Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive weakness of voluntary muscle. ALS is uncommon but not rare, with a lifetime risk of about 1 in 400. Nearly all patients with ALS will die from ALS, most from respiratory failure, and the median survival from onset of symptoms is 2 to 3 years. Treatment remains mostly supportive. Interventions stopping disease progression are nonexistent and those slowing progression unsatisfactory. There is a need to develop and quickly and cost-effectively evaluate better treatments.

This randomized platform trial investigates whether pridopidine, a sigma-1 receptor agonist, impacted disease progression among patients with amyotrophic lateral sclerosis.

In the first month of the new administration responsible for leading the US, the executive branch has issued a flurry of orders, including ones associated with the dismissal or resignation of tens of thousands of federal employees. Many of these have substantial consequences for science, medicine, and public health. Amidst the dizzying array of actions, it is difficult to know where to focus and how best to respond. However, the silencing of science and health-related communications through suppression or erasure of information, and the corresponding silence by many in the fields of biomedicine and public health, deserve special consideration.

This JAMA Patient Page describes harm reduction strategies for people who use drugs, which include testing for drug contaminants, overdose prevention, and reducing risk of infectious disease transmission.

To the Editor We believe that a recent Research Letter presented an overly strong interpretation of highly nuanced data that had residual confounding. The relationship between hormone therapies and breast cancer is complex, beginning with choosing comparator groups. Nonuse of hormonal contraception is not a base health state, but rather a culmination of health care access, preference, and need, which render this comparator biased in its own right. This does not preclude analyses comparing these groups, but necessitates intentionality in study design and thoughtful interpretation. The ideal comparator group for hormonal intrauterine device (IUD) users is unknown but needs to be situated within social and biologic plausibility. Of note, a study of 5113 patients with breast cancer diagnosed from 2000 to 2007 and 20 452 matched controls reported no increased risk in breast cancer in those using levonorgestrel-releasing IUDs compared with copper IUDs.

A man taking no regular medications had 1 month of small painless facial papules progressing over 1 week to vesicles and pustules. He reported unprotected sex with multiple partners and recent exposure to a person with active tuberculosis; rapid plasma reagin titer was normal; results of HIV and fluorescent treponemal antibody absorption tests were positive. What is the diagnosis and what would you do next?

Semaglutide, marketed as Ozempic, recently became the first glucagon-like peptide 1 (GLP-1) receptor agonist approved by the US Food and Drug Administration (FDA) to reduce the risk of worsening kidney disease, kidney failure, and death due to cardiovascular disease in adults with type 2 diabetes (T2D) and chronic kidney disease (CKD), a common complication of T2D.

This Viewpoint discusses a Centers for Medicare and Medicaid Innovation volunteer greenhouse gas emissions reporting and technical assistance program for hospitals and hospital systems.

We were late and getting later by the minute. I was driving my friend to the train station,

Physicians’ best medical advice for care does not always align with patients’ wishes. While many causes of this harmful and costly discordance are postulated, poor communication of shared goals tops many lists. In “Planning Our Escape,” poetry becomes a window into better understanding a patient’s refusal of treatment by offering a moving counternarrative to uncompromising medical advice. The speaker describes a friend with “thigh sarcoma” whose doctors “floated the idea of amputation,” after which he “floated up to visit” for a week spent outdoors instead. The implied clinical narrative of hospital confinement, surgery, and the resulting physical impairment is countered by the poem’s story of a lively friendship characterized by unfettered activity that clearly informs the “escape” of the poem’s title. That the speaker joins his friend in his escapist impulse, changing the friend’s habitual response to questions about his life from “planning my escape” to “planning our escape,” both shows respect for his friend’s autonomy and betrays a hint of his own contrarian wish to be free of medicine’s demands. Without ever explicitly endorsing his friend forgoing potentially lifesaving treatment, evident in the poem’s heart-wrenching conclusion is an openness to empathizing with him that could serve as a crucial basis for reconsideration. Poetry, in its capacity to embrace both the finality of the image of 2 friends searching for something lost (on another backpacking trip to Hiroshima, Japan) and the ironic hope of later sharing sake with “friends we made that night and never saw again,” beautifully engages the challenges of leaving against medical advice.

In this narrative medicine essay, a mother, a palliative care physician, and a hospital chaplain describe a meeting discussing a young patient’s medical options for treating his rare brain tumor.

Time changed without incident in the hospital where everyone worked an extra hour, and anyone born then would be perpetually confused or late all the time, and anyone who died and quietly lay in a room, still waiting for love, still, wheeled down the hall with the photographs on the walls, several of her smiling with a child, or looking intense because her life was falling apart, yet she looked good in her black jeans, not sure what she is wearing now, she went out in a large black plastic bag, hiding all of her continuing to leave through the door, continuing to become time: the seconds, minutes, hours days years, but who’s counting, who knows.

It is not many years since all statistical investigations were to be distrusted because biometry was as yet no science at all. It was customary to present a few figures and to draw from them extensive and unusual interpretations without taking into account numerous conditions that bore on possible interpretations. The modern biometrician realizes that allowances must be made for all sorts of factors and possible errors in the accumulation of medical statistical material, and is inclined to present his results exactly for what they are. In all the fundamental books on vital statistics, students are warned to beware of interpretations from general death rates.

Immunotherapy stands as one of the most transformative breakthroughs in modern cancer treatment. These innovative therapies target signaling pathways used by cancer cells to induce T-cell exhaustion at immune checkpoints, allowing the cancer to evade immune detection. In the last 10 years, immune checkpoint inhibitors have achieved long-lasting responses and, in some cases, even cures for cancers that once had poor prognoses. However, the journey to proving the efficacy of immunotherapy in breast cancer has been anything but straightforward. It took 8 years after the initial approval of an immune checkpoint inhibitor for melanoma before breast cancer saw its first approval in 2019, when atezolizumab received an indication for metastatic triple-negative breast cancer (TNBC) based on the IMpassion130 trial. Shortly thereafter, the US Food and Drug Administration granted approval to pembrolizumab for metastatic TNBC, fueling optimism that patients with this aggressive form of cancer were on the cusp of reaping vast benefits from immune-based therapies. Yet excitement gave way to uncertainty following the negative results of IMpassion131, leading to the voluntary withdrawal of atezolizumab’s indication for TNBC. Although pembrolizumab remained in play, confidence in immune therapy for breast cancer had been shaken.

The method of freezing all suitable embryos before transfer to the uterus, known as the “freeze-all strategy,” has become common practice for in vitro fertilization (IVF) over the past decade. But for some individuals, this might not be the best option.

This Viewpoint discusses the 2025-2030 Dietary Guidelines for Americans report and highlights some of the topics reviewed, including ultraprocessed foods and reduced-fat vs whole-fat dairy.

Procedural prescription denials, which are particularly common for individuals with Medicaid, are often rationalized to prevent unnecessary spending. However, a study published in JAMA Network Open suggests these drug coverage denials might increase future spending on acute medical care.

Listen to the JAMA Editor’s Summary for an overview and discussion of the important articles appearing in JAMA.

A cross-sectional study recently published in JAMA Network Open found that heavy lifetime cannabis use may negatively affect working memory in the long term.

In Reply We appreciate the comments about our recent study.

Recent research has linked weight-loss surgery with several positive outcomes. Metabolic (bariatric) surgery may reduce the risk of major adverse liver outcomes in patients with obesity and cirrhosis due to metabolic dysfunction–associated steatohepatitis (MASH), according to research published in Nature Medicine.

This Special Communication discusses the changes introduced in the first-ever restatement of the law of medical malpractice by the American Law Institute.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of cancer treatment. Although chemotherapy drugs target abnormal cells, they can also damage peripheral nerve cells, disrupting signaling pathways and creating sensations of tingling, numbness, or burning.

This study compares hospitalization and mortality outcomes in vaccinated older adults with vs without restricted access to nirmatrelvir-ritonavir in Ontario.

This Medical News article is an interview with Anita Shukla, PhD, the Elaine I. Savage Professor of Engineering at Brown University, about the urgent need for engineering-directed research to curb antimicrobial resistance.