Why 'fibermaxxing' could help prevent disease, according to a top expert
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Medscape
2 minutes ago
- Medscape
Dato-DXd Shows Potential in Treating Lung Adenocarcinoma
This transcript has been edited for clarity. I'm Mark Kris, from Memorial Sloan Kettering, continuing a discussion about antibody-drug conjugates, or ADCs, and in this case, datopotamab deruxtecan, or Dato-DXd. This agent combines an anti-TROP2 antibody with a potent topoisomerase I inhibitor. It has had activity in a number of diseases, but the topic today is lung cancer. There has been a phase 3 randomized trial already. It's shown, compared to docetaxel, an improved rate of response by about 10% or so. It showed a small improvement in disease-free survival and about a 1-month improvement in overall survival over docetaxel. I think what this trial shows is that it clearly is an active agent, and I think it's useful to us for patients with adenocarcinoma, giving us an additional line of therapy. It would be a real judgment call when a patient needs a new line of therapy whether to give docetaxel or the Dato-DXd first. The drug is not yet approved for lung cancer but is obviously in the approval process now. The other thing noted in that phase 3 trial was that there was very limited activity. In fact, [there was] less activity than docetaxel in patients with squamous cell cancers. Clearly, that activity is largely limited to the adenocarcinoma patients, and I think that's where, if approved, it will finally be useful. The companion paper in the Journal of Clinical Oncology reports on the use of Dato-DXd in patients whose tumors have oncogenic drivers. They found a higher-than-expected response rate. It was in the twenties in an unselected population, but in the patients with EGFR mutations it was 36%, and in patients with ALK rearrangements in their tumors, it was 44%. I think this may be the place where it will be most useful. In 2025, we still don't have a therapy beyond standard chemotherapy after progression on osimertinib, and this may be a useful drug in that place. Again, it's useful in adenocarcinoma. To summarize, Dato-DXd is a drug in the regulatory approval process that clearly has activity in an unselected population of patients with adenocarcinoma. It's roughly comparable and slightly better than docetaxel. However, it's less effective than docetaxel in a squamous population. In addition, at least in other trials, it has shown some activity and perhaps even more activity in patients with drivers like EGFR or ALK .It may have some usefulness there. I think we're fortunate to have more new agents. We're fortunate to be able to make more choices to match drugs and side effects to specific patient characteristics and specific patient preferences. Once again, our job is better but it's hard. Clearly, the harder we work, the better we're going to make the course of illness for our patients.
Medscape
2 minutes ago
- Medscape
Patient Deaths, Inner Scars, and Physicians' Need to Grieve
In 2023, Molly Taylor, MD, MS, a pediatric oncologist and attending physician at Seattle Children's, sat in her parked car with tears streaming down her face. She was preparing to attend the memorial service for an 8-year-old patient she had lost a week prior. The patient's mother had asked Taylor if she could share a few words about the little girl. Taylor recalls this experience in 'We Grieve Too,' an essay originally published on the JAMA Network : As I stood up on stage in my technicolor dress, staring back into the tear-soaked faces of her classmates, teachers, neighbors, cousins, grandparents, soccer teammates, youth group friends, aunts, uncles, her younger brother, her dad, her mom — the village that surrounded this little girl during her short life — I had just one thought: I couldn't save her. Molly Taylor MD Taylor is not alone in experiencing grief tinged with guilt after losing a patient. Althoughthe prevalence of provider grief hasn't been widely examined, a JPSM review published in 2023 indicated that it's a significant issue in many areas of medicine. The review mentions 12 studies with 1137 healthcare providers showing that they commonly had moderate and sometimes long-term grief reactions after a patient's death. While it may feel as if doctors are expected to be detached from these feelings, they are, at the end of the day, simply human. Bearing the Burden of Outcomes Leeat Granek, PhD Leeat Granek, PhD, is a critical health psychologist and associate professor at York University School of Health Policy and Management in Toronto who publishes extensively on grief and loss. In her decades of research, Granek has learned that the grief physicians experience has a lot to do with their sense of responsibility toward their patients. Consequently, grief over a patient's death is colored with a sense of failure or guilt, even when they understand they weren't responsible for the outcome. 'And that's a really hard emotion to sit with,' Granek acknowledges. She notes that many physicians define error — and, subsequently, failure — as being dependent on outcomes. 'But that's not really the definition of an error,' she explains. '[Physicians] might make the exact same decision in the next case, and it would be lifesaving. So, there's this construction of a story around a negative outcome that goes back to the individual physician and how they experience grief.' When grief feels like failure, there can be reluctance to accept it. 'A lot of times in medicine, we think of it like a battle we're trying to fight against whatever disease process is happening that is endangering this life,' says Priya Roy, MD, a third-year fellow in cardiovascular medicine at The Ohio State University. 'We have a hard time saying, 'This person is dying — from a physiological standpoint — and maybe there isn't something we can do about it,' and I think that's what makes people really uncomfortable.' Granek points out that when her mother died of cancer at a young age, she experienced feelings of sadness, body aches, difficulty sleeping, etc. 'But I didn't feel a sense of failure or guilt because there was no perceived causality between her dying and something I've done,' she says. Long-term Connections Granek says that the depth of grief is also related to attachment with the deceased person. The result is that some medical specialties may experience more intense grief than others, for example, in oncology where patient care is often long term. The JPSM review noted that, in multiple studies, certain hospital specialties were particularly impacted by provider grief, such as adult and pediatric oncology, palliative care, pediatrics, perinatal care, emergency medicine, critical care, and surgery. A survey of 1000 members of the American College of Obstetricians and Gynecologists indicated that 53.7% of physicians caring for women who had a stillbirth reported high levels of grief; other symptoms reported included self-doubt (17.2%), depression (16.9%) and self-blame (16.4%). For Roy, that comes with the territory of working in the Coronary Care Unit (CCU). 'It might be easier in some capacity not to form bonds with your patients and hold everybody at arm's length,' she says. 'But I want to get to know my patients. I want to learn what's going on in their lives. I want them to tell me the things that scare them and the things that bring them joy so I can actually help them make decisions that will be beneficial to them.' Roy's personal experience of losing her father to cancer has informed her patient relationships, leading her to 'get closer to patients who were either nearing the end of their life or who have been dealt a devastating diagnosis,' she says, 'because I know what it feels like to feel alone in that.' Granek's personal experience with loss also shaped her career as a psychologist, specializing in grief and loss among healthcare professionals. Her mother lived with cancer for nearly 20 years before passing away in 2005 at age 33. During that time, the family formed strong bonds with the healthcare team. 'And then those relationships get severed,' Granek says. 'It's a weird experience, because you've had this intense, close, important relationship with this team and then you don't see them ever again.' The 'Good' Death There's also the nature of the death to consider. Was it a 'good death' as defined by The Institute of Medicine: 'one that is free from avoidable suffering for patients, families and caregivers in general accordance with the patients' and families' wishes.' Or a 'bad death' where the patient experienced unrelieved physical and emotional suffering — terms that feel loaded with responsibility and judgement, even if indirectly. Or was the death unexpected? 'Our colleagues in ICU or emergency room have very intense, brief interactions with patients at the end of their life, and it's a different sort of flavor, and that also complicates the grief,' acknowledges Taylor. Additionally, the frequency of patient loss can take a toll. Roy recalls the time her team lost five patients in 48 hours in the CCU. 'Some people can become sort of numb to the experience of losing patients,' says Roy. 'We're forced by the nature of the work that we do to compartmentalize to a certain extent. Maybe in the short term that's helpful to care for your other patients that day, but in the long term, it's not healthy. It eventually catches up with you.' Grief Unchecked and Untrained While everyone experiences grief, pathological bereavement outcomes (ie, complicated grief, traumatic grief, prolonged grief disorder) can develop if it is ignored. After losing her father, Roy recalls how her mother, a pulmonary critical care doctor, used work to distract herself from the devastation of her husband's passing. Christine Yu Moutier, MD 'The longer grief sits unattended and unprocessed, the more likely it's going to manifest in any number of other sequelae, like burnout, or sleep disruption or anger problems or substance abuse or even down the pathway to PTSD or suicide risk,' says Christine Yu Moutier, MD, psychiatrist and chief medical officer at the American Foundation for Suicide Prevention. In fact, a 2025 study reveals that physicians were three times more likely to have a job-related trauma or loss as part of the lead up to suicide as compared to the general population. Mark Greenawald, MD 'It's not a question of, 'Do we have grief?' We have grief every day,' says Mark Greenawald, MD, vice chair, family and community medicine at Virginia Tech Carilion School of Medicine. 'It's just a question of how we're processing it.' In his experience, learning to process grief isn't built into the medical school curriculum. Instead, Greenawald says he was trained to be compassionate for others, to hold suffering for patients and their families, which can be a lot to bear. That's not to say medical education turns a blind eye. 'Probably 20-30 years ago, I think the overall idea was, 'Don't get close to your patients, this is a job,' and the issue [of grief] was never really addressed,' says Prarthna Bhardwaj, MD, a hematologist and medical oncologist at Baystate Health in Massachusetts. 'You were told not to wear your heart on your sleeve with patients, because they are relying on you to be a professional.' Bhardwaj believes medical education has since evolved with 'a lot more focus on how to cope with what you experience and more emphasis on overall mental wellbeing. But we still have a long way to go.' Taylor says there's no explicit or formal way that dealing with patient loss is addressed in training. The focus is on reviewing procedures during morbidity and mortality rounds, not feelings. 'That can be a difficult venue for people to go about processing,' Taylor says. 'And if someone says, 'I did this differently, and I had a great outcome with a patient,' that doesn't serve anybody in the moment.' Greenawald puts it more bluntly: 'In healthcare, grief is seen as a sign of weakness or incompetence.' A Space to Grieve It's widely understood that COVID, and the overwhelming number of patient deaths that came with it, took a tremendous toll on healthcare workers. During the pandemic, hospitals were motivated to create what Taylor refers to as 'grief adjacent' programs and interventions to improve wellbeing. However, a physician must not only self-enroll in these but also take time outside of work to participate. Granek acknowledges that these interventions are well-intentioned but also problematic. 'I'm a psychologist; I have nothing against therapy or mindfulness programs,' she says. 'But those are very individual solutions to a global problem.' They are also reactionary, adds Greenawald. 'Crisis interventions are absolutely essential, but it's just the tip of the need.' So, what might help? Granek says that when she asks healthcare providers what would best help them cope with loss, they overwhelmingly respond that they want a space where their grief is acknowledged. 'Historically, on the physician side in medical culture, there hasn't been an intentional space created for grief,' says Taylor. To fill that gap, she has been deliberate about bolstering a community with her fellow oncologists. 'We have a space to debrief, but that's very informal,' she says, adding that the burden is on physicians to create these groups. In 2019, Greenawald began to wonder if something could be put in place to help clinicians without being too overt or elementary: a space to talk about difficult cases and their emotional impact. A year later, he launched PeerRXMed, a free, peer-supported program designed to help physicians and others on a care team form meaningful connections. Participants self-select a friend with whom they'll work through the program, requiring as little as a 15-second weekly check in. Today, PeerRXMed continues to thrive and eventually Greenawald hopes to develop an app. Roy and her classmate at the University of Pittsburgh School of Medicine, Kortni Ferguson, MD, launched their website BereaveMED in 2019 to provide a space where medical students experiencing grief and loss could share their stories and build community. The site also offers an extensive list of resources, including links to blogs, podcasts, support groups and research. Many in the field acknowledge the challenges in creating an in-house grieving space for healthcare providers, because there's no one-size-fits all solution; grief is contextual. Granek suggests the approach should be integrated into the day-to-day rather than something the physician needs to deal with outside of work. It also needs to be modeled from the top down in order to normalize it, starting with the chair of the department. She also notes that one must consider the issue of departmental dynamics. 'How well do the people get along? How competitive is this environment? You have to deal with the relational culture of the department before you can ask people to open up about their vulnerabilities.' 'The approach has to be systemic rather than individual,' Granek adds. 'And preferably that education starts early in medical education.' In the meantime, Moutier encourages physicians to talk about patient loss with someone they trust. 'Whether that's a mentor, a peer, a therapist, a grief counselor, a spouse,' she says, 'I think the problems are much more likely to be more intense and more severe if you're not talking about it.'
Washington Post
3 minutes ago
- Washington Post
Trump once hailed mRNA vaccines as a 'medical miracle.' Now RFK Jr. is halting advancement
WASHINGTON — President Donald Trump hailed as a 'medical miracle' the mRNA vaccines developed to combat the deadly COVID-19 pandemic in 2020. Now, his health secretary Robert F. Kennedy Jr. , is effectively halting the vaccine technology's advancement. Kennedy announced Tuesday that the federal government is canceling $500 million worth of mRNA research development contracts, putting an end to U.S.-backed hopes for the vaccine technology to prevent future pandemics, treat cancer or prevent flu infections.
