Methotrexate Fails to Show Benefit in Knee Osteoarthritis Trial

A new study published in the Journal of American Medical Association showed that methotrexate flops to show benefit in knee osteoarthritis trial. Despite earlier signs of pain relief in hand osteoarthritis, methotrexate did not improve pain or joint inflammation in a placebo-controlled trial for knee OA.

Osteoarthritis (OA) is the leading cause of disability globally due to the population’s rapid aging. Chronic joint pain and functional impairment are hallmarks of OA, which significantly lowers a person’s quality of life. The absence of effective treatments to treat OA symptoms or to halt the disease process and related structural development is one of the main obstacles to lessening the burden of OA on people and society.

According to a recent study, people with inflammatory hand osteoarthritis may experience less joint discomfort while using methotrexate. Whether methotrexate has comparable effects on inflammatory knee OA is yet unclear, though. Thus, to determine if methotrexate has symptom-relieving and disease-modifying effects for individuals with knee OA and effusion-synovitis, this study was carried out.

This clinical study that took place in 11 locations in China from July 18, 2019, until January 15, 2023. The patients with inflammatory knee OA who lived in the community and had effusion-synovitis on magnetic resonance imaging were included. Stratified by trial location, participants were randomly allocated (1:1) to receive either a placebo or methotrexate up to 15 mg weekly using block randomization. Over a 52-week period, the main outcomes for the intention-to-treat group were the change in knee visual analog scale (VAS) pain and the change in effusion-synovitis maximum area.

Out of the 278 individuals who underwent screening, 215 (mean [SD] age, 60.4 [7.4] years; 191 [89%] female) were randomly assigned to one of two groups (108 to receive methotrexate, 107 to receive a placebo), and 175 (81%) finished the experiment.

Over the course of 52 weeks, there was no significant difference in the changes in VAS pain or effusion-synovitis maximum area between the methotrexate and placebo groups (between-group difference: 0.3 mm [95% CI, −6.7 to 7.3 mm] for VAS pain; 0.1 cm2 [95% CI, −0.8 to 1.0 cm2] for effusion-synovitis maximal area).

None of the predetermined secondary outcomes showed any discernible differences between groups. About 32 individuals (29.6%) in the methotrexate group and 26 participants (24.3%) in the placebo group experienced at least one adverse event. Overall, in a placebo-controlled trial for knee OA, methotrexate did not reduce pain or joint inflammation, despite prior indications of pain alleviation in hand osteoarthritis.

Source:

Zhu, Z., Yu, Q., Leng, X., Xu, J., Ren, L., Wang, K., Huang, C., Pan, Y., Zhao, Y., Li, T., Mei, Y., Guan, M., Li, X., Zhang, Z., Wu, J., Chen, Y., Qu, Y., Zhu, X., Liao, Q., … Ding, C. (2025). Low-dose methotrexate for the treatment of inflammatory knee osteoarthritis: A randomized clinical trial. JAMA Internal Medicine. https://doi.org/10.1001/jamainternmed.2025.1359

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Early antibiotics may alter immune function in infants, suggests study

A new study led by researchers at the University of Rochester Medical Center (URMC) found that early-life exposure to antibiotics can impair an infant’s developing immune system, and that a naturally occurring metabolite may hold the key to reversing that damage.

Published in Cell, the study uncovered how antibiotic exposure during pregnancy and infancy may permanently weaken the immune system’s ability to fight respiratory infections like the flu. By analyzing both mouse models and human infant lung tissue, the researchers discovered that early antibiotics disrupt the gut microbiome’s ability to produce inosine, a molecule that serves as an important signal for developing immune cells.

By supplementing inosine in mice, however, the researchers were able to correct the immune system issues caused by antibiotics. The finding opens the door to potential therapeutic strategies to bolster immune memory in vulnerable infants.

“Think of inosine as a molecular messenger,” said senior author Hitesh Deshmukh, MD, PhD, chief of the Division of Neonatology at UR Medicine Golisano Children’s Hospital (GCH). “It travels from the gut to developing immune cells, telling them how to mature properly and prepare for future infections.”

The project was part of a long-term R35-funded NIH initiative — which are distributed to experienced investigators to study long-term projects — to investigate how early-life exposures shape lifelong disease risk, including asthma and chronic lung disease.

“We know that antibiotics can be lifesaving for infants, but they also disrupt the microbiome during a critical window of immune development,” said Deshmukh. “Our study identifies one way that disruption affects lung immunity, and more importantly, a way to potentially fix it.”

The disruption ultimately affects the formation of tissue-resident memory T cells, a specialized population of immune cells that reside in the lungs and provide long-term protection against viral infections. Without these cells, infants may remain vulnerable to severe respiratory illness well into adulthood.

“We’ve discovered that the gut microbiome acts as a teacher for the developing immune system,” Deshmukh explained. “When antibiotics disrupt this natural education process, it’s like removing key chapters from a textbook: the immune system never learns crucial lessons about fighting respiratory infections.”

The study compared infant mice exposed to common antibiotics (ampicillin, gentamicin, and vancomycin-the same ones frequently used in pregnant women and newborns) with those that maintained their natural gut bacteria. The following differences were found:

  • Antibiotic-exposed infant mice had significantly reduced populations of protective CD8+ T cells in their lungs
  • These mice showed impaired ability to form tissue-resident memory cells, specialized immune cells that live in the lungs and provide rapid protection against reinfection
  • The immune deficits persisted into adulthood, suggesting permanent changes to immune development

Using lung samples from an NIH-funded biobank run by URMC (BRINDL biobank), the team confirmed that similar immune deficits were present in human infants exposed to antibiotics. These infants not only showed fewer memory T cells but also demonstrated gene expression patterns similar to older adults, who are also at greater risk for respiratory infections.

Most importantly, supplementing antibiotic-exposed mice with inosine largely restored their ability to develop functional memory T cells and mount effective immune responses, offering a promising future avenue for potential therapies.

“This suggests we might be able to protect at-risk infants through targeted supplementation,” said Deshmukh. “While much more research is needed before this approach could be applied clinically, it gives us a path forward.”

The findings could influence future research on how to design interventions-including dietary supplements, metabolite therapies, or microbiome-supportive strategies—to help newborns develop stronger immune memory without relying solely on antibiotics or risky probiotics. The study also underscores the importance of balancing the life-saving benefits of antibiotics with careful stewardship, particularly during sensitive windows of immune development.

Deshmukh credits GCH neonatologist Gloria Pryhuber, MD, as instrumental in the research. Pryhuber’s BRINDL biobank of infant lung samples, collected through a 15-year NIH-funded effort, allowed the team to test their findings in human cells.

“This paper wouldn’t have been possible without Dr. Pryhuber’s generosity and expertise,” Deshmukh said. “The ability to compare our mouse model results to human cells was absolutely critical. It was one of the main reasons I came to Rochester (from Cincinnati Children’s Hospital) -to collaborate with her.”

Reference:

Stevens, Joseph et al., Microbiota-derived inosine programs protective CD8+ T cell responses against influenza in newborns, Cell, DOI:10.1016/j.cell.2025.05.013 

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Odisha NEET 2025 Counselling Begins- check complete schedule, eligibility criteria here

Odisha- Odisha has started the National Eligibility and Entrance Test-Undergraduate (NEET UG) Round 1 counselling for the academic year 2025 from July 22, 2025, on the official website of the Odisha Joint Entrance Examination (OJEE) board. This state-level counselling process is important for NEET-qualified candidates seeking admission to MBBS and BDS courses under 85% state quota seats in Odisha.

In this regard, the OJEE board has issued a notification detailing the guidelines/instructions for the registration process for the preparation of the state merit list based on NEET UG 2025 All India Rank (AIR), which will be used for subsequent counselling & admission in the state quota seats of state MBBS and BDS Courses 2025-26.

The Odisha NEET counselling process consists of four rounds, including spot counselling. However, further rounds will be conducted based on the vacant seats. Except for institute reporting and document verification purposes, the Odisha NEET counselling 2025 process will be conducted in online mode. Below is the complete schedule-

Also Read: UP DGME commences Round 1 NEET 2025 counselling registrations, check complete details

SCHEDULE

S.NO

PARTICULARS

DATES

1

Round 1 Registration & Choice Filling

July 22–26, 2025

2

Document Verification.

July 29–31, 2025

3

Provisional Merit List Release.

August 2, 2025

4

Choice Locking Deadline.

August 3, 2025

5

Round 1 Seat Allotment Result.

August 6, 2025

6

Reporting to Colleges (Round 1).

August 7–12, 2025

7

Round 2 Registration (if applicable).

September 2025

8

Mop-up Round & Stray Vacancy Rounds.

October 2025

ELIGIBILITY

1 The only people eligible to apply for Odisha NEET 2025 counselling are Indian citizens, OCIs, NRIs, and PIOs.

2 Candidates must have passed the Science stream, Physics, Chemistry, Biology, and English sections of the Class 12 Board exam. They must also have received at least 50% of the possible points in Physics, Chemistry, and Biology at the Class 12 Science level for General Candidates (GE), 40% for SC/ST candidates, and 45% for benchmark disability candidates (PC-GE). For candidates in the SC/ST category who are physically challenged, a minimum score of 40% is necessary.

3 To apply for the Odisha MBBS/BDS 2025 counselling, a candidate must have passed the NEET 2025 test. The counselling process won’t be open to those who haven’t applied for or qualified for NEET 2025.

ELIGIBILITY FOR NRI

1 The NRI candidates, who have qualified the NEET UG 2025, are eligible.

2 NRI means the children or wards of a person of Indian origin residing outside India. Such candidates have to submit the following documents in support of NRI eligibility.

i Documents claiming that the sponsor is an NRI (Passport, Visa of the sponsor).

ii Relation of NRI with the candidate.

iii Affidavit from the sponsor that he/she will sponsor the entire course fee of the candidate, duly notarised.

iv Embassy Certificate of the Sponsorer (Certificate from the Consulate).

v All affidavits done in foreign countries must be endorsed by the Embassy of India for authentication purposes.

STEPS TO REGISTER FOR THE ODISHA NEET UG 2025 COUNSELLING

STEP 1- Go directly to the official Odisha NEET 2025 counselling website, or Select “New Candidate Registration”.

STEP 2- Click the ‘I Agree’ checkbox after reading the guide.

STEP 3- After entering the candidate’s name, date of birth, gender, security pin, and NEET application number, click Submit.

STEP 4- Upload the required files and enter additional required information.

STEP 5- Pay the INR 1,000 registration cost online with a credit card, debit card, or net banking.

DOCUMENTS

1 NEET 2025 scorecard.

2 NEET 2025 admit card.

3 Marksheet and certificates of Class 10.

4 Marksheet and certificates of Class 12.

5 Domicile Certificate (if applicable).

6 Caste/Community Certificate (if applicable).

7 PwD Certificate (if applicable).

RESERVATION

The reservation policy of State Government will be followed for selection, and shall be Scheduled Tribe (ST) – 12%, Scheduled Caste (SC) – 8%, Physically Challenged (PC) – 5% of each category, Ex-Servicemen (ES) – 3%, Green Card Holders (GC) – 5%, State Government Schools (SG) – 15% (shall be horizontal covering all vertical reservations as well as unreserved Group) and EWS – 10% (when appropriate number of seats have been increased to accommodate such EWS quota). (Any other reservation category, if notified by the Govt., shall also be applicable.)

FEE STRUCTURE

S.NO

COLLEGE

FEES

1

Hi-Tech MCH, Bhubaneswar

6,50,000

2

Hi-Tech MCH, Rourkela

5,50,000

3

DRIEMS Institute of Health Sciences & Hospital

6,50,000

SEAT MATRIX

S.NO

COLLEGE NAME

MBBS SEATS

BDS SEATS

1

MKCG Medical College, Berhampur

250

–

2

SCB Medical College, Cuttack

250

63

3

VIMSAR, Burla

200

–

4

Kalinga Institute of Medical Sciences, Bhubaneswar

250

100

5

Hi-Tech Medical College, Rourkela

100

100

6

Institute of Dental Sciences, Bhubaneswar

–

100

7

Others (Govt. & Pvt.)

850

–

TOTAL

2,100 MBBS

363 BDS

To view the notification, click the link below 

https://medicaldialogues.in/pdf_upload/notification-295686.pdf

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NPPA Panel Rejects Dr Reddy’s Omez ODT Plea For Seperate Price, Finds No Therapeutic Edge

New Delhi: In a decisive move against what it viewed as an unjustified price escalation, the Multi-Disciplinary Committee (MDC) under India’s drug pricing regulator, the National Pharmaceutical Pricing Authority (NPPA), has rejected Dr Reddy’s Laboratories’ application for a special price of Rs 17.90 per tablet (excluding GST) for its Omeprazole orally disintegrating tablet (ODT) 20 mg, branded as Omez ODT.

The Committee found no sufficient therapeutic justification to support the request, calling the formulation “a tablet dosage form already covered under the Schedule-I of DPCO, 2013.”

According to minutes from the 66th MDC meeting held on March 3, 2025, the company initially approached the National Pharmaceutical Pricing Authority (NPPA) on November 6, 2024, seeking a separate/special price under Para 11(3) of DPCO, 2013. However, the panel pointed out that the existing ceiling price for Omeprazole 20 mg tablet is Rs 4.42 per tablet (S.O. No. 1489(E) dated 27.03.2025), significantly lower than the price sought.

Earlier in the 64th meeting on December 6, 2024, the Committee examined Dr. Reddy’s technical arguments but found them lacking. It clearly noted:

“There is no incremental specified therapeutic rationale of Omeprazole Orally Disintegrating tablet over the Omeprazole Enteric Coated Tablets.”

On that basis, the Committee had recommended rejecting the application. Following this, Dr. Reddy’s submitted a representation on December 24, 2024, requesting a personal hearing and was allowed to present its case during the 65th MDC meeting on January 23, 2025.

After further deliberations and submission of additional documents via email dated January 24, 2025, the Committee met again in its 66th session to re-examine the applicability of Para 11(3). The Committee observed that the provision of the Para 11(3) of the DPCO, 2013 read as below:

(3) Notwithstanding anything contained in sub-paragraph (1) and (2), in the case of injections or inhalation or any other medicine for which dosage form or strength or both are not specified in the Schedule-I of the Drugs (Prices Control) Order, 2013, the Government may fix and notify separate ceiling price or retail price for such formulations with specified therapeutic rationale, considering the type of packaging or pack size or dosage compliance or content in the pack namely liquid, gaseous or any other form, in the unit dosage as the case may be, conforming to Indian Pharmacopeia or other standards as specified in the Drugs and Cosmetics Act, 1940 (23 of 1940) and the rules made thereunder for the same formulation.

It reiterated the scope of the provision: “Para 11(3) may be invoked in case of injections or inhalation or any other medicine for which dosage form or strength or both are not specified in the Schedule-I.”

The panel made it unequivocal that Omez ODT doesn’t qualify:

“The applied formulation is in tablet form and the dosage & strength of the same is mentioned in the Schedule-I. Therefore, the current application does not fall in the purview of Para 11(3).”

The Committee thus reaffirmed its earlier stance and formally recommended to reject the application. It noted;

“The current application does not fall in the purview of Para 11(3). Hence, the committee recommended to reject the application.”

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Study finds health care provider stigma toward substance use disorder varies sharply by condition and provider

A new national study from Columbia University Mailman School of Public Health, with colleagues at the University of Miami Miller School of Medicine, University of Chicago, National Opinion Research Center, and Emory University finds that stigma toward patients with substance use disorders (SUD) remains widespread among U.S. health care providers—and varies significantly across types of substances.

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How our brains are drawn to and spot faces everywhere

If you have ever spotted faces or human-like expressions in everyday objects, you may have experienced the phenomenon of face pareidolia. Now, a new study by the University of Surrey has looked into how this phenomenon grabs our attention, and could be used by advertisers in promoting future products.

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Study finds stopping HRT leads to a period of higher risk of bone fracture for most women

A new study has found that the bone fracture protection women get from menopausal hormone therapy (MHT, also known as HRT) disappears within a year of stopping treatment.

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Rethink the 10,000-a-day step goal; study suggests fewer steps are just as effective

A study led by the University of Sydney suggests that walking 7,000 steps a day offers similar health benefits to walking 10,000, across several outcomes.

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Many high street health tests are unfit-for-purpose and need greater regulation, warn experts

Many self-tests available on the UK high street are unfit-for-purpose and need much greater regulation to ensure they are safe and reliable, conclude two studies published by The BMJ.

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Overweight, Obese Patients Show Better Survival After Shockable In-Hospital Cardiac Arrest Events: Study

USA: A recent study published in the Resuscitation journal sheds light on the complex relationship between body mass index (BMI) and survival outcomes in patients experiencing in-hospital cardiac arrest (IHCA). Conducted by Dr. Nobuhiro Ikemura and colleagues from the UMKC Healthcare Institute for Innovations in Quality, Kansas City, the study analyzed data from over 56,000 patients to understand how BMI influences both survival to discharge and neurologically favorable outcomes.

“The study of 56,411 in-hospital cardiac arrest patients found that underweight individuals (BMI <18.5 kg/m²) had significantly lower odds of favorable neurological survival (OR 0.64) and survival to discharge (OR 0.76), regardless of rhythm type,” the researchers reported. “In contrast, overweight and obese patients showed improved outcomes (OR ~1.17), but only in cases with shockable rhythms. No survival benefit was observed for individuals with very high obesity levels.” 

Using data collected from the Get With The Guidelines-Resuscitation registry between 2006 and 2012, the researchers categorized patients based on BMI: underweight (<18.5 kg/m²), normal (18.5–24.9), overweight (25.0–29.9), obese (30.0–34.9), and very obese (≥35.0). Two key outcomes were assessed: survival to hospital discharge and favorable neurological status at discharge, defined as a cerebral performance category (CPC) score of 1.

The key findings were as follows:

  • Among 10,219 patients with shockable cardiac rhythms, 29.4% achieved favorable neurological survival.
  • In the same group, 38.7% survived to hospital discharge.
  • Overweight patients with shockable rhythms had a 17% higher likelihood (OR 1.17) of favorable neurological outcomes compared to those with normal BMI.
  • Obese patients with shockable rhythms had a 16% higher likelihood (OR 1.16) of favorable neurological outcomes.
  • Underweight patients with shockable rhythms had significantly lower odds (OR 0.64) of favorable neurological survival.
  • Among 46,192 patients with non-shockable cardiac rhythms, survival advantages were not seen in overweight or obese individuals.
  • In the non-shockable rhythm group, underweight patients had poorer neurological outcomes (OR 0.76).
  • Underweight patients with non-shockable rhythms also had lower overall survival to discharge (OR 0.85).
  • There were no significant outcome differences in other BMI categories among patients with non-shockable rhythms.

The findings highlight that BMI plays a varying role depending on the type of cardiac arrest rhythm. While being overweight or obese may offer a protective advantage in cases of shockable rhythms, this benefit does not extend to non-shockable events. Regardless of rhythm type, underweight individuals consistently had the poorest outcomes.

The authors caution that these results should be interpreted in the context of certain limitations. The registry discontinued the collection of height and weight data after 2012, which may limit the applicability of findings to current resuscitation practices, especially given evolving treatment guidelines.

“Despite this, the study provides valuable insights into how body composition may influence cardiac arrest outcomes and highlights the need for tailored clinical strategies that consider BMI as a potential prognostic factor. Further research is needed to explore the underlying mechanisms and to evaluate whether weight-related interventions could impact post-arrest survival and recovery,” the authors concluded.

Reference:

Ikemura, N., Spertus, J. A., Cho, Y. J., Jones, P. G., Jawad, M. A., O’Keefe, E. L., & Chan, P. S. (2025). Association Between Body Mass Index and Survival Outcomes for In-Hospital Cardiac Arrest. Resuscitation, 110671. https://doi.org/10.1016/j.resuscitation.2025.110671

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