Zap the Skull to Treat Rheumatoid Arthritis Pain?

 Rheumatoid arthritis (RA) patients saw significant reductions in pain with transcranial direct current stimulation (tDCS) delivered at home, a sham-controlled trial reported here indicated.

After 4 weeks of treatment, patients receiving active stimulation showed reductions from baseline in self-reported pain averaging 33.5 points on a 100-point scale, compared with a 14.1-point decline among patients using the same device but inactivated, according to Stephanie Pilotti, MSc, of Universidade Federal do Rio Grande do Sul in Porto Alegre, Brazil.

The difference of 19.4 points was significant (P=0.003), Pilotti told attendees at the European Alliance of Associations for Rheumatology annual meetingopens in a new tab or window.

RA may be an inflammatory joint disease, but pain is still transmitted through the nervous system and thus may be amenable to neurological interventions. Pilotti observed that numerous studies in animal models and humans have established that when pain signalling becomes chronic, plasticity in the central nervous system (CNS) can, over time, alter how these signals are processed. Pain may be amplified and sensitivity to pain can increase to the point of allodynia (interpreting normal touch sensations as painful). One study she cited found that RA patients develop this sort of central sensitization "even in the absence of active inflammation."

One non-drug approach to alleviating chronic pain has been tDCS. Some studies have found that it can relieve pain from fibromyalgiaopens in a new tab or window and a variety of other chronic pain statesopens in a new tab or window. The theory is that it normalizes pain signalling, Pilotti explained, without dulling sensation from genuinely injurious stimuli.

For the new study, her group enrolled 34 women with stable RA not marked by extreme inflammation, randomizing them in equal numbers to active or sham therapy. Eligibility criteria included rating their pain at 40 or higher out of 100. Patients for whom tDCS would be contraindicated (those with epilepsy or cranial metallic implants, for example) were excluded, as were those with concomitant rheumatologic conditions.

Patient age averaged about 56, with a median RA duration of 10 years. Mean 28-joint Disease Activity Score values were just over 2.8. They rated their pain as fairly severe: averaging 72 points in the group randomized to active tDCS and 63 in the sham-treated control group.

The tDCS device resembled a cloth helmet. Patients were instructed to put it on for 20-minute sessions once a day for 5 days each week for 4 weeks; they were supervised remotely, however. Active treatment consisted of 2 mA of current. In the control group, some current was delivered briefly at the beginning and end of each session in an effort to maintain blinding.

In addition to rating their pain, patients also completed other self-evaluations, including their use of analgesic drugs (days/week). Blood samples were taken as well to measure RA and inflammation markers, plus brain-derived neurotrophic factor (BDNF) to get an objective look at CNS responses to treatment.

At the 4-week evaluation, weekly analgesic use had fallen by 2.3 days with active treatment versus a 1.4-day decrease among controls (P=0.025). No significant change was seen in maximum pain pressure threshold, but the minimum threshold rose by 1.0 kg/cm² in the active treatment group versus an increase of 0.4 kg/cm² in the sham group (P=0.003).

Changes in other measures, such as physical function, fatigue, and sleep quality, did not differ significantly between active and sham treatment. Nor were there any between-group differences in RA-related markers including tumor necrosis factor, interleukin-1, or interleukin-6. However, mean BDNF levels rose with active treatment while it declined in the sham group (P=0.002).

Pilotti and colleagues also checked in with participants 3 months after completing the 4-week program to have them rate their pain. It rebounded from the immediate post-treatment levels in both groups and the between-group difference was no longer significant; the absolute means remained below baseline, however.

Active treatment did not appear to induce more adverse events such as headache, scalp pain, itching, insomnia, and trouble concentrating relative to sham therapy. No severe problems occurred in either group, and all patients completed the 4-week treatment.

"This approach may represent a valuable adjuvant to the management of chronic pain in RA patients," Pilotti concluded.

Disclosures

No external funding for the study was reported.

Pilotti and other authors declared they had no relevant financial interests.

Primary Source

European Alliance of Associations for Rheumatology

Source Reference: opens in a new tab or windowPilotti S, et al "Effect of home-based transcranial direct current stimulation on pain in rheumatoid arthritis patients with low inflammatory activity: a randomized, double-blind, sham-controlled clinical trial" EULAR 2025; Abstract OP0280.

https://www.medpagetoday.com/meetingcoverage/eular/116074

Cancer Care Advocates in D.C. Ask Congress to Protect Independent Community Oncology

 Patients, Survivors, and Care Providers Meet with Lawmakers on Issues of Affordability and Care Access

More than 100 advocates from 23 states are assembling on Capitol Hill today to meet with their members of Congress and ask for support of independent community oncology. The advocates, including patients, survivors and their family members, oncologists, hematologists, pharmacists and pharmacy team members, and practice administrators, are gathering under the banner of the Community Oncology Alliance (COA) and asking members of Congress to implement policy fixes that increase the affordability of treatment, remove obstacles to care, and ensure practice longevity so future patients have easy access to care. COA and its advocates are holding almost 100 meetings with members of Congress and their staff.

While on the Hill, advocates are asking Congress to prioritize three goals:

1. Increase Patient Affordability. Differences in payments to hospitals versus independent practices and abuse of the 340B Drug Pricing Program are raising costs for patients. Advocates are asking Congress to pass site-neutral payment legislation and reform the 340B Program.
2. Remove Patient Access Obstacles. Insurers and middlemen, like pharmacy benefit managers (PBMs), are instituting unnecessary obstacles to cancer care, and the Centers for Medicare & Medicaid Services has banned medication delivery. Advocates are asking for reform of the prior authorization system, the passage of PBM reform, and the passage of the Seniors’ Access to Critical Medications Act (H.R. 2484) to allow patients with cancer to receive critical drugs through the mail.
3. Ensure Patient Access. For too long, practices have faced Medicare payments that do not keep up with inflation due to fee schedule cuts and outdated policies, making it harder to keep their doors open. Additionally, the Inflation Reduction Act (IRA) has put providers in the middle between drug manufacturers and the government drug price negotiations which threatens to dramatically cut reimbursement. COA advocates are asking Congress to address low physician payments and ensure they do not fall behind inflation. They’re also asking for a technical fix to the IRA that takes providers out of the negotiation process, removing them from harm’s way.

“All patients deserve access to local, high-quality, and affordable cancer care. Unfortunately, current policies make this reality more out of reach than ever,” says Nicolas Ferreyros, managing director of COA. “We must address abusive middlemen like PBMs, reimbursement rates that have not even keep up with inflation, and misguided public policy to move the needle for America’s patients. As cancer treatments advance, there is more hope than ever for patients battling cancer. To make this hope accessible for all, we must protect independent community oncology and the policies that support it.”

https://mycoa.communityoncology.org/news-updates/press-releases/june-2025-hill-day-press-release

'AI scientist’ suggests combinations of widely available non-cancer drugs can kill cancer cells'

 An ‘AI scientist’, working in collaboration with human scientists, has found that combinations of cheap and safe drugs – used to treat conditions such as high cholesterol and alcohol dependence – could also be effective at treating cancer, a promising new approach to drug discovery.

The research team, led by the University of Cambridge, used the GPT-4 large language model (LLM) to identify hidden patterns buried in the mountains of scientific literature to identify potential new cancer drugs.

To test their approach, the researchers prompted GPT-4 to identify potential new drug combinations that could have a significant impact on a breast cancer cell line commonly used in medical research. They instructed it to avoid standard cancer drugs, identify drugs that would attack cancer cells while not harming healthy cells, and prioritise drugs that were affordable and approved by regulators.

The drug combinations suggested by GPT-4 were then tested by human scientists, both in combination and individually, to measure their effectiveness against breast cancer cells.

In the first lab-based test, three of the 12 drug combinations suggested by GPT-4 worked better than current breast cancer drugs. The LLM then learned from these tests and suggested a further four combinations, three of which also showed promising results.

The results, reported in the Journal of the Royal Society Interface, represent the first instance of a closed-loop system where experimental results guided an LLM, and LLM outputs – interpreted by human scientists – guided further experiments. The researchers say that tools such as LLMs are not a replacement for scientists, but could instead be supervised AI researchers, with the ability to originate, adapt and accelerate discovery in areas like cancer research.

Often, LLMs such as GPT-4 return results that aren’t true, known as hallucinations. However, in scientific research, hallucinations can sometimes be beneficial if they lead to new ideas that are worth testing.

“Supervised LLMs offer a scalable, imaginative layer of scientific exploration, and can help us as human scientists explore new paths that we hadn’t thought of before,” said Professor Ross King from Cambridge’s Department of Chemical Engineering and Biotechnology, who led the research. “This can be useful in areas such as drug discovery, where there are many thousands of compounds to search through.”

Based on the prompts provided by the human scientists, GPT-4 selected drugs based on the interplay between biological reasoning and hidden patterns in the scientific literature.

“This is not automation replacing scientists, but a new kind of collaboration,” said co-author Dr Hector Zenil from King’s College London. “Guided by expert prompts and experimental feedback, the AI functioned like a tireless research partner—rapidly navigating an immense hypothesis space and proposing ideas that would take humans alone far longer to reach.”

The hallucinations – normally viewed as flaws – became a feature, generating unconventional combinations worth testing and validating in the lab. The human scientists inspected the mechanistic reasons the LLM found to suggest these combinations in the first place, feeding the system back and forth in multiple iterations.

By exploring subtle synergies and overlooked pathways, GPT-4 helped identify six promising drug pairs, all tested through lab experiments. Among the combinations, simvastatin (commonly used to lower cholesterol) and disulfiram (used in alcohol dependence) stood out against breast cancer cells. Some of these combinations show potential for further research in therapeutic repurposing.

These drugs, while not traditionally associated with cancer care, could be potential cancer treatments, although they would first have to go through extensive clinical trials.

“This study demonstrates how AI can be woven directly into the iterative loop of scientific discovery, enabling adaptive, data-informed hypothesis generation and validation in real time,” said Zenil.

“The capacity of supervised LLMs to propose hypotheses across disciplines, incorporate prior results, and collaborate across iterations marks a new frontier in scientific research,” said King. “An AI scientist is no longer a metaphor without experimental validation: it can now be a collaborator in the scientific process.”

The research was supported in part by the Alice Wallenberg Foundation and the UK Engineering and Physical Sciences Research Council (EPSRC).

Reference:
Abbi Abdel-Rehim et al. ‘Scientific Hypothesis Generation by Large Language Models: Laboratory Validation in Breast Cancer Treatment.’ Journal of the Royal Society Interface (2025). DOI: 10.1098/rsif.2024.0674

https://www.cam.ac.uk/research/news/ai-scientist-suggests-combinations-of-widely-available-non-cancer-drugs-can-kill-cancer-cells

Cardiac Effects of Modern Breast Radiation Therapy

Eva Berlin, Kyunga Ko, Lin Ma, Ian Messing,Casey Hollawell, Amanda M. Smith, Neil K. Taunk, Vivek Narayan, Jenica N. Upshaw, Amy S. Clark,  Payal D. Shah, Hayley Knollman, Saveri Bhattacharya, 
Daniel Koropeckyj-Cox, Jessica Wang

Abstract

Background

Radiation therapy (RT) improves breast cancer outcomes, but cardiac morbidity remains a concern.

Objectives

This study sought to evaluate changes in cardiac function after RT and the relationship between cardiac dose metrics and echocardiography-derived measures of function.

Methods

In a longitudinal cohort study of women with breast cancer, radiation cardiac dose metrics and core lab quantitated echocardiographic measures of cardiac function were evaluated. Dose metrics included the whole heart, left ventricle, right ventricle, and left anterior descending artery (LAD). Echocardiographic measures included left ventricular ejection fraction (LVEF), longitudinal strain, circumferential strain, E/e’ (ratio of early diastolic mitral inflow velocity to early diastolic mitral annular tissue velocity), Ea/Es (ventricular arterial coupling; ratio of effective arterial elastance to end systolic elastance), and right ventricular fractional area change. The mean change in echocardiographic measures over time and the association between cardiac dose metrics and echocardiographic measures were estimated by repeated-measures multivariable linear regression via generalized estimating equations.

Results

The cohort included 303 participants (median age 52 years, 33.3% African American) who received adjuvant RT (2010-2019) with a median mean heart dose of 1.19 Gy (Q1-Q3: 0.75-2.61 Gy), were followed over a median of 5.1 years (Q1-Q3: 3.2-7.1 years). Across all participants, there was a modest increase in LVEF (52.1% pre-RT to 54.3% at 5 years; P < 0.001) but a worsening in sensitive measures of function, such as circumferential strain (−23.7% pre-RT to −21.0% at 5 years; P = 0.003). Among left-sided/bilateral breast cancer participants, changes in cardiac function were observed across all parameters (P < 0.05). The maximum LAD dose was associated with a modest worsening in LVEF, longitudinal strain, circumferential strain, and E/e′.

Conclusions

Over a median of 5.1 years, modest changes in cardiac function were observed with RT. Maximum LAD dose was associated with a worsening in systolic and diastolic function parameters.

https://www.jacc.org/doi/10.1016/j.jaccao.2025.01.012

Cancer Patients Get Lost in the Red Tape of Utilization Management

 Utilization management (UM) is a set of insurance practices used to control costs by managing when, how, and whether certain treatments are approved. But for people with cancer, these practices can cause more harm than help.

The Insurance Maze: How Cancer Patients Get Lost in the Red Tape of Utilization Management reveals the real-world impact of UM across different insurance types—Employer Plans, Medicare Advantage, and Traditional Medicare.

Drawing on a national survey of 1,201 people treated for cancer, the report shows that insurance red tape is widespread and can delay diagnosis and treatment, impose administrative burdens, lead to unexpected costs, and erode trust in the healthcare system.

---

Our report highlights how insurance red tape can impact people with cancer:

• 85% faced prior authorization for cancer treatments, 76% in the last year alone, often multiple times.
• 43% of Employer Plan respondents underwent prior authorization for five or more different types of cancer treatments in the last year.
• 29% reported diagnosis delays; 40% reported treatment delays due to authorizations.
• 14% experienced abrupt coverage stoppages in the past year; 64% of those experienced treatment interruption.
• Among those who dealt directly prior authorization, 51% lost up to a full business day, 27% lost up to 2-3 business days, and 12% lost a full business week or more dealing with a single authorization incident.
• 95% of prior authorization requests were ultimately approved, highlighting the inefficient and overly broad use of UM in cancer care.
• 36% reported worsened stress, 34% reported worsened finances, and 29% reported reduced trust in the healthcare system as a direct result of insurance problems.
• Respondents with Employer Plans reported the most administrative burden and greatest red tape impacts, followed by Medicare Advantage, then Traditional Medicare.

The results of this report make it clear that many people with cancer face insurance red tape and administrative inefficiencies that obstruct access to timely, high-quality care. UM and other cost-containment strategies must be designed to support, not delay or deny, affordable cancer treatment. Reforming these systems is essential to reducing burden in patients, improving outcomes, and ensuring that administrative processes facilitate, rather than hinder, care. Policymakers, insurers, employers, and advocates must collaborate to streamline UM processes, increase transparency, and prioritize person-centered care, allowing patients to focus on recovery, not red tape.

This report provides a robust, patient-informed snapshot of the current challenges in accessing cancer care. The findings can guide: policymakers seeking data to support insurance reform; insurers, pharmacy benefit managers, and payors aiming to improve coverage practices; employers evaluating benefit designs; researchers exploring the human impact of insurance barriers; and journalists reporting on healthcare access, policy and equity.

https://www.cancercare.org/redtape

Brain Death Cannot Be Determined by Imaging, Study Shows

 

• CT perfusion and angiography failed to meet sensitivity and specificity thresholds to determine brain death.
• Neither should be used as standalone tests to establish death by neurologic criteria, the researchers said.
• If used as supportive evidence, findings must be weighed against clinical assessments to minimize false-positives.

CT perfusion and CT angiography did not meet sensitivity and specificity thresholds of 98% to determine death by neurologic criteria (commonly referred to as brain death), a cohort study showed.

Qualitative brainstem CT perfusion had a sensitivity of 98.5% and a specificity of 74.4%, and quantitative brainstem CT perfusion was not diagnostically accurate, reported Michaël Chassé, MD, PhD, of the Centre Hospitalier de l'Université de Montréal, and co-authors. Qualitative whole-brain CT perfusion showed a sensitivity of 93.6% and a specificity of 92.3%.

CT angiography sensitivity ranged from 75.5% to 87.3%, and specificity ranged from 89.7% to 91.0%, the researchers reported in JAMA Neurologyopens in a new tab or window. The findings were also presented at the Critical Care Reviews Meetingopens in a new tab or window in Belfast, Ireland.

"Neither CT perfusion nor CT angiography met the prespecified threshold of greater than 98% for both sensitivity and specificity. Consequently, they should not be used as standalone tests to establish death by neurologic criteria," Chassé and colleagues wrote.

"However, they may offer supportive evidence in situations where the bedside examination is incomplete or confounded, but their findings must be weighed against a thorough clinical assessment to minimize false-positive determinations," they added.

Brain death occurs in people who have sustained catastrophic brain injury with no evidence of function of the brain as a whole, a state that must be permanent according to current guidelinesopens in a new tab or window. False-negative brain death criteria may prolong futile organ support, and false-positive criteria may lead to an erroneous declaration of death, the researchers noted.

"Although clinical evaluation forms the cornerstone of death by neurologic criteria, its validity can be influenced by confounding factors, such as the effects of sedative medications, traumatic injuries to the skull, or severe metabolic derangements," they wrote. "In these circumstances, death by neurologic criteria guidelines recommend additional ancillary investigation to determine the absence of brain blood flow or perfusion."

CT angiography visualizes blood flow within large cerebral vessels, and CT perfusion assesses tissue-level microvascular perfusion. "Importantly, neither technique measures neuronal function itself, which is what is assessed clinically or with functional tests, such as electroencephalography or evoked potentials," Chassé and co-authors pointed out.

In 2023, the American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society, and Society of Critical Care Medicine issued joint updated brain death guidelinesopens in a new tab or window, noting that while CT angiography has been used with increasing frequency to assist with brain death diagnoses, "available data demonstrate a lack of validation and the potential for false positives."

The World Brain Death Projectopens in a new tab or window also proposed international guidelines recently, saying ancillary tests like CT perfusion and CT angiography needed further study.

Chassé and colleagues studied 282 patients with a mean age of 57.8 years in 15 Canadian intensive care units from 2017 to 2021; nearly half (47%) were female. They included consecutive, critically ill adults with a Glasgow Coma Scale (GCS) score of 3 and no confounding factors who were at high risk of death by neurologic criteria. (The GCS ranges from 3 to 15, with 3 being the worst score and 15 the best.)

Causes of brain injury included hemorrhagic stroke in 53% of patients, anoxic brain injury in 21%, traumatic brain injury in 14%, ischemic stroke in 5%, infection in 1%, and tumor in 0.4%. Ultimately, 204 patients (72%) were declared dead by standardized clinical criteria.

The researchers assessed contrast-enhanced brain CT perfusion with CT angiography reconstructions performed within 2 hours of a blinded, standardized clinical brain death exam. Clinical assessments occurred a median of 64.5 minutes after ancillary testing.

CT perfusion and CT angiography images were interpreted independently by two experienced neuroradiologists blinded to all clinical information, including results from the clinical exam. "Interrater reliability was excellent for all ancillary tests," Chassé and co-authors said: κ ranged from 0.81 to 0.84.

Fourteen patients (5%) experienced minor adverse events, and no serious adverse events occurred.

The study had several limitations, Chassé and colleagues acknowledged. "We used the clinical determination of death by neurologic criteria as the reference standard, which, although widely accepted, has known limitations," they wrote.

Most imaging was performed within the first few days of injury, and whether accuracy would be similar later -- after patients may have had prolonged life-sustaining therapies -- is unknown, they added.

Disclosures

This work was funded by the Canadian Institutes of Health Research.

Chassé reported receiving grants from the Canadian Institutes of Health Research during the conduct of the study. Co-authors reported receiving grants and fees from other groups and having diagnostic patents.

Primary Source

JAMA Neurology

Source Reference: opens in a new tab or windowChassé M, et al "Computed tomography perfusion and angiography for death by neurologic criteria" JAMA Neurol 2025; DOI: 10.1001/jamaneurol.2025.2375.

https://www.medpagetoday.com/neurology/generalneurology/116076

'Docs Should Turn Away From ACIP's Vaccine Recommendations, Ex-Member Says'

 A recently ousted member of the CDC's Advisory Committee on Immunization Practices (ACIP) said Thursday that she is recommending that physicians go to sources other than ACIP for vaccine scheduling recommendations.

"It puts us in a very dangerous place if we can't trust the national recommendations made by ACIP," said Helen Chu, MD, professor of allergy and infectious diseases at the University of Washington, in Seattle. "We do have to start turning to other sources. So what I've been telling people is that they can go to the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists for pregnant persons, and the American Academy of Family Physicians. These groups are still working to review the evidence and to put out science-based recommendations."

On Monday, HHS Secretary Robert F. Kennedy Jr. removed all 17 ACIP membersopens in a new tab or window, including Chu, saying in an HHS press releaseopens in a new tab or window that the agency is "prioritizing the restoration of public trust above any specific pro- or anti-vaccine agenda." The move was widely decried by public health advocates, one of whom called it "reckless, shortsighted, and severely harmful."

"My fear is that we are going to turn into a country where each state is going to have to make its own decisions," Chu said during an online press conference hosted by Sen. Patty Murray (D-Wash.). "Fortunately, Washington state is a place where we have experts and scientists who work together. There are other states where this may not exist, or where they may not choose to recommend vaccines. So that is going to create a lot of chaos."

"We do have to start turning to other sources" besides ACIP for vaccine recommendations, said Helen Chu, MD, of the University of Washington in Seattle. (Photo courtesy of Sen. Patty Murray's office)

On Wednesday, Kennedy named eight new membersopens in a new tab or window to ACIP; several have made controversial statements about vaccines and about COVID. One new member, Robert Malone, MD, an early pioneer of mRNA technology, questioned the severity of COVIDopens in a new tab or window and suggested that millions of Americans were hypnotized into taking the COVID-19 shots; another, Vicky Pebsworth, PhD, RN, of the University of Michigan, is a board member with the vaccine-choice group National Vaccine Information Centeropens in a new tab or window (formerly Dissatisfied Parents Together), a group that is widely considered to be a leading source of vaccine misinformation.

Asked her opinion of the new members, Chu said that she didn't know enough about them to comment. "I can tell you that the members in the past have been people who have worked extensively in the vaccine space, who have been devoting their lives to vaccine policy," she said. "And so I hope that the new members will do the same, will take this very seriously, and will make sure that the decisions they make are for the good of the American public."

Chu also was asked about the vetting process she underwent to get on the committee. "For me, the process took 2 years," she said. "We are initially asked to apply to be on the committee, then we submit letters of recommendation, then all of our credentials are reviewed, and then we go through an extensive process of reviewing our conflicts of interest and making sure that we are unbiased when we serve on this committee."

For her part, Murray was very vocal in her opposition to Kennedy's actions, calling his decision to remove all the ACIP members "dangerous [and] practically unthinkable." "He's already packing the panel with people who advocated letting COVID rip through our communities, who serve as board members of vaccine disinformation groups, who promoted conspiracies and quack treatments for COVID and measles -- and he's just getting started. It is really just about impossible to underscore how reckless and unprecedented this is."

"Let's be clear: RFK Jr. is not just crossing a red line for public health," she continued. "He is sprinting into dangerous, uncharted territory in support of totally deranged conspiracies, and he is dragging us all along with him. He is putting our communities and our families in harm's way ... These recommendations [from ACIP] are trusted by healthcare providers as they talk to their patients and discuss their personal health decisions, and these recommendations affect whether health plans, including Medicare and Medicaid, are required to cover vaccines at zero cost to patients, [and whether] insurance companies can force Americans to foot the bill for vaccines that keep them safe."

Asked by MedPage Today whether the Senate was planning to do anything in response to Kennedy's actions, Murray said, "My Republican colleagues who voted for him need to speak up now, loudly, and they need to tell Secretary Kennedy that this is not acceptable. We need to put in place the members that were there that were vetted, as you just heard, not people that he has picked overnight, that we're just getting some of the names now, and they have some very serious background [issues] that I'm worried about."

https://www.medpagetoday.com/infectiousdisease/vaccines/116051