'Breast Cancer Overdiagnosis Risk May Be Substantial for Older Women'

 Older women screened for breast cancer were at a considerable risk of being overdiagnosed, according to a large retrospective cohort study.

Researchers found that an estimated 31% of breast cancers among screened women from the ages of 70 and 74 were potentially overdiagnosed, reported Ilana Richman, MD, MHS, of the Yale School of Medicine in New Haven, Connecticut, and colleagues.

Moreover, the risk of overdiagnosis grew with advancing age: For women ages 75 to 84, 47% of cases were potentially overdiagnosed; while an estimated 54% of breast cancers were potentially overdiagnosed among women 85 years and older.

When stratified by life expectancy, the estimated proportion of breast cancers overdiagnosis was 32% for screened women with a life expectancy or more than 10 years, 53% for women with a life expectancy of 6 to 10 years, and 63% among women with a life expectancy of 5 years or less.

The researchers did not find statistically significant reductions in breast cancer-specific death associated with screening in women ages 70 and older.

"Whether harms of overdiagnosis are balanced by benefits and for whom remains an important question," wrote Richman and colleagues in the Annals of Internal Medicineopens in a new tab or window. "Overdiagnosis should be explicitly considered when making screening decisions, along with considering possible benefits of screening."

Richman and colleagues noted that in recent years there has been greater recognition that overdiagnosis -- "which may be defined as detecting a cancer, often through screening, that would not have caused symptoms in a person's lifetime" -- represents an important harm from breast cancer screening.

The findings pointed to about 2% absolute risk for overdiagnosis after 15 years of screening. But whether that rate should be considered high, Richman and colleagues said, depends on several factors, including benefits.

"Given uncertainty about the relative balance of benefits and harms of screening in this population, patient preferences, including risk tolerance, comfort with uncertainty, and willingness to undergo treatment, are important for informing screening decisions," they wrote.

In an editorial accompanying the studyopens in a new tab or window, Otis Brawley, MD, and Rohan Ramalingam, both of Johns Hopkins University in Baltimore, pointed out that the discussion of overdiagnosis of breast cancer is distinct from the question of whether mammography saves lives.

High-quality, routine mammography programs do save lives -- at least for women in the age group evaluated in this study, and probably for women from the ages of 40 and 80 as well, they argued.

"Unfortunately, the public messaging does not put enough emphasis on 'high-quality' nor 'routine mammography programs,'" they observed. "Until the advent of objective prognostic markers to identify indolent types of cancer, we (physicians and patients) should realize that a small but significant proportion of those cured of cancer do not need cure. An effective, objective test would spare these women the inconvenience of unnecessary therapy."

Ultimately, they suggested the answer to the overdiagnosis problem is further study of cancer genomics.

"We need to move to a 21st-century definition encompassing both the biopsy and pathologic appearance as well as genomics," the editorialists said. "The 21st-century definition of cancer will recognize that breast cancer is not one entity but many distinct diseases with potentially different patterns of behavior calling for different treatments and, sometimes, no treatment."

For the study, Richman and colleagues compared the cumulative incidence of breast cancer among women 70 and older who continued to undergo screening in the next interval versus those who did not. Overdiagnosis was measured as the absolute difference in the cumulative incidence of breast cancer among women who were screened versus not screened at cohort entry.

Using data from the SEER-Medicare registry linked to a 5% sample of Medicare fee-for-service beneficiaries, the authors included 54,635 women (mean age 77.2 years, 88% white) in their analysis. Life expectancy was 10 years or less for 41% of the cohort, and 15% were considered frail.

Median follow-up times were 13.7 years among women ages 70 to 74 years, 10 years for women ages 75 to 84 years, and 5.7 years for women 85 years and older.

In adjusted analyses, the cumulative incidence of breast cancer for women screened and not screened was:

• 6.1 cases per 100 women (95% CI 5.7-6.4) versus 4.2 (95% CI 3.5-5.0) among those 70 to 74 years of age
• 4.9 cases per 100 women (95% CI 4.6-5.2) versus 2.6 (95% CI 2.2-3.0) among women ages 75 to 84 years
• 2.8 cases per 100 women (95% CI 2.8-3.4) versus 1.3 (95% CI 0.9-1.9) in women ≥85 years

Thus, the authors pointed out the absolute risk difference between groups was "similar" across age groups, ranging from 1.5 to 2.3 cases per women screened.

"The higher proportion of overdiagnosed cases among older women reflects the fact that although the absolute risk is similar across age groups, the cumulative incidence of breast cancer is lower among older women who have greater competing mortality," they wrote.

Disclosures

This study was funded by the National Cancer Institute.

Richman has received grants from the National Institutes of Health/National Cancer Institute, and salary support from CMS. A co-author reported research funding from Genentech, AstraZeneca, and Johnson & Johnson.

Brawley reported relationships with Grail/Illumina, Agilent, Incyte, PDS Biotech, and Lyell Immunopharma.

Primary Source

Annals of Internal Medicine

Source Reference: opens in a new tab or windowRichman I, et al "Estimating breast cancer overdiagnosis after screening mammography among older women in the United States" Ann Intern Med 2023; DOI: 10.7326/M23-0133.

Secondary Source

Annals of Internal Medicine

Source Reference: opens in a new tab or windowBrawley O, Ramalingam R "Understanding the varying biological behaviors of breast and other types of cancer to avoid overdiagnosis" Ann Intern Med 2023; DOI: 10.7326/M23-1895.

https://www.medpagetoday.com/hematologyoncology/breastcancer/105793

'Some Health Workers See Double the Risk for Fatal Drug Overdoses'

 Certain healthcare workers including registered nurses (RNs) were at increased risk for fatal drug overdoses, a longitudinal study from 2008 to 2019 found.

After adjustment for various factors, the risk for overdose death was more than twofold higher for RNs (HR 2.22, 95% CI 1.57-3.13) and social or behavioral health workers (HR 2.55, 95% CI 1.74-3.73) when compared with non-healthcare workers, reported Mark Olfson, MD, MPH, of Columbia University Irving Medical Center in New York City, and colleagues.

Increased risk was seen among healthcare support workers as well (HR 1.60, 95% CI 1.19-2.16), while physicians, health technicians, and other treating or diagnosing health workers had no higher risk, according to the findings in the Annals of Internal Medicine

opens in a new tab or window.

"When people think about who's at risk for drug overdose deaths, what comes to mind are often young, white, unemployed men," Olfson told MedPage Today. "So the finding that there were several groups of healthcare workers that were at significantly higher risk than other workers, that was a surprise."

Overall, approximately 0.07% of the 176,000 healthcare workers and 0.07% of the 1.66 million non-healthcare workers in the study died of a drug overdose during the more than 10 years of follow-up. Age- and sex-standardized total overdose deaths rates per 100,000 ranged from 2.3 for physicians to 11.0 for nurses to 15.5 for social or behavioral health workers, as compared with 7.3 for the non-healthcare worker group.

Results were "generally similar" when broken down by either opioid-related overdose deaths or unintentional overdose deaths, according to the researchers.

Broadly speaking, healthcare workers are not seen as having a higher risk for drug overdose because of their "low-risk sociodemographic profile," according to the researchers, with Olfson adding that the field is disproportionately female and includes people with higher education and higher incomes.

The researchers suggested that several factors could place healthcare workers at increased risk for drug overdose death including:

• Relatively easy access to opioids and other controlled prescription drugs
• Job stress and job-related burnout, which have been tied to increased risk for opioid use disorder and/or risk for overdose
• Routinely doing physically strenuous tasks that can lead to musculoskeletal injuries and use of opioids to manage pain

Olfson stressed that these factors were "somewhat speculative."

Previous researchopens in a new tab or window has indicated higher rates of prescription drug misuse among RNs, so data on higher risk of overdose deaths among that group was not surprising, according to Olfson. In addition, studiesopens in a new tab or window have found that RNs working in positions with "higher levels of psychological or physical strain" are more likely than their peers with lower levels of strain to report nonmedical drug use.

But Olfson said he had not expected that healthcare support workers would have nearly twice the risk of an opioid-involved overdose death (adjusted HR 1.84, 95% CI 1.22-2.54).

He noted that there are more than 6 million healthcare support workers, such as nursing home workers and home health aides. The positions are low-paid, repetitive, and offer little opportunity for advancement, he said, adding that these workers are disproportionately middle-age women of color compared with other workers in healthcare.

Support workers who frequently lift and move patients, have "among the very highest rates of occupational injury ... higher than even construction workers. So there may be a hidden risk in that," Olfson said.

As for the higher rates of drug overdose deaths among social or behavioral health workers, that is "unlikely to be explained by occupational access to controlled substances or physical strain," Olfson's group wrote. However, there may be subgroups of individuals -- substance use disorder (SUD) counselors, for example -- who have a personal history of substance use problems that may place them at higher risk of overdose, Olfson noted.

Given the attention to higher rates of suicide among physicians and that some overdoses are intentional, Olfson said he expected overdose deaths in that group would be higher. But a 2020 meta-analysis

opens in a new tab or window found that suicide death rates were lower among male physicians than men in general, and males still dominate the profession, Olfson's group stated.

Study Details

Olfson and colleagues used the Mortality Disparities in American Communitiesopens in a new tab or window sample, which links data from the 2008 American Community Surveyopens in a new tab or window (ACS) to cause-of-death certificate records from the National Death Index from 2008 to 2019. The 2008 ACS data was administered to 2.9 million addressees and had a 97.9% response rate.

"We took essentially 1% of American adults who are employed and just followed them forward to see who dies of what," Olfson explained.

In terms of demographics, a majority of the RNs, social or behavioral health workers, and healthcare support workers were white, female, married, and living in urban settings. RNs were on the younger side (ages 26-35) while the other two groups were older (ages 46-55).

The primary outcome measure was total drug overdose deaths -- those coded with an underlying cause-of-death code for unintentional, intentional, or undetermined-intent drug poisoning in combination with other cause-of-death poisoning codes related to opioids, cocaine, and other drugs.

Study limitations included the fact that it did not capture the "recent shifts in the opioid landscape," that occupational status was assessed only once, and the risk for "misclassification" within the death certificate due to stigma and "social pressure" from family members not to classify a death as an overdose.

Expanded Resources

In terms of addressing this issue, Olfson urged employers to educate their staff about the addiction potential of opioids and other medications, as well as to train supervisors to look for warning signs of substance use problems.

He stressed the importance of healthcare workers with SUDs receiving confidential evidence-based treatment, given the stigma around the problem.

While a few specialized programs tailored to physicians with SUDs have been developed, Olfson said he could not find comparable programs for other healthcare workers.

He pointed out that physicians account for roughly 5% of the healthcare workforce. Based on the current analysis, this group is at a lower risk for overdose death than other non-healthcare workers, he added.

"It's not that they [physicians] don't deserve access to quality care -- everyone does," Olfson said. But "in terms of targeting scarce resources, there are higher-risk populations to focus on," he stated.

Disclosures

The study was supported by the National Heart, Lung, and Blood Institute and the U.S. Census Bureau.

Olfson disclosed a relationship with the New York State Office of Mental Health. A co-author disclosed support from the National Institute on Drug Abuse and the National Institute of Mental Health.

Primary Source

Annals of Internal Medicine

Source Reference: opens in a new tab or windowOlfson M, et al "Fatal drug overdose risk of healthcare workers in the United States" Ann Intern Med 2023; DOI: 10.7326/M23-0902.

https://www.medpagetoday.com/psychiatry/addictions/105795

Ginkgo in Pact with Merck to Improve Biologic Manufacturing

 Ginkgo Bioworks (NYSE: DNA), which is building the leading platform for cell programming and biosecurity, today announced a new collaboration with Merck, known as MSD outside of the United States and Canada, focused on improving biologic manufacturing.

Ginkgo will apply its expertise and capabilities in cell engineering, ultra high-throughput multiplexed screening, protein characterization and process optimization to improve production efficiency and increase yields. Under the terms of the collaboration, Ginkgo is eligible to receive, in aggregate, up to $490 million in upfront research fees, research milestone fees, option license payments and commercial milestone payments.

https://finance.yahoo.com/news/ginkgo-bioworks-announces-collaboration-merck-110100998.html

Why Embattled Apellis Stock, A Former Highflier, Just Took Another Hit

 Astellas Pharma (ALPMY) won Food and Drug Administration approval for a rival to Apellis Pharmaceuticals' (APLS) eye-disease treatment Syfovre and embattled APLS stock toppled again.

The Astellas approval comes via its recent acquisition of Iveric Bio. Over the weekend, the FDA signed off on the drug, Izervay, as a treatment for geographic atrophy. Meanwhile, Apellis stock has struggled as of late after the company confirmed a handful of patients have experienced swelling in their eyes following Syfovre injections.

Wedbush analyst Laura Chico noted the Izervay approval wasn't expected until later this month.

"With a second competitor in the market, this admittedly shifts the Syfovre prescribing calculus for physicians," she said in a note to clients.

On today's stock market, APLS stock tumbled 3.6% to close at 23.65, paring much steeper losses in earlier action. Astellas stock surged 10.6% to 15.40.

APLS Stock: Company Investigates Safety Issues

There are key differences between Astellas' Izervay and Apellis' Syfovre. Izervay is given every 28 days while the label for Syfovre recommends administration every 25 to 60 days, Chico said.

Investors in APLS stock will likely focus on the emergence of retinal vasculitis, a side effect the American Society of Retina Specialists noted in a letter last month. As of July 29, there were seven cases of retinal vasculitis among more than 68,000 vials of Syfovre distributed.

Apellis says it hasn't discovered any manufacturing issues impacting the quality of Syfovre. The company also hasn't found any quality issues or contaminant. Further, it hasn't indicated a single drug lot involved in the side effects.

"It remains unclear how long the assessments will take to uncover potential drivers," Chico said. "With a new product now available for geographic atrophy in Izervay, we presume physicians will be less incentivized to trial Syfovre amidst uncertainty around the safety events."

She cut her price target to 29 from 32 and kept her neutral rating on APLS stock.

https://www.investors.com/news/technology/apls-stock-why-embattled-apellis-just-took-another-hit-to-the-chin/

DaVita upped to Buy from Neutral by UBS

 Target to $142 from $100

https://finviz.com/quote.ashx?t=DVA&ty=c&ta=1&p=d

PBS Rolls Out 'Climate Psychology Therapist' For Armageddon-Coping Session

  by Steve Watson via Summit News,

In a segment that looked like something out of Monty Python, PBS NewsHour brought on a therapist to help people suffering from ‘climate anxiety’ on Sunday.

Anchor John Yang announced the “climate psychology therapist,” noting “This summer, millions of Americans are experiencing firsthand the effects of climate change. Triple-digit temperatures for days on end, smoke from record-setting wildfires fouling the air, warming oceans, bleaching coral reefs…”

“Psychologists say that can be a positive thing, spurring people to action. But for some people, it becomes an overwhelming sense of despair or anxiety,” Yang continued, adding “Psychologists call it climate anxiety. This week, we asked people about their emotional responses to climate change.”

We were then treated to seven troubled individuals who have reached the end of their mental tethers from watching too much climate fear porn, before one Leslie Davenport appeared to urge “it’s really important to acknowledge that if you’re feeling that on any level of intensity, it really means you’re paying attention, you care, you’re empathetic to what’s happening to our world.”

Davenport then encouraged the mentally crippled armageddon obsessed climate tweakers to “Talk about it, talk about it to other people who are like-minded, receptive, ‘I feel that way too,’ so that it’s not as isolating.”

She continued, “there are a lot of what are called climate cafes, or climate circles, that can be found by an easy online search, where people just get together often online, remotely, and just say what they’re feeling what they’re experiencing, what people have found helpful.”

Davenport added that there is even a “climate-aware therapist directory” that the poor babies can turn to.

Watch:

Is it any wonder hordes of normies are suffering from mental meltdown when every news channel they switch to is telling them the world is literally boiling and on fire?

https://www.zerohedge.com/political/pbs-rolls-out-climate-psychology-therapist-armageddon-coping-session

Collegium Announces $50 Million Accelerated Share Repurchase Program

 Collegium Pharmaceutical, Inc. (Nasdaq: COLL), a leading, diversified specialty pharmaceutical company committed to improving the lives of people living with serious medical conditions, today announced that it has entered into an Accelerated Share Repurchase ("ASR") agreement with Jefferies LLC to repurchase $50 million of the Company’s common stock. Collegium will execute the ASR as part of the $100 million share repurchase program authorized by its Board of Directors in January 2023. Upon completion of this ASR, Collegium will have $50 million remaining under the program.

“The accelerated share repurchase program reinforces our confidence in Collegium's core business, financial strength and strategy,” said Joe Ciaffoni, President and Chief Executive Officer of Collegium. “Our organization is well positioned to maximize the value of our differentiated pain portfolio while executing a disciplined capital deployment strategy. We are committed to effectively deploying capital to create value for our shareholders through focused business development, rapid debt paydown and opportunistic share repurchases.”

Under terms of the agreement, Collegium will pay $50 million to Jefferies LLC and will receive an initial delivery of approximately 1.7 million shares, based on the $23.49 closing stock price of Collegium’s common stock on August 4, 2023, representing approximately 80% of the total shares the Company expects to repurchase under the ASR agreement. The final number of shares repurchased will be based on the volume-weighted average prices of Collegium’s common stock during the term of the ASR and subject to adjustments related to the terms and conditions of the ASR agreement. The final settlement of the ASR is expected to be completed in the fourth quarter of 2023. As of June 30, 2023, Collegium had approximately 34.7 million shares outstanding.

https://www.biospace.com/article/releases/collegium-announces-50-million-accelerated-share-repurchase-program/