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Medscape
9 hours ago
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- Medscape
Brain Cell Transplant Slows Rare Neurodegenerative Disease
Replacing mutant microglia with healthy donor-derived microglia has emerged as a promising treatment for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). In a small study of eight patients with ALSP, replacing dysfunctional microglia with normal microglia using traditional bone marrow transplantation (BMT) halted the progression of ALSP and improved neurologic function. 'The critical next step is to validate these results in a larger clinical trial, which is already underway,' principal investigator Bo Peng, PhD, professor, Institute for Translational Brain Research, Fudan University in Shanghai, told Medscape Medical News . The study was published online on July 10 in Science . From Mice to Men ALSP is a rare, progressive neurological disease with an average age of onset of 43 years and an average life expectancy of only 3-5 years after symptoms begin. There is no cure and there are few treatments. ALSP is caused by mutations in the colony-stimulating factor 1 receptor gene (CSF1R), which is critical to development and survival of microglia. Mutations in this gene lead to microglial dysfunction and reduced numbers of these key brain immune cells. In earlier work, Peng and his team developed mouse models of ALSP which exhibit hallmark features of the disease including reduced numbers of microglia, myelin abnormalities, axonal swelling and motor impairments, and cognitive decline. To test whether microglial replacement could alter disease progression in mice with ALSP, the investigators tested two approaches: traditional BMT and microglia replacement by BMT (Mr BMT), a protocol that combines pharmacological depletion of microglia with traditional BMT. Both approaches effectively replaced mutant microglia with wild-type counterparts and successfully reversed myelin defects, axonal swellings, and motor and cognitive impairments in the animals. To translate this to the clinic, they performed traditional BMT in eight patients with ALSP. Although traditional BMT alone typically does not achieve efficient Mr in healthy brains, the inherent CSF1R deficiency in patients with ALSP creates a 'competitive disadvantage' for the recipient's resident microglia, allowing traditional BMT to achieve effective replacement, the researchers explained in their paper. In the 2 years following Mr, MRI and clinical evaluations indicated 'halted disease progression, preserved motor function, and stabilized cognitive abilities,' the team reported. By contrast, untreated patients with ALSP exhibited rapid worsening of brain pathology over a shorter time frame. The findings in these eight patients also provide a 'mechanistic explanation' for a prior clinical case in which an individual with ALSP, initially misdiagnosed with adult-onset metachromatic leukodystrophy, exhibited long-term stabilization after traditional BMT. 'While the path forward is active with the ongoing trial, traditional BMT becoming a widely accessible 'clinic-ready' standard treatment for ALSP is still estimated to be several years away, contingent upon successful trial outcomes, long-term safety data, and subsequent regulatory approvals,' Peng told Medscape Medical News . Beyond ALSP Peng also said Mr 'holds significant theoretical promise' for treating other neurological diseases involving microglial dysfunction, including Alzheimer's disease (AD). 'Genome-wide association studies have identified TREM2 as one of the major risk genes in sporadic AD. TREM2 mutation may cause or accelerate the progression of AD. In a 2020 paper in Cell Reports , we proposed that we can replace the TREM2 -mutated microglia with TREM2 -normal cells to treat this disease,' Peng added. In a Science perspective , Siling Du, PhD, and Jonathan Kipnis, PhD, with the Brain Immunology and Glia Center, Washington University in St Louis congratulated Peng and colleagues for demonstrating in humans that 'correcting a microglial gene defect through cell replacement can arrest disease progression.' Du and Kipnis agreed that the potential implications of this research extend beyond ALSP. For example, a recent study demonstrated that microglial replacement can also rescue pathology in a mouse model of Krabbe disease, a monogenic neurodegenerative disorder caused by mutations in the gene encoding galactosylceramidase. In addition, traditional BMT has also been shown to arrest disease progression in a mouse model of Rett syndrome — a severe neurodevelopmental condition caused by loss-of-function mutations in the gene encoding methyl-CpG binding protein 2. 'Together, these findings highlight the therapeutic potential of microglial replacement in modifying the course of monogenic neurological diseases,' Du and Kipnis said. Looking ahead, they said it will be important to establish the optimal donor cell source to achieve 'scalable, safe, and durable microglial replacement.' 'It is also not yet clear whether the systemic toxicity caused by pretransplant conditioning can be minimized without compromising engraftment. Future strategies must strike a balance between replacement efficiency, systemic toxicity, and the functional competence of engrafted cells,' they wrote. 'Moving forward, it may ultimately become possible to reprogram the brain's immune landscape from within and find the best microglial replacement approach not only for microgliopathies but for a spectrum of neurological diseases,' Du and Kipnis concluded.
Medscape
3 days ago
- Health
- Medscape
New Glioma Guidelines Incorporate WHO Reclassification
Newly updated guidelines from the American Society for Radiation Oncology (ASTRO) capture the World Health Organization (WHO)'s 2021 reclassification of glioblastoma as grade 4 adult-type diffuse gliomas. The new ASTRO guidelines and the WHO reclassification incorporate newly discovered molecular markers with histologic findings, which allow clinicians to more precisely diagnose and treat these tumors. The term glioblastoma now refers only to IDH wild-type gliomas, which grow more quickly and are more aggressive that IDH mutant gliomas. The guidelines also incorporate the use of newer imaging techniques. The ASTRO guidelines were last updated in 2016. According to guideline co-author Steve E. Braunstein, MD, PhD, the treatment of older and/or medically frail patients was one of the topics the guidelines task force spent the most time discussing. Despite 'dozens and dozens of high-quality clinical trials that have been done, there are still areas where we don't have a clear consensus or a clear, high-level evidence-based approach for treating those patients…who are somewhat older or more medically frail,' Braunstein told Medscape Medical News in an interview. The task force observed that even assessing two or three factors like performance status and age doesn't really capture the patient and how they're going to best respond to therapy. The guidelines offer suggested dose-fractionation regimens for radiation therapy (RT) guided by the patient's age and functional status with shorter courses conditionally recommended for older patients and those with indications of frailty. Supportive care is conditionally recommended in lieu of chemoradiation for patients with markers of severe frailty, who are often at an increased risk for complications from intensive treatments. However, for both groups — older/more frail and severely frail patients — the appropriate treatment approach should flow from a multidisciplinary, patient-centered discussion. 'We recognize that we need to do more to understand these patients in a deeper way in order to bestow upon them appropriate personalized recommendations,' said Braunstein, who is also vice chair of radiation oncology at the University of California San Francisco. Reirradiation Conditionally Recommended for WHO Grade 4 Diffuse Glioma The task force conditionally recommended reirradiation for WHO grade 4 diffuse glioma recurrence for selected adult patients with good functional status, following a multidisciplinary, patient-centered discussion. This discussion would address indications and techniques for reirradiation, specifically diagnostic and treatment considerations and systemic therapy in the reirradiation setting. At least one expert interviewed by Medscape Medical News questioned this recommendation. 'For recurrent glioblastomas, they suggest that reirradiation is an option…the endorsement of that approach is fairly significant,' said Patrick Y. Wen, MD, is director of the Center for Neuro-Oncology at Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School in Boston. 'In fact, we actually don't know if reirradiation works.' He added that the guidelines could be more balanced in outlining the limitations of reirradiation. 'We all do it because there's nothing else to do, but that doesn't mean it's a great choice.' Wen, who was not involved in the development of the guidelines, said there has only been one randomized trial, which compared Avastin [bevacizumab], which is standard of care, with bevacizumab and radiation. Although patients who received the combination had decreased progression-free survival, there was no improvement in overall survival. Wen noted that there has only been one randomized trial, which compared Avastin [bevacizumab], which is standard of care, with bevacizumab and radiation. Although patients who received the combination had improved progression-free survival, there was no improvement in overall survival. 'So you could interpret that as the only randomized study out there…showing no survival benefit.' There is a trial being conducted by the European Organisation for Research and Treatment of Cancer, the LEGATO trial, that is currently evaluating whether reirradiation and lomustine improves survival compared with standard lomustine chemotherapy alone. The data that do exist supporting the use of reirradiation come entirely from retrospective studies, he added. 'There's huge selection bias with retrospective data because the patients, who you would radiate are the ones that have small tumors and that are probably in decent shape, so they're going to do better.' In addition to making the conditional recommendation for reirradiation, the task force acknowledged care disparities for patients from diverse backgrounds. More Studies Needed to Examine Barriers to Access, Clinical Trial Enrollment 'There are great disparities in the care of patients, who are coming from different backgrounds,' said Braunstein. 'Those are a function of things that could include age, geography, insurance status, ethnic background, and race, among others. We really want to ensure that we're giving every patient with this terrible diagnosis, the opportunity to have the best care possible.' As part of the discussion, the task force reviewed the literature on health disparities and adult high-grade glioma, calling to attention the need for more studies that examine barriers to access and the need to increase clinical trial enrollment for underserved populations. Other key recommendations for patients with grade 4 adult-type diffuse gliomas include: Fractionated RT for those who have undergone biopsy or resection; optimal timing and fractionation schedules for adjuvant RT are included. Concurrent temozolomide chemotherapy and RT are recommended following biopsy or resection. Alternating electric field therapy — a cancer treatment using low-intensity, intermediate frequency electrical fields — is conditionally recommended following RT for those with tumors in the upper regions of the brain (ie, supratentorial disease). Braunstein reported relationships with Elekta GT Medical Tech (consultant) and Icotec Medical (honoraria, travel expenses).
Medscape
4 days ago
- Health
- Medscape
Workplace Burnout: Lessons From Professional Cycling
With the world's most grueling and prestigious cycling race — the Tour de France — in full swing, Medscape Medical News turned its focus to athlete burnout to ask: What can healthcare professionals learn from professional athletes? In 2019, the World Health Organization's (WHO's) International Disease Classification, 11th Revision added burnout to its official compendium of diseases, categorizing it as a 'syndrome' that results from 'chronic workplace stress that has not successfully been managed.' The definition came into effect in 2022. Burnout, according to the WHO, is characterized by 'feelings of energy depletion or exhaustion; increased mental distance from one's job, or feelings of negativism or cynicism related to one's job; and reduced professional efficacy.' But professor of occupational health psychology at Birkbeck, University of London, London, England, Gail Kinman, PhD, said that to tackle burnout, it is crucial to distinguish and recognize it as a response to chronic workplace stress that hasn't been managed, rather than as a disease. 'In healthcare, burnout has traditionally been seen as an inevitable cost of caring or, even worse, a badge of honor,' she told Medscape Medical News . 'Framing burnout as a disease can unintentionally pathologize normal human responses to excessive and sustained pressure. This risks reinforcing the idea that the individual is somehow deficient or needs fixing…Burnout [impacts] not only individual workers but also patients and teams and undermines the effectiveness of the healthcare system as a whole.' Optimizing the Fatigue-Recovery Balance As healthcare workers continue to push their physical and mental limits, professional athletes are trained to do so. But many go past the point of overtraining and overreaching to experience full burnout, just like healthcare workers who go past the point of emotional and physical exhaustion. 'Stage races like the Tour de France are among the most demanding competitions and are extremely stressful, physically and mentally, for athletes. Good performance in these competitions is the result of teams' ability to optimize the fatigue-recovery balance of cyclists, including both leaders and other teammates,' Franco Impellizzeri, PhD, a former cycling coach and former head of research at the MAPEI Sport Research Centre, Varese, Italy, and current professor of sport and exercise science and medicine at the University of Technology Sydney, Ultimo, Australia, told Medscape Medical News . Franco Impellizzeri, PhD It is a complex process, he said, where the one who makes the fewest mistakes comes out on top. Professor of sport and health psychology at York St John University, York, England, Daniel Madigan, PhD, told Medscape Medical News that, despite increased awareness of burnout, it continues to rise among athletes. Daniel Madigan, PhD 'It is definitely something that takes second place over the emphasis on physiology, training, and overtraining,' he said. 'It leads to loss of motivation, reduced performance, worse physical and mental health, and can ultimately lead to dropout from sport. But athletes may not want to share their perceptions for fear of stigma associated with mental health.' Burnout as a Symptom of Systemic Issues Burnout, he said, manifests the same way in healthcare professionals: It affects their health, well-being, and performance, and can ultimately lead them to abandon their careers. 'I think being able to have more control over what you do and when is likely the most important factor — and for healthcare professionals, this is likely a function of their line managers and environment,' he said. 'It is [also important] to increase autonomy, enhance communication, and build psychologically safe environments, where mistakes can be made and opinions are valid.' Kinman agreed, stressing it was not the responsibility of the individual to cope with challenging working conditions but rather to address systemic issues. 'Poor work-life balance is a key driver of burnout, as long shifts, being on call, and the inability to mentally disconnect from professional responsibilities can breed unhealthy rumination and impair physical and emotional recovery processes,' she said, adding that doctors particularly also struggle with perfectionism, something which is reinforced throughout their training. 'The real solution lies in addressing the systemic causes of stress, such as work overload, intensity, lack of autonomy, poor leadership, moral distress, inadequate support, and unhealthy organizational cultures that fail to prioritize psychological safety, which cause burnout to develop in the first place.' 'We have learned that burnout is best considered a gradual, dynamic process that unfolds over time…This is important because it highlights opportunities for early recognition and intervention when individuals are showing early signs of emotional exhaustion, detachment, and cynicism,' Kinman said. It Takes a Team Impellizzeri said greater awareness of burnout among sporting professionals has led to athletes and teams now employing a range of specialists to look after various aspects of well-being, including nutritionists, psychologists, and fitness coaches. 'Addressing the mental aspects and the factors that influence psychological responses are now integral parts of athlete management,' he said. 'Also, wearables and new technologies now allow the collection of more biometric data to monitor health status. From a scientific point of view, we definitely know more now, especially about the physiological effects.' For former American professional cyclist turned coach for Empirical Cycling, which trains world tour teams and regional competitors, Kolie Moore, some of the most powerful interventions to manage workplace stress and prevent burnout are the simplest. 'Each profession has a different method of coping with or avoiding burnout that would be instructive for others. With our clients who are healthcare professionals, proper nutrition and hydration at work are not only keys to a good afternoon workout and quality sleep, but they seem to improve focus and alertness during the shift too,' he told Medscape Medical News . 'Monitoring step count and subjective stress levels per day can also give insights into energy expenditure and mental load. Tracking these over time…could give healthcare workers an idea about how much acute and chronic stress their jobs have, as long as the limitation of the choices going into the model are understood.' But unlike professional cyclists who 'often have agents and coaches to advocate for their best interests,' he stressed that such representation is missing for healthcare professionals, raising the question: Who is looking out for those who care for the sickest? Pedro Manonelles, MBBS, international chair of sports medicine at Universidad Católica San Antonio de Murcia, Murcia, Spain, and former president of the governing board of the Spanish Society of Sports Medicine, said the pressure athletes and healthcare workers face to perform is similar, highlighting the importance of proper rest. Pedro Manonelles, MBBS 'Efforts should be made to develop realistic, yet positive, perceptions of competition in athletes. Reducing training loads and, in severe cases, complete rest from sports for weeks is often necessary — and same with psychological support,' he told Medscape Medical News . Such advice is applicable to the healthcare world, where hospitals could work with staff to develop realistic workplans, better understand the impact of intense workloads, and provide more breaks throughout the day. A Fading Flame Professor of sports science at the University of Agder, Kristiansand, Norway, and one of the world's leading minds in the science of endurance sports, Kerry Stephen Seiler, PhD, said a race like the Tour de France continues to highlight just how far athletes are willing to push, something that won't be coming to an end anytime soon. 'The training loads are huge, the travel and camp schedule is extreme, the physical risks are to the point of life and death,' he said. A few months ago, he was brought in to work with Australian Cycling, and at an event, he sat next to a recently retired South African cyclist. Their conversation inevitably led to one on risk and injury. 'I asked him what made him decide to retire. He told me that when his young son was pushing him around in a wheelchair, he decided it was no longer worth it. He was finished, and he did not want his children to have to do that anymore. Is that burnout? Well, the flame of competition fire fades out because a keen sense of mortality and perspective sets in.'
Medscape
4 days ago
- Health
- Medscape
Smartphone Data Reveal Patterns of Psychopathology
Information on mobility, phone usage, sleep-wake patterns, and other passive data collected by smartphones is associated with behavioral markers linked to multiple forms of psychopathology, including general mental health burden, new research showed. In a large observational study of community-based adults, researchers found that smartphone sensors that measure daily activities captured distinct behavioral signatures that may help identify when mental health symptoms are worsening. The findings add to a growing body of work on digital phenotyping, which analyzes passive data collected by smartphones and wearables to identify behavioral patterns in real time. Although not ready for the clinic, researchers said the new analysis suggests a number of potential applications for smartphone sensing, which could be used alongside clinician-rated and self-reported measures, offering moment-by-moment insight into patients' lived experience and an opportunity for timely intervention. 'This study helps us understand the breadth of psychopathology that smartphone sensors can detect and how specific those markers are to different forms of mental illness,' lead author Whitney R. Ringwald, PhD, assistant professor and Starke Hathaway Endowed Chair in Clinical Psychology at the University of Minnesota, Minneapolis, told Medscape Medical News . 'It offers a way to assess psychological functioning in daily life and monitor mental health symptoms more continuously, especially outside the clinic setting,' she added. The study was published online on July 3 in JAMA Network Open . Linking Data to Symptoms Until now, behavioral studies utilizing smartphone data were typically small and focused on a single disorder like depression or schizophrenia. But that approach may overlook how symptoms interact and overlap across diagnostic boundaries, researchers said. To capture a fuller picture, Ringwald and colleagues used the hierarchical taxonomy of psychopathology, a framework that organizes mental health symptoms into transdiagnostic domains. These include internalizing, detachment, somatoform, antagonism, disinhibition, and thought disorder. 'One of the major contributions of the study is that earlier research has looked at only a few DSM [diagnostic and statistical manual of mental disorders] disorders,' Ringwald said. 'We took a wider view by measuring symptom dimensions that span most forms of psychopathology and used a much larger sample.' The cross-sectional study enrolled 557 adults (83% women; mean age, 30.7 years; 81% White individuals). Participants completed a baseline mental health survey, which investigators used to calculate a general measure of overall psychiatric symptom burden, called a p-factor. They then underwent 15 days of smartphone-based monitoring. Their personal devices collected data via global positioning system (GPS), accelerometer, screen use, call logs, and battery metrics. Researchers extracted 27 behavioral markers from the data, such as time spent at home (from GPS data) and sleep duration (from accelerometer data). They then mapped these markers to participants' scores across psychopathology domains, measuring the strength of the association by the coefficient of multiple correlation (R) between each of the six domains and the 27 markers. Identifying Patterns Detachment (R, 0.42; 95% CI, 0.29-0.54) and somatoform (R, 0.41; 95% CI, 0.30-0.53) symptoms showed the strongest associations. High detachment was linked to such behavioral markers as reduced walking, more time at home, and fewer locations visited. Somatoform symptoms, which are often overlooked in mobile sensing studies, were similarly tied to low physical activity. Other associations included low battery charge in individuals with high disinhibition — which researchers suggest may reflect planning deficits — and fewer, shorter phone calls among those with elevated antagonism. Internalizing symptoms had subtler links, including briefer, more frequent screen interactions. The researchers also correlated behavioral patterns with participants' baseline p-factor. Those with higher baseline p-factor scores were more likely to have sensor data that revealed reduced mobility (standardized β, -0.22; 95% CI, -0.32 to -0.12), later bedtimes (standardized β, 0.25; 95% CI, 0.11-0.38), more time spent at home (standardized β, 0.23; 95% CI, 0.14-0.32), and lower phone battery levels (standardized β, -0.16; 95% CI, -0.30 to -0.01). These patterns, the authors suggest, may reflect shared impairments in motivation, planning, or cognitive control across multiple forms of mental illness. If validated, such behavioral indicators could help clinicians recognize when symptoms are escalating, even in the absence of a clear diagnostic label. Digital Phenotyping: Another Clinical Tool? Although not ready for clinical use, the findings point to several promising applications. If integrated into care, smartphone sensing could help providers passively track symptoms that could indicate relapse, allowing clinicians to deliver timely interventions based on real-world behavior. This could be especially valuable for patients who struggle to report changes or have limited access to care, researchers said. 'It's not a replacement for clinical care, but a potential complement that gives us a richer picture,' Ringwald said. She noted that digital phenotyping could eventually support just-in-time interventions — for example, prompting a brief therapeutic strategy when a person shows signs of behavioral withdrawal or disruption. Ringwald emphasized that important steps remain before the technology is ready to be implemented. 'This is still early-stage research,' she said. 'We need larger, more diverse samples, better sensor calibration, and strategies for interpreting data at the individual level before we can integrate this into care.' Promise and Precautions In an accompanying editorial, Christian A. Webb, PhD, and Hadar Fisher, PhD, both of Harvard Medical School in Boston, described the study as 'an important contribution to the growing field of digital phenotyping.' The research 'demonstrates the potential value of this approach, linking everyday behaviors to transdiagnostic symptom dimensions,' they wrote. They cautioned, however, that behavioral data should not be overinterpreted. 'Digital behavioral data are just that — behavioral. They are rough proxies for internal mental states, not direct readouts of mood or thought,' the authors wrote. A single signal could carry different meanings depending on context. 'The same signal could reflect intense physical activity, fear, or excitement.' To be clinically useful, they added, the technology must be accurate, scalable, and ethically implemented. 'The dream is scalable, low-burden, personalized care that meets people where they are,' Webb and Fisher wrote. 'If we can get the science and safeguards right, smartphones may become not only ubiquitous in our pockets but also invaluable in our clinical toolkits.'
Medscape
5 days ago
- Health
- Medscape
Does Romosozumab Deserve Its Black Box Warning?
Osteoporosis drug romosozumab showed no increased risk for the development of cardiovascular (CV) events compared with anabolic osteoporosis drugs, contrary to its black box warning, new research found. 'These findings suggest there is no heightened risk for major adverse cardiovascular events in patients with osteoporosis treated with romosozumab compared to the anabolic agents teriparatide or abaloparatide,' the authors reported at ENDO 2025: The Endocrine Society Annual Meeting. 'Further observational data is required to concur with such findings, which may lead to a discontinuation of the black box warning,' they said. Romosozumab, a monoclonal antibody targeting sclerostin, has a unique dual action of anabolic properties (increasing bone formation while reducing resorption and improving bone mineral density while reducing vertebral fracture risk). The drug is injected monthly for 12 months, after which time its anabolic effects decline and patients must transition to other antiresorptive therapies, such as bisphosphonates or denosumab, to maintain gains in bone density. Although the FDA approved romosozumab for osteoporosis management, it has given a black box warning after clinical trials (including the ARCH study) comparing romosozumab with alendronate suggested an increased risk for serious CV events, including myocardial infarction, stroke, and CV death. The drug is therefore contraindicated in patients with hypocalcemia and those who have had a myocardial infarction or stroke within the previous year. However, data on those risks has been highly inconsistent, first author Maxim John Levy Barnett, MD, of Jefferson-Einstein Hospital, Philadelphia, told Medscape Medical News . 'Most previous studies on this issue show a nonsignificant trend toward a higher risk but do not reach statistical significance,' he said. Even the ARCH trial 'showed a trend of higher incidence of adverse outcomes, but it was not statistically significant,' he noted. New Findings To further investigate the risks, Barnett and colleagues evaluated data on patients with osteoporosis in the TriNetX database, including 14,760 patients treated with romosozumab and 45,302 treated with either teriparatide or abaloparatide anabolic agents. For the propensity score analysis, patients in the two groups were matched for age, sex, race, glycated hemoglobin, hypertension, chronic kidney disease, ischemic heart disease, cerebrovascular disease, diabetes, and other factors. After matching, the romosozumab group had 14,288 patients compared with 14,362 in the anabolic agent group. Patients had a mean age at baseline of 70.5 years, 94% were women — as the drug is approved in the US for women only — and 71% were White. With a mean follow-up of 5 years (including the 1-year treatment with romosozumab), there was a nonsignificant trend toward a reduced risk for CV incidents among those treated with romosozumab (relative risk [RR], 0.601; P = .0692). The romosozumab group also had significantly lower ischemic heart disease rates than the anabolic agent group (RR, 0.848; P = .0017). In addition, those receiving romosozumab had a lower risk of acute myocardial infarction (RR, 0.654; P < .0001). Likewise, acute heart failure, either systolic or diastolic, was also significantly lower in the romosozumab group (RR, 0.664; P = .0029). 'After propensity-score matching, there was still a significant reduction [with romosozumab], which was a surprise,' Barnett said. 'Three out of the 4 outcomes actually showed a significant decrease in risk with romosozumab.' 'To the best of my knowledge, similar trends have not been noted in other studies,' he said, adding that there have been no significant changes to romosozumab's treatment regimen or other factors that might explain differences in risk since the issuance of the black box warning. 'It is important to note that this was not the primary objective of the noninferiority study, and it was not powered for this endpoint,' Barnett said. The findings nevertheless add to evidence from others showing results that call into question the concerns behind the black box warning. 'There is no substantial evidence for cardiovascular risk and this medication; nonetheless, the black box warning is present,' Barnett said. Commenting on the study, Tiffany Kim, MD, of the University of California, San Francisco, who co-moderated the session, agreed that 'these are definitely interesting findings that add to growing data that romosozumab may not be associated with increased cardiovascular risk.' She noted that, as intended, 'any black box warning has a big effect on how clinicians consider and talk to a patient about the risks of a medication.' 'From a medico-legal perspective, I always inform my patient so they aren't surprised if they read this later, and so that I can document that they accept the benefits outweigh the risk for their individual situation.' 'This study adds to the reassuring literature that romosozumab may not be associated with increased risk of cardiovascular disease,' Kim said. 'In my clinical practice, I only consider anabolic therapy for my patients with severe osteoporosis at high fracture risk who really need treatment, so having more data about the CV risk helps with my clinical decision-making and with discussions with my patients about the risks and benefits of this drug.' In terms of caveats, Kim noted that 'the study did a good job of matching for medical comorbidities, but there may be other factors that cause a clinician to prescribe the drugs that are associated with cardiovascular disease.' 'This study is a helpful addition to the literature, but it's hard to be definitive in an observational study,' she added.
