Tuesday, January 07, 2025

 

Early cancer screening could save Canadian healthcare system nearly half a billion dollars over patients’ lifetime



Expensive, lifesaving treatments could be drastically reduced if Canada followed the U.S. model and started screening for breast cancer at 40



University of Ottawa




Cancer screening is key to saving patients’ lives since an earlier stage diagnosis improves survival rates, decreases morbidity, and leads to less intensive treatments. Early detection also has the potential to save Canada’s health care system major money. The United States adopted breast cancer screening for women in their Forties due to an increase in the incidence of breast cancer in younger women, with recent research from the University of Ottawa confirming this rise.

Lead author Dr. Anna Wilkinson, an Associate Professor in the Faculty of Medicine at the University of Ottawa (uOttawa) and a GP oncologist at The Ottawa Hospital (TOH) Cancer Centre and with a team of researchers from uOttawa, including Dr. Jean Seely, and TOH – including Dr. Moira Rushton, a medical oncologist at the Ottawa Hospital Cancer Centre – collaborated with Sunnybrook Research Institute to examine the cost-effectiveness of breast cancer treatments at an earlier stage.

Dr. Wilkinson gave us an overview of this work, which was published in JAMA:

Question: What are the proven benefits of early detection of breast cancer?
Anna Wilkinson: “When breast cancers are detected at an early stage, less intensive treatments can be employed such as lumpectomies instead of mastectomies, single (sentinel) node biopsies instead of removing all the lymph nodes in the armpit, and often omitting chemotherapy and radiotherapy.

Breast cancer survival is predicated by stage at diagnosis: the 5-year net survival for stage I breast cancer is 100 percent which, subsequently, declines to 92%, 74% and 23% with stage II, III and IV breast cancers.”

Q: Why was it important to review the costs of screening now?
AW: “Recent debate over whether women aged 40 to 49 should be screened for breast cancer has crystallised the importance of understanding the economics of screening. In investigating this topic, we realised that cost effectiveness analyses are outdated and do not reflect expensive new advances that have become standard of care.”

Q: What are the most recent advances and why has cost effectiveness not been incorporated?
AW: “The last few years have seen an explosion in exciting innovations in breast cancer treatment, which have resulted in improved breast cancer survival. These treatment successes translate into skyrocketing cost increases for advanced stage breast cancers. For example, new targeted therapies for high-risk stage II and III hormone sensitive breast cancers can cost nearly $142K over two years and over $210K for three years in the metastatic setting. A highly effective antibody drug conjugate for HER2 positive and HER2 low breast has a cost of $166K for one year of therapy and immunotherapy for triple negative breast cancer is $153K for one year of therapy. Stage IV costs for certain subtypes can rise past $500,000.

“Traditional costing models use population-level databases that have inherent time lags in data availability and do not reflect rapidly evolving costs. Our costing calculations were unique because all costs along the breast cancer continuum were included such as: diagnosis; pathology; radiology; surgery; radiation oncology; hospital stay; pharmacy; nursing; and palliative care costs.”

Q: What kind of savings do you foresee?
AW: “We found that screening a cohort of women annually for breast cancer starting at age 40 to 74 saves the Canadian health care system $459.6M over these women’s lifetime with 3,499 breast cancer deaths averted and 52,367 life years gained. This translates into a savings of $1, 880 for every women screened. The costs of screening mammograms and diagnostics are easily offset by treating cancers at earlier stages when it is less expensive.”

Q: What kind of impact could early screening policy for breast cancer and other diseases have?
AW: “In an era where we will continue to see ever-more expensive, rapidly evolving treatments for cancer, diagnosing cancers early is a cost saving measure. We should see this study as a call for similar analyses of the cost effectiveness of early screening for colon, lung and cervical cancers. Evidence of costs savings with cancer screening could target the health inequities created by different cancer screening practices across Canada. The adoption of inclusive cancer screening presents a means to save money and optimize health equity, while improving cancer morbidity and mortality.”

 

New research reveals groundwater pathways across NA continent




Princeton University, Engineering School

Aerial view of meandering river 

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An aerial view of the Taylor Park watershed in Gunnison County, Colorado.

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Credit: Drew Bennett




Researchers from Princeton University and the University of Arizona have created a simulation that maps underground water on a continental scale. The result of three years’ work studying groundwater from coast to coast, the findings plot the unseen path that each raindrop or melted snowflake takes before reemerging in freshwater streams, following water from land surface to depths far below and back up again, emerging up to 100 miles away, after spending from 10 to 100,000 years underground.

The simulation, published Jan. 6 in the journal Nature Water, shows that rainfall and snowmelt flow much farther underground than previously understood and that more than half the water in streams and rivers originates from aquifers once thought to be so deep as to be walled off from streams. These unexpected findings have major implications for tracking pollution and predicting the effects of climate change on groundwater, which supplies half of all drinking water in the United States.

Spanning the continental United States and parts of Canada and Mexico, the simulation tracks the flow of groundwater and measures the vast distances and depths it travels before discharging into streams across more than 3 million square miles (7.85 million square kilometers). The researchers accomplished this with a high-resolution hydrological simulation that allowed them to track the water moving through underground systems.

The research team included Reed Maxwell, Princeton’s William and Edna Macaleer Professor of Engineering and Applied Science and a professor at Princeton’s High Meadows Environmental Institute; Chen Yang, a former associate research scholar at Princeton (now at Sun Yat-sen University in China); and University of Arizona professor Laura Condon.

They found that groundwater can travel underground for hundreds of kilometers before emerging as streamflow. In the Midwest, groundwater flows long distances — especially where the mountains meet the plains. One groundwater flow along the base of the Rocky Mountains spanned 148 miles (238 kilometers). The study also revealed groundwater’s vast connection networks: Almost 90% of U.S. watersheds take in water from one neighbor and pass it to another.

The findings bear staggering implications. While out of sight, groundwater constitutes 99% of the world’s unfrozen fresh water and provides drinking water to 145 million Americans. It is also essential to our food supply, irrigating 60% of agriculture worldwide. But groundwater is being depleted at an alarming rate — and it’s long been difficult to model. This study’s new retrospective analyses and predictive simulations provide opportunities to track this vital resource and understand the far-reaching impacts of leakages from the likes of oil and gas well pads.

“Interconnections between the watersheds isn’t just important for streamflow,” said Maxwell. “This also tells us how long contamination will persist in groundwater. Widespread pollutants like nitrate and PFAS can take these long journeys to the stream, making them harder to manage and even longer-lived.”

The second important new discovery is that groundwater from very deep aquifers contributes significantly to streamflow. Maxwell’s team found that deep groundwater from aquifers 10 to 100 meters below the surface contributed more than half of the baseflow in 56% of the subbasins. The greatest depths occurred in regions with the steepest topography gradients, such as the Rocky and Appalachian mountain ranges.

Taylor Park reservoir in Gunnison County, Colorado

Credit

Drew Bennett

 

Integrating historic data stands to improve climate models in the Global South



Researchers showed how records from missionaries and early explorers in 19th century Tanzania could be used to mitigate a legacy of scientific neglect




McGill University

Letter from a missionary to Tanzania in 1880 commenting on weather 

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Transcription of a letterfrom a missionary in the field and addressed to Mr Wright (Henry Wright, General Secretary of the Church Missionary Society), dated 2 Feb. 1880, and written from Mpwapwa, Tanzania.

 "Just a line to let you know we are all well. This wet season has been extremely dry so that there is great scarcity of food between Unyanyembe + the coast. Until the latter end of last week we have had no rain here excepting the few showers which fell in November + December which we thought were the commencement of the masika [rainy season]. Everything appeared to be scorched up, or nearly, so much of our land has had to be resewn."

Researcher's comment:

"The rainy season in Mpwapwa normally starts at the beginning of December. Thus, this letter indicates that there was 2 months of unseasonal drought in Dec. 1879 – Jan. 1880. "

 

 

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Credit: Church Missionary Society Archive




An international team led by McGill University researchers has devised a way to improve the accuracy of climate change models for the Global South by integrating historical records kept by missionaries and other visitors.

To show how it could be done, a cross-disciplinary team of researchers that included climate scientists, data analysts and a historian integrated data from 19th century missionary archives in Tanzania with current data for the region provided by climate modellers. They devised a way to quantify the historic records, which tended to be anecdotal as opposed to scientifically recorded. The result was to provide a longer record of climate change in the region than had previously been available, which has the capacity to enhance the accuracy of climate change models. Their work was published recently in Climate of the Past.

“The general scientific neglect of the Global South is only now starting to be gradually corrected by institutions in these regions,” explained Philip Gooding, a researcher at McGill’s Indian Ocean World Centre and the lead author of the study. “Tanzania is typical of many tropical regions in the Global South, in that evidence of climatic changes before the mid-20th century has yet to be gathered or analyzed.” Gooding said. “This is partly because climate change research is often more difficult in such regions. For example, it is difficult to conduct tree ring analysis in tropical regions because many tropical species do not provide annual rings, or they respond differently to climate variability. Meanwhile, analysis of lake sediments suggests multi-decadal trends, rather than annual or seasonal climatic conditions.” So, he said, researchers looked to historical documents.

Missionaries and explorers track changing patterns of rainfall and drought

The researchers looked at historical climate records for the towns of Ujiji, Tabora and Mpwapwa in central Tanzania between 1856-1890. All are at a similar latitude, with rainy seasons of similar duration and in similar months.

European “explorers” and early imperialists passed through the region from the late 1850s. They noted their observations about the weather and gathered information about previous seasons and years from local people. Representatives of various missionary societies based in Europe came to stay for longer periods from the 1870s. Their records provide a more consistent and reliable source of information, according to the researchers.

A record of rainfall patterns over a 30-year period in the 19th century

Although their letters and diaries varied greatly in terms of what was noted, the Europeans were interested in documenting climate conditions, including variability in rain, periods of drought, floods and harvests, as well as the conditions of pastures and fields.

The information is sufficient, for the period from 1856 to 1890, to provide a picture of climate trends over the long term, especially when combined and integrated with modelled data.

Information with a complicated origin and legacy

The researchers are conscious the origin of the historic data is problematic and carries with it a complicated legacy.

“Missionary accounts of the hardships of droughts acted as one of the justifications for European intervention in African affairs, in ways that failed to increase drought resiliency. It was a heavily racialized, and problematic discourse that infantilized and brutalized those who soon became colonized peoples,” Gooding said.

However, integrating this data into climate models stands to improve their accuracy, he said. He believes the methodology developed in his study can be applied more broadly in the Global South.

“Using climate model data alone is rather uncertain due to a lack of verification with observations over this region,” said Melissa Lazenby, a climatologist from the University of Sussex and co-author of the article. “By adding and integrating the documentary data to the climate modelling data, this research provides a more robust and credible picture of what happened in such regions in the past. This therefore helps verify climate models over this data-sparse region and can help in providing more accurate and credible future projections.”

 

Typical cost of developing new pharmaceuticals is skewed by high-cost outliers


Using average costs distorts public discussions about drug development costs



RAND Corporation




The typical cost of developing new medications may not be as high as generally believed, with a few ultra-costly medications skewing public discussions about the cost of pharmaceutical research and development, according to a new RAND study. 

Using a novel method to assess spending on research and development for 38 drugs that were recently approved by the U.S. Food and Drug Administration, researchers found that the mean, or average, cost of developing a new drug was much higher than the mid-point (median) cost of development. 

Researchers estimated a median direct research and development cost of $150 million compared to a mean of $369 million. 

Costs were higher after adjusting for earnings drug developers could have made if they had invested these amounts in other activities and for drugs that never made it to the market. With these adjustments, researchers estimated a median research and development cost of $708 million across the 38 drugs examined, with the average cost rising to $1.3 billion driven by a small number of high-cost outliers. 

The average cost of developing a new drug was 26% lower when excluding just two drugs, dropping from $1.3 billion to $950 million. The findings are published in the journal JAMA Network Open. 

“Our work suggests that it may not be as costly to develop the typical new drug as has been previously estimated,” said Andrew Mulcahy, the study’s lead author and a senior policy researcher at RAND, a nonprofit research organization. “Reliable research and development cost estimates are essential to assessing the appropriateness of incentives such as patent regulatory exclusivity and other rules that assure that drug developers can achieve fair returns on their investments.”

Remarkable developments in medicine, including breakthroughs such as COVID-19 treatments and cures for hepatitis C, have resulted from investments in drug research and development. These successes have played out through a vigorous debate on the extent to which U.S. drug price regulation might decrease investments in new drugs. 

The pharmaceutical industry argues lower prices will have catastrophic effects on research and development. In contrast, the Congressional Budget Office has projected that efforts to reduce drug prices for Medicare beneficiaries would cut the number of new drugs by just 1% over 30 years. 

RAND researchers estimated spending on new drug research and development by examining annual public disclosures about such spending that companies report to the U.S. Securities and Exchange Commission. The analysis included information about more than 200 publicly traded companies during 2014-2019.

The study used Citeline’s Trialtrove database about clinical trials to help examine the clinical trial activity for each of the 38 new drugs that were approved for clinical use by the FDA in 2019. 

To better account for variation in clinical research intensity and the full scope of delivering new drugs to market, the study calculated costs per patient-month using 6-year, company-wide R&D cost and activity data from all of the drug developers examined. 

The study found that 20 large companies accounted for 81% of all patient-months and had 27% lower mean and median costs per patient-month compared to other drug companies.

Researchers say their findings that the average cost of developing a new drug is skewed by a few ultra-costly medications suggests that the median cost of bringing drugs to market probably is a better tool to use during policy discussions about high drug costs in the U.S.

“The novel approach we used provides us with greater confidence that we are capturing more of the spending that goes into research and development as compared to previous studies of this nature,” Mulcahy said. 

Support for the study was provided by Arnold Ventures. Other authors of the study are Stephanie Rennane, Daniel Schwam, Reid Dickerson, Lawrence Baker and Kanaka Shetty.

RAND Health Care promotes healthier societies by improving health care systems in the United States and other countries.

 

Young salmon may face hungry new competition from juvenile sablefish along northwest coast



Sablefish eat larger prey for their size than salmon, and a lot more of it.



Peer-Reviewed Publication

NOAA Fisheries West Coast Region

Juvenile sablefish with prey 

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Scientists examined the stomach contents of juvenile sablefish in coastal waters, finding evidence of their voracious appetite including other fish almost as big as they are.

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Credit: Elizabeth Daly/CIMERS




There is a new mouth to feed in the coastal waters of the Northwest where juvenile salmon first enter the ocean, and it’s a hungry one.

Over the last two decades large numbers of juvenile sablefish have increasingly spread into coastal waters from central Oregon north to northern Washington. New research published in the journal Marine and Coastal Fisheries shows the influx follows the warming of ocean temperatures off the West Coast. It matches reports of fishing boats catching more small sablefish closer to shore.

The finding means that salmon may face new competition from sablefish at a critical time in their life cycle, which is already at risk from climate change. Adult sablefish live for many years in deep offshore waters along the ocean floor. Juvenile sablefish—like young salmon— first feed and grow along the highest layers of water near the surface that teem with life. Sablefish are voracious eaters, often consuming large prey and lots of it.

“They are around the same size as juvenile salmon, but they can eat bigger prey and much more prey than salmon can at the same size,” said Elizabeth Daly, an ecologist with the joint NOAA-Oregon State University Cooperative Institute for Marine Ecosystem and Resources Studies in Newport, Oregon. She is the lead author of a new paper documenting increased competition between the two species, which both support important commercial fisheries off the West Coast.

Eating Bigger, and More

Researchers on NOAA Fisheries survey examine nets full of juvenile sablefish collected in the same coastal waters where salmon spend their first months at sea. Photo by Greg Williams/Pacific States Marine Fisheries Commission

The young sablefish eat much the same thing as juvenile salmon do, but a lot more of it, Daly said. She and her team discovered this by examining their stomach contents. For instance, even small sablefish consumed several times more krill than yearling Chinook salmon. The scientists did not find clear evidence of sablefish consuming young salmon, but based on the size of their other prey, they certainly could.

Other research has documented a similar influx of juvenile sablefish in waters off Alaska, although the new study did not include Alaska.

Salmon numbers and survival vary so widely from year to year that it’s difficult to detect a specific impact from sablefish competition on salmon survival. However, the scientists suggest that the direct overlap of sablefish in the waters where young salmon first feed and grow may put salmon at a competitive disadvantage. That would be especially true if continued ocean warming makes food harder to find.

Salmon spend most of their lives in the ocean, which remains the most unpredictable chapter in their life cycle. The competition from sablefish comes during their first risky months at sea, when they are trying to eat and grow fast enough to stay ahead of predators.

“We now know that prey resources are extremely important for salmon growth and survival during this critical early marine period,” said Brian Burke, research scientist at NOAA Fisheries Northwest Fisheries Science Center, and coauthor of the research. “But unraveling the impact of competition on salmon is extremely difficult. This new data helps us understand how species interact in our coastal environment. They also point to potential changes from continued ocean warming due to climate change.”

Sablefish Outnumbering Salmon

Juvenile sablefish were most numerous in coastal waters off Oregon and Washington in 2020, which was a boom year for the species. They outnumbered juvenile salmon so much that year that sablefish were approximately:

  • Four times more numerous than subyearling Chinook salmon
  • 32 times more numerous than yearling Chinook salmon
  • 13 times more numerous than coho salmon

The sablefish also had significantly more food in their stomachs at the time.

Salmon consumed significantly less food in areas with numerous sablefish, said Brandon Chasco, a coauthor and research scientist with the Washington Department of Fish and Wildlife Quantitative Synthesis and Reporting Unit. “When sablefish were there, juvenile salmon ate less,” he said. “Whether they’re disrupting salmon feeding, or if salmon avoid them as potential predators, we are not sure.”

Climate change projections have indicated a rising risk to salmon in the ocean, since higher ocean temperatures often reduce salmon survival. The additional competition from sablefish could make things even rougher. Sablefish, in contrast, could benefit if the juveniles that have expanded into coastal waters grow into adults that add to the population.

Fishing crews have recently reported catching many smaller adult sablefish, likely the result of more juveniles joining the populations. “Regardless of what happens to the sablefish, we know they are increasingly competing with salmon in these waters,” Daly said.


Researchers on NOAA Fisheries survey examine nets full of juvenile sablefish collected in the same coastal waters where salmon spend their first months at sea.

 

Credit

Greg Williams/Pacific States Marine Fisheries Commission

Hauling in Sablefish (IMAGE)

NOAA Fisheries West Coast Region

 

Dinosaurs roamed the northern hemisphere millions of years earlier than previously thought, according to new analysis of the oldest North American fossils




University of Wisconsin-Madison

Dino-Gabriel Ugueto 

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An artist’s rendering shows how Ahvaytum bahndooiveche may have appeared in a habitat dating to around 230 million years ago.

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Credit: Illustration by Gabriel Ugueto




MADISON — How and when did dinosaurs first emerge and spread across the planet more than 200 million years ago? That question has for decades been a source of debate among paleontologists faced with fragmented fossil records. The mainstream view has held that the reptiles emerged on the southern portion of the ancient supercontinent Pangea called Gondwana millions of years before spreading to the northern half named Laurasia.

            But now, a newly described dinosaur whose fossils were uncovered by University of Wisconsin–Madison paleontologists is challenging that narrative, with evidence that the reptiles were present in the northern hemisphere millions of years earlier than previously known.

The UW–Madison team has been analyzing the fossil remains since they were first discovered in 2013 in present-day Wyoming, an area that was near the equator on Laurasia. The creature, named Ahvaytum bahndooiveche, is now the oldest known Laurasian dinosaur, and with fossils estimated to be around 230 million years old, it's comparable in age to the earliest known Gondwanan dinosaurs.

            UW–Madison scientists and their research partners detail their discovery Jan. 8, 2025, in the Zoological Journal of the Linnean Society.

            "We have, with these fossils, the oldest equatorial dinosaur in the world — it's also North America's oldest dinosaur," says Dave Lovelace, a research scientist at the University of Wisconsin Geology Museum who co-led the work with graduate student Aaron Kufner.

            Discovered in a layer of rock known as the Popo Agie Formation, it took years of careful work by Lovelace and his colleagues to analyze the fossils, establish them as a new dinosaur species and determine their estimated age.

            While the team doesn't have a complete specimen — that's an exceedingly rare occurrence for early dinosaurs — they did find enough fossils, particularly parts of the species' legs, to positively identify Ahvaytum bahndooiveche as a dinosaur, and likely as a very early sauropod relative. Sauropods were a group of herbivorous dinosaurs that included some famously gigantic species like those in the aptly named group of titanosaurs. The distantly related Ahvaytum bahndooiveche lived millions of years earlier and was smaller — much smaller.

            "It was basically the size of a chicken but with a really long tail," says Lovelace. "We think of dinosaurs as these giant behemoths, but they didn't start out that way."

Indeed, the type specimen of Ahvaytum bahndooiveche, which was full-grown but could have been slightly bigger at its maximum age, stood a little over one foot tall and was around three feet long from head to tail. Although scientists haven’t found its skull material, which could help illuminate what it ate, other closely related early sauropod-line dinosaurs were eating meat and would likely have been omnivorous.   

The researchers found the few known bones of Ahvaytum in a layer of rock just a little bit above those of a newly described amphibian that they also discovered. The evidence suggests that Ahvaytum bahndooiveche lived in Laurasia during or soon after a period of immense climatic change known as the Carnian pluvial episode that has previously been connected to an early period of diversification of dinosaur species.

The climate during that period, lasting from about 234 to 232 million years ago, was much wetter than it had been previously, transforming large, hot stretches of desert into more hospitable habitats for early dinosaurs.

Lovelace and his colleagues performed high-precision radioisotopic dating of rocks in the formation that held Ahvaytum’s fossils, which revealed that the dinosaur was present in the northern hemisphere around 230 million years ago. The researchers also found an early dinosaur-like track in slightly older rocks, demonstrating that dinosaurs or their cousins were already in the region a few million years prior to Ahvaytum.

"We're kind of filling in some of this story, and we're showing that the ideas that we've held for so long — ideas that were supported by the fragmented evidence that we had — weren’t quite right,” Lovelace says. “We now have this piece of evidence that shows dinosaurs were here in the northern hemisphere much earlier than we thought."

While the scientific team is confident they've discovered North America's oldest dinosaur, it's also the first dinosaur species to be named in the language of the Eastern Shoshone Tribe, whose ancestral lands include the site where the fossils were found. Eastern Shoshone tribal elders and middle school students were integral to the naming processAhvaytum bahndooiveche broadly translates to "long ago dinosaur" in the Shoshone language.

Several tribal members also partnered with Lovelace and his UW–Madison colleagues as the researchers sought to evolve their field practices and better respect the land by incorporating the knowledge and perspectives of the Indigenous peoples into their work.

"The continuous relationship developed between Dr. Lovelace, his team, our school district, and our community is one of the most important outcomes of the discovery and naming of Ahvaytum bahndooiveche," says Amanda LeClair-Diaz, a co-author on the paper and a member of the Eastern Shoshone and Northern Arapaho Tribes. LeClair-Diaz is the Indian education coordinator at Fort Washakie school and coordinated the naming process with students and tribal elders — a process that started under her predecessor, Lynette St. Clair.

"Typically, the research process in communities, especially Indigenous communities, has been one sided, with the researchers fully benefiting from studies," says LeClair-Diaz. "The work we have done with Dr. Lovelace breaks this cycle and creates an opportunity for reciprocity in the research process."

A University of Wisconsin Geology Museum field crew is seen here in 2016 prospecting for additional material at the site in Wyoming where fossils of Ahvaytum bahndooiveche were discovered in 2013. The researchers are Aaron Kufner (left) and Jennifer Lien.

Credit

Photo by David M. Lovelace

UW Geology Museum scientist David Lovelace removing sediment from around a fossil in plaster cast as he works in the museum’s specimen preparation room in Weeks Hall at the University of Wisconsin–Madison on June 3, 2024.

Credit

Photo by Jeff Miller/UW–Madison