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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Drawing from a large retrospective dataset collected between 2016 and 2025 and leveraging extensive support from the South Carolina Clinical & Translational Research (SCTR) Institute, including biostatistical and regulatory guidance, clinical research infrastructure, laboratory services and Nexus data resources, Wagner and Borsum identified a strong association between profound vitamin D deficiency and earlier gestational age at delivery. Wagner credited SCTR’s comprehensive support as instrumental to the study’s success.

Without SCTR, we as a team would never have been able to accomplish what we did. It’s a phenomenal infrastructure and an incredible gift to any researcher.”

While the team has not yet established a definitive causal relationship, the findings add to a growing body of evidence suggesting that optimizing a patient’s vitamin D status before and during pregnancy may improve both maternal and fetal health outcomes.

Why vitamin D might matter in pregnancy

Vitamin D is a vital nutrient that is known primarily for helping the body to absorb calcium and maintain normal bone, muscle, nerve and immune health. But as Wagner and fellow MUSC basic and translational scientist Bruce W. Hollis, Ph.D., discovered in earlier randomized controlled trials, vitamin D acts as a building block for hormones that play an important role in pregnancy.

“Vitamin D impacts literally thousands of genes in the body,” said Wagner. Research suggests that vitamin D helps the development of the placenta, the temporary organ that grows in a pregnant woman to nourish the fetus. It also appears to help support healthy immune function and may reduce the risk of serious complications like preeclampsia and gestational diabetes.

One crucial function vitamin D seems to serve is helping the mother’s immune system to adapt to pregnancy. Because a baby in utero contains genetic material from both parents, the mother’s body must learn to tolerate something that is partially foreign. Vitamin D may help to regulate that process, supporting a healthy pregnancy and fetal development.

Beyond pregnancy: Vitamin D’s broader health role

According to Wagner and Borsum, vitamin D may shape long-term health more than immediate outcomes. Some of the effects of deficiency may begin early in development, altering how genes function and potentially influencing the baby’s health for years, or even decades, to come.

Even outside of pregnancy, vitamin D deficiency is far more common than many people realize. Modern lifestyles often limit time spent outdoors, reducing the body’s ability to produce vitamin D from sunlight. At the same time, food sources provide only a small portion of the vitamin D most people need. As a result, many individuals do not reach healthy vitamin D levels.

Some groups are at higher risk for deficiency, including people with darker skin, those who work indoors, individuals who regularly use sunscreen and people with limited mobility or chronic health conditions that keep them inside.

The team stresses that sunscreen remains essential for protecting against skin cancer. However, people with limited sun exposure may benefit from discussing their vitamin D levels and potential supplementation with their health care provider.

“We have to balance the importance of sunshine and vitamin D with the risk of skin cancer,” said Borsum. “But this further emphasizes the vast role vitamin D plays.”

Emerging research suggests that vitamin D helps to regulate thousands of genes throughout the body, particularly those involved in immune function. Low levels have been associated with autoimmune diseases such as lupus and multiple sclerosis as well as certain cancers.

Challenges of turning research into practice and future directions

Despite growing evidence supporting the importance of vitamin D, Wagner said changing clinical practice can be difficult. Unlike prescription medications, vitamin D is inexpensive, widely available and cannot be patented, which means there is less commercial impetus to promote its use. “No one’s going to make billions off of this,” Wagner explained. “So, it then becomes a public health issue.”

As researchers continue to build evidence about the role of vitamin D in pregnancy and overall health, Wagner and Borsum see the next steps as educating health care providers, continuing to investigate vitamin D’s long-term effects and increasing public awareness.

“We learn about vitamin D’s role in bone health, but no one teaches us about the various roles in pregnancy, especially this relationship with preterm birth we are uncovering,” Borsum explained. “I always tell my friends and family who are thinking about becoming pregnant to make sure they are sufficient!”

As researchers continue to uncover vitamin D’s far-reaching effects, Wagner and Borsum hope the growing body of evidence will encourage more conversations about a nutrient that may shape health across generations.

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The study — published in the journal JAMIA Open, and co-authored with University of Toronto professor Enid Montague and Dr. Onil Bhattacharyya of Women’s College Hospital — involved nine physicians completing simulated patient encounters both with and without the use of AI scribes. These digital tools are capable of recording audio and using it to generate structured, regulatory-compliant clinical notes for a patient’s medical chart — the record physicians use to document their care.

The researchers used video recordings of each appointment to analyze how physicians spent their time. They found that when the scribes were in use, the doctors spent significantly less time documenting.

“We know healthcare workers are experiencing burnout, which is associated with compromised patient safety and increased potential for errors, and can contribute to physician turnover,” says Murray.

“We also know that administrative tasks contribute to said burnout, so we want to find ways to reduce that strain.”

The study is part of a multi-phase project between University of Toronto’s Wellness and Health Enhancement Engineering Lab and the Centre for Digital Health Evaluation, Women’s College Hospital Institute for Health System Solutions and Virtual Care. The team’s previous research compared the usability and performance of six AI scribe products; only the three performing tools were then used in this subsequent study.

Without the AI scribes, physicians spent more than one-third of each simulated patient encounter on note taking. In addition to saving time during the patient interaction, Murray hopes incorporating AI will lead to more timely documentation.

“Documentation often gets delayed because there’s just so much to do and the days are so busy; this can make it less accurate,” says Murray.

“I hope with this technology we see a reduction in things like charting being done after hours or days later. That would also create a reduction in cognitive labour with physicians having to remember what happened during appointments that occurred days prior.”

Researchers also observed an unexpected change in how some physicians kept track of their thoughts during appointments where AI scribes were used. The shift in workflow highlighted the role note taking can play in diagnosis.

“The most interesting finding for me was seeing how physically creating the charts throughout the appointment prompted thinking and more clinical decision-making questions from the doctors,” says Murray.

“When the scribes were in use, we saw the adoption of scratch pads for note taking to help physicians remember to ask follow-up questions.”

With the scribes, instead of spending appointments switching between the patient and typing on the computer, physicians documented differently. Rather than charting throughout, physicians shifted toward reviewing and editing the AI-generated documentation after it had been produced. This resulted in fewer interruptions during the simulated encounters.

One of the overarching goals of the project is to generate Ontario-specific research around AI technology in healthcare as Ontario physicians operate within different privacy regulations than their U.S. counterparts, which could affect how AI scribes are integrated into clinical practice.

“When the studies were first coming out, we were seeing them come from these large U.S.-based hospital systems,” says Murray.

“So for us, it was really about focusing on the Canadian context and, even more specifically, within Ontario. It’s not to say that we were the only ones in the space, but there was a gap in the literature looking at how AI impacts primary care delivery and what that means for Canadian healthcare.”

Murray, who has been studying AI scribes since 2023, has seen changes to the technology itself, with more customizable features and better integration into existing platforms but also in the conversations around the technology’s potential. As the technology has become more widely adopted, expectations have also begun to change.

“When the technology was new, the conversation was very much that this would solve all our problems,” says Murray.

“Now that’s shifted to, ‘hey maybe this is just one piece of the overall documentation burden that we’re seeing,’ because charts are not the only administrative burden facing physicians. We’re also thinking about things like referrals, prescription orders, billing and regulatory expectations that are contributing to administrative work.”

While the study relied on simulated patient encounters, more research will be needed to understand how AI scribes perform in everyday clinical practice.

For example, as the technology is more widely adopted, Murray wants to know how receptive patients will be to the use of AI scribes in the course of their care.

“Are they appreciative of the differences in communication? Are there hesitancies in terms of being recorded and who has access to these recordings,” says Murray.

“I wonder about the impact for different patient populations as well. What happens when physicians who are almost always using AI scribes suddenly have one patient that doesn’t consent to it being used in their care? This research has opened a lot more discussions and possibilities to consider.”

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The National Institutes of Health and American Heart Association-supported study, described July 27 in the journal Obesity, represents the latest findings from ongoing research led by Daisy Duan, M.D., an assistant professor of medicine and the study’s primary author, on how time-restricted eating without caloric restriction may change the body’s weight and other functions.

Other studies on time-restricted eating, Duan says, examined it with respect to either intentional or unintentional calorie restriction. The new study, she said, focused on whether restricted meal timing while ensuring consistent calorie intake would change other obesity-related factors, such as eating behavior, inflammation, and appetite hormones.

More than 100 million adults with obesity and 115 million adults with prediabetes in the United States are at an increased risk of cardiometabolic complications, such as high blood pressure, heart attack and stroke, and these numbers are expected to rise. Intermittent fasting — an umbrella term for structured patterns of fasting and eating that focus on changing when a person eats instead of reducing calories or avoiding certain foods — has broadly been linked to weight loss and may benefit individuals with either or both conditions.

Broadening clinical understanding of time-based dietary interventions, Duan’s team investigated whether health benefits linked to intermittent fasting and other time-based dietary plans are caused by weight loss alone or if other biological mechanisms are also involved.

In the 12-week study, a predominantly female (92%) and Black (92%) cohort of adults (ages 18–69 years) with obesity and prediabetes or diet-controlled type 2 diabetes were randomly assigned to a 10-hour time-restricted eating (TRE) schedule (19 adults) or a 16-hour usual eating pattern (UEP) schedule (20 adults).

All study participants received the same adapted Dietary Approaches to Stop Hypertension (DASH) diet — a heart-healthy diet that emphasizes limiting red meats, high-fat foods, sugar and salt intake — and the caloric intake of each person was personalized to maintain their starting weights.

All meals were prepared and provided by the Johns Hopkins ProHealth Clinical Research Unit in Baltimore, Maryland, under the supervision of research dieticians.

Before and after the study, participants provided fasting blood samples that were used to measure inflammation markers and appetite hormone levels and completed a Three-Factor Eating Questionnaire — a tool that captures how a person interacts with and thinks about food. The researchers used both to track and compare physical and psychological changes over time.

Notably, at the study’s conclusion, the researchers observed similar and modest weight loss in both the group that followed the time-restricted eating (median 2.7%) and the usual eating pattern (median 2.5%) meal schedules.

At the end of the study, participants from both groups reported greater restraint around food, a reduced tendency to eat when stressed, and a lower susceptibility to hunger overall after the study’s conclusion. However, the appetite hormones (ghrelin and leptin) and the inflammation markers (C reactive protein, cortisol and sRAGE) were comparable between TRE and UEP participants.

“We saw that people who followed a 10-hour time-restricted eating schedule lost weight and positively changed their eating habits without calorie restriction,” says Duan. “But we did not identify any unique, body-wide health benefits linked to the dietary strategy beyond that.”

Future directions for the research include exploring how time-restricted eating shapes weight loss maintenance in people who have successfully lost weight through other interventions, such as via GLP-1 receptor agonists.

In addition to Daisy Duan, researchers who authored the study are Susan Carnell, Scott J. Pilla, Stephanie T. Chung, Jeanne M. Clark and Nisa M. Maruthur.

The study authors have the following conflict-of-interest disclosures to share: Duan serves as a consultant for Rhythm Pharmaceuticals and receives honoraria from the American Diabetes Association. Carnell receives grant funding from Eli Lilly and Company. Clark participates on a Data Safety Monitoring Board for Eli Lilly and Company and serves on the advisory board of Novo Nordisk. Maruthur receives royalties from UpToDate. The other authors declare no conflicts of interest.

The study was supported by the National Institutes of Health (R03DK144349, R01DK126825, R01DK139324 and K23DK133690) and the American Heart Association (17SFRN33590069).

DOI: 10.1002/oby.70270

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Obesity is a complex, chronic disease influenced by biology, genetics, metabolism, the brain, and environmental factors—not simply a matter of willpower. The disease affects over 40% of American adults and costs over $173 billion annually in U.S. obesity-related medical care costs.

“This Statement highlights major advances in obesity science and outlines areas of research needed to improve our understanding of the disease, optimize treatment, personalize care and improve long-term health outcomes for people living with obesity,” said Daniel J. Drucker, M.D., of Mount Sinai Hospital in Toronto, Ontario, Canada, lead author of the Scientific Statement writing group. “The rapid adoption of highly effective obesity medications has changed the treatment landscape, but important questions remain about their long-term use, individualized treatment strategies, side effects and the best ways to measure treatment outcomes.”

The statement outlines what researchers know, what they still need to learn and where future research on obesity should focus.

Semaglutide, tirzepatide and other GLP-1 based therapies have transformed obesity treatment and helped us better understand the disease. They are now being used not only for treatment of overweight and obesity, but also for improving comorbidities including heart disease, sleep apnea, kidney and liver disease, and being investigated for other diseases such as cancer, substance use disorders, arthritis and infertility.

If left untreated, obesity can cause poor metabolic and mental health, and a reduced ability to perform the basic physical tasks and movements needed for everyday living.

However, there are safety considerations with GLP-1s including the medications’ direct effects, consequences of rapid weight loss, and areas where long-term risks and outcomes remain uncertain.    Research supports that obesity is a chronic disease that requires long-term treatment. People with obesity who stop treatment after reaching their goal weight often gain it back and experience worsening of other health issues such as blood pressure, cholesterol and blood sugar levels. Studies show that people can maintain much of their weight loss when transitioning to lower-dose therapies or different medications after initial treatment.

The Statement identifies these key questions and priorities for future research on obesity:

• How the body regulates and store fat
• Why obesity manifests differently in individuals and how this affects treatment
• Redefining treatment targets beyond weight loss
• How the body responds to anti-obesity medications over time
• Health outcomes with anti-obesity medications
• How safe new anti-obesity medications are for long-term use

“Advancing research across these six priority areas will help transform obesity care by deepening our understanding of disease biology, improving treatment precision, defining meaningful clinical outcomes and optimizing the safe and effective use of emerging therapies,” Drucker said. “We need larger, longer and more diverse studies, as well as greater use of real-world data to understand treatment outcomes.”

The Endocrine Society develops Scientific Statements to explore the scientific basis of hormone-related conditions and diseases, discuss how this knowledge can be applied in practice and identify areas that require additional research. Topics are selected on the basis of their emerging scientific impact. Scientific Statements are developed by a Task Force of experts appointed by the Endocrine Society, with internal review by the relevant Society committees and expert external reviewers prior to a comment period open to all members of the Society.

Other statement authors are Ania M. Jastreboff, Harlan M. Krumholz and Michelle Van Name of Yale University School of Medicine in New Haven, Conn.; Jamy D. Ard of Wake Forest University School of Medicine in Winston-Salem, N.C.; Kevin D. Hall of AstraZeneca Inc.; Lee M. Kaplan of Geisel School of Medicine at Dartmouth in Hanover, N.H.; and Donna H. Ryan of Louisiana State University in Baton Rouge, La.

The statement, “Obesity Science, Research Gaps, and Opportunities in the New Era of Obesity Medicines – an Endocrine Society Scientific Statement,” was published online in the Society’s journal, Endocrine Reviews.

The Scientific Statement is part of the Society’s Center on Obesity, a broader initiative to advance obesity research and care.

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Six of the 19 members of the Scientific Advisory Committee on Nutrition (SACN) have conflicts of interest that its own rules deem ‘significant’ and should preclude them from being appointed, reports freelance journalist Sophie Borland.

SACN is a powerful group of experts that provides nutritional advice to the government on issues including artificial sweeteners, ultra-processed foods, and dietary guidelines for babies, young children and the over 65s. Their reports are used to inform national policy as well as NHS healthy eating recommendations.

One SACN adviser was until recently a long-serving senior member of the British Nutrition Foundation – a charity funded by firms including Coca Cola, Nestlé, and Mondelez, parent company of Cadbury’s.

Four other advisors have received research funding from the meat, dairy and nut industries, including one who has also taken a grant from Danone, the world’s largest yoghurt maker.

Today’s figures come two years after an initial investigation by The BMJ revealed that more than half of SACN’s advisors at the time had ties to the food industry.

The BMJ’s findings were highlighted in a major House of Lords report into diet and obesity and, last September, SACN updated its code of practice to state that “individuals are only eligible to be SACN members if they do not hold significant interests in relation to the food, drink, diet or supplement industry.”

A spokesperson for the Department of Health and Social Care (DHSC) explained that current SACN advisors must not take on any new interests that are “at odds” with the updated policy, and can only be reappointed if they meet the updated policy.

“All SACN members are due to meet the new interests policy within the next two years,” they added. “In the meantime, existing members with any significant interests are excluded from relevant discussions.”

But experts argue that scientists with financial ties to the food industry should not be involved in influencing policy and have called for the conflicts to be removed “immediately”. Some said that at least some previous financial relationships should also rule out involvement even once lapsed.

The BMJ analysed SACN’s latest register of interests, published in June 2026, and found that six of the members declared “significant” conflicts of interest that the committee itself highlights with a note next to the declaration.

A further three were recorded by SACN as having “relevant” interests to the food industry, which are considered less serious. This includes receiving research funding from or undertaking consultancy work with smaller food firms.

The BMJ also identified other potentially serious conflicts of interests not flagged by SACN. This includes one advisor who is a “distinguished fellow” of the American Society for Nutrition, an organisation funded by organisations including Mondelez, Nestle and Pepsico. Five other members are on the UK’s Nutrition Society, which receives sponsorship from Pepsico for conferences.

Chris van Tulleken, a professor of infection and global health at University College London and author of the book Ultra-Processed People, says: “This is not an allegation that individual members are acting improperly or deliberately influencing SACN’s conclusions. However, research shows that conflicts of interest do affect beliefs and behaviour, as well as eroding trust in decision-making and advice.”

He adds: “The problem is structural. SACN’s authority depends on its independence, and these interests weaken public confidence and confer credibility on commercial actors that harm human health and scientific integrity.”

Rob Percival, head of policy at food and farming charity the Soil Association, welcomed the tightening of SACN’s policy but said it needs to be applied robustly. “I would suggest that the conflicted members of SACN need to leave the committee immediately and there needs to be open recruitment for non-conflicted members to stand in their place through an appropriate process.”

SACN’s updated rules allow members to stay on if they drop their significant conflict of interest, regardless of how long they had been working with the food industry beforehand or how much money they received.

But Percival argues that “once a scientist has received funding in relation to a product or is in a financial relationship with a manufacturer they should not be involved in policy making or regulatory decisions that pertain to that product.”

The BMJ’s findings come as SACN is working on recommendations on nutrition and maternal health, vitamin D requirements, and infant feeding. At its June meeting it considered whether to make new recommendations on topics including ultra-processed foods, artificial sweeteners, protein intake, and wholegrain foods, and agreed to keep these on its “watching brief.”

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To bridge this gap, the paper introduces a “digital behavioral infrastructure”—a theory-driven approach that leverages digital health apps as essential structural companions, helping patients build sustainable habits during the medication’s peak efficacy window. The paper maps how two well-validated theories of behavior change, social cognitive theory and behavioral economics, can be leveraged to drive medication persistence, side-effect mitigation, and durable weight loss.

Geoff Cook, CEO of Noom, a leading behavior change company, suggests an idea called the “habit window.” By dialing down constant food cravings, described by patients as “food noise,” GLP-1 drugs free up mental energy, opening a unique opportunity for patients to build healthier daily routines. He also proposes that GLP-1 therapy, when combined with behavioral support, may spark lifestyle change via the “Fresh Start” effect.

Digital companion programs use targeted strategies to address the three biggest hurdles of GLP-1 therapy. Personalized digital reminders can help patients stay consistent with their medication, while interactive symptom management features can help reduce gastrointestinal side effects so patients do not quit early. Finally, structured skill-building can help users establish sustainable eating and exercise routines before biological appetite cues return to baseline when treatment stops.

“Given the high rate of GLP-1 discontinuation,” said Cook, “the objective becomes building healthy behaviors while the habit window is pharmacologically open. While the habit window is a hypothesis, the features suggested in the paper are not theoretical. In fact, these features are part of the Noom app today, as this is exactly how we’ve built Noom’s GLP-1 Companion to take advantage of fast and slow thinking, system 1 and system 2. Most exciting of all is we will be supporting the research program outlined in Table 1 of the paper with RCTs to shed light on the problems, mechanisms, and interventions raised in the paper.”

While early observational data shows promising results, the paper stresses that prospective, randomized trials are needed to fully test the “habit window” framework. Ultimately, pairing biological appetite control with digital behavioral coaching could mark the difference between temporary weight loss and a lifetime of improved health.

Cook G. Digital Behavioral Infrastructure for Glucagon-Like Peptide-1 Pharmacotherapy: Viewpoint on Persistence, Tolerability, and Postcessation Durability

J Med Internet Res 2026;28:e104227

URL: https://www.jmir.org/2026/1/e104227

DOI: 10.2196/104227

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These efforts have shaped modern psychiatry by establishing common, criteria-based systems for diagnosing mental disorders across institutions and national borders.

However, a new study, led by researchers at the University of Copenhagen, suggests that major challenges remain. In the study, 1,038 psychiatrists and physicians working in psychiatry from 19 countries were presented with nine written patient case descriptions. Each participant was assigned two cases and asked to determine the most appropriate diagnosis.

The results surprised the researchers.

“Our study shows that when two psychiatrists diagnose the same patient, they will agree only 55% of the time. We consider that worryingly low. In fact, it is similar to the levels reported in some of the studies conducted in the 1970s, which prompted the development of standardised diagnostic criteria in the first place,” says Professor and Consultant Psychiatrist Julie Nordgaard.

“This is not about psychiatrists doing a poor job. Rather, it reflects the fact that, despite the existence of diagnostic systems, clinicians continue to differ in how they interpret symptoms and which features they consider most important. We need a greater degree of consensus, otherwise patients risk receiving changing diagnoses and treatments,” she adds.

Same symptoms, different diagnoses

The study found substantial variation in diagnostic agreement across different mental disorders. Diagnoses within the schizophrenia spectrum proved particularly challenging.

“Cases that could be diagnosed either as schizophrenia or schizotypal disorder generated especially high levels of disagreement. In many of these cases, agreement among participants was well below 50%,” says PhD candidate Mateo Boberg, the study’s first author.

According to Boberg, one reason is that symptoms frequently overlap across psychiatric disorders. For example, obsessive thoughts may occur in both obsessive-compulsive disorder (OCD) and schizophrenia.

“These are not random errors. There is a clear pattern to the disagreements. This likely reflects the fact that diagnostic categories are not as clearly defined as we have assumed, when experienced psychiatrists can interpret the same symptom presentations so differently.”

Diagnostic uncertainty undermines research

Disagreement about diagnoses is an obvious concern for patients. But the researchers argue that diagnostic uncertainty also threatens the reliability of some kinds of psychiatric research¸ explains Professor Mads Gram Henriksen:

“In research, it is essential that we know exactly what we are studying. If a considerable part of participants enrolled in a study on treatment of personality disorders actually suffer from schizophrenia, the study’s results become difficult to interpret. Which condition is the treatment having – or not having – an effect on? Personality disorders or schizophrenia?”

The researchers argue that progress in psychiatric research risks remaining limited until there is a clearer and more widely shared understanding of what mental disorders are and how they can be distinguished from one another. Greater diagnostic agreement, they say, is a prerequisite for the breakthroughs needed to improve patient care.

“WHO’s ICD-10 diagnostic system, which participants in the study used to assess the cases, contains more than 200 diagnoses, a complexity that may contribute to uncertainty. At the same time, many psychiatric conditions are inherently multifaceted,” says Julie Nordgaard and concludes:

“In our view, it is necessary to take a step back and develop more precise descriptions of psychiatric disorders so that clinicians can distinguish them more clearly. It may also be necessary to reduce the number of diagnostic categories.”

The study, Reliability of Psychiatric Diagnoses in the 21st Century, has been published in Frontiers in Psychiatry.

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