The research was led by Dima Mazen Qato of the USC Mann School of Pharmacy and Pharmaceutical Sciences and the USC Schaeffer Center for Health Policy & Economics, in collaboration with researchers from the Johns Hopkins Bloomberg School of Public Health and NORC at the University of Chicago.

Using nationally representative data from nearly 5,000 community-dwelling U.S. adults ages 62 to 85, researchers compared medication and supplement use in 2015–2016 with use in 2021–2023.

They found that polypharmacy, defined as taking five or more prescription medications at the same time, increased from 31% to 35.7%. Dietary supplement polypharmacy also increased, from 12.6% to 16.7%.

The concurrent use of drug regimens with potentially major interactions declined from 25.7% to 22.3%. However, the therapeutic classes most frequently involved in these regimens remained largely unchanged. In 2021-23, more than 1 in 5 older adults were taking medications that placed them at risk for a potentially major drug interaction.

Antidepressants, statins and antiplatelet therapies were the most commonly used medications involved in potentially major interactions among older adults.

“These findings underscore the need for continuing efforts to improve medication safety among older adults,” Qato said. “Efforts to reduce polypharmacy and harmful drug interactions should focus on commonly used interacting regimens, particularly those involving antidepressants.”

The study’s co-authors are Shyam Krishnan Ondanat Veetil and Qingrong “Jessica” Li of USC Mann; Jocelyn Wilder of NORC at the University of Chicago; and Rupshikha Sen and G. Caleb Alexander of the Johns Hopkins Bloomberg School of Public Health.

The study used data from the National Social Life, Health and Aging Project, which is supported by the National Institute on Aging (R01AG043538).

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Overall, 443 participants aged ≥65 years who use ≥5 drugs regularly were included. At the end of the trial, fewer patients in the medication review group had potentially inappropriate prescriptions compared with patients in the usual care group (29.9% versus 70.8%). Likewise, there was less medication overuse (34.2% versus 64.1%) and medication underuse (44.9% versus 73.2%). Furthermore, 337 missing vaccinations (against influenza, pneumonia, COVID-19, and/or shingles) were recommended in the medication review group.

“The pharmacist-led comprehensive medication review to counsel physicians in oncological rehabilitation wards was highly feasible and substantially improved the medication quality of older cancer patients with polypharmacy,” said corresponding author Ben Schöttker, PhD, of the German Cancer Research Center.

URL upon publication: https://onlinelibrary.wiley.com/doi/10.1111/joim.70161

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What is the focus of your current research, and why is it important?

This study investigates memorable health messages that young adults receive on social media. This is important because our study suggests that memorable health messages are now being recalled from influencers and strangers online, rather than trusting doctors, friends, or family members.

What inspired this line of inquiry?

The Theory of Memorable Messages traditionally says that we recall lifelong messages from trusted individuals in our networks. However our study finds that young people’s most memorable health messages are coming from strangers and influencers on social media. Most didn’t even follow the influencer, so they came across them only once. Some recalled these messages for 6+ years. Memorable messages can last a lifetime.

What are some key findings or developments so far?

Memorable health messages were both problematic and empowering. Some promoted universal health prescriptions like using mouth tape to change the shape of your jaw, drinking 2 cups of spearmint tea per day to help with PCOS, or avoiding seed oils. Others promoted autonomy in health such as viewing health as holistic and seeing mental health as a part of overall well being.

How could this work potentially impact the field or the wider public?

It changes everything we know about how memorable messages work. The fact that someone’s most memorable health message comes from a stranger/influencer who likely has a financial stake in people following their health recommendations and buying their products is alarming.

What are the next steps or upcoming milestones in your research?

Digital health literacy interventions, including platforms on social media dedicated to teaching digital health literacy are crucial. Interventions and training should take the form of short form content and be posted on TikTok and Instagram. As a content creator myself, I actively share my research findings in this space with a following of over 34,000 followers. We need more scientists online.

To speak with Pfender more about the study and its findings, reach out to mediarelations@udel.edu.

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For the review, 7 meta-analyses were included, encompassing more than 3 million participants. Unrestricted assessments showed small positive associations between prenatal paracetamol exposure and both autism and ADHD, but after restricting assessments to higher-quality meta-analyses and studies, effect estimates were substantially attenuated and approached null. No robust epidemiological evidence supported a causal association.

“A widely debated question deserves more than headlines—it deserves robust evidence. Our findings show that the apparent association between prenatal paracetamol exposure and autism or ADHD weakens as methodological quality improves, challenging the interpretation of a causal link and supporting evidence-based decisions during pregnancy,” said first author Hoda Tayebi Hillali, DDS, MSc, of the University of Santiago de Compostela, in Spain.

URL upon publication: https://onlinelibrary.wiley.com/doi/10.1111/dmcn.70512

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A new study in Management Science finds that a human-plus-algorithm approach could help the FDA focus its limited review resources on medical devices whose safety is harder to assess, while potentially reducing future recalls. The study found that FDA could catch more unsafe devices and spend less time on the ones that don’t need scrutiny, with a 40.5% reduction in review workload, 32.9% improvement in the recall rate–FDA’s current recall rate is 10.3%–and up to an estimated $1.7 billion in annual healthcare savings from fewer device replacements.

Researchers from Indiana University, Harvard Kennedy School, and Emerging Health Consulting built a tool that flags which submissions are safe bets, which are risky enough to reject after a short scrutiny, and which need more careful human expert consideration. The machine-learning system estimating recall risk, and coupled with a data-driven policy, recommends which medical devices could be cleared or rejected algorithmically with minimal human oversight and which cases should be flagged for in-depth human review.

“AI is most useful in this setting when it works alongside human judgment, not when it tries to replace it,” said Soroush Saghafian, co-author. “An algorithm can systematically identify patterns in thousands of devices and their predicate histories, but there will always be cases where the evidence is ambiguous, or the stakes are too high for an automated decision. By reserving those cases for expert review, the FDA can use its human expertise where it matters most while making the overall process more efficient.”

The system works with predicate devices, or devices that may look similar enough, or “substantially equivalent,” to an existing approved device on the market that regulators could be reasonably confident is safe and effective. Researchers sought to make the comparison system more informative by looking systematically at the history of predicate devices, particularly how old the predicate devices were and their recall status, to estimate the likelihood that the new device would eventually be recalled.

For the devices, an optimization model set thresholds in an algorithm for three categories: devices that could be cleared, devices that may carry a high enough risk to be rejected and devices in between that should be reviewed by human experts, balancing the goal of identifying potentially unsafe devices with the FDA’s limited review capacity.

“Right now, the FDA has to devote substantial resources to reviewing medical devices even when the available evidence suggests they pose relatively little risk,” said Mohammad Zhalechian, lead author. “Our results suggest that a data-driven approach could help distinguish the straightforward cases from the ones that deserve a closer look. The goal isn’t to replace FDA reviewers—it’s to give them better information about where their time and expertise can have the greatest impact.”

The study and its findings coincide with an existing regulatory conversation. In 2023, the FDA put out a draft guidance about predicate selection best practices, proposing to evaluate predicate devices based on safety track record rather than just availability. The study’s model speaks directly to that proposal by tracking predicate recall history and age, a safety track record that the FDA’s own guidance pushes for. If tools like this can inform the direction the FDA takes, the result could be more safety, more efficient use of resources, and more money saved.

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• The majority of respondents (61.5%) reported a lack of awareness of best practices for providing non-English medication instructions to patients or pharmacies.
• Most (80.5%) did not know whether the pharmacy provided translated labels.
• Only 5.9% used the prescription’s free-text field to flag the need.
• More than one-fourth of prescribers (27.8%) were unsure whether the pharmacy received their communications about instruction translation.
• Few respondents (8.3%) informed patients that they could request non-English medication instructions from their pharmacy.
• Many prescribers (69.8%) doubted their patients got accurate written instructions.
• The obstacles named most often were time constraints (69.2%), lack of translation resources (62.7%), reaching interpreters between visits (51.5%) and inability to use a non-Latin alphabet (40.8%).

Why It Matters: These findings highlight the critical need to coordinate language services between institutions and among patients, prescribers, and pharmacy team members.

Prescriber Practices and Barriers to Providing Prescription Medication Instructions for Patients With a Non-English Language Preference

Corresponding Author: Beatriz Manzor, PharmD, BCPS, et al

University of Michigan College of Pharmacy, University of Michigan, Ann Arbor, Michigan

Permanent link

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Through multiple recurrences of cancer and, decades later, a diagnosis of a rare blood disorder, she became an expert in helping clinicians communicate effectively during time-limited visits – and in helping patients hear what doctors say in helpful, hopeful ways.

In her new book Clinical Communication, Dr. Harpham from Dallas, shares personal stories to illustrate a patient perspective on clinicians’ words that help and those that unwittingly cause distress.

“Just like a medicine, clinicians’ words can help or harm,” she explains.

The burden of being a ‘good patient’

According to Dr. Harpham, a first visit for a medical concern is not the first step for those patients. Many wrestled with fear, self-doubt and decisional paralysis before making the appointment.

At doctor visits, a simple greeting can become complicated. For example, Dr. Harpham didn’t know how to answer when a nurse greeted her with “How are you?” at an appointment. She was unsure whether to report her physical symptoms, such as the exhaustion with any exertion, or the anxiety and sadness she has been dealing with. Or should she project confidence, to be taken seriously and be a model patient?

“I stammered, frozen with uncertainty,” she recalls. “Different sides of me competed to answer, leaving me tongue-tied.”

Dr. Harpham says this kind of exchange captures the psychological tightrope patients walk – balancing honest reporting with their needs to maintain hope, appear competent, and not be seen as difficult.

Her advice to doctors is to be specific, asking “How have you been feeling since we last spoke?” or “What brings you in today?”, to remove ambiguity. Dr. Harpham reminds patients that “doctor visits are not social visits.”

Speaking to apprehensive patients

Dr. Harpham sympathises with challenges of today’s healthcare due to advances in medicine: doctors have more to discuss and less time to discuss it. She argues that brief expressions of compassion can improve the care they provide and help patients respond in helpful, hopeful ways.

“Words have the power to comfort and inspire patients living on the front lines where the pain is felt and the pills are swallowed,” Dr. Harpham explains. “No matter how medicine changes, nothing can diminish the healing potential of well-chosen words.”

When patients report new symptoms after delaying out of fear, she suggests doctors build connection with compassion: “Coming in is difficult. I understand trying to give it time to go away. I’m glad you are here today. Now let’s see what we can do.”

For false alarms, she suggests: “You did the right thing. Better a false alarm than a missed opportunity.”

Dr. Harpham also delves into the fraught area of discussing conditions with a poor prognosis. Insights and tips for clinicians help patients too, she suggests, by guiding them to healthy ways to process the truth and manage uncertainty.

When breaking bad news, she appreciated doctors who prepared her first: “I wish I had better news for you today,” or “This is going to be difficult for me to say and, I expect, difficult for you to hear.” She says such warnings, delivered calmly, communicate both sorrow and competence, which patients need when their world is changing.

One of Dr. Harpham’s most surprising insights as a patient involves waiting for test results. Rather than hoping for good news, she encourages patients – and doctors – to hope for ‘accurate news’.

‘Good news’ sets up a binary: results are either good or bad. Accurate news, however, provides the information needed to make wise decisions and respond in helpful ways. It honours the complexity of medical reality, where partial responses and stable disease all carry meaning. And it helps patients manage the uncertainty while waiting for results.

“More than I hope for good news, I hope for accurate news – however long I have to wait,” she says.

Advice for doctors

For a wide variety of common scenarios, she models phrases and approaches that show compassion and foster trust needed for effective communication:

• Encourage patients’ candid descriptions: “Reporting symptoms is not complaining but, rather, providing information that helps your care.” This reassures patients that they are not being judged.
• Reassure after false alarms: “You did the right thing. Better a false alarm than a missed opportunity.” This encourages patients to seek care promptly in the future.
• Prepare patients for the toll of adhering to instructions: “All these tests and treatments demand a lot of your time and effort. When you keep us informed of any difficulties following through, we may be able to make changes without compromising your chance of the best outcome.” This acknowledges the stress and grief that accompany therapies and helps clinicians personalise prescriptions.
• Encourage a healthy approach to necessary aids: “Choosing to use a cane is choosing to make life the best it can be.” This reframes aids as a tool of empowerment.

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This guideline is an update to the 2015 Help Eliminate Pain in Kids & Adults (HELPinKids&Adults) Collaborative recommendations. The authors hope this guideline, aimed at clinicians who administer vaccines, organizations that offer vaccination services, as well as people who receive vaccines and their support persons, will provide updated evidence-based guidance to help ease distress that may come with vaccination.

The authors suggest evidence-based interventions across the 5P framework: process, procedural, physical, pharmacologic, and psychological, emphasizing that people who are being vaccinated and their caregivers should choose the option that works best for them.

Key recommendations:

• Process: Education of all groups from administrators to vaccine recipients about distress-reducing interventions, and use of these
• Procedural: Adoption of methods, such as rapid injections, that minimize distress and promote more positive vaccination experiences
• Physical: For infants 12 months and younger, oral solutions such as breastfeeding, bottle-feeding, sweet-tasting liquids, or pacifiers
• Pharmacological: Topical anesthetics at injection sites for all ages
• Psychological: Distraction techniques, such as toys and singing for infants, and music and digital distractions or toys and games for older children and adults

“Building on earlier work, the guideline provides new research-based tools and practical strategies to help health system leaders, health care providers, people receiving vaccines, and those supporting them improve the vaccination experience. The goal is to make vaccination a more positive experience, reduce fear, and help people feel more comfortable getting vaccines in the future,” says Dr. Taddio.

To help reduce vaccination distress, the guideline recommends choosing coping strategies before and/or during vaccination, framed around the CARD system (Comfort–Ask–Relax–Distract), an evidence-based tool developed by several of the authors.

With this updated guidance, the authors hope to lessen the stigma around needles and encourage vaccination.

“Since the COVID-19 pandemic, confidence in vaccines has declined, and vaccination rates have been low among both adults and children,” Dr. Taddio says. “This makes the updated guidance especially timely for vaccine providers and organizations looking to follow best practices to make vaccination a more positive experience for everyone.”

“Reducing distress during vaccine injections: 2026 clinical practice guideline update” is published September 21, 2026.

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Emergency contraception is used to prevent pregnancy after unprotected sex. It can be used when no contraception was used or if a contraceptive method fails, as with a broken condom, or in the event of sexual assault.

Common methods of emergency contraception include copper intrauterine devices and pills. The most widely used pill is levonorgestrel, a progestin-only medication sold in many countries as “Plan B,” “Next Choice,” or similar brand names. An alternative is the Yuzpe regimen, an older method that combines estrogen and progestin.

More effective, fewer side effects

The review, led by researchers from Oregon Health & Science University, USA, pooled data from 87 randomized controlled trials involving approximately 36,000 women of reproductive age. The majority of studies (79 trials) were conducted in China, with additional trials from the UK, Cuba, and multi-country settings. The authors compared mifepristone against levonorgestrel, the Yuzpe regimen, and copper intrauterine devices.

Compared with levonorgestrel, both low-dose (under 25 mg) and mid-dose mifepristone (25-50 mg) prevented more pregnancies and were associated with fewer overall side effects. Low-dose mifepristone showed a 27% relative reduction in pregnancies compared with levonorgestrel. This was rated as high-certainty evidence, meaning that further research is very unlikely to change the result.

When compared with the Yuzpe regimen, mifepristone showed an even larger advantage, cutting pregnancy risk substantially while also sharply reducing rates of nausea and vomiting. Evidence comparing mifepristone with copper intrauterine devices remained too limited to draw firm conclusions, based on only two included trials.

“Mifepristone in low-to-mid doses is a highly effective emergency contraceptive option that clinicians should know about,” explains Dr Shaalini Ramanadhan, lead author of the review. “As an anti-progestin, it works differently than the other steroid hormone-based methods like levonorgestrel and combined estrogen and progestin pills to delay or block ovulation. This different mechanism is part of why it has a different side-effect profile compared to the other two methods.”

The main trade-off identified across nearly all comparisons was a lower risk of nausea and vomiting with mifepristone, but a higher likelihood of delayed menstruation compared with other types of emergency contraception. Given that a delay in menstruation could be interpreted as a sign of treatment failure or pregnancy, the authors explain that this side effect could be a potential source of stress and anxiety for individuals seeking emergency contraception.

Where reported, however, treatment satisfaction was equal to or higher among those who received mifepristone versus alternative methods.

Political and legal barriers limit access

Despite the strong evidence behind the drug’s effectiveness as emergency contraception, the authors note there are still many barriers to access.

In some countries, drug authorities have approved mifepristone at higher doses (typically 200 mg) in combination with misoprostol specifically for medical termination of early pregnancy, not as emergency contraception. Scientific evidence is growing around the potential use of mifepristone and other anti-progestins as a routine method of contraception, for treating fibroids, for preventing and treating breast cancer, and for treating abnormal bleeding. However, because mifepristone is widely associated with abortion, it also faces intense political scrutiny, legal restrictions, and targeted bans and barriers in various countries.

“Expanding options for emergency contraception is important,” says Dr Ramanadhan. “The evidence shows that mifepristone has benefits beyond abortion care, including as an effective form of emergency contraception. In some countries, recognition of this additional use may help expand access, increase familiarity with the medication, and create new opportunities for people to benefit from it.”

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In a paper published in The Lancet, the team found that the injections were more effective at keeping the virus suppressed than the tablets and called for efforts to make this treatment more accessible worldwide.

Although HIV is incurable, antiretrovirals can help people live long, healthy lives and greatly reduce the risk of the virus being transmitted to other people. About 1.6 million adolescents (aged 10 to 19 years of age) live with HIV.

Professor Sarah Pett (UCL Innovative Clinical Trials Unit), Chief Investigator of the LATA trial, said: “HIV-positive adolescents as a group have historically done worse on antiretrovirals compared to adults. There is bullying and stigma associated with taking pills every day. Long-acting injectables taken every two months can help young people to lead a more normal life.

“The benefits of this form of treatment for adolescents is stronger than we have seen for adults. Previous trials in adults have shown only that injectables are no less effective than tablets.

“Our results support making injectables more widely available to groups such as adolescents who may not do so well on daily tablets. Nine out of 10 adolescents with HIV live in Africa yet currently this treatment is not accessible to them.”

The LATA (Long-Acting Treatment in Adolescents) trial was conducted in five clinics in Kenya, South Africa, Uganda and Zimbabwe. It involved 476 adolescents aged 12 to 19 who were randomly assigned either a daily tablet, which is standard care, or a long-acting injectable (cabotegravir and rilpivirine), a relatively new way to treat HIV.

Those participating in the trial had been on tablet treatment for more than a year, had HIV that was fully suppressed (undetectable), and had not previously experienced treatment failure.  Almost all the participants in LATA had had HIV since birth.

The research team found that, after just under two years (96 weeks), only two adolescents (1%) on injectables experienced confirmed viral rebound (two viral load measurements, measured at least seven days apart), where the amount of virus in the blood increases, compared to 15 (6%) in the daily tablets group. Increases in viral load can harm people’s long-term health, increasing the number of dormant cells infected with HIV, and in some cases can lead to the infection being passed on to partners or offspring.

Nearly all (94%) adolescents in the long-acting injectables group said the eight-weekly injections were a lot easier than taking medicines daily.

A few challenges need careful consideration regarding the use of long-acting injectables in lower resource settings. The injectables are more expensive than standard daily tablets because the drugs are still on patent, and are more costly to make. In addition, rilpivirine needs to be kept refrigerated during its supply and storage. Skilled nursing staff are also required to administer the injections every eight weeks, whereas appointments for people taking tablets may be as infrequent as every three or six months. There is no agreement yet about a generic version of the injectable treatment.

Presently, adolescents aged 12 years and older as well as adults can be prescribed the injectables in the US, Europe and other high-income settings but in Africa, bar a few clinics, the treatment is not yet available.

The World Health Organization currently recommends the injectables as an “alternative” option for adults and adolescents on daily tablets who are successfully suppressing their virus and do not have active hepatitis B. This stance may be strengthened as a result of the LATA trial findings.

Corresponding author Dr Deborah Ford (UCL Innovative Clinical Trials Unit) said: “The lack of availability of injectable treatments in Africa risks increasing inequalities in HIV care, leaving most people living with HIV without access to treatments that are available in high-income settings.

“This gap may widen further with second- and third-generation injectables being trialled that may require doses just twice a year.”

Dr Mutsa Bwakura-Dangarembizi, trial physician and Principal Investigator of the site in Harare, Zimbabwe, said: “The LATA trial finding that the eight-weekly injections were much better for keeping the virus undetectable, were well tolerated and strongly preferred by adolescents, is really exciting news. But we have a major problem right now in Africa and in other low-and-middle income settings, where these long-acting injectables are simply not available for use. This problem needs to be addressed to enable us to use these injectables in the groups that need them the most, i.e. adolescents living with HIV.”

The trial received funding from the European Union through EDCTP-2 (the second European and Developing Countries Clinical Trials Partnership) and Johnson & Johnson Innovative Medicines. Johnson & Johnson Innovative Medicines provided the injectable rilpivirine and ViiV Healthcare provided injectable cabotegravir. The sponsor was UCL.

The LATA trial scientific collaboration included researchers from all four participating countries and participants were enrolled and followed from five trial sites: Baylor College of Medicine Children’s Foundation, Uganda; Joint Clinical Research Centre (JCRC), Uganda; University of Zimbabwe Clinical Research Centre (UZCRC), Zimbabwe; Moi University Clinical Research Centre, Kenya; and Durban International Clinical Research Site – Enhancing Care Foundation, South Africa.

The study also involved social science, pharmacology and health economic researchers at the London School of Hygiene and Tropical Medicine, Radboud University Medical Center, and the University of York respectively.

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This means more emergency department visits, more frequent and longer hospitalizations, poorer mental health and greater risk of premature death.

However, there is a sliver of good news. The number of older adults who took medications that may impair cognition declined significantly between 2011 and 2022, according to a recent study conducted by researchers at the University at Buffalo.

They examined data from 2,796 older adults with cognitive disorders who were living independently. Their exposure to these inappropriate drugs dropped from 39.3% in 2011 to 29.3% in 2022.

“This is a population with some mental issues that relate to the central nervous system. These drugs also act on the central nervous system, so they can be too much for older adults if inappropriately used,” says Haowen Hsu, PharmD, postdoctoral fellow in the Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences. He is the first author of the study that was published Aug. 4 in the Journal of the American Geriatrics Society.

The importance of ‘deprescribing’ drugs

For instance, a patient who has been treated for anxiety for years with a benzodiazepine, such as Xanax, or a sleep aid, such as Ambien, may need to be weaned off or prescribed a smaller amount because these drugs can impair balance, coordination and cognition.

“A central word for patients in this age group is ‘deprescribing,’ which means, for example, removing inappropriate medications and decreasing the frequency or the dosage. In some cases, it means replacing the current medication with a milder alternative,” Hsu says. “This is why it’s so important for health care providers to work closely with community pharmacists and homecare nurses to optimize medication safety.”

The researchers started with the American Geriatric Society’s Beers Criteria, a list of some 100 medications that can be harmful to older adults. Then they narrowed the focus – looking specifically at adults who have been diagnosed with a cognitive disorder to figure out additional risks.

The study participants, whose data came from a Medical Expenditure Panel Survey, represent approximately 29.7 million older Americans with cognitive disorder across 2011-2022. Hsu and the team compared people who had been prescribed at least one of these potentially problematic medications with those who had not.

While the researchers didn’t investigate reasons behind the drop in exposure to the drugs, Hsu says that over the past two decades, both clinicians and researchers have paid more attention to medications for older adults. And this slow but consistent change likely reflects ongoing efforts in geriatric care and medication safety.

“We were happy to see the percentages of harm decline over that 11-year period,” he says. “However, one-third of our target population is still exposed to these harmful medications, which isn’t good.”

Connection to Team Alice initiative

Indeed, older adults in general are susceptible to drug interference or inappropriate prescriptions, sometimes resulting in higher mortality rates, as examined in UB’s larger interdisciplinary, ongoing initiative Team Alice.

The initiative was named after Alice Brennan, who died in 2009 after being prescribed a muscle relaxant medication that is recognized on the Beers Criteria as being inappropriate. The health care system failed to recognize the error, and she died after six weeks of avoidable complications. Alice’s daughter, Mary Brennan-Taylor, brought her mother’s story to UB researchers looking to drive systemic change to protect others from harm.

Hsu started this current study soon after he joined the pharmacy school and Team Alice to work in the UB Patient Safety Learning Laboratory.

“This work extends a series of national analyses our group has published on potentially inappropriate medications, quality of life, and health care use in older adults,” says David Jacobs, PharmD, PhD, associate professor of pharmacy practice who is a principal investigator on Team Alice.

“It is especially important as older adults with cognitive disorders are the least able to tolerate medications that worsen memory or thinking, yet nearly one in three are still receiving them. Most of these patients have a regular source of care so these medications can be identified and addressed with their care team.”

Along with Jacobs, Team Alice’s co-principal investigators Ranjit Singh, MD, associate professor and interim chair of the Department of Family Medicine in the Jacobs School of Medicine and Biomedical Sciences at UB, and Robert Wahler, PharmD, clinical associate professor of pharmacy practice, contributed to the study. Other contributors include Collin Clark, PharmD, clinical associate professor of pharmacy practice, and Steven Feuerstein, information systems analyst in the Jacobs School.

Along with highlighting the importance of careful medication reviews during outpatient visits, this study suggests integrating clinical assessment tools in acute care and ambulatory settings, such as the Drug Burden Index, to evaluate the cumulative burden of central nervous system-active medications and help reduce potentially preventable harm.

And finally, it recognizes the need for additional studies to determine whether strategies to optimize medication use can improve the quality of life and reduce hospitalizations and emergency room visits for older adults with cognitive issues.

Number of older adults now exceeds share of young children

Their findings come at an auspicious time. The U.S. Census Bureau just reported that for the first time in human history, people age 65 and older worldwide outnumber children from infancy to age 5.

Living longer, however, doesn’t necessarily mean additional healthy years. This same report notes that almost 75% of adults 65 and older live with two or more chronic health issues. And more conditions lead to more medications, some of which can be harmful to aging bodies and brains.

“This is an issue that has been building for decades, but the growth of the older adult population has arrived sooner than we expected,” Hsu says. “This means that health care professionals need to pay closer attention than ever to medication safety, especially for older adults experiencing cognitive decline or other complex health concerns.”

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The reactions experienced by some people after vaccination are, in most cases, mild and temporary. They result from activation of the immune system by the vaccine, enabling the body to learn to recognise antigens – characteristic molecules of the virus present in the vaccine – and thereby prepare to better fight off any future infection. This activation can cause local inflammation at the injection site (redness and swelling) or more peripheral symptoms such as fatigue or fever. However, the response varies considerably from person to person, ranging from no reaction at all to pronounced flu-like symptoms.

“Whilst we know that older people tend to experience fewer reactions to vaccination because of age-related declines in immune function, and that the vaccine dose can influence the severity of side effects, the biological mechanisms underlying these individual differences in symptoms have remained poorly understood,” explains Arnaud Didierlaurent, Associate Professor at the Center for Vaccinology (UNIGE/HUG) and in the Department of Pathology and Immunology at the Faculty of Medicine, UNIGE.

The role of our immune ‘‘capital’’

To investigate these differences, the researcher and his team monitored the immune systems of 51 healthy individuals recruited at HUG who received two doses of an mRNA vaccine against COVID-19. As side effects generally occur one to two days after vaccination, particularly after the second dose, participants were monitored for seven days following each injection.

“This study allowed us to identify an important role for an interferon-related antiviral defence system in explaining differences in side effects between individuals. This innate immune defence system helps us, in particular, to fight viral infections. The more active a person’s natural interferon response is, even before vaccination, the more pronounced their reactions to vaccination are likely to be,” explains Natacha Madelon, Senior Research and Teaching Assistant at the Center for Vaccinology and first author of the study.

Interferon is produced by cells when they are infected with a virus, alerting neighbouring cells and preparing them to defend themselves. But not everyone starts from the same ‘baseline’. “For reasons we do not yet fully understand – but which may be linked to genetic factors, a particular microbiome or a previous inflammatory episode – some individuals have a stronger  interferon-related immune signature before receiving the vaccine, which appears to influence how strongly they react to vaccination,” explains Arnaud Didierlaurent.

Differences emerge after the second dose

The research team identified a second potential mechanism in an animal model. Following the first vaccination, the body develops antibodies and T cells capable of recognising the vaccine antigen. When a subsequent dose is administered, this acquired immunity can rapidly amplify the activation of certain innate immune cells, notably monocytes, a type of white blood cell. These cells then react more strongly, attracting more inflammatory cells to the injection site.

These findings open up new avenues for vaccine research. In particular, they suggest that it may eventually be possible to better distinguish between the mechanisms needed to generate a robust immune response and those that primarily contribute to the symptoms experienced following vaccination. Prof. Didierlaurent’s team is now seeking to determine whether these same mechanisms occur with other types of vaccines.

In the long term, this research could contribute to the development of vaccines that are better tolerated while remaining just as effective. “In any case, a mild reaction, or even the absence of symptoms following vaccination, does not in any way mean that the vaccine is ineffective. The severity of side effects is therefore not, in itself, an indicator of how well a vaccine is working” concludes Arnaud Didierlaurent.

This research was supported by the HUG Private Foundation, the Giorgio Cavaglieri Foundation and Moderna.

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