What: A large analysis of data from nearly 400,000 healthy U.S. adults followed for more than 20 years has found no association between regular multivitamin use and lower risk of death. The study, led byresearchersat the National Institutes of Health’s National Cancer Institute, was published June 26, 2024, in JAMA Network Open.
Many adults in the United States take multivitamins with the hope of improving their health. However, the benefits and harms of regular multivitamin use remain unclear. Previous studies of multivitamin use and mortality have yielded mixed results and been limited by short follow-up times.
To more deeply explore the relationship between long-term regular multivitamin use and overall mortality and death from cardiovascular disease and cancer, the researchers analyzed data from three large, geographically diverse prospective studies involving a total of 390,124 U.S. adults who were followed for more than 20 years. The participants included in this analysis were generally healthy, with no history of cancer or other chronic diseases.
Because the study population was so large and included lengthy follow-up and extensive information on demographics and lifestyle factors, the researchers were able to mitigate the effects of possible biases that may have influenced the findings of other studies. For example, people who use multivitamins may have healthier lifestyles in general, and sicker patients may be more likely to increase their use of multivitamins.
The analysis showed that people who took daily multivitamins did not have a lower risk of death from any cause than people who took no multivitamins. There were also no differences in mortality from cancer, heart disease, or cerebrovascular diseases. The results were adjusted for factors such as race and ethnicity, education, and diet quality.
The researchers noted that it is important to evaluate multivitamin use and risk of death among different kinds of populations, such as those with documented nutritional deficiencies, as well as the potential impact of regular multivitamin use on other health conditions associated with aging.

Before a cell commits fully to the process of dividing itself into two new cells, it may ensure the appropriateness of its commitment by staying for many hours — sometimes more than a day — in a reversible intermediate state, according to a discovery by researchers at Weill Cornell Medicine. Their revelation of this fundamental feature of biology includes details of its mechanisms and dynamics, which may inform the development of future therapies targeting cancers and other diseases.
In their study, published June 26 in Nature, the researchers developed new tools allowing them to track over time the activation state of E2F, a transcription factor protein long known as the master switch for initiating division in mammalian cells. They found unexpectedly that E2F, before being fully activated, can remain in a potentially lengthy state of partial and reversible activation that may end in full commitment to cell division or a reversion to the usual, non-dividing, “quiescent” state.
Although the role of this pre-commitment state of cell division is not yet entirely clear, it appears to be a safety mechanism to avoid inappropriate cell division, and may also activate DNA-repair functions. In any case, it appears to be a basic — and until now undiscovered — aspect of cell biology, with likely implications for understanding cancer, wound healing, and other cell division-related processes.
“We suspect, for example, that some types of cancer cell linger in this intermediate, pre-division state to improve their chances of survival,” said study senior author Dr. Tobias Meyer, the Joseph Hinsey Professor of Cell & Developmental Biology and a professor of biochemistry at Weill Cornell Medicine.
The study’s first author — and co-corresponding author with Dr. Meyer — is Dr. Yumi Konagaya, a postdoctoral researcher in the Meyer Laboratory during the study, now a principal investigator at Riken, a national research institute in Japan.
Cell division is the basic process underlying the growth and development of living things, and even in adult organisms is necessary for the repair of wounds and the general maintenance of tissues. While it has been known that the division process starts in a cell when various input signals trigger the activation of E2F, how this works has always been something of a mystery. The activation process is, in principle, highly sensitive to input signals, yet these signals are very prone to fluctuate — so how does the cell avoid constant, inappropriate E2F activations and cell divisions?
To answer this question, Dr. Konagaya developed the first-ever set of methods for tracking, in individual cells, the detailed activation status of E2F and its signaling partners as the cells move from their usual quiescent state into the division process. With these new tools, she observed that E2F, which is activated by multiple chemical modifications called phosphorylations, often remains in an extended, partial-activation, “primed” state in which some but not all of the necessary phosphorylations have occurred.

“It became clear that cells can stall in this primed state for more than a day before returning to quiescence or advancing to cell division,” Dr. Konagaya said.
It seems likely, according to the researchers, that this intermediate primed state allows cells time to sense and integrate the usual, fluctuating cell division input signals, smoothing this “noise” and reducing the chance of inappropriate division. But the researchers suspect that this state has other functions too, including to facilitate DNA repair, since cells in this state show signs of activated DNA-repair processes. A DNA-repair function could benefit cancer cells as well as healthy cells, Dr. Meyer noted.
“Cancer cells often die when they divide because of the DNA damage they have accumulated, but this intermediate state induces DNA damage-repair machinery, so maybe some cancers use this state to repair themselves before dividing,” he said.
The researchers plan to follow up in part by exploring the role of this intermediate pre-division state in cancers. In principle, having learned the tell-tale phosphorylation pattern of this intermediate state, they could develop tests for identifying cancers in this state, which could help in optimizing treatments.

Engineers at the University of California San Diego have developed a pill that releases microscopic robots, or microrobots, into the colon to treat inflammatory bowel disease (IBD). The experimental treatment, given orally, has shown success in mice. It significantly reduced IBD symptoms and promoted the healing of damaged colon tissue without causing toxic side effects.
The study was published June 26 in Science Robotics.
IBD, an autoimmune disorder characterized by chronic inflammation of the gut, affects millions of people worldwide, causing severe abdominal pain, rectal bleeding, diarrhea and weight loss. It occurs when immune cells known as macrophages become overly activated, producing excessive levels of inflammation-causing proteins called pro-inflammatory cytokines. These cytokines, in turn, bind to receptors on macrophages, triggering them to produce more cytokines, and thereby perpetuating a cycle of inflammation that leads to the debilitating symptoms of IBD.
Now, researchers have developed a treatment that successfully keeps these cytokine levels in check. A team led by Liangfang Zhang and Joseph Wang, both professors in the Aiiso Yufeng Li Family Department of Chemical and Nano Engineering at UC San Diego, engineered microrobots composed of inflammation-fighting nanoparticles chemically attached to green algae cells. The nanoparticles absorb and neutralize pro-inflammatory cytokines in the gut. Meanwhile, the green algae use their natural swimming abilities to efficiently distribute the nanoparticles throughout the colon, accelerating cytokine removal to help heal inflamed tissue.
What makes these nanoparticles so effective is their biomimetic design. They are made of biodegradable polymer nanoparticles coated with macrophage cell membranes, allowing them to act as macrophage decoys. These decoys naturally bind pro-inflammatory cytokines without being triggered to produce more, thus breaking the inflammatory cycle.
“The beauty of this approach is that it’s drug-free — we just leverage the natural cell membrane to absorb and neutralize pro-inflammatory cytokines,” said Zhang.
The researchers have ensured that their biohybrid microrobots meet rigorous safety standards. The nanoparticles are made of biocompatible materials, and the green algae cells used in this study are recognized as safe for consumption by the U.S. Food and Drug Administration.

The microrobots are packed inside a liquid capsule with a pH-responsive coating. This coating remains intact in the acidic environment of the stomach acid, but dissolves upon reaching the neutral pH of the colon. This ensures that the microrobots are selectively released where they are needed most. “We can direct the microrobots to the diseased location without affecting other organs,” said Wang. “In this way, we can minimize toxicity.” The capsule keeps the functionalized algae in the liquid phase until their release.
The capsule was administered orally to mice afflicted with IBD. The treatment reduced fecal bleeding, improved stool consistency, reversed IBD-induced weight loss and reduced inflammation in the colon, all without apparent side effects.
The research team is now focusing on translating their microrobot treatment into clinical studies.
This work is supported by the Defense Threat Reduction Agency Joint Science and Technology Office for Chemical and Biological Defense (HDTRA1-21-1-0010).

Researchers led by Kannosuke Yabe, Asuka Kamio, and Soichi Inagaki of the University of Tokyo have discovered that in thale cresses histone H3 lysine-9 (H3K9) methylation, conventionally thought to be a mark of turning off gene transcription, can also turn on gene expression via the interactions of two other proteins and histone marks.The molecular mechanisms demonstrate that rather than functioning as a simple “off switch,” H3K9 methylation is more like a “dimmer switch” that fine-tunes DNA transcription. The discovery suggests there might be similar mechanisms in other organisms, too. The findings were published in the journal Science Advances.
DNA is often called the “blueprint of biological organisms.” However, calling it the “toolbox of cells” might be more accurate because cells also need to control which genes, the basic building blocks of DNA, are transcribed, or in other words, “turned on or off.” This is epigenetics, and it involves the complex interactions of many types of proteins, such as histones. H3K9 methylation is an epigenetic mark associated with turning off DNA transcription. Even though H3K9 methylation was discovered 25 years ago, not all of its molecular mechanisms have been clarified.
“Biological systems are so complex,” says Inagaki, the principal investigator, “that it is almost impossible for us to understand exactly how life works. But we can try to understand a tiny part of it. The regulation of gene activity is fundamental to life and is connected to a lot of biological phenomena.”
The researchers chose to investigate the molecular mechanisms of gene regulation in Arabidopsis thaliana, commonly known as thale cresses. The team used a technique called chromatin immunoprecipitation sequencing (ChIP-seq). This technique provides a detailed view of how proteins interact with DNA. It can be used to analyze the locations of protein modifications very precisely, making it a befitting tool to investigate histone methylation. Then, the results of H3K9 methylation’s peculiar role came in.
“At first, I did not pay attention to the results of the analysis,” Inagaki remembers, “and did not do any further research on the subject for about a year. I overlooked the finding because it was so unexpected. But one day I had a eureka moment and everything made sense in my head. After that, proving the hypothesis that H3K9 methylation had a dual role went smoothly.”
H3K9 methylation’s dual role is achieved via two other proteins, LDL2 and ASHH3. LDL2 helps to turn off genes by removing another histone mark, H3K4 methylation. ASHH3 turns the gene on by stopping LDL2 from working via a third histone mark, H3K36 methylation. The complex relationship of the 3 histone marks (H3K9, H3K4, H3K36) determines the gene’s activity.
“I’m happy that we discovered the fundamental aspect of gene regulation by H3K9 methylation, even though many studies around the function and controlling mechanisms of H3K9 methylation have been conducted in many organisms. I hope that this finding will stimulate further scientific endeavors to elucidate how gene regulation works,” Inagaki says, already thinking about future research.

A new study published by an international multidisciplinary team of researchers including faculty at Binghamton University, State University of New York, documents the first case of Down syndrome in Neandertals and reveals that they were capable of providing altruistic care and support for a vulnerable member of their social group.
The research, led by anthropologists at the University of Alcalá and the University of Valencia in Spain, studied the skeletal remains of a Neandertal child, whom they affectionately named “Tina,” found at Cova Negra, a cave in Valencia, Spain long known for yielding important Neandertal discoveries.
“The excavations at Cova Negra have been key to understanding the way of life of the Neandertals along the Mediterranean coast of the Iberian Peninsula and have allowed us to define the occupations of the settlement: of short temporal duration and with a small number of individuals, alternating with the presence of carnivores,” said University of Valencia Professor of Prehistory Valentín Villaverde.
The researchers made micro-computed tomography scans of a small cranial fragment of the right temporal bone, containing the ear region, to reconstruct a three-dimensional model for measurement and analysis. Tina suffered from a congenital pathology of the
inner ear associated with Down syndrome that produced severe hearing loss and disabling vertigo. This individual survived to at least 6 years of age, but would have required extensive care from other members of their social group.
“This is a fantastic study, combining rigorous archaeological excavations, modern medical imaging techniques and diagnostic criteria to document Down syndrome in a Neandertal individual for the first time. The results have significant implications for our understanding of Neandertal behavior,” said Binghamton University Professor of Anthropology Rolf Quam.
Researchers have known for decades that Neandertals cared for disabled individuals. However, to date, all known cases of social care among Neandertals involved adult individuals, leading some scientists to discount this as truly altruistic behavior and instead to suggest it more likely represented reciprocal exchange of help between equals.
“What was not known until now was any case of an individual who had received help, even if they could not return the favor, which would prove the existence of true altruism among Neandertals. That is precisely what the discovery of ‘Tina’ means,” said Mercedes Conde, professor at the University of Alcalá and lead author of the study. The study, “The child who lived: Down syndrome among Neandertals?” was published in Science Advances.

Ovarian cancer, often diagnosed at an advanced stage, presents significant treatment challenges because patients tend to develop resistance to conventional therapies quickly. Despite aggressive treatment, recurrence rates remain high, and managing this disease effectively requires innovative approaches. Poly-adenosine ribose polymerase (PARP) inhibitors have emerged as a treatment option, targeting specific DNA repair mechanisms in cancer cells. However, their use is often limited by toxicity and emerging drug resistance.
A new study led by researchers at Moffitt Cancer Center introduces an adaptive therapy approach that could optimize PARP inhibitor maintenance therapy, offering a more personalized and potentially less toxic treatment option for patients. Their work is featured as the cover article of the June 19 issue of Cell Systems.
PARP inhibitors are a targeted therapy that block a protein that helps repair damaged DNA. This can keep cancer cells from repairing themselves once they’ve been damaged by chemotherapy, resulting in cancer cell death. Despite their effectiveness, traditional dosing methods of administering the maximum tolerated dose often result in severe side effects and dose reductions, compromising treatment efficacy.
Moffitt researchers utilized mathematical modeling and in vitro experiments to compare adaptive dosing strategies. They developed a model to test various adaptive schedules and found that dose modulation based on tumor response was superior to skipping doses.
“Adaptive therapy tailors treatment to the tumor’s dynamics, allowing us to adjust drug levels to match a patient’s specific disease characteristics,” said Alexander Anderson, Ph.D., study author and chair of the Integrated Mathematical Oncology Department at Moffitt. “Our findings suggest that modulation, rather than skipping doses, can halve the amount of drug used while maintaining its effectiveness. This approach reduces toxicity and can potentially delay the development of resistance.”
The team conducted time-lapse microscopy to observe ovarian cancer cell populations under different treatment schedules. Their model revealed that continuous dose modulation effectively managed the tumor using significantly less medication than traditional methods. In vivo experiments confirmed these results, demonstrating the practical viability of the adaptive approach. While the results are promising, the research continues to validate and refine adaptive therapy strategies.
“A mathematical modeler by training, this project gave me the unique opportunity to conduct my own in vitro experiments to calibrate and test my models. Not only was this a fun and rewarding experience, but it demonstrated to me the power of closely integrating theory and experiments,” said Maximilian Strobl, Ph.D., lead author who conducted this work while pursuing a doctorate and postdoc at Moffitt. “I believe such an iterative and interdisciplinary approach will be crucial in developing more effective ways to schedule cancer treatment.”
Their work was supported by the National Cancer Institute (U01CA23282, U01CA261841, R01CA249016, R01CA272601) and the Moffitt Center of Excellence for Evolutionary Therapy.

Chemotherapy is known to cause behavioral side effects, including cognitive decline. Notably, the gut microbiome communicates with the brain to affect behavior, including cognition.
“For the first time ever, our Intelligut Study found that the gut microbiome has been implicated in cognitive side effects of chemotherapy in humans,” said senior author Leah Pyter, associate professor of psychiatry and neuroscience with The Ohio State University Wexner Medical Center and College of Medicine. “The potential connection between the gut and the brain would allow us to create treatments for the gut to treat the brain.”
Study findings are published in the journal Brain, Behavior, and Immunity.
This clinical longitudinal observational study explored whether chemotherapy-induced disruption of the gut microbiome relates to cognitive decline and circulating inflammatory signals.
Fecal samples, blood and cognitive measures were collected from 77 patients with breast cancer before, during and after chemotherapy.
Research highlights Chemotherapy induces microbiome disruption and inflammation. The resulting microbiome disruption relates to cognitive decline and inflammation. Those cognitively impaired have unique chemotherapy-induced microbiome alterations.”We found that patients treated with chemotherapy who showed decreases in cognitive performance also had reductions in the diversity of their gut microbiome,” said Pyter, also a researcher with Ohio State’s Institute for Behavioral Medicine Research and member of the Cancer Control Research Program at The Ohio State University Comprehensive Cancer Center — Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC — James).

This research builds on Pyter’s prior research in mouse models that found chemotherapy-induced shifts in the gut microbiome cause neurobiological changes and behavioral side effects.
The current study indicates that an association between gut microbiome and cognitive performance exists in humans as well.
“Side effects of chemotherapy are common and may reduce quality of life, but these side effects can be dismissed as ‘part of chemotherapy’ and therefore overlooked and under-treated,” Pyter said. “We believe that gut microbiome-focused interventions, such as fecal microbial transplantation, may improve behavioral side effects of chemotherapy.”
OSUCCC — James researchers are also conducting research studies on how the gut microbiome impacts cancer treatment effectiveness and its role in reducing or increasing cancer risk.
“Chemotherapy is a very important tool for stopping many cancers and side effects should not deter patients who would benefit from this type of therapy from pursuing it, but we know the side effects of some treatment regimens can be quite challenging for patients to complete,” said David Cohn, MD, interim chief executive officer of the OSUCCC — James. “It’s a careful tightrope of walking between effective cancer control and side effect management — and our team is working every day, in the hospital clinics and the lab, to develop ways to manage the side effects of disease treatment with an eye toward quality of life.”
Ohio State researchers collaborated with The Research Institute at Nationwide Children’s Hospital for this study.
This study was supported in part by a National Institutes of Health grant and Ohio State Wexner Medical Center.

The acceleration of space exploration, promoted by astronaut recruitment and private space travel, heralds an imminent future where space travel becomes increasingly common. However, numerous questions persist regarding the physical changes that humans undergo in space. Known effects of weightlessness include muscle atrophy, reduced bone density, and fluctuations in body fluid distribution.
However, recent research on mice and other organisms has uncovered a range of other changes. In this study, blood samples were collected from six astronauts during and after their 120-day mission on the ISS to characterize these changes. Extracellular DNA and RNA in the blood samples were analyzed in a process called “liquid biopsies.”
Previous studies have shown that mitochondria are released from cells into the bloodstream during space missions. This study confirmed that mitochondria are involved in responses to the space environment and can be isolated using CD36 as a marker. This technique allows the condition of extracellular mitochondria to be estimated and the cell type they originate from to be identified.
This process has successfully elucidated previously unknown systemic responses to the space environment, including brain, eyes, heart, vascular system, lungs, and skin changes. A similar analysis of mouse samples revealed that mice experience changes similar to those observed in humans and that mitochondrial changes are induced in response to gravity changes.

A study led by a Brigham investigator evaluated a novel device that automatically measures blood pressure at the wrist, generating hundreds of readings within days that may help clinicians determine cardiovascular risk and improve hypertension care
High blood pressure, the leading risk factor for death worldwide, is present in one in every two adults. Only one-quarter of individuals with hypertension have their blood pressure under control, highlighting the need for innovative strategies for blood pressure management. A study led by an investigator from Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, evaluated a cuffless monitor that uses optical sensors to record blood pressure continually and efficiently, without disruption to the patient. The study, published in Frontiers in Medicine, highlights promising advancements in hypertension diagnosis, risk assessment and management that may be enabled by use of cuffless devices.
“The successful management of hypertension depends on patients being able to take blood pressure measurements easily and reliably outside of the traditional doctor’s office setting,” said corresponding author Naomi Fisher, MD, of the Division of Endocrinology, Diabetes and Hypertension at Brigham and Women’s Hospital. “Cuffless devices have the potential to revolutionize hypertension management. They provide many more readings than traditional devices, during both the day and night, which can help confirm the diagnosis of hypertension and guide medication titration.”
Medical guidelines increasingly recommend the incorporation of at-home blood pressure monitoring into hypertension diagnosis and management. This is because isolated blood pressure readings taken at a clinician’s office may be inaccurate: for some, blood pressure tends to rise in medical settings (“white coat hypertension”) while others have normal blood pressure during examination despite hypertensive readings at home (“masked hypertension”).
Time-in-target-range (TTR) describes how often a patient’s blood pressure is in the normal range, and it is emerging as a promising metric of cardiovascular risk. But TTR requires more frequent blood pressure readings that can feasibly be obtained by patients with traditional blood pressure cuffs, which can be inconvenient, burdensome and sometimes uncomfortable for patients.
Fisher, who designed and led the study, collaborated with co-authors from Aktiia SA, a Swiss biotechnology company, to analyze over 2.2 million blood pressure readings from 5,189 subjects in Europe and the U.K. who wore a cuffless wrist monitor manufactured by Aktiia. On average, the Aktiia device collected 29 readings per day, a substantial increase from the number of blood pressure readings patients typically take with home devices (guidelines recommend four per day, which is more than most patients measure). Over a 15-day period, the researchers obtained an average of 434 readings from each patient.
By calculating TTR over a 15-day period, the researchers were able to risk stratify participants by percentage of readings in target range and compare these classifications to those generated via traditional measurement patterns, using either 24-hour or week-long daytime monitoring schedules. They found that the traditional methods misclassified 26 and 45 percent of subjects, respectively, compared to the reference TTR. They determined that continual monitoring for seven days is required to obtain 90 percent or greater accuracy in hypertension risk classification, a frequency of measurement that may only be possible with cuffless monitors.
Though the cuffless device studied here has not been approved by the U.S. Food and Drug Administration, it has been validated in multiple studies and is available for over-the-counter purchase in Europe and the U.K. Work to evaluate and set standards for such devices in the U.S. is ongoing.
“For the first time, by using a cuffless device, we can collect continual out-of-office blood pressure readings and use these data to calculate a new metric, time-in-target-range, which shows great promise as a predictor of risk,” Fisher said. “The use of cuffless devices could create a shift in the paradigm of blood pressure monitoring and hypertension management.”

Researchers from the LKS Faculty of Medicine of the University of Hong Kong (HKUMed) and the Harvard TH Chan School of Public Health have provided the first comprehensive evidence of the benefits of statin use in elderly patients, addressing longstanding uncertainties. The robust evidence demonstrated that continuous statin therapy resulted in a substantial relative risk reduction in cardiovascular diseases (CVDs) of 21% for those aged 75-84 and 35% for those aged 85 or above, without any heightened safety concerns.
The pioneering study marks a significant milestone, as it provides powerful real-world evidence on statin use in the elderly population using advanced analytical methods. The findings were published in the journal, Annals of Internal Medicine.
Background
CVD is a leading healthcare burden globally, particularly in aging populations. Effective management of high cholesterol is a crucial intervention in the prevention of CVDs. According to the latest ‘Population Health Survey’ in Hong Kong, 65.6% of individuals aged 65-84 have high cholesterol. While statins have been used for decades to improve lipid profiles and reduce the risk of CVDs, there is little consensus on the use of statins for primary prevention in patients aged 75 or above in the existing international clinical guidelines. The uncertainty of statin use for this population is due in part to the underrepresentation of the elderly population in randomised controlled trials (RCTs), leaving this important clinical question unresolved in real-world practice. This study used real-world data to quantify the long-term benefits and risks associated with statin therapy in primary prevention among older adults to inform decision-making on statin initiation in this large and growing population.
Research methods and findings
The research team, led by Professor Eric Wan Yuk-fai from the Department of Family Medicine and Primary Care under the School of Clinical Medicine, and the Department of Pharmacology and Pharmacy of HKUMed, analysed the public electronic medical records from the Hospital Authority from January 2008 to December 2018 of over 80,000 older individuals in Hong Kong who had suboptimal lipid levels and high-risk conditions, such as diabetes or other risk factors for CVDs. The study investigated the relationship between statin therapy and the risk of CVD incidence in this population with a novel analytical approach known as target trial emulation. The method incorporated the key features of RCTs in the study design for observational studies, substantially reducing the bias typically associated with traditional observational studies.
The findings indicate that the continual use of statins was linked to a 21% reduction in relative risk and an absolute risk reduction of 5% over five years in CVDs among people aged 75-84. The relative risk reduction was an even more substantial 35%, and the absolute risk reduction after five years was 12.5% in those aged 85 or above. The study also found no increased risk of major adverse events, including liver dysfunction or myopathies, identified with statin use in this population.

Significance of the study
The study confirmed the benefits and safety of statin use for primary prevention of CVDs in the older population, which suggests that advanced age should not be a discriminatory factor for high-risk patients regarding the benefits of statin therapy. Considering the increasing burden related to CVDs in the aging population globally, this study provides significant evidence to support the prescription of statin therapy for the primary prevention of CVDs in this vulnerable population.
‘These findings have significant implications for informing clinical decisions regarding the initiation of statin therapy for this increasingly large population group,’ said Professor Cindy Lam Lo-kuen, Danny D B Ho Professor in Family Medicine, Department of Family Medicine and Primary Care, School of Clinical Medicine, HKUMed. ‘This study also pioneered a new research method to explore many more important but unanswered clinical questions related to the care of the elderly in real-world practice.’
The successful application of target trial emulation to answer this research question also sheds light on future research in geriatric medicine. ‘The older population, especially very old adults, are generally underrepresented in the RCTs, leading to a lack of high-quality evidence on treatment for this specific population group,’ emphasised Professor Eric Wan Yuk-fai. ‘The innovative approach adopted in this study has the potential to generate high-quality evidence in the field of geriatric medicine, thereby advancing our understanding and improving healthcare outcomes for older populations.’