KEA to close option entry Facility for NEET 2024 Special Stray Vacancy Round Counselling tomorrow, see schedule

Karnataka- Karnataka Examination Authority (KEA) is going to close the option entry facility for National Eligibility and Entrance Test-Undergraduate (NEET UG) Special Stray Vacancy Round Counselling 2024 tomorrow.

KEA is conducting the NEET UG Special Stray Vacancy Round Counselling 2024 online seat allotment to not-reported Medical seats and unfilled-not-reported dental seats for the academic year 2024. The process of NEET UG Special Stray Vacancy Round Counselling 2024 started on November 19, 2024, and will end on November 29, 2024.

Also Read: KEA releases seat matrix for PG medical admissions 2024, details

SCHEDULE

S.NO

PARTICULARS

DATES

1

Display of seat matrix with fee structure.

November 19, 2024

2

Candidates are to pay the Medical/Dental course fee.

November 20 to November 22, 2024

3

Option Entry.

November 20 to November 24, 2024

4

Provisional seat allotment.

November 25, 2024

5

Final seat allotment.

November 26, 2024

6

Payment of balance fee if any.

November 26 to November 28, 2024

7

Last date for reporting to allotted colleges with documents.

November 29, 2024

Meanwhile, as per the official notice in this regard, candidates who have not been allotted any Medical seat in KEA in any of the rounds or after allotment of a Medical seat surrendered the medical seat by forfeiting the Caution Deposit are only eligible to participate in Special Stray Vacancy Round for the available Medical / Dental seats. Candidates who have been allotted a Dental seat through KEA in any of the rounds can participate in a Medical seat but not in a dental seat again.

MEDICAL/DENTAL COURSE FEE DETAILS

MEDICAL

S.NO

INTERESTED ‘IN’

PAY

CANDIDATES GET THE ELIGIBILITY TO ENTER OPTIONS

1

‘P’ Seats

Rs. 12,00,867/-

Allowed to enter ‘G’ and ‘P’ Seat options and eligible to enter for all types of dental seats.

2

‘P’ Seats in Private University.

Rs. 22,15,750/-

Allowed to enter ‘G’ and ‘P’ Seats and ‘P’ seats in Private University options and eligible to enter for all types of dental seats.

DENTAL

3

‘G’ Seats

Rs. 96,058/-

Allowed to enter only ‘G’ Seat options.

4

‘P’ Seats & ‘P’ seats in Private University

Rs. 4,00,000/-

Allowed to enter ‘G’ and ‘P’ Seats and ‘P’ seats in Private University options. (Candidate has to pay the balance fee after the announcement of results).

5

‘N’/’Q’ Seats

Rs. 6,00,000/-

Allowed to enter all types of seat options (Candidate has to pay the balance fee after the announcement of results).

To view the notice, click the link below

https://medicaldialogues.in/pdf_upload/kea-ends-fee-payment-facility-for-neet-ug-special-stray-vacancy-round-counselling-2024-today-261870.pdf

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Promising Results for Late-Liver-Stage Attenuated Malaria Parasite Vaccine in Early Trial

Netherlands: A recent trial investigating the safety and efficacy of a late-liver-stage attenuated malaria parasite vaccine has shown promising results, potentially paving the way for a more effective and long-lasting malaria prevention strategy.

The vaccine being tested, known as GA2, involves the use of Plasmodium falciparum, the parasite responsible for the most severe form of malaria. In the small trial, GA2 demonstrated a promising immune response and protective efficacy, highlighting the need for further investigation to confirm these findings. The findings were published online in the New England Journal of Medicine on November 20, 2024.

Currently, licensed malaria subunit vaccines provide only modest, short-lived protection against malaria, which has made it difficult to effectively combat the disease, particularly in regions with high transmission rates. Therefore, Olivia A.C. Lamers, Meta Roestenberg, Leiden University Medical Center, the Netherlands, and colleagues investigate live-attenuated Plasmodium falciparum malaria parasites use as a vaccine strategy. This approach involves inoculating individuals with a weakened form of the malaria parasite, designed to stimulate the immune system without causing the disease. The live-attenuated vaccine is believed to offer more robust immune responses than traditional subunit vaccines, which often target only specific proteins of the parasite.

For this purpose, the researchers conducted a double-blind, controlled clinical trial to assess the safety, side-effect profile, and efficacy of immunization using a second-generation genetically attenuated parasite (GA2). This was a mei2 single knockout P. falciparum NF54 parasite, which extended development into the liver stage. In stage A, participants were exposed to bites from 15 or 50 infected mosquitoes. In stage B, healthy adults were randomly assigned to receive bites from GA2, GA1 (early-arresting parasite), or placebo. After three immunization sessions, the researchers compared the protective efficacy of GA2 against P. falciparum infection with that of GA1 and placebo.

The primary endpoints included the number and severity of adverse events and blood-stage parasitemia following exposure to GA2-infected mosquitoes and controlled human malaria infection.

Based on the study, the researchers reported the following findings:

  • Adverse events were similar across all trial groups.
  • Protective efficacy against subsequent controlled human malaria infection was observed in 89% of participants in the GA2 group.
  • Protective efficacy was observed in 13% of participants in the GA1 group.
  • No protective efficacy was observed in the placebo group (0 of 3 participants).
  • A significantly higher frequency of P. falciparum–specific polyfunctional CD4+ and Vδ2+ γδ T cells was found in participants who received GA2 compared to those who received GA1.
  • GA2 and GA1 induced similar antibody titers targeting the P. falciparum circumsporozoite protein.

“Our findings indicate that parasites that arrest later during the liver stage (GA2) provide better protection compared to early-arresting sporozoites (GA1), representing a promising advancement toward developing a next-generation malaria vaccine,” the researchers wrote.

“However, the conclusions of this trial are limited by the small sample size and the extensive range of immunologic analyses conducted. Further studies with larger participant groups are needed to more comprehensively assess the safety profile of GA2,” they concluded.

Reference:

DOI: 10.1056/NEJMoa2313892

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Zerlasiran Achieves Over 80 Percent Reduction in Lipoprotein(a) Levels in ASCVD Patients: Phase 2 Trial Results

USA: In a significant advancement for cardiovascular disease treatment, a recent Phase 2 randomized clinical trial demonstrated the efficacy of Zerlasiran, a small-interfering RNA (siRNA) therapeutic, in significantly lowering lipoprotein(a) [Lp(a)] levels.

The findings, published in the Journal of the American Medical Association (JAMA), revealed that zerlasiran demonstrated a favorable safety profile and achieved a reduction of over 80% in time-averaged lipoprotein(a) levels during 36 weeks of treatment in patients with atherosclerotic cardiovascular disease (ASCVD).

Elevated Lp(a) levels are increasingly recognized as an independent cardiovascular risk factor linked to conditions such as coronary artery disease, stroke, and peripheral arterial disease. However, current therapeutic options for targeting Lp(a) specifically remain limited.

Zerlasiran, designed to inhibit LPA gene expression—responsible for Lp(a) production—was administered via subcutaneous injections at varying dosages. Its targeted mechanism of action represents a significant leap forward, addressing an unmet need for patients with high Lp(a) levels. Considering this, Steven E. Nissen, Cleveland Clinic Coordinating Center for Clinical Research, Cleveland, Ohio, and colleagues aimed to assess the impact of Zerlasiran, a small-interfering RNA designed to target hepatic production of apolipoprotein(a), on serum lipoprotein(a) levels.

For this purpose, the researchers conducted a multicenter trial involving patients with stable ASCVD and lipoprotein(a) levels ≥125 nmol/L at 26 sites across Europe and South Africa between January 2023 and April 2023, with follow-up until July 2024. Participants received either a placebo or Zerlasiran in varying doses and intervals.

The primary outcome measured was the time-averaged percentage change in lipoprotein(a) levels from baseline to 36 weeks, with extended follow-up to 60 weeks.

The study led to the following findings:

  • The study included 178 patients with a mean age of 63.7 years; 25.8% were female.
  • The median baseline lipoprotein(a) concentration was 213 nmol/L.
  • A total of 172 patients completed the trial.
  • Compared to the pooled placebo group, the least-squares mean time-averaged percent change in lipoprotein(a) concentration from baseline to week 36 was:
    • −85.6% for the 450 mg every 24 weeks group.
    • −82.8% for the 300 mg every 16 weeks group.
    • −81.3% for the 300 mg every 24 weeks group.
  • The median percent change in lipoprotein(a) concentration at week 36 was:
    • −94.5% for the 450 mg every 24 weeks group.
    • −96.4% for the 300 mg every 16 weeks group.
    • −90.0% for the 300 mg every 24 weeks group.
  • Injection site reactions, including mild pain, were the most common treatment-related adverse effects, occurring in 2.3% to 7.1% of participants on the first day after administration.
  • There were 20 serious adverse events reported in 17 patients, none of which were related to the study drug.

The findings revealed that Zerlasiran achieved over 80% reductions in time-averaged lipoprotein(a) concentrations over 36 weeks with doses of 300 mg every 16 weeks or 300 mg and 450 mg every 24 weeks. Sustained reductions were observed up to 60 weeks after the initial dose.

“The treatment was well-tolerated, with no safety concerns identified with the infrequent dosing schedule. These results highlight the potential of Zerlasiran and support its progression to Phase 3 clinical trials,” the researchers concluded.

Reference:

Nissen SE, Wang Q, Nicholls SJ, et al. Zerlasiran—A Small-Interfering RNA Targeting Lipoprotein(a): A Phase 2 Randomized Clinical Trial. JAMA. Published online November 18, 2024. doi:10.1001/jama.2024.21957

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CKD Patients with Diabetes at All Stages at higher Risk of Lower Extremity Amputation, suggests study

USA: A recent database study has highlighted a concerning trend in patients suffering from chronic kidney disease (CKD), revealing that those with comorbid diabetes mellitus (DM) face a significantly higher risk of lower extremity amputation (LEA) compared to their counterparts without diabetes.

“Patients with CKD stage 5 and diabetes were 30 times more likely to undergo a lower extremity amputation compared to those with CKD stage 5 but without diabetes,” the researchers wrote in the Journal of Diabetes and its Complications.

Chronic kidney disease, a condition marked by the gradual loss of kidney function, often coexists with other serious health issues, particularly diabetes. Diabetes mellitus is known to contribute to a range of complications, including neuropathy, poor circulation, and infections, all of which can increase the likelihood of amputation. In CKD patients, these factors are compounded by impaired kidney function, which can hinder the body’s ability to fight infections and heal wounds.

Lower extremity amputation is a severe and often dreaded complication of DM. In light of this, Dhruv Nandakumar, University of Texas Southwestern Medical School, Dallas, TX, USA, and colleagues sought to assess how DM influences LEA rates in patients across different stages of chronic kidney disease.

For this purpose, the researchers analyzed a commercially available de-identified database, reviewing data from 2010 to 2023 to identify patients undergoing lower extremity amputation and those diagnosed with CKD. The study included patients with and without diabetes who were followed for at least five years. LEA rates were then compared across all five stages of CKD between patients with diabetes and those without.

Key Findings:

  • Higher LEA Rates for Diabetic Patients:
  • Patients with diabetes exhibited significantly higher rates of all types of lower extremity amputation (LEA) across all stages of CKD, including overall, minor, and major LEA, compared to those without diabetes.
  • Increased Risk in CKD Stage 5:
    • Patients with DM and CKD stage 5 (end-stage renal disease) were 30 times more likely to undergo any LEA compared to those without diabetes at CKD stage 5 (OR 30.2).
    • The likelihood of undergoing minor LEA in DM patients with CKD stage 5 was 29 times higher than in non-diabetic CKD stage 5 patients (OR 28.9).
    • Diabetic patients with CKD stage 5 had a 40 times greater risk of requiring major LEA compared to their non-diabetic counterparts (OR 40.1).
  • Minor LEA More Common than Major LEA:
  • Across all CKD stages, minor LEAs were more frequently performed than major LEAs, regardless of diabetes status.
  • LEA Rates Increase with CKD Progression in Diabetic Patients:
  • In patients with diabetes, LEA rates significantly increased as CKD progressed from stages 2 to 5, with a notable surge between stages 4 and 5 (OR 2.6).
  • No Significant LEA Increase Between CKD Stages 1 and 2:
  • For patients with diabetes, there was no significant increase in LEA rates between CKD stages 1 and 2 (OR 1.1).

“To our knowledge, this study represents the first large retrospective database analysis comparing lower extremity amputation rates in patients with CKD, both with and without diabetes,” the researchers wrote.

“The findings indicate that patients with diabetes face a significantly higher risk of LEA at all stages of CKD. Foot and ankle surgeons managing diabetes-related foot conditions should be aware of the potential impact of declining renal function on these patients’ outcomes. These results warrant further investigation to confirm and expand upon the observed trends,” they concluded.

Reference:

Nandakumar, D., Johnson, M. J., Lavery, L. A., Conover, B. M., Raspovic, K. M., Truong, D. H., & Wukich, D. K. (2024). Lower extremity amputation rates in patients with chronic kidney disease: A database study comparing patients with and without diabetes mellitus. Journal of Diabetes and its Complications, 38(11), 108876. https://doi.org/10.1016/j.jdiacomp.2024.108876

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Is antibiotic prophylaxis necessary for patients undergoing extracorporeal membrane oxygenation?

In recent times, the utilization of Extracorporeal Membrane Oxygenation (ECMO) has increased. By employing ECMO in the ICU, the care for adult and pediatric patients suffering from acute respiratory or cardiac failure can be enhanced. Recent research study examined the use of antibiotic prophylaxis for patients undergoing Extracorporeal Membrane Oxygenation (ECMO). ECMO patients are highly susceptible to infections, with high rates of sepsis and nosocomial infections. The study objectives were to investigate whether antibiotic prophylaxis can decrease 30-day mortality and prevent the occurrence of nosocomial infections in ECMO patients. A systematic review and meta-analysis were conducted, including 5 retrospective studies with a pooled population of 7,996 patients.

Results on Mortality and Infections

Regarding 30-day mortality, the random-effects model found no statistically significant difference between the antibiotic prophylaxis group and the non-prophylaxis group (OR 0.76; 95%CI 0.37–1.59). For the rate of nosocomial infections, the fixed-effect model showed an OR of 0.81 (95%CI 0.71–0.92) in favor of the antibiotic prophylaxis group, with a number-needed-to-treat of 39.7 patients.

Quality of Evidence

The quality of evidence for both outcomes was assessed as very low, indicating high risks of bias, inconsistency, and potential confounding factors. The retrospective nature of the studies and small sample sizes limit the reliability of the conclusions.

The study findings suggest that antibiotic prophylaxis may have no significant impact on reducing 30-day mortality in ECMO patients, but may decrease the incidence of nosocomial infections, albeit with a high number needed to treat. However, these results are provisional due to the low quality of available evidence.

Recommendations for Future Research

The authors recommend conducting high-quality prospective studies, including randomized controlled trials, to further investigate the specific clinical questions regarding the use of antibiotic prophylaxis in ECMO patients. More research is needed to determine the optimal antibiotic regimen, duration of prophylaxis, and the potential impact on different ECMO patient populations and infection outcomes.

Key Points

1. The study examined the use of antibiotic prophylaxis for patients undergoing Extracorporeal Membrane Oxygenation (ECMO), as ECMO patients are highly susceptible to infections with high rates of sepsis and nosocomial infections.

2. The study objectives were to investigate whether antibiotic prophylaxis can decrease 30-day mortality and prevent the occurrence of nosocomial infections in ECMO patients. A systematic review and meta-analysis were conducted, including 5 retrospective studies with a pooled population of 7,996 patients.

3. Regarding 30-day mortality, the random-effects model found no statistically significant difference between the antibiotic prophylaxis group and the non-prophylaxis group. For the rate of nosocomial infections, the fixed-effect model showed a lower rate in the antibiotic prophylaxis group, with a number-needed-to-treat of 39.7 patients.

4. The quality of evidence for both outcomes was assessed as very low, indicating high risks of bias, inconsistency, and potential confounding factors. The retrospective nature of the studies and small sample sizes limit the reliability of the conclusions.

5. The study findings suggest that antibiotic prophylaxis may have no significant impact on reducing 30-day mortality in ECMO patients, but may decrease the incidence of nosocomial infections, albeit with a high number needed to treat. However, these results are provisional due to the low quality of available evidence.

6. The authors recommend conducting high-quality prospective studies, including randomized controlled trials, to further investigate the specific clinical questions regarding the use of antibiotic prophylaxis in ECMO patients. More research is needed to determine the optimal antibiotic regimen, duration of prophylaxis, and the potential impact on different ECMO patient populations and infection outcomes.

Reference –

Orso D, Fodale CM, Fossati S, Venturini S, Fonda F, Cugini F, Comisso I, Crapis M, Cacciavillani L, Bove T. Do patients receiving extracorporeal membrane-oxygenation need antibiotic prophylaxis? A systematic review and meta-analysis on 7,996 patients. BMC Anesthesiol. 2024 Nov 12;24(1):410. doi: 10.1186/s12871-024-02796-z. PMID: 39533181; PMCID: PMC11556216.

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Icotrokinra shows impressive results in moderate to severe plaque psoriasis in phase 3 trial

Icotrokinra is an investigational oral peptide that blocks interleukin (IL)-23 receptor, which plays a significant role in the pathogenesis of moderate to severe plaque Psoriasis and other IL-23 mediated diseases.

Topline results from a phase 3 trial evaluating icotrokinra in patients with moderate to severe plaque psoriasis (PsO) has revealed impressive results.

The Phase 3 study met its co-primary endpoints of Psoriasis Area and Severity Index (PASI) 90b and Investigator’s Global Assessment (IGA) of 0/1c response at week 16 and response rates continued to improve through week 24.

Once daily icotrokinra showed significant skin clearance versus placebo in adults and adolescents with moderate to severe plaque psoriasis. At week 16, nearly two-thirds (64.7%) of patients treated with icotrokinra achieved IGA scores of 0/1 (clear or almost clear skin), and 49.6% achieved PASI 90, compared to 8.3% and 4.4% on placebo, respectively. Further increases in response rates continued to be observed at week 24, with 74.1% of patients treated with icotrokinra achieving IGA scores of 0/1, and 64.9% achieving PASI 90.1 Safety data was found to be consistent with the Phase 2 FRONTIER 1 and 2 studies. A similar proportion of patients experienced adverse events (AEs) between icotrokinra and placebo, with 49.3% and 49.1% of participants experiencing a treatment emergent adverse event (TEAE) at week 16.

Furthermore, positive topline results from the Phase 3 ICONIC-TOTALd study showed once daily icotrokinra met the primary endpoint of IGA of 0/1 at week 16 compared to placebo. Comprehensive results from ICONIC-LEAD and ICONIC-TOTAL are being prepared for presentation at upcoming medical congresses and will be shared with health authorities in planned submissions.

“We are excited to see impressive Phase 3 results with once-daily icotrokinra treatment aligned with our Phase 2 study of this first-in-class targeted oral peptide that selectively blocks the IL-23 receptor,” said Liza O’Dowd, Vice President, Immunodermatology Disease Area Lead, Johnson & Johnson Innovative Medicine. “The majority of people living with moderate to severe plaque psoriasis are eligible for, but are still not receiving, advanced therapies. Icotrokinra has the potential to offer once-daily oral therapy that could help address the needs and preferences of people living with plaque psoriasis.”

Other studies in the Phase 3 ICONIC clinical development program are ongoing, including ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2, which will evaluate the safety and efficacy of icotrokinra compared with both placebo and deucravacitinib in moderate to severe plaque PsO. The Phase 3 ICONIC-PsA program which will investigate icotrokinra in psoriatic arthritis will be initiated in the beginning of 2025.

About Plaque Psoriasis

Plaque psoriasis (PsO) is a chronic immune-mediated disease resulting in overproduction of skin cells, which causes inflamed, scaly plaques that may be itchy or painful. It is estimated that eight million Americans and more than 125 million people worldwide live with the disease.Nearly one-quarter of all people with plaque PsO have cases that are considered moderate to severe. On Caucasian skin, plaques typically appear as raised, red patches covered with a silvery white buildup of dead skin cells or scale. On skin of color, the plaques may appear darker and thicker and more of a purple, gray or dark brown color. Plaques can appear anywhere on the body, although they most often appear on the scalp, knees, elbows, and torso. Living with plaque PsO can be a challenge and impact life beyond a person’s physical health, including emotional health, relationships, and handling the stressors of life. Psoriasis on highly visible areas of the body or sensitive skin, such as the scalp, hands, feet, and genitals, can have an increased negative impact on quality of life.

About Icotrokinra (JNJ-77242113, JNJ-2113)

Investigational icotrokinra is the first targeted oral peptide designed to selectively block the IL-23 receptor, which underpins the inflammatory response in moderate to severe plaque PsO and other IL-23-mediated diseases. Icotrokinra binds to the IL-23 receptor with single-digit picomolar affinity and demonstrated potent, selective inhibition of IL-23 signaling in human T cells. The license and collaboration agreement established between Protagonist Therapeutics, Inc. and Janssen Biotech, Inc., in 2017 enabled the companies to work together to discover and develop next-generation compounds that ultimately led to icotrokinra. Icotrokinra was jointly discovered and is being developed pursuant to the license and collaboration agreement between Protagonist and Johnson & Johnson. Johnson & Johnson retains exclusive worldwide rights to develop icotrokinra in Phase 2 clinical trials and beyond, and to commercialize compounds derived from the research conducted pursuant to the agreement against a broad range of indications.

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Tirzepatide can reduce mortality risk among heart failure with preserved heart function and obesity: Study

Weight-loss and diabetes drug tirzepatide can reduce the risk of death or worsening heart failure for patients with heart failure, preserved heart pump function and obesity, new research from UVA Health reveals.

The drug, from pharmaceutical company Eli Lilly and Co., was tested in the SUMMIT clinical trial at 146 sites in the United States and abroad. A total of 731 patients with diastolic heart failure and a body mass index (BMI) of 30 or above were randomized to receive injections of either tirzepatide or a harmless placebo. The researchers then followed the patients for a median period of two years.

During that time, 56 placebo recipients died or suffered worsening heart failure, compared with only 36 of those receiving tirzepatide. Further, the tirzepatide recipients were more likely to drop pounds-losing, on average, 11.6% of their body weight.

“This class of drugs continue to show benefits far beyond weight loss,” said researcher Christopher Kramer, MD, chief of UVA Health’s Division of Cardiovascular Medicine. “This drug will become an important part of the armamentarium for patients with obesity-related heart failure and preserved heart function.”

Obesity and Heart Failure

Diastolic heart failure, also known as heart failure with preserved ejection fraction, is a condition in which the heart’s left ventricle grows stiff and can no longer pump blood properly. The form of heart failure represents nearly half of all heart failure cases. (Heart disease, in general, is the leading cause of death in the United States – it’s responsible for one in five deaths, killing someone every 33 seconds.)

Obesity is a major contributing factor to heart failure, so Kramer and his collaborators in the SUMMIT trial wanted to see if tirzepatide, a weight-loss drug already approved by the federal Food and Drug Administration, could help.

The trial found that tirzepatide offered substantial benefits for managing diastolic heart failure, reducing deaths, preventing hospitalizations and generally benefiting recipients’ health and quality of life. For example, recipients saw improvements in how far they could walk in six minutes, as well as substantial decreases in a biological indictor used to measure inflammation and predict risk of serious cardiovascular events.

Side effects seen in the tirzepatide group consisted of gastrointestinal issues such as nausea and diarrhea, and these were mostly mild or moderate, the researchers reported Saturday at a meeting of the American Heart Association in Chicago.

A Closer Look

Kramer, a cardiovascular imager, also led a magnetic resonance imaging substudy looking at how tirzepatide, sold under the brand name Zepbound, affected recipients’ heart structure and function. The researchers found beneficial reductions in both left ventricular mass (weight of the heart) and in the amount of surrounding fat tissue. The reduction in LV mass correlated with the reduction in body weight, as well as with decreases in left ventricular volumes.

“This drug is reversing the abnormal properties of the heart brought on by obesity,” Kramer said. “There is much more to these drugs than weight loss alone.”

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LEVI-04 Significantly Improves Pain and Function in Knee Osteoarthritis, finds study

Researchers have identified LEVI-04 as a novel p75NTR-Fc fusion protein that improves pain and function significantly in individuals diagnosed with knee osteoarthritis (OA) with excellent safety. A recent study was published in ACR Meeting Abstracts conducted by Philip Conaghan and colleagues.

Osteoarthritis is one of the leading causes of chronic pain and disability, and highly effective alleviating therapies lack. “The therapy target has been excess neurotrophins, associated with OA and other pain conditions”. Earlier NGF-targeting therapies were effective in pain but resulted in serious joint complications. LEVI-04 is a first-in-class fusion protein, supplementing endogenous p75NTR to modulate the activity of neurotrophin and inhibit NT3, which has given promising preclinical and Phase I safety results. In this study, LEVI-04’s efficacy and safety were evaluated in patients suffering from knee OA.

It was a 20-week, multicenter RCT conducted in Europe and Hong Kong, which included 518 participants who were affected with painful (≥4/10 WOMAC) and radiographic (KL≥2) knee OA. The participants were randomized to receive either intravenous placebo or LEVI-04 at doses of 0.3, 0.1, or 2 mg/kg every four weeks until week 16 followed by safety follow-up until week 30.

  • Primary endpoint: Change in WOMAC pain score at week 17.

  • Secondary endpoints: Function, Patient Global Assessment, and more than 50% responder analyses on pain.

  • Imaging: Baseline inclusion/exclusion and safety assessment was done by X-rays of 6 major joints and MRI of knees.

Patient Profile:

  • Mean age: 63.1–65.4 years.

  • Mean BMI: 29.3–30.3.

  • Female patients: 51.5–61.5%

Efficacy:

  • WOMAC pain and function, both significantly improved from week 5 and week 17 (p < 0.05 compared with placebo for all dose levels).

  • A majority (>50%) of patients treated with LEVI-04 had ≥50% pain, and >25% had ≥75% pain at weeks 5 and 17.

Safety:

  • LEVI-04 was well-tolerated with no increase in serious adverse events (SAEs), treatment-emergent adverse events (TEAEs), or joint pathologies compared to placebo.

  • Incidence of anti-drug antibodies was low: 9 participants tested positive pre-dosing, and 6 tested positive during the study at the lowest detection limits.

LEVI-04, displayed significant and clinically relevant pain and function improvements while maintaining robust safety at all doses. This novel therapy seems to support the supplementation strategy of endogenous p75NTR for the treatment of OA and other pain diseases. Based on these promising Phase II results, Phase III studies are currently being designed to further evaluate the potential of LEVI-04 to revolutionize OA treatment.

Reference:

LEVI-04, a novel neurotrophin-3 inhibitor, substantially improves pain and function without deleterious effects on joint structure in people with knee osteoarthritis: A randomized controlled phase II trial. (2024, October 15). ACR Meeting Abstracts. https://acrabstracts.org/abstract/levi-04-a-novel-neurotrophin-3-inhibitor-substantially-improves-pain-and-function-without-deleterious-effects-on-joint-structure-in-people-with-knee-osteoarthritis-a-randomized-controlled-phase-ii/

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Psychiatric Disorders Significantly Increase Risk of Sudden Cardiac Death, reveals research

Researchers have found that patients with psychiatric disorders have a significantly increased risk for sudden cardiac death (SCD) in all age groups compared to the general population. A recent study was conducted by Jasmin M. and colleagues published in the journal Heart.

Individuals with psychiatric conditions have been known to be at a greater risk of allcause mortality than the background population. Previous studies have shown young psychiatric patients might have a fourfold risk of SCD. The purpose of the study was to provide a detailed description of the incidence of SCD cases in Danish patients aged 18 to 90 years by analyzing all deaths for one year.

The study analyzed all deaths among Danish residents aged 18–90 in 2010, corresponding to a population of 4.3 million. Death certificates and autopsy reports were reviewed to classify deaths as SCD or non-SCD. Psychiatric disorders were identified using the International Classification of Diseases, 10th revision (ICD-10) criteria, or by prescription records for psychotropic medications redeemed within the preceding year. The analysis adjusted for age, sex, and comorbidities to evaluate independent associations.

The key findings of the study were as follows:

Mortality and SCD Prevalence:

  • Total deaths were 45,703, of which 6,002 (13%) were SCD.

  • Patients with psychiatric disorders had 1.79–6.45 times higher SCD rates than the general population, with varying age dependencies (p < 0.001).

Independent Association With Psychiatric Disorders

  • Hazard ratio (HR) for SCD among patients with psychiatric disorders: 2.31 (2.19–2.43, p < 0.001).

  • Patients with schizophrenia had the highest risk, with an HR of 4.51 (3.95–5.16, p < 0.001).

Impact on Younger Patients:

  • For an 18-year-old with a psychiatric disorder, the expected decline in life expectancy was 10 years.

  • Among those 18 to 40 years old, 13% of excess lost life years were attributed to SCD.

This study demonstrated that psychiatric disorders significantly increase the risk of SCD across all age groups. The highest rates were observed in patients with schizophrenia, with young psychiatric patients suffering huge life expectancy reductions. Findings underline the critical need for proactive cardiovascular risk management in individuals with psychiatric conditions to reduce the disproportionate mortality burden.

Reference:

Mujkanovic, J., Warming, P. E., Kessing, L. V., Køber, L. V., Winkel, B. G., Lynge, T. H., & Tfelt-Hansen, J. (2024). Nationwide burden of sudden cardiac death among patients with a psychiatric disorder. Heart (British Cardiac Society), 110(23), 1365–1371. https://doi.org/10.1136/heartjnl-2024-324092

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History of endometriosis and fibroids linked to heightened risk of early death, states study

Women with a history of endometriosis and uterine fibroids might have an increased long term risk of premature death, finds a large study from the United States published by The BMJ today.

Endometriosis and uterine fibroids are common disorders among women of reproductive age. Endometriosis occurs when tissue similar to the lining of the womb grows in other places, such as the ovaries and fallopian tubes, while uterine fibroids are non-cancerous growths within or around the womb.

Growing evidence shows that both conditions are associated with a greater long term risk of chronic diseases, such as high blood pressure, heart disease, and some cancers, but their effect on risk of death before the age of 70 remains unclear.

To explore this further, researchers drew on information provided by 110,091 women taking part in the Nurses’ Health Study II who were aged 25-42 years in 1989 and had no history of hysterectomy before endometriosis or fibroids diagnosis, cardiovascular diseases, or cancer.

Starting in 1993 and every two years thereafter, these women reported any diagnosis of endometriosis (confirmed by laparoscopy) and uterine fibroids (confirmed by ultrasound or hysterectomy).

Other potentially influential factors including age, ethnicity, reproductive history, HRT and oral contraceptive use, regular use of aspirin or anti-inflammatory drugs, and other health-related issues were also taken into account.

During 30 years of monitoring, 4,356 premature deaths were recorded, including 1,459 from cancer, 304 from cardiovascular diseases, and 90 from respiratory diseases.

Overall, the rate of all-cause premature death for women with and without confirmed endometriosis was 2 and 1.4 per 1,000 person years, respectively.

After taking account of age and other confounding factors such as weight (BMI), diet quality, physical activity, and smoking status, endometriosis was associated with a 31% higher risk of premature death, largely driven by deaths due to gynaecological cancers.

Uterine fibroids were unrelated to all-cause premature death, but were associated with a greater risk of death due to gynaecological cancers.

The researchers acknowledge that these are observational findings that relied on self-reports, which can be prone to error, and included predominantly white healthcare workers, so results may not apply to other groups. Nor can they rule out the possibility that other unmeasured factors may have had an influence.

Nevertheless, this was a large study with regular follow-up over nearly three decades, which reduced potential recall errors.

As such, they conclude: “Our results suggest that women with a history of endometriosis and uterine fibroids might have an increased long term risk of premature mortality extending beyond their reproductive lifespan.”

These conditions were also associated with an increased risk of death due to gynaecological cancers. Endometriosis was also associated with a greater risk of non-cancer mortality. These findings highlight the importance for primary care providers to consider these gynaecological disorders in their assessment of women’s health.”

Reference:

Wang Y, Farland L V, Gaskins A J, Wang S, Terry K L, Rexrode K M et al. Endometriosis and uterine fibroids and risk of premature mortality: prospective cohort study BMJ 2024; 387 :e078797 doi:10.1136/bmj-2023-078797.

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