Trial Makes the Case for Treating Knee Osteoarthritis With Radiation

 A single course of low-dose radiation therapy led to significant reductions in pain and improvements in physical function in mild-to-moderate knee osteoarthritis (OA), a randomized trial from South Korea showed.

At 4 months, a significantly greater number of patients achieved clinically relevant symptomatic improvement with the low-dose course compared with sham treatment (70.3% vs 41.7%, P=0.014), reported Byoung Hyuck Kim, MD, PhD, of Seoul National University College of Medicine.

A very low-dose of radiation showed no significant benefit, but the study provides objective evidence for the efficacy of low-dose radiation therapy as a potential conservative treatment option, Kim said at the American Society for Radiation Oncology (ASTRO) annual meeting here.

OA affects an estimated 32.5 million U.S. adults, with the knee being the joint most commonly involved.

An unmet need in the treatment of knee OA exists between conservative care and invasive surgery, Kim explained. And while low-dose radiation therapy is a non-invasive and non-inflammatory option, the modality has lacked high-quality evidence to support its use, and its optimal dose has been uncertain, according to Kim.

Considering these are short-term results, ASTRO discussant Gopal Bajaj, MD, MBA, of the Inova Schar Cancer Institute in Fairfax, Virginia, observed that the long-term follow-up will help determine whether the response with low-dose radiation therapy is durable.

Kim presented the primary results of a three-arm multicenter trial (LoRD-KNeA) conducted in South Korea, which randomized 114 adults with mild-to-moderate knee OA to a single course of either low-dose radiation (3 Gy), very low-dose radiation (0.3 Gy), or sham radiation (0 Gy) over six fractions.

Eligible adults had to be ages 50 to 85 years and have primary knee OA (Kellgren-Lawrence grade 2-3, baseline walking pain score of 50-90 out of 100 on visual analog scale [VAS]). Use of concomitant analgesics, except for rescue medication, was restricted during the first 4 months, and re-irradiation was not allowed.

The primary endpoint of the trial was response at 4 months on the Outcome Measures in Rheumatology Clinical Trials/Osteoarthritis Research Society International (OMERACT-OARSI) system, with a positive response defined as either more than 50% improvement in pain and function and at least 20% absolute improvement, or at least 20% improvement in two or more of pain, function, and patient global assessment.

The response rate at 4 months in the very low-dose radiation group was 58.3%.

Secondary endpoints included responses at 1, 8, and 12 months, and Kim noted that 1-month responses were similar among the three groups, at roughly 60% in each.

"It is interesting to note that there is a very heavy placebo response," said Bajaj. "But the groups do separate," he added, noting that the 70% response rate in the low-dose arm "is quite good."

Kim also reported that a clinically meaningful improvement in the Western Ontario and McMaster Universities Arthritis Index score (used to assess pain, stiffness, and function in OA), was observed more frequently in the low-dose radiation group compared with sham (56.8% vs 30.6%, P=0.024).

There were no significant differences in the mean changes from baseline in other secondary outcomes, including VAS, patient global assessment, serum inflammatory markers, and the amount of rescue drug used. No treatment-related toxicity was reported.

"One thing to keep in mind is that the real-world experience that we all have will be clouded by analgesic use," Bajaj pointed out. "Not everyone gets to treat these patients in a controlled environment where we tell patients to stop taking their pain meds."

The results also need to be reproduced in a more diverse population, he added, and said future dose-finding studies could identify an effective dose range between 0.3 and 3 Gy.

Disclosures

The study was supported by funding from Korea Hydro & Nuclear Power.

Kim had no disclosures.

Bajaj reported relationships with Varian Medical Systems, Fuse Oncology, and Totipotent Capital.

Primary Source

American Society for Radiation Oncology

Source Reference: Kim BH, et al "Clinical effectiveness of single course low-dose radiation therapy in knee osteoarthritis: short-term results from the randomized, sham-controlled trial" ASTRO 2025; LBA 06.

https://www.medpagetoday.com/meetingcoverage/astro/117738

Patients with Opioid Use Disorder Diagnoses Increased 40 Percent from 2021 to 2024

 FAIR Health Releases Annual Update of Opioid Tracker, an Interactive Tool Tracking Opioid Use Disorder Nationally and State by State

 Nationally, among the commercially insured population, patients with opioid use disorder diagnoses showed an overall increase from 2021 to 2024, according to FAIR Health's Opioid Tracker. In 2021, there were 386 patients with opioid use disorder diagnoses per 100,000 patients, while in 2024 there were 539, an increase of 39.8 percent. This and other findings were reported today when FAIR Health released its annual update of the Opioid Tracker, a free, interactive tool tracking opioid use disorder among commercially insured patients nationally and state by state. A brief released simultaneously offers a user's guide to the Opioid Tracker.

The Opioid Tracker includes a heat map representing patients with opioid use disorder diagnoses per 100,000 patients receiving medical services in 2024 for each state. Clicking on a state displays an infographic for that state with opioid use disorder data from 2024. The infographic includes the top five procedure code categories by utilization, the top five procedure codes by aggregate allowed amounts,1 the change in the number of patients with opioid use disorder diagnoses per 100,000 patients from 2021 to 2024, and the distribution of patients by age and gender. There is also a similar infographic for the nation as a whole, along with a second national infographic showing the top five states for opioid use disorder diagnoses, the fastest-growing specialties, the distribution of places of service, and service type (professional versus facility) as a percentage of total allowed amounts. The source of the data is FAIR Health's repository of commercial health claims.

Among the key findings revealed by the Opioid Tracker:

• In 2024, Tennessee had the highest rate of commercially insured patients receiving treatment for opioid use disorder, with 1,447 patients with such a diagnosis per 100,000 patients. It was followed by West Virginia (1,323 patients), Kentucky (1,281 patients), Arkansas (1,218 patients) and Delaware (1,165 patients).
• Nationally in 2024, alcohol/substance abuse services and treatments constituted the procedure code category with the highest utilization for opioid use disorder among commercially insured patients, representing 39.5 percent of claim lines2 for all procedure code categories for that diagnosis.
• Nationally in 2024, H0018 (behavioral health short-term residential treatment program, no room and board, per diem) was the procedure code with the highest aggregate allowed amount for opioid use disorder among commercially insured patients, accounting for 12.7 percent of aggregate allowed amounts for that diagnosis. The average allowed amount for this code was $1,124.
• The highest percentage of opioid use disorder diagnoses among commercially insured patients were attributable to patients in the 31 to 40 age group, with 26.8 percent of the total age distribution in 2024 across the nation.
• Among commercially insured patients with opioid use disorder diagnoses nationally in 2024, males were 55.7 percent of patients with those diagnoses, while females were 44.3 percent.
• The fastest-growing specialty involved in the treatment of opioid use disorder nationally in 2024 was nurse practitioner, which increased 102 percent in percent of claim lines from 2021 to 2024. In second and third position, respectively, were physician assistant (69 percent) and psychiatric nurse (66 percent).

1	An allowed amount is the total negotiated, in-network fee paid to the provider under an insurance plan. It includes the amount that the health plan pays and the part the patient pays under the plan's in-network cost-sharing provisions (e.g., copay or coinsurance if the patient has met the deductible). The aggregate allowed amount for a given procedure is simply the sum of all the allowed amounts for that procedure in the applicable geographic area during the time frame.
2	A claim line is an individual service or procedure listed on an insurance claim.

For the Opioid Tracker, click here. For the user's guide to the Opioid Tracker, click here.

https://www.prnewswire.com/news-releases/patients-with-opioid-use-disorder-diagnoses-increased-40-percent-from-2021-to-2024-302566812.html

Failing Public Health Again? Analytical Review of Depression and Suicidality From Finasteride

 

Abstract

Background: Finasteride, widely prescribed for androgenetic alopecia, has long been suspected of causing severe neuropsychiatric reactions, including depression, anxiety, and suicidality, even after the drug is discontinued. This study systematically reviews evidence that supports this suspicion and analyzes the reasons for this delayed recognition.

Observations: Concerns about depression from finasteride were raised in several studies as early as 2002. Between the years 2017 and 2023, 4 independent analyses of adverse event reporting systems and 4 studies using data mining of healthcare records indicated a significant increase in the risk for depression, anxiety, and/or suicidal behavior with the use of finasteride. There has been, therefore, a two-decade delay in the realization of the incidences and the gravity of neuropsychiatric effects, allowing harm from a medicine prescribed for a cosmetic indication of hair loss.

Potential Harms and Implications: Over 20 years worldwide, hundreds of thousands may have endured depression, and hundreds may have died by suicide. According to the precautionary principle, such a risk from a cosmetic medication suggests a benefit-to-harm balance that justifies action to protect the public, and the burden of proving that the intervention is not harmful falls on manufacturers.

Causes for Delayed Risk Recognition: The long delay in recognizing the risks associated with finasteride exposure includes the manufacturer’s failure to perform and publish simple pharmacovigilance studies using database analyses and regulators’ failure to request such studies from the manufacturer or to perform them.

Conclusions and Relevance: Current evidence shows that finasteride use can cause depression and suicidality. A historical literature review discloses gaps between research evidence and regulatory steps. The lesson is that before approving a medication for the market, regulators should require manufacturers to commit to performing and disclosing ongoing postapproval analytical studies, and this requirement needs to be enforced.

J Clin Psychiatry 2025;86(4):25nr15862

https://www.psychiatrist.com/jcp/analytical-review-depression-suicidality-finasteride/

More Kids Using Sodium Nitrate in Suicide Attempts

 Amid an uptick in U.S. adolescents attempting suicide by using sodium nitrate and nitrate -- chemical compounds commonly used in food preservation -- researchers found several trends regarding affected youth, in a recent study.

Kids who died by sodium nitrate poisoning skewed older compared with kids who used other means (62% were 17- to 21-year-olds vs 36% in the non-sodium nitrate group). White kids comprised the majority of both groups (62% vs 73%, respectively), but Asian kids had the second highest prevalence in the sodium nitrate group (24%) while Black kids did in the non-sodium nitrate group (12%), according to Frank Pleban, PhD, of Tennessee State University in Nashville.

Notably, a higher proportion of kids in the sodium nitrate group had been hospitalized for mental health concerns in the year prior to their death compared to the non-sodium nitrate group (20% vs 9%). They were also more likely to have seen a healthcare provider within a month of their death (13% vs 8%) and more likely to have had a mental health emergency department visit in the year before their death (13% vs 9%), Pleban reported at the American Academy of Pediatrics annual meeting.

Kids who died by sodium nitrate poisoning were also less likely to have received mental health services than those who died by other methods (21% vs 26%), and were less likely to have had a history of substance use (6% vs 22%), or to have experienced maltreatment (6% vs 21%).

"There are a variety of prevention opportunities resulting from this work, including increasing awareness about the growing use of sodium nitrate and nitrate in self-harm, providing suicide prevention resources that specifically address this method, and informing the public about the ease of access to these chemical compounds online," Pleban said in a press release.

Sodium nitrate and nitrate can be easily purchased online as meat curing ingredients, and when ingested in certain quantities, can cause methemoglobinemia, leading to hypoxia and eventual death, he said during his presentation.

The findings on sodium nitrate and nitrate come amid recent concern regarding poisoning and youth suicide.

For instance, from 2000 to 2023, exposures to medications, dietary supplements, or psychoactive substances grew among kids, especially those exposures associated with suspected self-harm or suicidal intent, according to data from U.S. poison centers.

Increased rates of suspected suicide attempts by poisoning among kids and adolescents during the pandemic were also reported.

Pleban noticed a rise in using sodium nitrate and nitrate in suicide attempts when looking over data from the last few years, and said that addressing this method should be part of a broader public health approach to suicide prevention.

"In terms of prevention, it's limiting access and making sure that, when an overdose occurs, people are aware that it might be this substance," psychologist Julie Cerel, PhD, of the University of Kentucky in Lexington, who was not involved in the study, told MedPage Today.

As for different methods of suicide, there is a "moving target," she said, and this "calls for the need to have upstream prevention," including having recent healthcare visits focused on mental health.

For the study, researchers compared suicide deaths in 14- to 21-year-olds from sodium nitrate and nitrate with youth suicide deaths from other methods. Deaths occurred between 2018 and 2023, and were documented in the Pediatric National Fatality Review-Case Reporting System. There were 34 deaths in the sodium nitrate group and 4,544 deaths in the non-sodium nitrate group. Males represented 71% and 73% of the groups, respectively. Mean age was similar for both (16.7 years vs 16 years).

Additional studies are needed to examine the impact of safety interventions on the incidence of sodium nitrate and nitrate self-poisoning, Pleban noted.

Disclosures

The authors of the study reported receiving support from the Health Resources and Services Administration.

Pleban and Cerel did not report any relevant conflicts of interest.

Primary Source

American Academy of Pediatrics

Source Reference: Pleban F, et al "Emerging trend of sodium nitrite and nitrate self-poisoning: fatality review challenges and public health implications" AAP 2025.

https://www.medpagetoday.com/meetingcoverage/aap/117742

'Mitigating the Risk For Tardive Dyskinesia in Elderly Patients on Antipsychotics'

 While any patients taking an anti-dopaminergic agent may develop tardive dyskinesia (TD) -- a movement disorder hallmarked by abnormal and involuntary tics of the face, trunk, and limbs -- older adults are particularly vulnerable.

Being older than 55 is listed as a risk factor for developing TD in practice guidelines from the American Psychiatric Association (APA) on treating schizophrenia.

"Older adults treated with anti-dopaminergic medications are at greatest risk for development of tardive dyskinesia," noted Omar Ghosn, MD, of the University of California San Diego in La Jolla, and colleagues in a 2021 review.

"It is important to recognize risk factors and accurately diagnose TD early," they wrote. "New FDA-approved treatments and investigational agents are now available to manage the condition, however further research to optimally prevent and manage TD in the older adult population remains necessary."

Older People, Higher Prevalence

Development of TD can occur after treatment with dopamine receptor-blocking agents, like antipsychotics used to treat schizophrenia, due to dysregulation of dopamine transmission. Certain factors can increase TD risk, including longer duration of antipsychotic treatment, higher doses, and the use of first-generation versus second-generation agents.

But older patients have a heightened risk for TD even with shorter exposure to newer second-generation antipsychotics, according to a Neuropsychiatric Disease and Treatment review by Leslie Citrome, MD, MPH, of New York Medical College in Valhalla, and colleagues.

TD occurs at a rate of around 4% to 8% per year among adults treated with first-generation antipsychotics, which is about three times higher than rates among second-generation antipsychotic users, according to APA guidelines. In contrast, a study of 261 neuroleptic-naïve patients ages 55 and older reported cumulative TD incidences of 25%, 34%, and 53% after the first, second, and third year of first-generation antipsychotic use, respectively.

While lower antipsychotic doses can help mitigate TD risk in younger patients, this strategy isn't quite as effective in older adults. One study of 330 older adults with dementia (mean age 82.5 years) reported that 2.6% developed TD symptoms after being treated with risperidone -- a second-general antipsychotic -- at average doses of less than 1 mg/day for 1 year. On the other hand, another study of a mixed-age adult population treated at an average risperidone dose of 3.9 mg/day for 6 months reported no new cases of TD.

"The mechanism underlying age-related increased susceptibility is unclear but may be due to higher cumulative exposure to antipsychotics as well as an age-related decrease in dopaminergic neurons in the substantia nigra," Citrome's group noted.

Off-Label Use

Off-label antipsychotic use, especially in nursing homes, is another piece of the puzzle.

"Older adults residing in skilled nursing facilities are prescribed antipsychotic medications more often than community-dwelling older adults," Ghosn's group pointed out.

According to a 2010 study of elderly nursing home residents, 23.5% received at least one second-generation antipsychotic agent and 86.3% received their antipsychotic off-label. Most (56.9%) still received an antipsychotic for an evidence-based use, with higher use among older individuals and those with dementia.

"Antipsychotic medications, which are often the culprits for TD, are widely prescribed for older adults for a variety of reasons including psychotic spectrum and mood disorders as well as the behavioral and psychological symptoms of dementia (BPSD)," explained Ghosn and co-authors. "Although antipsychotic medications are not the first-line for treating BPSD, given the lack of FDA-approved medications for this indication and progressive severity of the illness, they are utilized off-label in 12.3% to 37.5% of patients for management of BPSD symptoms such as agitation, aggression, and psychosis."

Prevention and Management

"Given the prevalent prescription of dopamine receptor blockers for older adults, and the vulnerability of this population to develop this adverse effect, it is important for clinicians to accurately assess, monitor, and manage TD," Ghosn's group urged.

They advised following the adage "start low, go slow" to reduce the risk of TD with anti-dopaminergic drugs in older adults. "The clinician should aim to achieve the lowest effective dose, routinely re-evaluate whether antipsychotic medication is necessary for patients who do not have a primary psychotic disorder diagnosis, and regularly monitor for signs of TD," they said.

But for older patients who require antipsychotic treatment, quetiapine and clozapine are considered "less risky for causing TD [and] extrapyramidal symptoms," they noted. A review of 13 studies suggested that clozapine may help to reduce dyskinetic symptoms over time.

If moderate-to-severe TD symptoms persist, treatment with newer VMAT-2 inhibitors, including deutetrabenazine (Austedo, Austedo XR) and valbenazine (Ingrezza, Ingrezza Sprinkle), is recommended. A post-hoc analysis suggested that adults 55 and older may be more likely to achieve a maximal response from once-daily valbenazine than younger patients.

https://www.medpagetoday.com/spotlight/tardive-dyskinesia/117751

GeneDx joins $14.4 million NIH-funded genomic newborn screening study

 GeneDx (NASDAQ: WGS) announced its participation in BEACONS, a multi-state genomic newborn screening initiative that received $14.4 million in funding from the National Institutes of Health Common Fund Venture Program.

The three-year study will enroll up to 30,000 newborns across as many as 10 states to pilot the integration of whole genome sequencing into existing state newborn screening systems. Mass General Brigham and Ariadne Labs lead the collaboration, which includes Boston Children's Hospital, Albert Einstein College of Medicine, the Association of Public Health Laboratories, Case Western Reserve University, Baylor College of Medicine, and Illumina.

GeneDx will perform genomic sequencing and interpretation for the study, while governance and decision-making remain with public health and academic partners. The initiative aims to screen for hundreds of additional conditions that can be treated from birth, beyond the current standard newborn screening panel.

The study requires parental consent and education before enrollment. Parents will participate in surveys and interviews about their experiences, and a Community Advisory Board will address ethical, legal, privacy, and social considerations of newborn sequencing.

Robert Green, contact and co-lead investigator at Mass General Brigham and Ariadne Labs, stated that the initiative brings "the next generation of hope, giving families the option of genomic screening for hundreds of additional conditions that can be treated from birth."

The research team will select genetic conditions for screening based on input from rare disease advocates, state public health laboratories, and prior research evidence. The conditions chosen will be those that, when identified early, can meaningfully improve a child's health outcomes.

The project represents what organizers describe as the first national effort to evaluate whether genome sequencing can be implemented responsibly and sustainably through public health newborn screening programs in the United States.

https://www.streetinsider.com/Corporate+News/GeneDx+joins+%2414.4+million+NIH-funded+genomic+newborn+screening+study/25406638.html

Trump vows to press Xi on soybean dispute as farmers feel the strain

 President Donald Trump signaled Wednesday that he plans to push Chinese leader Xi Jinping on US soybean purchases when they meet, as American farmers grapple with fallout from his trade wars.

"The Soybean Farmers of our Country are being hurt because China is, for 'negotiating' reasons only, not buying," Trump wrote on his Truth Social platform.

"I'll be meeting with President Xi, of China, in four weeks, and Soybeans will be a major topic of discussion," he added.

Trump said last month that he would meet Xi on the sidelines of an Asia-Pacific Economic Cooperation (APEC) summit in South Korea starting at the end of October. He also said that he would travel to China next year.

The talks come after Washington and Beijing engaged in a tit-for-tat tariffs war earlier this year, imposing escalating duties on each other's exports.

While both sides have since agreed to de-escalate tensions, this has been a shaky truce with lingering effects.

Trump on Wednesday reiterated plans to use some US tariff revenues to aid farmers, while taking aim at his predecessor Joe Biden for not enforcing an earlier trade pact with Beijing that involved a step up in farm purchases.

Trump's aggressive trade policies and resulting fallout have weighed on US farmers, including hitting export markets like China.

The American Soybean Association (ASA) has urged Trump to prioritize soybeans in trade talks with Beijing.

It warned in August that Beijing's retaliatory tariffs are "shutting American farmers out of their largest export market going into the 2025 soybean harvest."

China is a top global buyer of soybeans, with the United States once being a major source for the world's second biggest economy.

But "the US has made zero sales to China in this new crop marketing year due to 20-percent retaliatory tariffs imposed by China in response to US tariffs," ASA President Caleb Ragland said last week.

"This has allowed other exporters, Brazil and now Argentina, to capture our market at the direct expense of US farmers," he added in a statement.

"The frustration is overwhelming," he said.

The first Trump administration provided aid to farmers too as his previous trade war gutted exports to what had been a massive market for US soybeans and pork, among other products.

During Trump's first presidency, retaliatory tariffs on the United States caused more than $27 billion in US agricultural export losses from mid-2018 to late-2019.

https://finance.yahoo.com/news/trump-says-push-chinas-xi-190515266.html