Discovery could lead to new clinical laboratory testing for cancer screening in new mothers
Any clinical laboratory test that returns unexpected results is worth looking into more deeply. Such was the case with a recent study conducted by the National Institutes of Health (NIH), which investigated cases of pregnant women who received “unusual” results to prenatal lab tests conducted at a dozen labs in North America.
Following cancer screening protocols that included rapid whole-body magnetic resonance imaging, NIH scientists discovered “previously undetected cancers in 48.6% of pregnant people who had abnormal results for prenatal cell-free DNA (cfDNA) testing used to screen for chromosomal disorders in the fetus,” according to an NIH news release.
“They looked like healthy young women, and they reported themselves as being healthy,” Diana Bianchi, MD, head of the Prenatal Genomics and Therapy Section for the Medical Genetics Branch at the NIH’s National Human Genetics Research Institute, and senior author of the government study, told the Associated Press (AP).
While cfDNA tests are not diagnostic, pathologists and clinical laboratory managers involved in genetic testing are likely familiar with them. The blood tests are used by expectant mothers to assess risk of a fetus with an abnormal number of chromosomes that could suggest disorders such as Down Syndrome, according to ARUP Laboratories.
Unexpected results from tests draw attention. This one seems to have a chance to get more traction with labs because the results point to a prenatal test having some success predicting cancer, even if incidentally.
“[The study participants] and their care providers need to take the results seriously and have additional testing because in that population there is a 48% risk of cancer,” Diana Bianchi, MD, senior author of the NIH study, told the AP. (Photo copyright: National Institutes of Health.)
Cancer Found in about Half of Those with Abnormal cfDNA
The NIH researchers started a long-term study, called IDENTIFY, to learn more about abnormal cfDNA results that could suggest cancer. Study participants must be:
Pregnant or postpartum with no known cancer.
Recipients of “unusual clinical cfDNA-sequencing results or results that are non-reportable (fetal aneuploidy status could not be assessed) from one of 12 different commercial laboratories,” they wrote in NEJM.
For the study’s initial cohort of 107 participants, researchers repeated cfDNA sequencing testing and coordinated standard medical diagnostic tests (such as Pap smears) and whole-body magnetic resonance imaging.
52 women (48.6%) were found to have “hidden cancers.”
32 had blood cancers.
20 had solid tumors in the breast, bile duct, colon, pancreas, lung, kidney, bone, and adrenal gland.
13 of the 20 with solid tumors were able to access “potentially curative treatments.”
55 women did not have cancer and may have obtained an unreliable cfDNA result.
“In this study, 48.6% of participants who received unusual or nonreportable clinical cfDNA-sequencing results had an occult cancer (cancer of unknown primary).
“Further study of DNA-sequencing patterns that are suggestive of occult cancer during prenatal screening is warranted,” the researchers wrote in NEJM.
Follow-Up Testing Needed
Cancers found in the study participants “included colorectal, breast, lung and pancreatic cancers, as well as lymphoma, cholangiocarcinoma and renal carcinoma. The screening test analyzes placental DNA fragments circulating in the maternal bloodstream to identify an extra chromosome or to determine the baby’s sex,” according to the NIH news release.
Bianchi told AP the study results also pointed to a “very chaotic” pattern in DNA-sequencing of women with cancer, and that more research is needed to find out who should be screened for cancer.
Clinical laboratories and pathologists who analyze cfDNA tests could take a leadership role in assessing current standards for the tests, determining how suspicious results are reported, and suggesting needed changes.
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.
Clinical laboratory managers should prepare for an increase in demand for measles testing, especially for children
Clinical laboratory managers should be on the alert for new cases of measles. The US Centers for Disease Control and Prevention (CDC) has reported a surge in the highly infectious disease. Public health experts pointed to declining vaccination coverage as the primary cause. Officials in other countries have also reported outbreaks.
In 2000, the US declared that measles had been eliminated, meaning it “is no longer constantly present in this country,” the CDC stated on its website. However, the agency noted travelers can still bring the disease into the country and that there have been sporadic outbreaks since then.
In a new study, published April 11, 2024, in the CDC’s Morbidity and Mortality Weekly Report (MMWR), the agency reported that it was notified of 97 confirmed cases in the first quarter of 2024. That compares to an average of five cases during the first quarters of 2020 through 2023, the agency stated. In total, 338 cases were reported to the CDC between Jan. 1, 2020, and March 28, 2024, so the latest outbreaks amount to 29%—nearly a third—of the total.
“While the risk for measles for the majority of the US population still remains low, it’s crucial that we take the necessary steps now to prevent the continued spread of measles and maintain elimination in the US,” Adria D. Mathis, MSPH, lead author of the CDC report, told Healthline. Mathis is affiliated with the CDC’s Division of Viral Diseases at the National Center for Immunization and Respiratory Diseases (NCIRD).
“We have seen, in the region, not only a 30-fold increase in measles cases, but also nearly 21,000 hospitalizations and five measles-related deaths. This is concerning,” Hans Henri P. Kluge, MD (above), WHO Regional Director for Europe, told BBC News. “Vaccination is the only way to protect children from this potentially dangerous disease.” Clinical laboratories in the US that identify a case of measles from a positive test must report that result to public health labs. Thus, wise lab managers will track the rise in measles cases and prepare for increased demand for measles testing. (Photo copyright: World Health Organization.)
Renewed Threat to the US, Other Countries
The recent cases “represent a renewed threat to the US elimination status,” and “underscore the need for additional efforts to increase measles, mumps, and rubella (MMR) vaccination coverage, especially among close-knit and under-vaccinated communities,” Mathis told Healthline.
The MMWR report notes that most of the new cases were in persons under age 20, and that almost all were “in persons who were unvaccinated or whose vaccination status was unknown.” Most of the importations, the report states, were “among persons traveling to and from countries in the Eastern Mediterranean and African WHO [World Health Organization] regions; these regions experienced the highest reported measles incidence among all WHO regions during 2021–2022.”
In the US, vaccination coverage has been below 95% for three consecutive years. That is the “estimated population-level immunity necessary to prevent sustained measles transmission,” according to the federal agency. In 12 states and the District of Columbia, the coverage rate is below 90%. In total, “approximately 250,000 kindergarten children [are] susceptible to measles each year,” the CDC report states.
Measles vaccination coverage has declined globally, “from 86% in 2019 to 83% in 2022.” This left nearly 22 million children under the age of one susceptible to the disease, the report notes.
Earlier Measles Outbreaks in the US
The CDC performed its latest analysis following two larger measles outbreaks in 2019 among under-vaccinated populations in New York state.
The Associated Press (AP) reported that the 2019 epidemic, which totaled 1,274 cases nationwide, “was the worst in almost three decades and threatened the United States’ status as a country that has eliminated measles by stopping the continual spread of the measles virus.”
A vaccine for the disease first became available in 1963. Prior to its availability, “there were some three million to four million cases per year,” AP reported. Most people recover, but “in the decade before the vaccine was available, 48,000 people were hospitalized per year. … About 1,000 people developed dangerous brain inflammation from measles each year, and 400 to 500 died,” AP noted, citing CDC data.
US Not Alone in Fight against Measles
Other countries also are reporting spikes in measles cases. In a recently published rapid risk assessment, the Canadian government reported a total of 29 cases as of March 15, 2024, of which 21 were reported since Feb. 28.
“That’s already the largest annual total since 2019 and more than double the number of cases reported last year, as medical experts fear the number will rise while more Canadians travel in and out of the country this month for March break,” CBC News reported.
“New projections from a team at Simon Fraser University (SFU) in British Columbia show the grim possibilities,” CBC News reported. “The modelling suggests that vaccine coverage of less than 85% can lead to dozens of cases within small communities—or even hundreds if immunization rates are lower.”
Numbers are far worse in parts of Europe. In a February 2024 news release, the World Health Organization reported that in 2023, more than 58,000 people in its European region were infected by the disease, “resulting in thousands of hospitalizations and 10 measles-related deaths.”
According to WHO epidemiological data, countries in Central Asia, which is part of WHO’s European region, reported some of the highest numbers:
15,111 in Kazakhstan,
13,735 in Azerbaijan, and
7,044 in Kyrgyzstan.
The Russian Federation reported 12,723 cases and Turkey reported 4,559.
A WHO European Region Measles and Rubella Monthly Update notes that more than half of the regionwide cases—31,428—were reported in the last three months of 2023. More than 15,000 cases were reported in December. That compares to just 163 cases reported in 2021 and 942 in 2022. Nearly half of the cases were among children under the age of five.
Lack of Vaccinations among Children Blamed for Outbreaks
One factor that has led to the increase in measles cases was the disruption to immunization services caused by the COVID-19 pandemic. “This has resulted in a significant accumulation of susceptible children who have missed their routine vaccinations against measles and other vaccine-preventable diseases,” the WHO reported.
Among the region’s 53 member states, 33 had eliminated measles, WHO reported, but “this achievement remains fragile. To retain this status, a country must ensure that transmission of the virus following any importation is stopped within 12 months from the first reported case.”
In the UK, which reported 231 cases last year, the National Health Service has launched a campaign to improve vaccination rates, the BBC reported, noting that “more than 3.4 million children aged under 16 are unprotected and at risk of becoming ill.”
However, a public health campaign built on vaccination is successful only if a high rate of individuals get vaccinated. The Baby Boomer and Gen X generations had high rates of vaccination for smallpox, polio, etc. because the parents saw individuals in their family and neighborhood who became infected and suffered lifechanging consequences. They recognized that vaccination was a simple thing to provide protection from a potentially deadly infection.
Clinical laboratory managers and pathologists will want to follow the CDC’s ongoing reports of the number of cases of measles in this country. Today, the absolute number of new measles cases is relatively small. At the same time, in communities experiencing an outbreak of even a few measles cases, physicians may want to increase the volume of measles tests they order for their patients.
Pathologists and clinical laboratories have an opportunity to help create newborn rWGS programs in their parent hospitals and health systems
Diagnosing disease in infants is particularly difficult using typical clinical laboratory testing and modalities. Thus, the use of rapid Whole Genome Sequencing (rWGS) is gaining acceptance when such a procedure is deemed “medically appropriate” based on the child’s symptoms.
In “Whole Genome Sequencing for Newborns Gains Favor,” Robert Michel, Editor-in-Chief of Dark Daily’s sister publication The Dark Report wrote, “Evidence is swiftly accumulating that use of rapid Whole Genome Sequencing for certain children in NICUs can enable diagnostic insights that guide effective interventions. Further, these pilot rWGS programs in children’s hospitals are showing a solid return on investment because of improved care. It is predicted that more hospitals may soon offer rWGS.”
Conducted at Tufts Medical Center in Boston, the researchers found that “Whole genome tests are nearly twice as good as narrower tests at unearthing genetic abnormalities that can cause disease in infants—the study found 49% of abnormalities, compared to 27% with more commonly used tests targeting particular types of genetic diseases,” the Associate Press reported.
The AP story follows the medical journey of a now 4-year-old who was diagnosed with a rare bleeding disorder. The nearly fatal condition was only caught because broad genetic testing found she suffered from factor XIII deficiency, a blood disorder characterized by the inability to clot properly.
“I’ve been doing clinical trials of babies for over 40 years,” neonatologist Jonathan Davis, MD (above), Chief, Division of Newborn Medicine at Tufts Children’s Hospital at Tufts Medical Center and Professor of Pediatrics, Tufts University School of Medicine, told the AP. “It’s not often that you can do something that you feel is going to really change the world and change clinical practice for everyone.” Clinical laboratories that work with oncologists to treat children suffering from cancer will understand Davis’ enthusiasm. (Photo copyright: Tufts Medicine.)
Incorporating Rapid Whole Genome Sequencing into Infant Care
Genetic diseases are responsible for 41% of infant deaths, according to a Rady Children’s Institute press release, which goes on to say the usage of rWGS may significantly improve the odds for infants born with genetic disorders.
“Broad use of genomic sequencing during the first year of life could have a much greater impact on infant mortality than was recognized hitherto,” said Stephen Kingsmore MD, President/CEO, Rady Children’s Institute for Genomic Medicine, which was one of the additional study sites for the Tufts Medicine researchers.
Genetic testing is already used to predict infant health outcomes, but the Tufts study highlights further developments that could improve the process. Prenatal genetic testing can be utilized both through carrier testing to determine any potential genetic red flags in the parents, and during prenatal screening and diagnostic testing of the fetus.
When an infant presents symptoms after birth, rWGS can then be implemented to cast a broad net to determine the best course of treatment.
According to ScienceDaily, the Tufts study found rWGS “to be nearly twice as effective as a targeted gene sequencing test at identifying abnormalities responsible for genetic disorders in newborns and infants.”
However, the rWGS tests took an average of six days to come back, whereas the targeted tests took only four days, ScienceDaily reported. Also, there is not full consensus on whether a certain gene abnormality is actually the cause of a specific genetic disorder.
“Many neonatologists and geneticists use genome sequencing panels, but it’s clear there are a variety of different approaches and a lack of consensus among geneticists on the causes of a specific patient’s medical disorder,” Jill Maron, MD, Vice Chair of Pediatric Research, Tufts Medical Center, and a co-principal investigator of the Tufts study, told Science Daily.
rWGS Costs versus Return on Investment
Some also question the upfront cost of genetic testing. It can be high, but it’s coming down and Maron stresses the importance of the tests.
“Genome sequencing can be costly, but in this targeted, at-risk population, it proves to be highly informative. We are supportive of ongoing efforts to see these tests covered by insurance,” she told ScienceDaily.
Each of the doctors associated with the Tufts study emphasized the importance of this testing and the good that can be done for this vulnerable group. The potential value to the children, they say, far outweighs the drawbacks of the testing.
“This study provides further evidence that genetic disorders are common among newborns and infants,” Kingsmore told ScienceDaily, “The findings strengthen support for early diagnosis by rapid genomic sequencing, allowing for the use of precision medicine to better care for this vulnerable patient population.”
For clinical laboratories, there is also good news about reimbursement for rWGS. In a story published last fall KFF Health News wrote, “Since 2021, eight state Medicaid programs have added rapid whole-genome sequencing to their coverage or will soon cover it, according to GeneDX, a provider of the test. That includes Florida … The test is also under consideration for coverage in Georgia, Massachusetts, New York, and North Carolina, according to the nonprofit Rady Children’s Institute for Genomic Medicine, another major provider of the test.”
“Collectively, these developments are encouraging children’s hospitals, academic centers, and tertiary care centers to look at establishing their own rWGS programs,” wrote Michel in The Dark Report. “In settings where this is appropriate, hospital and health system-based clinical laboratories have an opportunity to take an active role in helping jump start a newborn rWGS program in their institutions.”
Pathologists should continue to monitor rWGS, as well as prenatal and carrier testing, to have a full awareness of its growing use in infant and young child cancer screening.
As with clinical laboratories, worker shortage is affecting large retail pharmacy chains and independent pharmacies alike
Staffing shortages in clinical laboratories and anatomic pathology groups caused by the Great Resignation is having a similar impact on retail pharmacy chains. Consequently, pharmacy chains are reducing store hours and even closing sites, according to USA Today.
As Dark Daily covered in “Clinical Laboratories Suffer During the ‘Great Resignation,” the US Bureau of Labor Statistics reported that from August 2021 through December 2021, the healthcare and social assistance workforce saw nearly 2.8 million workers quit—an average of 551,000 people during each of those months. By comparison, in December 2020, 419,000 healthcare workers left their jobs.
Pharmacies now report similar shortages in qualified workers, partly due to the sharp decrease in revenue from COVID-19 vaccinations, but also due to worker burnout. Both developments have counterparts in clinical laboratories as well.
“I’m concerned that without the help from the COVID-19 vaccinations that everyone needed, these pharmacies that were able to tough it out for another year or two might not be able to continue,” B. Douglas Hoey, PharmD, CEO of the National Community Pharmacists Association (NCPA), told USA Today. Clinical laboratories that processed large numbers of SARS-CoV-2 diagnostics have experienced the same sudden drop in revenue causing similar difficulties maintaining staffing levels. (Photo copyright: Cardinal Health.)
Staffing Shortages Leading to Safety Concerns
According to the Washington Post’s coverage of a study conducted in 2021 of 6,400 pharmacists in various retail and hospital environments, a majority did not feel they could conduct their jobs efficiently or safely.
“75% of the pharmacists in [the] survey disagreed with the statement ‘Sufficient time is allocated for me to safely perform patient care/clinical duties.’”
“71% said there were not enough pharmacists working to ‘meet patient care/clinical duties.’”
“65% said ‘payment for pharmacy services’ did not support their ‘ability to meet clinical and non-clinical duties.’”
“Workplace conditions have pushed many pharmacists and pharmacy teams to the brink of despair,” said the board of trustees of the American Pharmacists Association (APhA) in a press release, the Washington Post reported. “Pharmacy burnout is a significant patient safety issue. It is impacting patients today with delayed prescription fulfillment, unacceptable waits for vaccines and testing, and potential errors due to high volume, long hours, and pressure to meet performance metrics.”
This is a sentiment that has been repeated across every facet of healthcare—including in clinical laboratories—where staff shortages are being felt.
Shortage of Pharmacists or Lack of Morale?
In “Drugstores Make Slow Headway on Staffing Problems,” the Associated Press outlined from where it believes the staffing problems originate. “There isn’t a shortage of pharmacists. There’s just a shortage of pharmacists who want to work in those high-stress environments that aren’t adequately resourced,” Richard Dang, PharmD, Assistant Professor of Clinical Pharmacy at the University of Southern California (USC), told the Associated Press.
“The pressure never let up. No matter how mind-numbing and repetitive the work could get, we had to work with constant vigilance, as there was absolutely no room for error,” Bator wrote.
“We techs were left unsupported and unmentored throughout the pandemic,” she continued. “No one cared if we were learning or growing in our job, and there was little encouragement for us to enter training or residency programs. We were just expendable foot soldiers: this is not a policy that leads to long-term job retention.”
Healthcare workers feeling burnt out and under-appreciated during the pandemic led to mass resignations that produced staffing shortages throughout the industry. It appears this trend has caught up to pharmacies as well.
Workforce Wasn’t Ready
Local and chain pharmacies played an important role in the COVID-19 pandemic. Pharmacists distributed COVID-19 tests and treatment to their communities. But for many it was a struggle to keep up.
Stefanie Ferreri, PharmD, Distinguished Professor in Pharmacy Practice and Chair of the Division of Practice Advancement and Clinical Education at University of North Carolina’s Eshelman School of Pharmacy, told the Associated Press that she felt the expanding role of pharmacies in public health was “awesome” but stated that “the workforce wasn’t quite ready” for what took place during the pandemic.
Much like Bator recounted in her essay, pharmacy workers suddenly had new responsibilities, longer working hours, and little room for error.
“There are multiple stories about pharmacists just getting overwhelmed. The stress level and burnout is high,” Dima M. Qato, PharmD, PhD, told USA Today. Qato is Hygeia Centennial Chair and Associate Professor (with tenure) in the Titus Family Department of Clinical Pharmacy at the University of Southern California. “So, pharmacists leave, and stores have to shorten” their hours, she added.
Scheduling and Patience Can Help
What can be done to soften some of the issues staff shortages are causing? Ferreri suggests that pharmacies set appointment times for regular customers so that a pharmacist’s workload can be more predictable. An appointment system can ease stress for both the pharmacist and patient. Ferreri advises customers to be patient when it comes to their prescriptions. She suggests patients give pharmacies more than a day’s notice for refills.
“I think on both sides of the counter, we need to all have grace and realize this is a very challenging and stressful time for everyone,” said Brigid Groves, PharmD, Vice President, Pharmacy Practice at the American Pharmacists Association.
With burnout, staff shortages, and stress affecting nearly every aspect of the healthcare industry, having patience with each other will go a long way to helping clinical laboratories, pharmacies, and patients navigate the road ahead.
