Zerlasiran may prevent heart disease by lowering lipoprotein(a) concentrations: JAMA

A new study revealed that Zerlasiran is not just safe and tolerable but also effective in substantially reducing the levels of lipoprotein(a) [Lp(a)] which is a key factor in the development of atherosclerotic cardiovascular disease (ASCVD) and calcific aortic stenosis. The key findings of this study were published in the Journal of American Medical Association.

This comprehensive study was conducted across several countries including the US, the Netherlands, the UK and Australia from November 2020 to August 2023. This research enrolled healthy participants as well as the patients with stable ASCVD, all of whom expressed Lp(a) serum concentrations more than 150 nmol/L. This diverse group underwent treatment through randomized doses of Zerlasiran or placebo by exploring both single and multiple-dose administrations to evaluate the safety, tolerability and impact of the drug on Lp(a) levels.

Zerlasiran operates by targeting and suppressing the hepatic synthesis of apolipoprotein(a), thereby lowering the circulating levels of Lp(a). The outcomes of this study highlights no serious adverse events among the participants. Also, the drug demonstrated a remarkable ability to lower Lp(a) concentrations with the most notable reductions observed in the multiple-dose groups. After two doses, the participants saw a reduction in Lp(a) levels by up to 99% from baseline in some dosage groups that was sustained significantly over time.

These findings are crucial despite considering the absence of approved pharmacological treatments to address high Lp(a) levels which is a hereditary condition notoriously difficult to manage through lifestyle changes or existing cholesterol-lowering medications. The success of this study signals Zerlasiran as a effective drug for individuals with increased Lp(a) to be a potentially transformative addition to the arsenal against ASCVD and calcific aortic stenosis.

The study highlighted the importance of this advancement by illuminating the ability of Zerlasiran to significantly reduce Lp(a) levels with infrequent dosing that could revolutionize the approach of prevention and management of the cardiovascular disease. Zerlasiran continues through the pipeline of clinical trials and regulatory review which helps in resolve the anticipation of the wide-reaching implications of this new treatment. If approved, Zerlasiran could significantly impact the prevention of cardiovascular disease by marking a critical shift in the treatment strategy of high-risk individuals throughout the globe.

Source:

Nissen, S. E., Wolski, K., Watts, G. F., Koren, M. J., Fok, H., Nicholls, S. J., Rider, D. A., Cho, L., Romano, S., Melgaard, C., & Rambaran, C. (2024). Single Ascending and Multiple-Dose Trial of Zerlasiran, a Short Interfering RNA Targeting Lipoprotein(a). In JAMA. American Medical Association (AMA). https://doi.org/10.1001/jama.2024.4504

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All permitted seats will be considered as recognised seats: NMC clarifies

New Delhi: While answering the Frequently Asked Questions (FAQs) regarding the Postgraduate Medical Education Regulations (PGMER) 2023, the National Medical Commission (NMC) recently clarified that once permitted, the concerned postgraduate medical course shall be considered as recognised and therefore, the “seats permitted will be considered as recognised seats for registration of the degree awarded.”

Postgraduate Medical Education Board (PGMEB) of the NMC stated this while providing clarification regarding the doubts and queries raised by various stakeholders regarding the PGMER 2023.

Medical Dialogues had earlier reported about the final Post-Graduate Medical Education Regulations, 2023 (PGMER 2023), which laid down the rules and regulations regarding admission, counselling, and other details related to the postgraduate medical courses.

Answering the question of whether the college is required to apply for recognition of PG seats, the Commission clarified, “As per PGMER-2023, once permitted, the course for the qualification will be considered recognised and seats permitted will be considered as recognised seats for registration of the degree awarded. Medical colleges/institutions running such courses will be considered as accredited medical colleges/institutions for the said course of qualification. And all permitted seats will be considered as recognised seats.” 

Also Read: How many leaves allowed for PG medical students? NMC specifies in PGMER FAQs

“Therefore, medical colleges/institutions need not apply for recognition of PG course. Colleges/institutions shall submit an Annual Self-Declaration as per the requirement of MSMER-2023 regulations. For the current year, the Post-graduate Medical Education Board (PGMEB) will soon issue a public notice for the medical colleges/institutions to submit their Annual Self-Declaration for the year 2023 (01.01.2023 to 31.12.2023),” it further mentioned.

Addressing the issue of permission and recognition, Chapter III of PGMER 2023 mentions, “Once permitted, the course for the qualification will be considered recognised and seats permitted will be considered as recognised seats for registration of the degree awarded. Medical colleges/Institutions running such courses will be considered as Accredited Medical colleges/Institutions for the said course of qualification.”

The requirement for getting recognised by NMC is no longer applicable for the undergraduate medical seats as well. Releasing the Minimum Standard Requirements (MSR) 2023 regulations for UG medical courses, NMC removed the concept of permitted vs recognised medical seats. Therefore, as per the existing rules, degrees obtained by MBBS students after completion of their medical courses shall automatically be considered to be recognised.

Medical Dialogues had been reporting about the troubles faced by students across the country with the pending recognition from the NMC. The absence of recognition for the permitted seats used to cause trouble for the MBBS graduates, who would face problems in obtaining permanent registration in the absence of recognition for their respective batches. They were unable to initiate their medical practice or participate in the counselling process for postgraduate medical education as well.  In the case of PG medical students, lack of recognition used to create trouble for the doctors to get their additional qualifications registered.

To view the FAQs issued on PGMER 2023, click on the link below:

https://medicaldialogues.in/pdf_upload/faqs-on-pgmer-2023-236046.pdf

Also Read: PGMER 2023: PG Medicos must Fulfill these Conditions to Appear in Final Exam, Details

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86.9 per cent TB treatment success rate until Dec 2023: Sources

New Delhi: India has made tremendous progress in the elimination of Tuberculosis from the country, the treatment success rate surged to 86.9 per cent by December 2023, marking the highest rate in nine years, according to sources.

Under the leadership of Prime Minister Narendra Modi, the Government of India is aggressively pursuing the elimination of TB from the country by 2025, five years ahead of the global sustainable development goals’ 2030 deadline related to TB.

According to the sources, however, there was a marginal increase to 85.5 per cent in 2022. “Over the last 9 years, despite one-third of notifications coming from the private sector, the programme was able to sustain a treatment success rate of above 80 per cent. In 2021, the success rate had reached 84 per cent and in 2022, it marginally increased to 85.5 per cent,” sources told ANI.

Also Read:Karnataka Health Minister writes to Centre seeking supply of anti-TB drugs

The Union Ministry of Health and Family Welfare spearheaded the national TB Elimination Programme with five key objectives: early diagnosis, prompt treatment with quality drugs, engagement with patients seeking care in the private sector, prevention strategies including contact tracing in high-risk and vulnerable populations, airborne infection control, and multi-sectoral response to address social determinants.

Under the National Strategic Plan for TB Elimination, over 1.4 billion people live in more than 800 districts and reporting units and are responsible for carrying out the Government of India’s five-year National Strategic Plans for TB Elimination along with the States/UTs.

According to an ANI report, The National Strategic Plan for TB Elimination was launched to achieve the target of ending TB by 2025 in mission mode. It is a multi-pronged approach that aims to detect all TB patients, with an emphasis on reaching TB patients seeking care from private providers and undiagnosed TB in high-risk populations.

“The programme has been implementing the four strategic pillars of Detect-Treat-Prevent-Build (DTPB) of the National Strategic Plan 2017-2025, which has led to the scaling up of free, high sensitivity diagnostic tests and algorithms and ensuring free TB drugs for all TB cases,” said a source with knowledge of the National Strategic Plan 2017-2025.  

Also Read:India TB Report-2024: 16 percent decline in new cases since 2015

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No link between COVID-19 virus and development of asthma in children, finds research

Philadelphia: Researchers from Children’s Hospital of Philadelphia (CHOP) have found in a new research that a SARS-COV-2 infection likely does not increase the risk of asthma development in pediatric patients.

The findings of study were published in the journal Pediatrics.

Respiratory viral infections early in life are risk factors for asthma. Since the SARS-COV-2 virus can cause severe lung inflammation and prolonged respiratory symptoms in certain patients, many families were concerned whether COVID-19 might trigger an asthma diagnosis in their children. CHOP established a team to further evaluate these concerns.

More than four years have passed since initial infections were reported in the United States, with testing for COVID-19 performed frequently at the beginning of the pandemic. These circumstances made for the perfect set of circumstances for a large retrospective cohort study.

“During the early days of the pandemic, we could isolate the effects of COVID-19 from other viruses and follow these patients long enough to observe the onset of asthma,” said first study author James P. Senter, MD, MPH, an attending physician in the Department of Pediatrics at CHOP. “We were also testing so frequently that we had a built-in control group to compare asthma symptoms and whether COVID-19 was a critical factor.”

This retrospective cohort study included more than 27,000 pediatric patients who received polymerase chain reaction (PCR) testing for SARS-COV-2 between March 1, 2020, and February 28, 2021. Patients were followed over an 18-month period.

The analysis found that testing positive for SARS-COV-2 had no significant effect on the likelihood of a new asthma diagnosis. However, children with known risk factors for developing pediatric asthma, such as race, food allergies, allergic rhinitis (or hay fever), and preterm birth – were more likely to associate with new SARS-COV-2 diagnoses.

Since the study focused solely on pediatric patients, not adult patients, more research will need to be done to assess patients at different ages and at longer intervals to further confirm there is no relationship between SARS-COV-2 and the development of asthma. Although new variants have emerged since the study was conducted, many of the fundamental elements of the original virus, which seem to reduce the allergic response produced in infected patients, have remained intact in current variants.

“This well-powered study reaffirms risk factors we know contribute to asthma development and provides clinically useful information to pediatricians and providers on the absence of risk of developing asthma as a result of COVID-19,” said senior study author David A. Hill, MD, PhD, an attending physician with the Division of Allergy and Immunology at CHOP. “We are hopeful that this study will put to rest an outstanding question on the minds of many their families.”

References: James P. Senter, MD, MPH; Laura K. Aisenberg, MD, PhD; Jesse W. Dudley, MS; Xianqun Luan, MS; Jing Huang, PhD; Chén C. Kenyon, MD, MSHP; David A. Hill, MD, PhD Pediatrics e2023064615. https://doi.org/10.1542/peds.2023-064615

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Nerve decompression may reduce pain in patients with diabetic peripheral neuropathy: Study

A recent study by the team led by Shai Rozen unveiled the effectiveness of nerve decompression surgery in patients requiring the treatment for painful Diabetic Peripheral Neuropathy (DPN). This condition usually affects millions globally and often leads to significant discomfort and pain in the lower extremities which severely impacts the quality of life. The key highlights of this study were published in the newest edition of Annals of Surgery. 

This rigorous double-blinded, randomized trial compared the outcomes of nerve decompression surgery against the observation and sham surgery. This study encompassed a broad age range of patients from 18 to 80 years and who had not found relief from one year of medical treatment. The research ensured a comprehensive analysis of the effectiveness of surgery by randomizing patients to either undergo nerve decompression on one leg with a sham surgery on the other or to an observation group.

After 12 months, the patients who underwent nerve decompression reported a significant reduction in pain when compared to the control group. With mean differences in pain scores significantly lower in both the right and left decompression groups. Also, both decompressed and sham-operated legs showed equal improvement initially which suggests a complex interplay of physical and psychological factors in pain perception.

However, the long-term findings which was observed at 56 months showed that patients who had undergone nerve decompression maintained a lower level of pain when compared to controls where the difference in pain scores were both clinically and statistically significant. Also, a direct comparison between decompressed and sham-operated legs revealed a clear advantage for the former that indicated a true effect of the surgery beyond placebo.

These crucial findings in the individuals with painful diabetic peripheral neuropathy suggests that nerve decompression surgery could become a cornerstone in the management of this challenging condition. The outcomes caution that the observed benefits necessitate further scrutiny despite being promising. Overall, the potential placebo effect highlighted by the initial improvement in sham-operated legs strongly underline the complexity of treating chronic pain conditions and the need for a deeper understanding of how surgical interventions exert their effects.

Reference:

Rozen, S. M., Wolfe, G. I., Vernino, S., Raskin, P., Hynan, L. S., Wyne, K., Fulmer, R., Pandian, G., Sharma, S. K., Mohanty, A. J., Sanchez, C. V., Hembd, A., & Gorman, A. (2024). Effect of Lower Extremity Nerve Decompression in Patients with Painful Diabetic Peripheral Neuropathy. In Annals of Surgery. Ovid Technologies (Wolters Kluwer Health). https://doi.org/10.1097/sla.0000000000006228

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New technology may analyze head sway and help diagnose vestibular disorders in patients: Study

A recent pilot study by the team led by Jennifer L. Kelly leveraged the advanced technology of the HTC Vive Pro Eye head-mounted display (HMD) to explore a novel method to effectively diagnose vestibular disorders that includes Meniere’s disease (MD) and vestibular hypofunction (VH). This cutting-edge approach focused to measure head sway and to potentially distinguish between the patients affected and healthy individuals. The key findings of this study were published in the recent issue of the Frontiers in Neurology journal.

The study involved 80 adult participants who were divided into 30 healthy controls, 32 with VH and 18 with MD. Each participant underwent a detailed postural control assessment using the HTC Vive Pro Eye HMD that meticulously recorded head sway movements in various directions: anterior–posterior (AP), medio-lateral (ML), pitch, yaw and roll.

The testing protocol included two visual load levels displayed through the HMD, one being a static star scene and the other being an oscillating star scene. Each visual scene lasted 60 seconds and was repeated twice to ensure consistency. The study measured the sway in each direction using the root mean square velocity (VRMS) for the first 20 seconds and the entire 60-second duration of each scene.

The results revealed significant findings in participants with VH. Under the static visual condition, the individuals with VH demonstrated a larger head VRMS in the AP direction and pitch during both the 20 and 60-second assessments when compared to the healthy controls. The dynamic visual condition further amplified these differences where the VH participants showed significant increase in head sway in all directions and at both time intervals. In contrast, the participants with MD did not show significant differences from either the control group or the VH group which indicated high variability and intermediate average head sway values.

These preliminary findings suggest that while head sway metrics collected via HMD are sensitive to VH, yet, they do not conclusively differentiate individuals with MD from healthy controls or those with VH. The study elucidates the potential of using head sway as a clinical tool to assess sensory integration necessary for postural control. Further research involving a larger sample size with the patients having more pronounced symptoms at the time of testing should be recruited.

Reference:

Kelly, J. L., Cosetti, M., & Lubetzky, A. V. (2024). Can head sway patterns differentiate between patients with Meniere’s disease vs. peripheral vestibular hypofunction? In Frontiers in Neurology (Vol. 15). Frontiers Media SA. https://doi.org/10.3389/fneur.2024.1347335

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Can probiotics plus vitamin D supplements benefit people with schizophrenia?

Previous studies have questioned whether gut microbe imbalances and vitamin D deficiency may be linked to schizophrenia. New research published in Neuropsychopharmacology Reports now indicates that taking probiotics plus vitamin D supplements may improve cognitive function in individuals with the disease.

For the study, 70 adults with schizophrenia were randomized to take a placebo or probiotic supplements plus 400 IU vitamin D daily for 12 weeks. Severity of the disease and cognitive function were evaluated by tests called the Positive and Negative Syndrome Scale (PANSS) and the 30-point Montreal Cognitive Assessment (MoCA), respectively.

A total of 69 patients completed the study. The MoCA score increased by 1.96 units in the probiotic-containing supplement group compared with the placebo group. Also, the percentage of patients with MoCA scores of 26 or higher (indicating normal cognition) rose significantly in the intervention group. Between-group differences in PANSS scores were not significant.

“Probiotics may be a novel way to treat mental disorders by regulating gut microbiota,” said corresponding author Gita Sadighi, MD, of the University of Social Welfare and Rehabilitation Sciences, in Iran.

References: Aida Mohammadi, Gita Sadighi, Ali Nazeri Astaneh, Maryam Tajabadi-Ebrahimi, Tahereh Dejam First published: 10 April 2024 https://doi.org/10.1002/npr2.12431

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Success with treat-to-target therapy in rheumatoid arthritis lasts up to two decades: Study

Netherlands: A recent article published in the Rheumatology journal has reported long-term clinical outcomes in early rheumatoid arthritis (RA) that was treated to target in the IMPROVED and the BeSt studies.

The study that followed participants in two of the first clinical trials to test the strategy revealed that success with “treat-to-target” therapy for early-stage RA lasted up to 2 years. The trials aimed at drug-free remission in one, low disease activity in the other

“The majority of patients in the trials had maintained the benefits when examined again after 7-10 following the trial’s ending, which was 12-20 years after starting treatment,” the researchers reported.

“In the follow-up exams, 91% of these patients had low disease activity (Disease Activity Score [DAS] <2.4), and 68% were in remission (DAS <1.6).”

Sascha L Heckert, Rheumatology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands, and colleagues conducted the study to assess disease outcomes after 20 and 12 years of patients with rheumatoid or undifferentiated arthritis (UA), treated-to-target in the BeSt and IMPROVED trials.

In the IMPROVED trial (inclusion from 2007-2010, duration five years), 610 patients with early RA/UA started methotrexate (MTX with prednisone bridging. The treatment target was remission (DAS < 1.6). Patients not in early remission were randomized to 1. cs disease-modifying antirheumatic drug (csDMARD) combination therapy or 2. bDMARD/csDMARD combination therapy.

In the BeSt trial (inclusion 2000–2002, duration ten years), 508 patients with early rheumatoid arthritis were randomized to: (a) sequential monotherapy, (b) step-up combination therapy, (c) initial csDMARD combination therapy, (d) initial bDMARD/csDMARD combination therapy. The treatment target was low disease activity (DAS ≤ 2.4).

These patients were invited for long-term follow-up between 2019–2022.

In the follow-up study, one-hundred-fifty-three ex-Best and 282 ex-IMPROVED patients participated after a median of 12 and 20 years since the study started.

The study led to the following findings:

  • In ex-BeSt and ex-IMPROVED patients, the rate of low disease activity was 91%, and 68% were in DAS remission.
  • Median SHS was 14.0 in ex-BeSt (IQR 6.0–32.5; progression since end BeSt 6.0, IQR 2.0–12.5) and 8 in ex-IMPROVED participants (IQR 3–16; progression since end IMPROVED 4, IQR 2–9).
  • Mean HAQ was 0.8 ± 0.6 in ex-BeSt (change since end BeSt: 0.3 ± 0.5) and 0.6 ± 0.6 in ex-IMPROVED participants (change since end IMPROVED: 0.06 ± 0.5).

In conclusion, At 12/20 years after the treatment initiation, most rheumatoid arthritis and undifferentiated arthritis who had been treated to target low DAS or DAS remission were in DAS remission and had limited functional disability.

Radiographic damage progression was mild, although not suppressed completely.

Reference:

Heckert, S. L., Maassen, J. M., Nevins, I., Baudoin, P., M, G., Huizinga, T. W., Bergstra, S. A., & Allaart, C. F. Long-term clinical outcomes in early rheumatoid arthritis that was treated-to-target in the BeSt and IMPROVED studies. Rheumatology. https://doi.org/10.1093/rheumatology/keae212

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No substantially different relative risk for kidney failure among three Anti-VEGF Drugs, finds study

A retrospective cohort study published in Ophthalmology Retina compared the risk of kidney failure among three commonly used anti-vascular endothelial growth factor (VEGF) drugs in patients with various eye diseases. The study aimed to assess whether there were differences in the relative risk of kidney failure associated with aflibercept (Eylea), ranibizumab (Lucentis), and bevacizumab (Avastin) when used for intravitreal injections.

This study was conducted by Cai CX and colleagues. Anti-VEGF drugs are a mainstay in the treatment of several eye diseases, including diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion. However, concerns have been raised regarding their potential systemic effects, particularly on renal function. This study sought to address whether there were differences in kidney failure risk among these drugs.

The retrospective cohort study analyzed data from over 240,000 adult patients who received intravitreal anti-VEGF medications for various eye conditions. The study focused on patients who had received at least 3 monthly treatments and were newly treated with anti-VEGF agents. The primary outcome assessed was the incidence of kidney failure among patients treated with aflibercept, ranibizumab, and bevacizumab.

The key findings of the study were as follows:

  • The study found no substantially different relative risk for kidney failure among the three anti-VEGF drugs.

  • The hazard ratios for kidney failure were similar across comparisons: 1.01 for aflibercept versus ranibizumab, 0.95 for ranibizumab versus bevacizumab, and 0.95 for aflibercept versus bevacizumab.

  • The safety profile of all three drugs was consistent, with no serious or severe treatment-emergent adverse events reported.

  • The most commonly reported adverse events were somnolence and dizziness.

  • While all three drugs are effective for treating eye diseases, there are differences in cost.

  • Bevacizumab, although off-label, was found to be significantly cheaper compared to aflibercept and ranibizumab.

The study provides reassurance to clinicians regarding the safety of anti-VEGF drugs concerning kidney failure risk. The findings suggest that clinicians can choose these drugs based on other factors, such as efficacy and cost, without concerns about differential renal risks. Further research may be needed to explore the long-term effects of these drugs on renal function.

Reference:

Cai, C. X., Nishimura, A., Bowring, M. G., Westlund, E., Tran, D., Ng, J. H., Nagy, P., Cook, M., McLeggon, J.-A., DuVall, S. L., Matheny, M. E., Golozar, A., Ostropolets, A., Minty, E., Desai, P., Bu, F., Toy, B., Hribar, M., Falconer, T., … Ryan, P. B. (2024). Similar risk of kidney failure among patients with blinding diseases who receive ranibizumab, aflibercept, and bevacizumab: an OHDSI Network Study. Ophthalmology Retina. https://doi.org/10.1016/j.oret.2024.03.014

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Dual antiplatelet therapy reduces symptomatic intracranial hemorrhage in stroke patients, confirms study

A recent research compared the safety and efficacy of Dual Antiplatelet Therapy (DAPT) and Intravenous (IV) Tissue Plasminogen Activator (t-PA), the two prominent treatments for acute minor ischemic stroke (AIS). The key findings of this meta-analysis were published in the Journal of Stroke and Cerebrovascular Diseases that found DAPT significantly reduced the symptomatic intracranial hemorrhage (sICH) and overall bleeding risk when compared to IV t-PA.

After following stringent Cochrane and PRISMA guidelines, this study meticulously analyzed the observational studies and clinical trials from PubMed, Scopus and Web of Science databases. This reserch encompassed a total of five studies which involved 3,978 DAPT-treated patients and 2,224 t-PA-treated patients, provided a comprehensive comparison of outcomes.

The analysis revealed no significant disparities in achieving favorable outcomes between the two treatment groups. Measures such as achieving modified Rankin Scale (mRS) scores of 0-1 and 0-2, as well as combined mRS scores, showed no statistically significant differences. Similarly, changes in National Institutes of Health Stroke Scale (NIHSS) scores from baseline and mortality rates exhibited comparable results between DAPT and IV t-PA recipients.

However, a notable contrast emerged in terms of safety profiles. The DAPT group demonstrated a significantly lower incidence of bleeding events, including symptomatic intracranial hemorrhage (sICH), when compared to those receiving IV t-PA. This finding underscores the potential advantage of DAPT in minimizing the risk of hemorrhagic complications associated with AIS treatment.

The study emphasized the importance of these findings to guide clinical decision-making. While both treatments appear similarly effective in improving the outcomes, the markedly lower risk of bleeding events with DAPT suggests its potential superiority in terms of safety.

Overall, these findings hold profound benefits for the clinicians tasked with selecting the most appropriate treatment strategy for patients presenting with acute minor ischemic stroke. The healthcare professionals can make more informed decisions customized to need of every individual patient by weighing the efficacy and safety profiles of DAPT and IV t-PA. Further validation and implementation of these findings have the potential to enhance the outcomes and redefine the standard of care for individuals who are affected by AIS.

Reference:

Abbas, A., Hamad, A. A., El Din Moawad, M. H., Ewis, D. K., Youssef, R. A., Hamouda, H., Hassan, M. A., Aladawi, M., Elfil, M., Meshref, M., & Al-Mufti, F. (2024). Dual antiplatelet therapy versus intravenous tissue plasminogen activator with acute minor ischemic stroke: A systematic review and meta-analysis of safety and efficacy. In Journal of Stroke and Cerebrovascular Diseases (p. 107704). Elsevier BV. https://doi.org/10.1016/j.jstrokecerebrovasdis.2024.107704

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