyncHealth coordinates a secure data exchange amongst key healthcare stakeholders such as Medicaid, hospitals, clinics, federally qualified health centers, primary care providers, OB-GYNs and substance use disorder clinics. 
The program is designed to identify mothers and infants who are in need of care. The pilot identifies high-risk patients based on a wide variety of factors — including race, ethnicity, ZIP code and medical history — and it contacts providers so they can design a holistic care plan for their high-risk patients.
CyncHealth’s program for maternal and postpartum care also keeps providers informed about their patients’ real-time health data. For instance, let’s say a pregnant woman goes to the emergency department because she feels dizzy and is then diagnosed with high blood pressure. CyncHealth would notify all her treating providers to ensure they perform appropriate follow-up care. Interventions like these are important, as hypertension is a huge factor that contributes to maternal morbidity.
“This is a newer program, so we don’t have longitudinal data just yet. But what we hope to see in the data is that [adverse] outcomes — whether they be postpartum complications, or issues that could lead to death like in a pulmonary embolism or hemorrhaging after childbirth — can can be followed up on more rapidly than without this type of information exchange,” Bland said.
CyncHealth plans to keep this program running in the future, according to Bland. To measure its impact, she said the nonprofit will track how many notifications it sends to providers and how many were acted upon. CyncHealth will also look at how maternal mortality and morbidity data changes over time in Omaha.
This summer, HHS recognized CyncHealth’s Omaha program as one of the top 25 winners of Phase I of its health equity-focused postpartum care challenge. 
“That recognition is really just underscoring the work that we’ve done to build a broad health information network,” Bland said. “When you have that foundation, you can really start to improve population health because it takes a data exchange to be able to react more quickly to information.”
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While few employers provide retiree health benefits, the ones that do are using Medicare Advantage plans more and more, a new analysis found.
Currently, only 13% of large employers — or companies with 200 or more employees — offer retiree health benefits, the Kaiser Family Foundation (KFF) report showed. Of this group, 50% provide these benefits through a Medicare Advantage plan, up from 26% in 2017. 
For firms with 5,000 or more workers providing retiree benefits, 60% use Medicare Advantage plans, up from 29% in 2017.
Additionally, of the large firms providing retiree benefits with a Medicare Advantage plan, 44% don’t offer any other choice for coverage, the survey discovered. 
The KFF report relied on data from the 2022 KFF Employer Health Benefits Survey. KFF worked with NORC at the University of Chicago and Davis Research to conduct the survey, which included interviews with business owners and human resource and benefits managers at 2,188 firms.
A major reason for firms turning to Medicare Advantage plans for retirees is financial. About 27% of all large firms chose these plans due to cost; 20% of firms with 200 to 999 workers and 42% of firms with 1,000 or more workers selected cost as the top factor driving their decisions. Other reasons cited for choosing MA plans were their administrative simplicity, better coverage options and flexibility for enrollees.
This shift could have several effects on retirees, KFF said.
“As the share of large employers offering retiree health benefits to Medicare-eligible retirees continues to decline, firms that still offer these benefits are increasingly turning to Medicare Advantage, often to lower their own financial liability, which raises questions about the implications for retirees, employers and the Medicare program,” KFF stated in the report. “For some large employers, the shift to Medicare Advantage appears to be a strategy to maintain benefits for their retirees, without terminating coverage or adopting other changes that more directly shift costs onto retirees.”
One of these implications is the impact this approach could have on retirees’ access to physicians and hospitals, the report said. They’ll also have to go through prior authorization, which could limit their access to some services. If they’re not happy with their network, they would have to completely give up their retiree benefits, KFF said.
Another implication is the impact on Medicare spending, as Medicare pays more for enrollees in Medicare Advantage plans than traditional Medicare, according to KFF.
The report comes as Medicare Advantage enrollment in general is becoming more popular. A separate KFF report found that about 48% of Medicare beneficiaries are enrolled in Medicare Advantage plans. This number could cross the 50% threshold as soon as next year.
At the same time, there is a growing desire to scrutinize MA plans given that some believe they are misleading for seniors and actually drive up costs for the Centers for Medicare and Medicaid Services. CMS recently released a requirement — effective January 1 — that bans MA plans from advertising on television without approval from the agency.
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Value-based care has been viewed primarily as a cost-center to the hospital budget that requires upfront investment in the infrastructure without a guarantee for shared savings down the road. A risky bet.
And if you’re doing value-based care right, with greater focus and attention paid to preventive care services, it could result in decreased use of hospitals for acute care needs. Downright threatening to the very existence of a hospital system that is reliant on volume.
For these very reasons, hospital executives might shy away from value-based care.
And yet transition to value-based care is necessary and inevitable. If not out of concern for the out of control spend on healthcare, it is a necessary response and adaptation to the formidable market forces.
Consider these example shifts –

More than 50% of the hospitals saw negative hospital contribution margins this year with continued lower utilization of hospital services post-pandemic.
Greater than 50% of Medicare members are projected to enroll in MA plans in 2023. These health plans will need to hit their medical loss ratio (MLR) if they are to be successful. What that translates to, is a need to control costs and therefore a greater number of VBC arrangements that will be offered in the markets. A hospital that knows how to play in VBC will see an increase in the number of members they serve. And those that don’t will miss out.
Add to that, the relentless market disruption and competition from non-traditional health care entrants (Amazon, Walmart) and the continued market consolidation.
With CMS’s bold aim to transition 100% of its traditional Medicare payments to VBC payments by 2030, it will only serve to accelerate the forward momentum adopted by private payers

Collectively, what these signal is that ‘status quo’ is a regression move for a hospital system. So, how then is a hospital system to balance the simultaneous need of strengthening overall financial sustainability and achieving objectives of value-based care?
It is by utilizing the levers available in value-based care that are not available in the fee-for-service world.
How exactly?
It comes down to strategizing across three areas:

Leveraging data to achieve cost savings AND improve revenue growth
Creating ‘stickiness’ for members at critical points
Targeting and eliminating inefficiencies and waste

Leveraging data to achieve cost savings and improve revenue growth 

A big upside of a VBC participation is that you receive data from payers you otherwise would not. This includes data on use of services occurring outside of your hospital system.
Use the data to assess cost inefficiencies for services occurring outside of your hospital. And target those for redirection of services to your facility to win on cost savings and revenue earned. A double win.
What specialty categories is your facility cost-advantageous in the market? Start there. These could be procedures, imaging, deliveries, etc.
A comparative analysis may reveal that you are cost advantageous in orthopedic and GI procedures. Identify and align with those providers to educate and redirect care to your facility.
Patients win with potential lower out of pocket spend. Your hospital wins with new patient volume, and shared savings potential.

Creating stickiness (aka brand loyalty) 

One of the most critical, yet often overlooked transition points is your hospital and ER discharge process.
Patients remember the last thing you do for them when they leave your hospital. And if that includes handing them a piece of paper with instructions to schedule a follow-up appointment, it signals ‘we don’t really care what you do after you leave the hospital’.
It is also a big missed opportunity to share that their care is coordinated within your integrated system and their provider.
When you schedule a follow-up appointment before they leave the hospital/ER –

It ensures an appointment is made for timely follow-up (AND your hospital readmit reduction program will thank you for penalties avoided).
Eliminates the need for telephonic follow-up AND associated cost savings!
And gives you a golden opportunity to build your brand loyalty by delivering a key message.

What is the key message? That their care is better coordinated when they go to your hospital. When members go outside of your ACO network of facilities, you lose the visibility to coordinate or influence their care and outcomes.
Investing time and effort into this basic function is impactful on multiple fronts. But often overlooked, due to staffing shortages or availability of systems to coordinate it or due to a new ‘shiny object’ that seem more advanced.
Patients win with better overall care and you win their loyalty and long-term value for their overall care needs in the future. 

Targeting and eliminating inefficiencies & waste 

A common mistake that hospitals make with access to troves of new data is get distracted, enter a decision paralysis or tackle too many opportunities at once.
While conducting data analytics, target your cost savings opportunity identification for utilization that occurs outside of your hospital. This is your low-hanging fruit potential.
This typically is high-cost and high-spend activity post-acute care settings, use of high-cost drugs with generic alternatives, utilization of free-standing ERs, high-cost imaging facilities, etc.
Participating in a value-based care payment model does not have to be a win-lose proposition as these example strategies show. Through deliberate planning and focused execution, you can create an overall winning proposition that supports your financial health and keeps patients at the forefront of your efforts.
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An Amgen drug that employs two different mechanisms to lead to weight loss has early-stage clinical data showing durable effects, laying the groundwork for a Phase 2 test as the pharmaceutical giant continues to chase rival obesity drugs from Novo Nordisk and Eli Lilly.
Patients in the Phase 1 study were randomly assigned to receive the experimental Amgen drug, code-named AMG 133, or a placebo, either as a single dose or multiple ascending doses given as a subcutaneous injection every four weeks. Those participants were obese but did not have other medical conditions, including diabetes.
In the 26 patients who received multiple ascending doses, Amgen reported that the drug led to an average of 7.2% weight loss at the lowest dose and an average 15.5% weight loss at the highest dose by day 85. The company added that the weight loss was maintained at the highest doses for up to 150 days following the third and final administration of the drug. Data from three of the six multiple dose-ascending cohorts were reported. The other three were not included due to data analysis that is still ongoing, Amgen said in an investor presentation Monday.
Amgen presented the preliminary data over the weekend during the 20th World Congress of Insulin Resistance, Diabetes and Cardiovascular Disease Hybrid Conference. With the encouraging results, the Thousand Oaks, California-based pharmaceutical giant said Monday that it plans to start a Phase 2 study in early 2023.
AMG 133 is an antibody-peptide conjugate designed with one part that activates a target called GLP-1 and the other that blocks a different target called GIPR. In preclinical research, Amgen reported this dual approach led to weight loss as well as improvement in other metabolic measures.
“AMG 133 was designed based on preclinical and human genetic data that strongly suggest GIPR inhibition as a strategy for weight loss, especially in combination with GLP-1 agonism,” David Resse, Amgen’s executive vice president of research and development said in a prepared statement. “We are encouraged by these Phase 1 results with once-monthly dosing of AMG 133, specifically, the degree, rate and durability of the weight loss.”
In the Phase 1 study, the most common side effects reported were nausea and vomiting. Amgen characterized these side effects as mild and transient. These problems were associated with the first dose and most of them resolved within 48 hours, the company said.
With AMG 133, Amgen is chasing Novo Nordisk’s semaglutide, a GLP-1-activating drug that won its first FDA approval in 2017 for treating type 2 diabetes. The once-weekly injectable molecule is marketed as Ozempic in that indication. Last year, the FDA approved semaglutide for chronic weight management, where the drug is marketed as Wegovy. In the four 68-week pivotal studies supporting Wegovy’s regulatory submission, treatment led to an average 12.4% weight loss.
Eli Lilly is also looking to add weight loss to the label of its drug, Mounjaro, which was approved earlier this year for treating type 2 diabetes. Mounjaro is a peptide drug designed to activate both GIP and GLP-1. Clinical research in type 2 diabetes showed that the drug also led to weight loss. In its report of third quarter financial results last month, Lilly said it planned to initiate a rolling submission for the drug in obesity this year, completing the application soon after the second of two Phase 3 tests has data, which are expected in April 2023.
Comparing weight loss data across clinical trials is tricky, as these drugs were not tested head to head. But despite trailing the regulatory progress its rivals, Amgen hopes AMG 133’s once-a-month dosing provides patient convenience and a competitive edge versus the once-weekly dosing of Wegovy and Mounjaro.
In a Monday research note, William Blair analyst Matt Phipps wrote that weight reductions of around 15% after three doses of AMG 133 compares favorably with the Phase 3 results posted by the Novo Nordisk and Lilly drugs at 12 weeks, with the caveat that Amgen’s results are from a smaller group of patients. Nevertheless, Phipps characterized the rate and magnitude of body weight reductions as “impressive.” He added that the pharmacokinetic and pharmacodynamic data support less frequent dosing than other drugs in the class with the potential to go beyond every four week dosing in a maintenance setting.
However, Phipps said the lack of biomarker data leave many questions about the role of blocking GIPR versus activating it the way that Lilly’s drug does. William Blair has previously noted the potential for GIPR antagonism to affect bone mineral density and bone strength.
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As nurses battle burnout amid a major workforce shortage, a new partnership aims to provide relief. The United Health Foundation (UNF) — the philanthropic arm of UnitedHealth Group — and the American Nurses Foundation (ANF) have teamed up to launch the three-year, $3.1 million Stress & Burnout Prevention Pilot program.
The program aims to improve work environments for nurses and remove the stigma associated with asking for mental health care. The curriculum will focus on ways to identify and reduce stress before it escalates. It will also help nurses learn how to talk about their stress and burnout and support their colleagues. While it will help all nurses, the program is especially geared toward nurses of color and those under the age of 35.
“Research and data have shown that these groups have been particularly negatively impacted by the pandemic both emotionally and mentally,” an ANF spokesperson wrote in an email. “It is important that we listen to the insights and experiences of these nurses, and make them feel heard and supported.”
For the program, UHF and ANF are working with four health systems: BayCare Health System in Tampa Bay, Florida; Indiana University Health in sites across the state; University of South Alabama Health Hospital in Mobile, Alabama; and Wayne Health Care in Newark, New York. These organizations will work to train 16 nurses, who will then implement the pilot with about 640 nurses. Findings from the program will then be incorporated into a national awareness and education campaign.
“Establishing a multi-site pilot will enable us to conduct programming and establish evaluation metrics that will assess more deeply the cultural change over time,” the ANF spokesperson said. “Over three years, the content will go through an iterative evolution, drawing from learnings and real experiences gathered from the pilot sites to inform the national initiative – feasibility and reach. If successful, the impact will be measured uniformly across all pilot sites and will be replicable at a national level.” 
The initiative aims to tackle issues discovered by the ANF in its recent Pulse on the Nation’s Nurses Survey. It found that 71% reported feeling stressed, 69% said they’re frustrated, 65% said they’re exhausted, 49% said they’re burnt out and 58% said they’re overwhelmed.
A separate survey conducted by the ANF found that 34% of nurses do not feel emotionally healthy and 42% are experiencing trauma from the Covid-19 pandemic.
“Few could have predicted how unprecedented and demanding the past two and a half years have been for all of us, let alone our country’s nursing staff,” said Mary Jo Jerde, RN and senior vice president of the UnitedHealth Group Center for Clinician Advancement, in a news release. “Nurses have played a vital role throughout this critical period and we’re committed to ensuring they have the resources they need to deliver care across the country.”
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