Trials come with a multitude of tribulations. Funding for clinical trials can be elusive. Regulatory hurdles are many. Participants are hard to recruit and sometimes even harder to retain. Protocols can be unwieldy, and trial timelines can stretch endlessly. And even when completed, trials can yield results that defy expectations and challenge interpretation. As former National Institutes of Health Director Donald Fredrickson remarked more than 60 years ago, trials “strain our resources and patience, and they protract the moment of truth to excruciating limits.” And yet, clinical trials remain the bedrock of evidence-based medicine—and perhaps always will. When the stakes are highest, the medical community looks to trials to provide the certainty—or at least the clarity—needed to act.
Science Journals
In the US Preventive Services Task Force Recommendation Statement titled “Aspirin Use to Prevent Preeclampsia and Related Morbidity and Mortality,” published in the September 28, 2021, issue of JAMA, there were inconsistencies between Table 1 and the Practice Considerations section. Table 1 incorrectly stated, “Recommend low-dose aspirin if the patient has ≥2 moderate-risk factors. Consider low-dose aspirin if the patient has 1 of these moderate-risk factors.” Table 1 has been updated to accurately state, “Pregnant persons with 2 or more moderate-risk factors may also benefit from low-dose aspirin.” The Recognition of Risk Status section was also updated to list specific moderate risk factors more clearly and to fully align with those risk factors named in Table 1. This article was corrected online.
When a government detains a person, it assumes a duty of care. That person’s health—and survival—depends on whether the detaining authority provides adequate care, maintains health-promoting conditions, and responds to medical needs. Mortality in detention is thus a sentinel measure of whether the state is meeting its custodial obligation to provide humane conditions and adequate medical care, an obligation grounded in constitutional due process principles, domestic detention standards, and international human rights norms.
This study estimates annual mortality rates among individuals detained in US Immigration and Customs Enforcement facilities and summarizes age and cause of death patterns from 2004 through January 2026.
This Viewpoint discusses the financial and opportunity costs of mandatory health care training modules and how a reassessment based on adult learning theory could improve patient safety and professional growth while reducing burnout.
In the US Preventive Services Task Force Recommendation Statement titled “Screening for Breast Cancer: US Preventive Services Task Force Recommendation Statement,” published in the June 11, 2024, issue of JAMA, a relative risk reduction and its supporting reference incorrectly reflected earlier data. On page 1923, in the “Benefits and Comparative Benefits of Early Detection and Treatment” section, the relative risk reduction reported as 0.88 (95% CI, 0.73-1.00; 9 trials) should have read 0.92 (95% CI, 0.75-1.02; 9 trials). In the reference list, reference 44 should have read Nelson HD, Fu R, Cantor A, Pappas M, Daeges M, Humphrey L. Effectiveness of breast cancer screening: systematic review and meta-analysis to update the 2009 US Preventive Services Task Force recommendation. Ann Intern Med. 2016;164(4):244-255. doi:10.7326/M15-0969. This article was corrected online.
Virtual and remote trials represent a critical shift in how interventional research is conducted, with participants engaging in clinical trials from where they live or work rather than making repeated visits to brick-and-mortar research sites. Leveraging the increasingly widespread use of smartphones, personal computers, and the internet—all accelerated during the COVID-19 pandemic—decentralized trials relying on digital tools to engage participants remotely have proliferated rapidly. Institutional review boards now permit completely remote informed consent, based on digitally delivered information rather than face-to-face contact between participants and study personnel. Study medications, investigational devices, and biospecimen collection materials can be shipped directly to participants’ homes instead of being distributed during in-person study visits. Smartphone and other mobile devices are used to collect patient-reported data in real time, capturing symptom and quality-of-life patterns as participants experience them in their everyday lives. Wearable sensors and connected devices can also continuously monitor participants’ vital signs, physical activity, and other physiological parameters in their usual living environments, generating longitudinal data streams in place of intermittent study clinic-based measurements.
This clinical trial compares whether tobramycin plus vancomycin compared with vancomycin alone reduces deep surgical site infections among patients with periarticular tibial fractures who are at high risk of infection .
The study compared whether applying tobramycin and vancomycin powders topically to a surgical incision during closure of definitive fixation was more effective than applying vancomycin powder alone in reducing deep surgical site infection in periarticular tibial fractures.
This Viewpoint discusses 3 US Centers for Medicare & Medicaid Services (CMS) drug pricing models and how a pivot toward international reference pricing could affect consumers, manufacturers, and drug pricing policy.
This cross-sectional study examines access to mifepristone through retail and mail-order pharmacies following the US Food and Drug Administration’s (FDA) removal of its in-person dispensing requirement.
This retrospective cohort study examines the safety, efficacy, and patient-reported outcomes of device-enabled transcatheter tricuspid valve replacement in patients with symptomatic, severe tricuspid regurgitation.
The toxicity of many of the heavy metals has been known for generations, yet these substances have not been regarded as a menace to human health except in limited instances where industrial conditions or occupational circumstances exposed workers to the chemical hazards in some uncommon way. However much the student of vocational diseases might become concerned with the effects of metallic poisons, the treatises on public health and personal hygiene rarely discuss them except in a casual manner. As a consequence of modern economic and social changes, the latent dangers of poisoning from certain heavy metals are now suddenly presented to the public at large. To gasoline and the automobile we owe the nation-wide concern about lead; suicides and syphilis have awakened a new interest in mercury not merely as a drug but also as a poison; and now the advent of the “bootlegger” and home brew has brought copper to our toxicologic attention.
To the Editor A recent article compared the real-world effectiveness of the 2 available immunization strategies against respiratory syncytial virus (RSV): passive infant immunization with the long-acting monoclonal antibody nirsevimab vs maternal vaccination with the RSV prefusion F protein (RSVpreF) vaccine. Nirsevimab was associated with lower risk of RSV-related hospitalization, admission to the pediatric intensive care unit, need for ventilatory support, and oxygen treatment. Nonetheless, we believe caution is warranted before drawing conclusions about the superiority of either strategy.
In Reply We appreciate the opportunity to respond to comments by Dr Manzoni and colleagues about our study comparing passive infant immunization with nirsevimab and maternal immunization with the RSVpreF vaccine for the prevention of RSV-related hospitalization in newborns.
To the Editor A recent study reported that a tuberculosis (TB)-specific mobile health text-messaging program delivered during TB treatment increased biochemically verified continuous abstinence at 6 months in Bangladesh and Pakistan and was associated with lower mortality. Tobacco cessation during TB care is a major, practical priority, and this trial provides encouraging evidence for scalable support.
The great classical poet Horace wrote “Ars Poetica” around 19 BCE, his famous poem that uses the techniques of poetry itself to describe what poetry is and how it functions. Most memorably, perhaps, he declares that poetry must both “delight and instruct.” Since then, many poets have written their own versions of “Ars Poetica,” offering their own meditations regarding poetry as an art form. In this venerable and contentious tradition we can locate “Ars Poetica Medica,” which grapples with the possibilities of an art of medical poetry. Notably, echoing Horace, the poem’s diction is frankly didactic, with clear instructions like “First, step back/from the body.” Yet the poem also delights, perhaps unexpectedly given medicine’s distancing and diseases, with beautiful moments like “If meaning is the poem’s breath/then form is bone to brace the chest.” Thus the speaker proves medical poetry worthy of not just Horace’s definition of poetic art, but also of later poets, who, like the US physician-poet William Carlos Williams, insisted poetry must see our amazing world as it truly is. The speaker quotes “No ideas but in things,” Williams’ familiar admonition that poetry resist lofty notions of art and instead witness what is right before us (as he indelibly saw a hungry elderly woman savoring plums or a red wheelbarrow glistening in the rain). The poem’s final couplet affirms what medical poetry’s unflinching gaze reveals is authentically poetry—“To build a frame with words/to hold what words can’t say.”—that delights and instructs, yes, but also never looks away.
To the Editor The prevailing one-size-fits-all paradigm of breast cancer screening—largely based on age and fixed intervals—was designed during an era with limited risk stratification, few prevention pathways, and limited ability to tailor imaging intensity. Pragmatic randomized clinical trials, such as WISDOM, are therefore essential to generate evidence with a prevention strategy that can reallocate resources from women at lower risk of breast cancer to those at higher risk.
To the Editor Individualized, risk-based approaches to cancer screening aspire to resolve shortcomings of the traditional population- and age-based approach. Yet, until now, reliable evidence was not available to appropriately evaluate whether tailoring breast cancer screening according to cancer risk can increase benefits and reduce harms compared with the current approach. We therefore commend the WISDOM (Women Informed to Screen Depending on Measures of Risk) study, which provided crucial insights into risk-based breast cancer screening’s effects. However, we are concerned about the limited potential of risk-based screening for reducing harms, notably overdiagnosis, which involves diagnosis of cancers that do not progress to become symptomatic or harmful.
This JAMA Patient Page describes common symptoms and signs of endometrial cancer, how it is diagnosed and treated, and the prognosis.
First, step back from the body.
<p>by Jiazheng Quan, Xibao Zhao, Shaoying Chen, Hongrui Li, Wei Chen, Qianqian Di, Xunwei Li, Jiajing Zhao, Han Wu, Jin Chen, Yue Xiao, Zherui Wu, Weilin Chen</p>
RIG-I and STING are critical for mediating the RIG-I and cGAS-STING signaling pathways that guard against viral infection. Here, we report that ubiquitin-specific peptidase 39 (USP39) positively regulates the RIG-I and cGAS-STING pathways to induce antiviral innate immunity in vitro and in vivo. The USP39 deficiency impaired the antiviral immune response of macrophages, leading to low type I IFNs expression, and high RNA and (e.g., VSV, H1N1 PR8) DNA virus (e.g., HSV-1) replication<i>.</i> Moreover, USP39-deficient mice were more sensitive to VSV or HSV-1 infection than control mice. Conversely, USP39 overexpression promoted the antiviral immune response. Mechanistically, we found that USP39 regulates RIG-I protein expression by promoting pre-RIG-I mRNA splicing and maturation. In addition, we also revealed that USP39 interacts with and stabilizes STING protein by deubiquitinating K48-linked polyubiquitin of STING at K288. These data show that USP39 positively regulates RNA and DNA-virus-induced RIG-I and cGAS-STING signaling, respectively, by promoting post-transcriptional control of RIG-I and stabilization of STING. These data provide new insights and potential therapeutic targets to control viral infections.
<p>by Clayton Baker, Victor A. Ansere, Cossette I. Sanqui, Bérénice A. Benayoun</p>
Aging has effects on the immune system that are similar in men and women, but also reshapes their immune systems in unique, sex-specific ways. These sex-specific patterns of immune aging influence disease susceptibility, vaccine effectiveness, cancer survival, and responses to pharmacological therapies, and have direct implications for preventive medicine and clinical care. However, these differences in susceptibilities and responses are rarely considered in research, clinical trials, or treatment guidelines. By integrating knowledge of sex-specific immune aging with real-world outcomes from vaccines, cancer immunotherapy, and pharmacovigilance studies, this Essay argues that accounting for both sex and age is essential to advance personalized medicine.
Selective attention involves prioritising relevant sensory input while suppressing irrelevant stimuli. It has been proposed that oscillatory alpha-band activity (~10 Hz) aids this process by functionally inhibiting early sensory regions. However, recent studies have challenged this notion. Our EEG and MEG studies aimed to investigate whether human alpha oscillations serve as a 'gatekeeper' for downstream signal transmission. We first observed these effects in an EEG study and then replicated them using MEG, which allowed us to localise the sources. We employed a cross-modal paradigm where visual cues indicated whether upcoming targets required visual or auditory discrimination. To assess inhibition, we utilised frequency-tagging, simultaneously flickering the fixation cross at 36 Hz and playing amplitude-modulated white noise at 40 Hz during the cue-to-target interval. Consistent with prior research, we observed an increase in posterior alpha activity following cues signalling auditory targets. However, remarkably, both visual and auditory frequency-tagged responses amplified in anticipation of auditory targets, correlating with alpha activity amplitude. Our findings suggest that when attention shifts to auditory processing, the visual stream remains responsive and is not hindered by occipital alpha activity. This implies that alpha modulation does not solely regulate 'gain control' in early visual areas but rather orchestrates signal transmission to later stages of the processing stream.
In the olfactory system, adult-neurogenesis results in the continuous reorganization of synaptic connections and network architecture throughout the animal’s life. This poses a critical challenge: How does the olfactory system maintain stable representations of odors amidst this ongoing circuit instability? Utilizing a detailed spiking network model of early olfactory circuits, we uncovered dual roles for adult-neurogenesis: one that both supports representational stability to faithfully encode odor information, and also one that facilitates plasticity to allow for learning and adaptation. In the main olfactory bulb, adult-neurogenesis affects neural codes in individual mitral and tufted cells but preserves odor representations at the neuronal population level. By contrast, in the olfactory piriform cortex (PCx), both individual cell responses and overall population dynamics undergo progressive changes due to adult-neurogenesis. This leads to representational drift, a gradual alteration in stimulus-evoked activity patterns. Both processes are dynamic and depend on experience such that repeated exposure to specific odors reduces the drift due to adult-neurogenesis; thus, when the odor environment is stable over the course of adult-neurogenesis, it is spike-timing-dependent plasticity that leads representations to remain stable in the PCx; when those olfactory environments change, adult-neurogenesis allows cortical representations to track environmental change. Whereas perceptual stability and plasticity due to learning are often thought of as two distinct, often contradictory processes in neuronal coding, we find that adult-neurogenesis serves as a shared mechanism for both. In this regard, the quixotic presence of adult-neurogenesis in the mammalian olfactory bulb that has been the focus of considerable investigation in chemosensory neuroscience may be the mechanistic underpinning behind an array of complex computations.