Researchers tracked “excess deaths” among adults aged 25 to 44 years and found disparate causes to blame
Studies conducted at the University of Minnesota and Boston University found that mortality rates among young adults have risen substantially since 2010 due to a variety of factors, pointing to a possible “mortality crisis” as they get older.
The researchers used data from the Centers for Disease Control and Prevention (CDC) and US Census Bureau to analyze nearly 3.4 million deaths in the US between 1999 and 2023 among adults aged 25 to 44 years, according to a Boston University press release.
They then used mortality data from 1999 through 2010 to project expected death rates for the later years and compared those projections to the actual post-2010 mortality rate to calculate the number of “excess deaths,” defined as “those [deaths] above what had been projected for a given period.”
“What we didn’t expect is how many different causes of death have really grown for these early adults,” said study lead author Elizabeth Wrigley-Field, PhD, of the University of Minnesota, in a U of M pressrelease. “It’s drug and alcohol deaths, but it’s also car collisions, it’s circulatory and metabolic diseases—causes that are very different from each other. That tells us this isn’t one simple problem to fix, but something broader.”
From that perspective, clinical laboratories could be part of the solution in tracking down these early conditions and steering young patients towards healthier outcomes.
“The rise in opiate deaths has been devastating for Americans in early and middle adulthood,” said sociologist Elizabeth Wrigley-Field, PhD, of the University of Minnesota in a press release. (Photo copyright: University of Minnesota.)
One-Two Punch
In 2019, excess mortality amounted to 41.7 deaths per 100,000 population, nearly 35% higher than expected, the researchers wrote. Then, in 2021 during the pandemic, excess mortality from all causes was nearly three times higher: 116.2 deaths per 100,000 population. In 2023, excess mortality decreased, but only to 79.1 deaths per 100,000 population.
“As a result, early adult mortality was 70.0% higher in 2023 than it would have been had pre-2011 trends continued,” the researchers wrote in Jama Network Open.
Speaking with Healio, Wrigley-Field described a “one-two punch that these age groups have seen: first, rising mortality since 2010; then the pandemic, only partially recovered from.”
Five causes accounted for nearly 75% of the excess deaths in 2023, the researchers found:
Drug poisoning, such as opiate overdoses (31.8%)
Residual natural causes (16%)
Transport-related deaths, such as motor vehicle accidents (14.1%)
Alcohol-related deaths (8.5%)
Homicide (8.2%)
The researchers also found that cardiometabolic conditions accounted for 9.2% of excess deaths. These include metabolic, circulatory and endocrine, and nutritional conditions, they noted.
Study co-author Andrew Stokes, PhD, of Boston University characterized the latter as a red flag, according to the Boston University press release. “Usually, it takes a lifetime to manifest cardiovascular disease and related mortality,” he said.
“Our findings underscore the urgent need for comprehensive policies to address the structural factors driving worsening health among recent generations of young adults,” he said in the U of M press release. “Solutions may include expanding access to nutritious foods, strengthening social services, and increasing regulation of industries that affect public health.”
Policy Measures
In their paper, the researchers suggested that policymakers should pay more attention to underlying causes such as opioid use, alcohol consumption, and traffic safety, as well as “ongoing consequences of the COVID-19 pandemic—which may be expressed in causes of death related to long-term consequences of infection, medical disruption, and social dislocation—and to deleterious health trends that predated it.”
“Individuals might not necessarily be able to reverse those factors, or their consequences, on their own, but public health collectively has been very successful at improving health through policies like tobacco regulation, to name one example,” Wrigley-Field told Healio.
She added that “the cardiometabolic causes of death stand out because these are really a bellwether of population health. These causes tend to be very responsive to the fundamentals of healthy living: healthy food, exercise, sleep, limited exposure to tobacco and air pollution, and limited experience of excessive stress.”
Young adults have also been dealing with the “expansion of industries that affect public health—processed foods and beverages, prescription drugs and OxyContin, alcohol, combined with this creeping effect of the obesity epidemic,” Stokes said.
He added: “These are the ages, 25 to 44, in which behaviors become entrenched and life course risks start to develop. And if we’re seeing this excess mortality in this generation now, it’s also an indication of what may happen to population health as a whole in decades ahead as this generation ages.”
This information can inform physicians and laboratorians about what diagnostic tests to consider for young people showing symptoms, even if their ages traditionally don’t indicate a chronic condition.
New owner plans to take the pharmacy company private as it continues to shutter retail locations
Last year, Walgreens announced plans to close a large number of its stores “due to financial difficulties and ongoing environmental pressures,” according to Becker’s Hospital Review. Dark Daily has covered the struggles facing all of the major pharmacy companies in many ebriefs over the past few years.
Now, in another sign of the financial woes facing retail pharmacy chains, Walgreens Boots Alliance (WBA) announced in March that it had agreed to be acquired by private equity firm Sycamore Partners. As part of the $10 billion deal, Sycamore will take WBA private, according to a company press release.
The sale is valued at up to $23.7 billion when debt is included. The company’s brands include Walgreens and Duane Reade in the US, and Boots in the UK.
The deal follows WBA’s plans to close approximately 1,200 US retail locations over the next 30 months. The pharmacy company announced the plan last October as it reported an $8.6 billion net loss for the 2024 fiscal year.
“You have a business that is shrinking, and then you layer on losses and cash burn, all of that was the perfect recipe for what we are seeing today,” Jefferies research analyst Brian Tanquilut told Reuters following the March announcement.
WBA said the deal is expected to close in Q4 of calendar year 2025, pending approval by regulators and its shareholders. The agreement includes a “go-shop” provision that allows the company to consider other proposals.
“Given the size and number of moving parts involved—a potential split of the US business, Boots, and Health—we don’t expect a competing bid to come over the top,” Leerink Partners analyst Michael Cherny told Reuters.
“Sycamore will provide us with the expertise and experience of a partner with a strong track record of successful retail turnarounds,” said Walgreens Boots Alliance CEO Tim Wentworth (above) in a press release. “We believe this agreement provides shareholders premium cash value, with the ability to benefit from additional value creation going forward from monetization of the VillageMD businesses.” (Photo copyright: Walgreens Boot Alliance.)
Long Way Down for Walgreens Boots Alliance
The purchase price of this sale demonstrates how far WBA has fallen since its formation in 2014, when Walgreen Co. completed a merger with Alliance Boots GmbH, a large retail group headquartered in Switzerland.
At its peak in April 2015, WBA had a market valuation of more than $100 billion, according to financial reports.
Analysts have pointed to industrywide challenges that have also affected rivals CVS and Rite Aid, according to reports in The New York Times and the Associated Press (AP). These include rising operating costs, declining reimbursement for prescription drugs, and stiff competition from discount retailers such as Amazon and Walmart.
“We are at a point where the current pharmacy model is not sustainable, and the challenges in our operating environment require we approach the market differently,” said WBA CEO Tim Wentworth during a June 2024 call with analysts, the AP reported.
News Outlets Report Questionable Moves Over the Years
Reuters, however, pointed to questionable moves by Stefano Pessina, the former executive chairman of Alliance Boots who became CEO of WBA following completion of the merger in 2014. Pessina is also WBA’s largest shareholder, Reuters noted.
In October 2015, WBA offered $9.5 billion to acquire US pharmacy chain Rite Aid. But the company eventually backed away from the deal as regulators raised antitrust concerns, CNBC reported. Instead, in 2017, WBA paid $4.375 billion to acquire nearly 2,000 of Rite Aid’s 4,600 US retail locations.
“But that store footprint proved too big and soon after the acquisition, Walgreens started to close locations,” Reuters reported.
Billions Spent on Retail Clinic Plans
In July 2020, WBA announced a $1 billion deal with VillageMD to open as many as 700 primary care clinics at Walgreens locations. That deal gave WBA a 30% ownership stake in the provider.
Nine months later, Pessina stepped down as CEO to become executive chairman of the board. Taking his place was former Starbucks chief operating officer Roz Brewer. Under her watch, WBA spent an additional $5.2 billion to take a majority stake in VillageMD, which provides primary care services.
That deal has become a “cash drain,” on WBA, Reuters reported. CNBC noted that other retailers have also faced headwinds in their efforts to provide primary care services. Walmart said it would close its in-store health clinics, and CVS also shuttered dozens of clinics in New England and Southern California.
In March 2024, Wentworth revealed a turnaround plan that included $1 billion in cost cuts and closure of 160 VillageMD clinics, according to Fierce Healthcare. At the time, the company had already closed hundreds of stores in the US and UK, AP reported.
Wentworth followed that plan with October’s announcement to shutter an additional 1,200 retail locations.
Mizuho Bank analyst Ann Hynes told Reuters that, as a private company, WBA will be better positioned to deal with its challenges because it won’t have to answer to shareholders.
One likely move is a divestment of the company’s stake in VillageMD, Reuters reported. And the Boots portion of WBA’s business is a likely spinoff candidate, analysts told the news outlet.
The trade association is publicly promoting the benefits of biomarker testing and AI’s benefits to diagnostics
One of the core tenets to getting federal lawmaker support for business is to tell them what an industry does. In that vein, the American Clinical Laboratory Association (ACLA) has released a new promotion that highlights applications of companion diagnostics, rapid whole genome sequencing, drug screening, biomarker testing, and infectious disease management.
One of the end goals? To sway Congress to take action against proposed reimbursement cuts to clinical lab test rates.
The ACLA campaign, known as the “Power of Knowing,” took center stage during a panel discussion at the ACLA Annual Meeting, held Feb. 27 in Washington, DC. One objective, panelists said, is to draw attention to the profession’s role in prevention and early detection of diseases, according to report from Medtech Insight.
“The association is working hard to demonstrate to policymakers the value of clinical laboratory testing through the Power of Knowing as they make policy decisions on reimbursement and clinical laboratory infrastructure that’s necessary for robust patient access to these innovative diagnostics,” said panel moderator Elyse Oveson, according to Medtech Insight. Oveson serves as ACLA chief of advocacy operations.
In March 2024, ACLA released digital ads urging Congress to pass the Saving Access to Laboratory Services Act (SALSA), which would have prevented a 15% cut in Medicare reimbursement for approximately 800 laboratory tests.
“A sustainable reform of the Medicare payment system for clinical laboratory services is vital to protect and enhance patient care, foster innovation, and ensure the stability of clinical laboratories nationwide,” ACLA president Susan Van Meter said at the time.
“If patients don’t have their biomarkers profiled for them at diagnosis and again at progression, there’s a very real chance that they would be put on the incorrect therapy that could lead to them having real harm in their health. So, we view biomarkers as critical,” said Nikki Martin (above), senior director of precision medicine initiatives for the LUNGevity Foundation, during the 2025 ACLA Annual Meeting. (Photo copyright: LinkedIn.)
Martin told attendees that biomarker tests should be part of the standard of care in lung cancer diagnosis, Medtech Insight reported. These tests analyze blood or other patient samples to identify molecules associated with specific diseases.
“For patients with non-small cell lung cancer, biomarkers are everything,” said Martin during the panel discussion. Many patients with advanced metastatic cancer, she said, “are not receiving comprehensive biomarker testing, and if they’re not, then they’re at risk of having much worse outcomes.”
Edelmayer discussed progress in developing biomarker tests for early diagnosis of Alzheimer’s disease. “The momentum is palpable among the research community,” she said. “We’re now starting to see the shift into implementation and more types of tools and technologies being available to clinicians to help patients.”
However, Edelmayer acknowledged that progress in developing Alzheimer’s tests and treatments has been slow.
“There’s never going to be a single test to help diagnose Alzheimer’s disease,” she said. “We recognize that it’s going to be a combination approach.”
New Video Campaign
The campaign’s latest advertising is summed up in a 90-second sizzle reel in which clinical laboratory leaders discuss various ways in which the profession supports healthcare.
One theme in the video is the growing use of artificial intelligence (AI) in the profession. “AI-enabled diagnostics are tools that use machine learning to analyze vast amounts of data from patient records to genomic profiles,” said Kate Sasser, PhD, chief scientific officer of Tempus, in the video. “These systems can recognize patterns in the data that humans may not easily see and help clinicians detect diseases earlier and more accurately.”
“By harnessing these cutting-edge tools, we can move closer to a world where treatments are no longer one size fits all but are instead tailored to the unique genetic and molecular profile of each patient,” said Elias Zerhouni, MD, president and vice chairman of OPKO Health, in a recent video produced as part of the ACLA’s Power of Knowing campaign.
The campaign website includes additional videos as well as downloadable graphics that can be shared on social media.
Disclosures, mandated by the Affordable Care Act, provide a limited snapshot of claim denials
Claim denials have created financial headaches for virtually all healthcare providers, including clinical laboratories and anatomic pathology groups. Reliable data about denials is hard to come by, but a recent analysis by KFF (formerly the Kaiser Family Foundation) revealed that insurers selling plans on HealthCare.gov denied 19% of claims for in-network services in 2023, the latest year for which data is available.
This is the highest rate since 2015, when KFF began tracking the data, according to the analysis. Claim denials for out-of-network services were even higher, amounting to 37%.
Patients and doctors “are saying that it’s become an even bigger hassle in recent years than it has been in the past,” said Kaye Pestaina, JD, co-author of the report, in a video report from CNBC. Pestaina is a KFF vice president and director of the organization’s program on patient and consumer protection.
The analysis, released Jan. 27, noted that the Affordable Care Act (ACA) requires insurers to provide data about health plans to state and federal regulators as well as the public. “However, federal implementation of this requirement has so far been limited to qualified health plans (QHP) offered on the federally facilitated Marketplace (HealthCare.gov) and does not include QHPs offered on state-based Marketplaces or group health plans.”
“One thing that we’ve seen [when] surveying consumers across different insurance types is that they simply don’t know that they have an appeal right,” said Kaye Pestaina, JD (above), VP and director of KFF’s program on patient and consumer protection, in a video report from CNBC. “If appeals were used more often, it might operate as a check on carriers. From what we can see now, so few are appealed, so it’s not operating as a check.” Clinical laboratories and anatomic pathology groups don’t often see data about the rate of claims denials by payers made public. (Photo copyright: KFF.)
Scarce Information
The federal marketplace covers 32 states, which means that the data does not include the 18 other states or the District of Columbia, all of which have their own exchanges. Nor does it include employer-sponsored plans, Medicare Advantage plans, or Medicaid Managed Care plans.
“In the big picture, we’re still operating from a scarce amount of information about how carriers review claims,” Pestaina told the Minneapolis Star-Tribune.
Within this limited dataset, KFF found wide variation in denial rates among the parent companies of health plans. The companies with the highest rates were as follows:
Rates also varied by state, from a high of 34% in Alabama to a low of 6% in South Dakota. However, the report noted that these averages sometimes obscured wide variations within each state. For example, in Florida, the statewide average was 16%, but denial rates for individual insurers ranged from 8% to 54%.
In most cases, in-network denial rates did not vary much based on plan levels. Rates were 15% for Platinum plans, compared with 18% for Silver and Gold plans, and 19% for Bronze plans. The rate for catastrophic plans was 27%.
The data offered only limited insights about the reasons for claim denials. The federal Centers for Medicare and Medicaid Services (CMS), which administers the rules, requires plans to report denial reasons, but it allows for an “Other” category that accounts for the largest number of denials:
Other reason not listed – 34%
Administrative reason – 18%
Service excluded – 16%
Enrollee benefit limit reached – 12%
Lack of referral or prior authorization – 9%
Not medically necessary (excluding behavioral health) – 5%
Member not covered – 5%
Not medically necessary (behavioral health only) – 1%
“We hear anecdotal stories about certain treatments that are denied, that arguably should not have been denied,” Pestaina told the Star-Tribune. “How often is that happening? It’s difficult to come to a conclusion with the kind of ‘reason’ information we have here.”
Health Insurers Pushback
In addition to claim denials, CMS requires insurers to report the number of appeals once a claim has been denied.
“As in KFF’s previous analysis of federal claims denial data, we find that consumers rarely appeal denied claims and when they do, insurers usually uphold their original decision,” the report states.
In total, insurers on the federal exchange denied 73 million in-network claims. Among these, less than 1% (376,527) were appealed internally to the insurers, which upheld 56% of the denials.
The report notes that, in some cases, consumers have a right to an external appeal in which a third party reviews the claim. However, in a separate survey, KFF found that only 40% of all consumers, and 34% of Marketplace enrollees, were aware of that right.
Health insurers pushed back on KFF’s analysis. In a statement reported by the Star-Tribune, UnitedHealth Group described the numbers as “grossly misleading” because the dataset represents only 2% of total claims.
“Across UnitedHealthcare, we ultimately pay 98% of all claims received that are for eligible members, when submitted in a timely manner with complete, non-duplicate information,” the company stated. “For the 2% of claims that are not approved, the majority are instances where the services did not meet the benefit criteria established by the plan sponsor, such as the employer, state or Centers for Medicare and Medicaid Services.”
Researchers find genome sequencing identified conditions missed by standard newborn screening programs that use common clinical laboratory tests
Interim results from a large ongoing pilot study suggest that genome sequencing of newborn children may be more effective than traditional clinical laboratory screening for detection of early-onset genetic conditions. The researchers also found that parents were highly receptive to the idea of performing the sequencing on their newborns.
“The results show us that genome sequencing can radically improve children’s medical care,” said study co-author Joshua Milner, MD, chief of allergy, immunology, and rheumatology services at NewYork-Presbyterian/Columbia University Irving Medical Center, in a Columbia University press release.
“Genome sequencing allows us to detect things that cause serious illness and take action to prevent those illnesses in a significant number of children, not just a few rare cases. It should be instituted as the next standard for newborn screening because it can detect so much more than current methods,” said study co-author Joshua Milner, MD (above), chief of allergy, immunology, and rheumatology services at NewYork-Presbyterian/Columbia University Irving Medical Center, in a press release. Study finding suggest genetic sequencing can be more effective than clinical laboratory screening tests for early detection of genetic disorders. (Photo copyright: Columbia University.)
GUARDIAN Study Details
For the pilot study, the researchers sought consent from 5,555 families, with 4,000 (72%) agreeing to participate. The babies studied were born between September 2022 and July 2023. At that time, the researchers screened for 156 treatable conditions. Parents could also choose to add a panel of 99 neurodevelopmental disorders that do not have treatments, but where “affected children may benefit from early intervention,” the press release notes.
The total—255 genetic tests—included the 50 conditions in the standard Newborn Screening Program as a quality control, principal investigator Wendy Chung, MD, PhD, told Healio.
Among the 4,000 participants, 147 children (3.7%) screened positive for one of the conditions. Further testing confirmed diagnoses in 120 children. “Only 10 of these children were detected through standard screening,” the Columbia press release states.
The vast majority—92 of 120 children—were diagnosed with glucose-6-phosphate dehydrogenase (G6PD) deficiency. “G6PD is not included in traditional screening but individuals with G6PD deficiency can have moderate to life-threatening reactions to certain foods and medications which can easily be prevented by avoiding them,” the press release notes.
Screening for Previously Unscreened Treatable Disorders
The New York State Department of Health mandates free Newborn Screening (NBS) in which a blood sample is collected for testing, generally 24 to 36 hours after birth. The test screens for 50 disorders.
Genome sequencing, however, “offers an additional method to improve screening for conditions already included in NBS and to add those that cannot be readily screened because there is no biomarker currently detectable in dried blood spots,” the GUARDIAN researchers wrote in JAMA.
In the GUARDIAN study, families planning to give birth at an NYP hospital can authorize the researchers to perform genome sequencing of the same dried blood spots to screen for additional pre-selected genetic conditions. At present, the study screens for more than 450 conditions, according to the study website.
“It would be prohibitive to screen for all these diseases with standard testing, but with genomic screening, there’s minimal extra cost when adding a condition,” said study co-author Jordan Orange MD, PhD, chair of pediatrics at Columbia University’s Vagelos College of Physicians and Surgeons and physician-in-chief of NewYork-Presbyterian’s Morgan Stanley Children’s Hospital, in the Columbia press release. “We can screen for treatable disorders that we never thought of screening for before.”
GeneDX, which performs the genomic sequencing for GUARDIAN, issued a press release in which it listed other conditions that are not part of the standard screening. These include Long QT syndrome, which the company described as “a rare heart condition that may cause Sudden Infant Death Syndrome (SIDS) and can be treated with beta-blockers.”
GUARDIAN also detected conditions that came up as false negatives in the standard screening, Chung told Healio. One baby had a genetic variant that causes severe combined immunodeficiency disorder (SCID), a rare and often-fatal condition. Chung said that the genomic sequencing identified the condition while the standard newborn screening missed it.
“We know that a bone marrow transplant is a cure for these children, but safety and success are the highest when the transplant occurs in the first few months of life, before the child starts developing infections or other symptoms,” Milner said in the Columbia press release. “Only because of the genomic screening were we able to identify this child in time.”
Excluding the G6PD cases, the positive screening rate was 0.6%, twice the rate of standard screening. As of last November, more than 12,000 babies had been enrolled in the study. The researchers hope to enroll 100,000.
Advances in Genomic Sequencing Bring Benefits to NBS
“In my practice, I’ve seen many patients who’ve spent years going from doctor to doctor with symptoms that no one can explain. But by the time they receive a diagnosis, the window to best manage the disease has usually passed,” said Chung in the Columbia University press release.
Looking ahead, Chung told Healio that she’d like to expand outside of New York, “in part for generalizability to demonstrate that this is something that could be done with our national public health newborn screening system.”
She’d also like to cut the turnaround time from the current three weeks to one week, she said. And she’d like to drive down the cost.
“Families and pediatricians don’t need to go through those diagnostic odysseys anymore with the genomic technology we now have. We can make the diagnosis at birth,” she said.
The GUARDIAN study shows how advances in genetic testing are moving fast enough that the point has been reached where the classic clinical laboratory methodologies for newborn screening used for decades are becoming outmoded because of the superior performance/cost of genome sequencing.
