Pitavastatin Promotes Heart Health in HIV Patients by Stabilizing Atherosclerotic Plaques, New Study Finds

USA: A secondary analysis of the REPRIEVE randomized clinical trial has shed light on pitavastatin’s potential role in promoting atherosclerotic plaque stabilization among patients with HIV. The finding, published in JAMA Cardiology, emphasizes the drug’s ability to influence procollagen pathways, potentially transforming vulnerable atherosclerotic plaques into more stable coronary lesions.

Results from the secondary analysis suggest that pitavastatin significantly increases procollagen C-endopeptidase enhancer 1 (PCOLCE) levels, a key molecule involved in collagen synthesis and deposition. Elevated PCOLCE levels are linked to stabilizing atherosclerotic plaques, which play a pivotal role in reducing the risk of coronary events.

Patients with HIV are at an elevated risk of cardiovascular disease, partly due to chronic inflammation and immune activation. Pitavastatin’s ability to mitigate these risks through plaque stabilization offers a promising therapeutic approach for managing cardiovascular complications in this high-risk population.

In a mechanistic substudy of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) randomized clinical trial, pitavastatin was found to lower noncalcified plaque (NCP) volume. However, the specific proteins and gene pathways driving these changes in coronary plaque composition are yet to be identified. Considering this, Márton Kolossváry, Metabolism Unit, Massachusetts General Hospital, Harvard Medical School, Boston, and colleagues aimed to explore biological pathways beyond low-density lipoprotein cholesterol (LDL-C) and link statin effects to reduced NCP volume and enhanced plaque stabilization in people with HIV (PWH), targeted discovery proteomics and transcriptomics approaches will be employed.

For this purpose, the researchers conducted a post hoc analysis of the double-blind, placebo-controlled REPRIEVE randomized clinical trial, which included participants who underwent coronary computed tomography angiography (CTA), plasma protein analysis, and transcriptomic analysis at both baseline and a 2-year follow-up. The trial enrolled people with HIV from 2015 to 2018 at 31 research sites across the United States. Eligible participants were those without known cardiovascular diseases, taking antiretroviral therapy, and with a low to moderate 10-year cardiovascular risk.

Oral pitavastatin calcium, administered at a daily dose of 4 mg, was the intervention in this trial. The primary outcomes focused on the relative changes in plasma proteomics, transcriptomics, and noncalcified plaque (NCP) volume among participants receiving pitavastatin than those receiving a placebo.

The analysis revealed the following findings:

  • Among 558 participants (mean age 51 years; 82% male) in the proteomics assessment, 272 received pitavastatin, and 286 received a placebo.
  • Pitavastatin increased levels of procollagen C-endopeptidase enhancer 1 (PCOLCE), neuropilin 1 (NRP-1), major histocompatibility complex class I polypeptide-related sequence A (MIC-A), and B (MIC-B).
  • Pitavastatin decreased levels of tissue factor pathway inhibitor (TFPI), tumor necrosis factor ligand superfamily member 10 (TRAIL), angiopoietin-related protein 3 (ANGPTL3), and mannose-binding protein C (MBL2).
  • The greatest association was observed with PCOLCE, a rate-limiting enzyme in collagen deposition, showing an effect size of 24.3%.
  • Transcriptomic analysis showed increased expression of individual collagen genes and collagen gene sets.
  • Among 195 individuals with plaque at baseline, changes in NCP volume were most strongly associated with changes in PCOLCE levels (%change NCP volume/log2-fold change = -31.9%), independent of LDL-C level changes.
  • Changes in PCOLCE were most strongly associated with a reduction in the fibro-fatty component of NCP (%change fibro-fatty volume/log2-fold change = -38.5%).
  • There was a nonsignificant increase in calcified plaque (%change calcified volume/log2-fold change = 34.4%).

“Findings from this secondary analysis of the REPRIEVE randomized clinical trial suggest that PCOLCE may play a key role in the plaque-stabilizing effects of statins. This occurs through the promotion of collagen deposition in the extracellular matrix, which transforms vulnerable atherosclerotic plaque phenotypes into more stable coronary lesions,” the researchers concluded.

Reference:

Kolossváry M, Schnittman SR, Zanni MV, et al. Pitavastatin, Procollagen Pathways, and Plaque Stabilization in Patients With HIV: A Secondary Analysis of the REPRIEVE Randomized Clinical Trial. JAMA Cardiol. Published online December 11, 2024. doi:10.1001/jamacardio.2024.4115

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Setmelanotide Promising as Early Intervention for Rare Obesity in Young Children: Findings from VENTURE Trial

USA: Research shows that the melanocortin-4 receptor (MC4R) agonist setmelanotide effectively lowers BMI in children with early-onset severe obesity linked to single-gene variants that disrupt hunger regulation, satiety, and energy balance through the MC4R signaling pathway. The findings were published online in The Lancet Diabetes & Endocrinology on November 13, 2024.

Previous research has shown that aetmelanotide reduces hunger and weight in children aged 6 years and older with proopiomelanocortin (POMC) deficiency (including biallelic variants in proprotein convertase subtilisin/kexin type 1), leptin receptor (LEPR) deficiency, or Bardet-Biedl syndrome (BBS), all classified as MC4R pathway diseases. However, no approved therapies currently exist for children under 6 years with these conditions.

Against the above background, Prof Jesús Argente, IMDEA Food Institute, Madrid, Spain, and colleagues aimed to evaluate the efficacy and safety of setmelanotide in patients aged 2–5 years with POMC or LEPR deficiency or Bardet-Biedl syndrome through phase 3, open-label VENTURE trial.

The Phase 3, open-label, multicenter trial was conducted at six sites across the USA, the UK, Spain, and Australia. It included children aged 2–5 years with hyperphagia and obesity caused by biallelic POMC (including PCSK1) LEPR variants or genetically confirmed BBS. Participants received open-label subcutaneous setmelanotide once daily for 52 weeks, starting at a dose of 0.5 mg, which was increased every two weeks by 0.5 mg until the maximum dose based on weight was reached.

The primary goals at week 52 were to assess the percentage of patients achieving a reduction of 0.2 points or more in their BMI Z score—a measure that compares a child’s BMI to age- and sex-specific reference values—and the average percentage change in BMI. Secondary measures included safety, hunger levels, weight-related outcomes, and the impact on caregiver burden. 

The following were the key findings of the study:

  • Between March 8, 2022, and September 18, 2023, 13 patients were screened at six sites, and 12 were enrolled in the study (seven with POMC or LEPR deficiency and five with BBS).
  • One patient with BBS was excluded due to a BMI below the 97th percentile.
  • Of the 12 enrolled patients, 58% were male (seven), and 42% were female (five). The mean age of participants was 3.6 years. Eleven patients completed the trial.
  • At week 52, 83% achieved a reduction of 0.2 points or more in BMI Z score per WHO methodology.
  • The mean percent change in BMI from baseline at week 52 was −18% for the overall safety population.
  • Patients with POMC or LEPR deficiency had a mean BMI reduction of −26%, while those with BBS had a reduction of −10%.
  • Secondary endpoints showed mean reductions at week 52 of 3.4 in BMI Z score and 32.5% in the percentage of the BMI 95th percentile.
  • 91% of caregivers reported that patients were less hungry compared to baseline.
  • All adverse events were mild or moderate, the most common being skin hyperpigmentation, vomiting, nasopharyngitis, upper respiratory tract infection, and injection site reactions.
  • No serious adverse events, study discontinuations, or deaths were reported.

“To our knowledge, this is the first trial evaluating setmelanotide in patients under 6 years of age. The findings highlight the potential benefits of early intervention with the drug to manage obesity in this young population,” the researchers concluded.

Reference: Lancet Diabetes Endocrinol 2024; doi:10.1016/ S2213-8587(24)00273-0

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Study reveals Airway Challenges and Optimization of Intubation with Second-Generation supraglottic airway devices

Second-generation supraglottic airway devices (SADs) serve as both a ventilation tool and a pathway for certain types of intubation in challenging laryngoscopy situations. However, relying on blind intubation through SADs is not recommended due to challenges like requiring multiple attempts, low success rates, prolonged duration, potential for esophageal intubation, and risk of airway injury. Recent research study compared the use of LMA Protector and i-gel as conduits for fiber-optic guided tracheal intubation in adult paralyzed patients using PVC endotracheal tubes (ETT). The study aimed to assess the time to tracheal intubation via the two supraglottic airway devices (SADs) as the primary outcome, with insertion and intubation characteristics as secondary outcomes. A total of 66 patients within the age range of 18-70 years and with ASA physical status I/II were randomly allocated to groups for the comparison.

Results and Comparison of Airway Devices

The results indicated that there were no significant differences between LMA Protector and i-gel in terms of time to view the carina, tracheal intubation time, insertion characteristics, or adverse effects. Both devices showed comparable performance as conduits for fiber-optic guided tracheal intubation. The study findings suggested that grade 1 and grade 2 glottic views were achieved effectively with both devices, in line with previous literature supporting good glottic views with appropriately placed SADs.

Evaluation of Insertion and Intubation Parameters

The study also evaluated parameters like ease of insertion, intubation attempts, tracheal tube impingement, and oropharyngeal leak pressure, all of which were found to be statistically non-significant between LMA Protector and i-gel. While the i-gel exhibited more instances of tracheal tube impingement, the differences were not significant. Adverse effects such as blood stains on the device, oropharyngeal trauma, and postoperative complications like sore throat were similar in both groups, demonstrating comparable safety profiles for both SADs. The study acknowledged certain limitations, including the exclusion of patients with anticipated difficult airways or BMI > 35 kg/m2, which might impact the generalizability of the findings to broader patient populations. However, the research concluded that LMA Protector and i-gel are technologically equivalent when used as conduits for fiber-optic guided tracheal intubation with PVC ETT in adult paralyzed patients. The study emphasized the importance of these findings in enhancing airway management practices in clinical settings.

Key Points

– The study compared the LMA Protector and i-gel as conduits for fiber-optic guided tracheal intubation in adult paralyzed patients using PVC endotracheal tubes.

– Primary outcome was the time to tracheal intubation, with insertion and intubation characteristics as secondary outcomes.

– 66 patients aged 18-70 with ASA physical status I/II were randomly allocated to groups. – Results showed no significant differences between LMA Protector and i-gel in terms of intubation time, insertion characteristics, or adverse effects, indicating comparable performance.

– Evaluation of parameters like ease of insertion, intubation attempts, tracheal tube impingement, and oropharyngeal leak pressure showed non-significant differences between the two devices.

– Adverse effects such as blood stains, oropharyngeal trauma, and postoperative complications were similar in both groups, indicating comparable safety profiles for LMA Protector and i-gel.

Reference –

M. Bhardwaj et al. (2024). Comparison Of Fibreoptic-Guided Tracheal Intubation Through LMA Protector And I-Gel In Adult Paralysed Patients – A Randomised Comparative Study. *Indian Journal Of Anaesthesia*. https://doi.org/10.4103/ija.ija_656_24.

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Bedaquiline Monotherapy Clears Leprosy Bacteria Rapidly, claims research

Brazil: Bedaquiline monotherapy has demonstrated significant promise in treating multibacillary leprosy, showing remarkable effects on clearing Mycobacterium leprae and improving skin lesions, according to recent findings. The findings, published in the New England Journal of Medicine, highlight the potential of bedaquiline as a simplified, effective alternative to traditional multidrug therapy.

The study findings reveal that in patients with multibacillary leprosy, bedaquiline monotherapy effectively cleared M. leprae within four weeks of treatment. Additionally, improvements in the appearance of skin lesions were observed by the seventh week of treatment, indicating a rapid and sustained therapeutic response. These results emphasize bedaquiline’s ability to target the bacterial burden associated with multibacillary leprosy efficiently.

Standard multidrug therapy for leprosy is often linked to severe side effects, which can exacerbate the stigma and discrimination faced by individuals with the disease. Furthermore, the growing threat of drug-resistant leprosy highlights the urgent need for alternative drug combinations and shorter, safer treatment regimens.

Bedaquiline, originally approved for drug-resistant tuberculosis, is an innovative agent that inhibits the bacterial energy production pathway by targeting the ATP synthase enzyme.

Jaison Barreto, From the Research Division, Instituto Lauro de Souza Lima, Bauru (J.B., P.S.R.), and Fundação de Dermatologia Tropical e Venereologia Alfredo da Matta, Manaus (P.F.B.R.), Brazil, and colleagues conducted a proof-of-concept, open-label study in Brazil, assigning patients with previously untreated multibacillary leprosy to receive bedaquiline monotherapy for 8 weeks. Following this 8-week treatment, patients transitioned to standard multidrug therapy as defined by the World Health Organization and were monitored for 112 weeks.

The primary endpoint assessed was the change from baseline in the likelihood of positive Mycobacterium leprae growth in mouse footpads after 8 weeks of bedaquiline therapy. The study’s secondary endpoint focused on safety, while exploratory endpoints examined changes in clinical leprosy symptoms and the molecular viability of M. leprae using quantitative reverse-transcriptase–polymerase-chain-reaction analysis.

The study revealed the following findings:

  • The modified intention-to-treat analysis included nine patients.
  • The odds of positive M. leprae growth decreased from 100% at baseline to no growth after 4 weeks of bedaquiline monotherapy.
  • After 7 weeks of treatment, all patients showed improvement in the appearance of skin lesions compared to baseline.
  • Seven patients experienced at least one adverse event during treatment, and all events were classified as grade 1 or 2.

“The findings showed that Bedaquiline monotherapy cleared M. leprae in patients with multibacillary leprosy by 4 weeks of treatment and resulted in noticeable improvement in skin lesions by 7 weeks,” the researchers concluded.

Reference:

DOI: 10.1056/NEJMoa2312928

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Fluctuating blood pressure tied to problems with thinking skills, unravels study

Older adults whose blood pressure fluctuates over time may be more likely to have problems with thinking and memory skills, according to a study published in the December 11, 2024, online issue of Neurology®, the medical journal of the American Academy of Neurology. The association was found in Black participants but not in white participants in the study.

The study does not prove that fluctuations in blood pressure cause problems with thinking skills; it only shows an association.

“These results suggest that fluctuation in blood pressure is a risk factor for cognitive problems beyond the negative effects of high blood pressure itself,” said study author Anisa Dhana, MD, MSc, of Rush University in Chicago. “Older adults should be routinely monitored for their blood pressure and any changes over time so we can identify people who may have this issue and work to alleviate it, which could potentially help to prevent or delay cognitive problems.”

The study involved 4,770 people with an average age of 71; 66% were Black participants, and the remaining were white participants.

Participants had blood pressure tests at the beginning of the study and then every three years for an average of 10 years. They also completed thinking and memory skills tests at the beginning and at their last visit.

Overall, the participants had an average blood pressure of 138/78 mmHg. High blood pressure is defined as 130/80 mmHg and higher.

Black participants in the study had an average variation over time in their systolic blood pressure, which is the top number, of 18 mmHg, compared to 16 mmHg for white participants.

The participants were divided into three groups based on how much their blood pressure varied over time. For Black participants, those with the most variability in their blood pressure had lower scores on the cognitive tests than those with the least variability. The difference in scores was the equivalent of 2.8 years of cognitive aging.

For people taking blood pressure medications at the start of the study, there was no difference in scores on thinking tests at the end of the study among the groups with high and low blood pressure variation.

“With our aging society and the prevalence of Alzheimer’s disease, identifying prevention strategies to slow the decline of cognitive skills in older adults has become a public health priority,” Dhana said. “Managing blood pressure and its fluctuations is emerging as an essential risk factor that can be modified.”

A limitation of the study is that participants were Black and white people, so the results may not apply to people of other races.  

Reference:

Dhana, A., et al. (2024) Blood Pressure Variability and Cognition in Black and White Older Adults Over 18 Years of Follow-up. A Population-Based Cohort Study. Neurology. doi.org/10.1212/WNL.0000000000210151.

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Alpha blocker use in females with voiding difficulties and CKD linked to risk of fractures: Study

Alpha blocker use in females with voiding difficulties and CKD linked to risk of fractures suggests a study published in the BMC Nephrology.

Alpha blockers (ABs) are frequently prescribed to patients with chronic kidney disease (CKD), which is often complicated by refractory hypertension (HT). Although there have been several reports on the association between Alpha blocker use and the risk of fractures, their conclusions have not yet been drawn. Therefore, this study aimed to investigate the association between Alpha blocker use and the risk of fractures in patients with CKD. This population-based cohort study used patient data obtained between April 2008 and August 2021 from a large-scale Japanese medical claims database. Consecutive patients with CKD who were newly prescribed vs or non-Alpha blocker antihypertensive drugs were included; males and females were analysed separately. The Alpha blocker group was then divided into Alpha blocker for HT and voiding dysfunction (VD) groups according to the drug approval in Japan. The primary outcome was the first hospitalisation due to fracture, and the variables were evaluated with weighted Cox proportional hazard model using overlap weights. Results: A total of 65,012, 4,723, and 10,958 males constituted the non-Alpha blocker, Alpha blocker for HT (doxazosin), and Alpha blocker for VD (naftopidil, silodosin, tamsulosin, or urapidil) groups, respectively. A total of 31,887, 2,409, and 965 females constituted the non-AB, AB for HT (doxazosin or guanabenz), and AB for VD (urapidil) groups, respectively. In males, hazard ratio (HR) for primary outcome was not increased in the non-Alpha blocker and Alpha blocker for VD groups compared with the AB for HT group (HR, 0.70; 95% confidence interval [CI], 0.38–1.28 and HR, 1.33; 95% CI, 0.67–2.66, in the non-Alpha blocker and Alpha blocker for VD groups, respectively). Whereas, in females, although HR for the primary outcome was not increased in the non-Alpha blocker group (HR, 1.06; 95% CI, 0.56–1.99), it was significantly increased in the Alpha blocker for VD group (HR, 2.28; 95% CI, 1.01–5.16) compared with the Alpha blocker for HT group. Alpha blocker use in patients with CKD did not increase the risk of fractures when used for the treatment of HT; however, it increased the risk of fractures when used for the treatment of VD in females. These results suggest that Alpha blockers should be used with caution in these patients.

Reference:

Sunohara, K., Onogi, C., Tanaka, A. et al. Association between alpha blocker use and the risk of fractures in patients with chronic kidney disease: a cohort study. BMC Nephrol 25, 442 (2024). https://doi.org/10.1186/s12882-024-03892-5

Keywords:

Alpha blocker, use, females, voiding, difficulties, patients, CKD, linked, risk, fractures, sttudy , Sunohara, K., Onogi, C., Tanaka, A,BMC Nephrology, Alpha blocker, Hypertension, Chronic kidney disease, Fracture, Voiding dysfunction

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Eltrombopag Outperforms Standard Therapies for Pediatric Immune Thrombocytopenia in New Trial

USA: Findings from the PINES trial suggest that eltrombopag (Promacta) may offer improved outcomes for children with newly diagnosed immune thrombocytopenia (ITP) compared to standard first-line therapies.

Presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, the trial revealed that eltrombopag significantly increased the rate of durable platelet responses without needing rescue treatments. This was notably superior to standard first-line therapies, which included prednisone, intravenous immunoglobulin (IVIG), or anti-D globulin administered at specified doses.

Data from the PINES trial, presented at ASH 2024, indicate that eltrombopag may surpass the current standard of care in achieving platelet response for children with newly diagnosed pediatric ITP.

“Eltrombopag achieved a sustained platelet response rate of 65%, significantly higher than the 33% observed with standard therapies in children with newly diagnosed pediatric ITP,” the researchers reported.

Corticosteroids, intravenous immunoglobulin (IVIg), and anti-D globulin are commonly used as first-line treatments for newly diagnosed immune thrombocytopenia (ITP). Eltrombopag (epag), a thrombopoietin receptor agonist, received FDA approval in 2015 for use in children with chronic ITP. Kristin A. Shimano, University of California San Francisco Benioff Children’s Hospital, San Francisco, CA, and colleagues aimed to explore the efficacy of eltrombopag (epag) during the newly diagnosed phase of pediatric ITP, as its effectiveness in this stage remains unknown.

The PINES trial (NCT03939637) is a randomized, open-label, multicenter study sponsored by ICON and funded by Novartis. It included patients aged 1–<18 years with newly diagnosed ITP (≤3 months) and platelet counts <30 × 10⁹/L requiring treatment. Participants were randomized 2:1 to eltrombopag (epag) or one of three standard therapies (prednisone, IVIg, or anti-D globulin).

The primary endpoint was achieving ≥3 of 4 platelet counts >50 × 10⁹/L during weeks 6–12 without rescue treatment. Secondary endpoints assessed bleeding severity, quality of life (QoL), and rescue therapy usage. Statistical methods tested the superiority of epag over standard therapies.

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

  • Primary Endpoint: The eltrombopag (epag) arm had a significantly higher response rate than the standard of care (SOC) (65% versus 33%). The trial was closed early for efficacy following DSMB recommendation.
  • Participants: 118 patients (1–<18 years) were included in the intent-to-treat analysis (78 epag, 40 SOC). Median platelet counts at enrollment were 4 × 10⁹/L (epag) and 8 × 10⁹/L (SOC).
  • Bleeding Scores: Baseline median WHO bleeding scores were 2 (epag) versus 1 (SOC), and MBS scores were 3 (epag) versus 2 (SOC).
  • Rescue Therapy: Fewer patients required rescue therapy in the epag arm (19%) than in the SOC arm (46%).
  • Quality of Life (QoL): Both arms showed clinically meaningful QoL improvement based on KIT scores, with no significant differences between groups.
  • Adverse Events (AEs): Grade 3+ AEs were reported in 20 patients (6 SAEs) in the epag arm and six patients (3 SAEs) in the SOC arm. Common AEs included headache and epistaxis.
  • Severe Cases: There was one intracranial hemorrhage in the epag arm, but there were no thromboembolic events.
  • Follow-Up: Participants are completing 12 months of follow-up per protocol

“The findings showed that in children with newly diagnosed ITP needing pharmacologic treatment, epag results in a significantly higher rate of sustained platelet response without the need for rescue therapies compared to standard first-line treatments,” the researchers concluded.

Reference: https://ash.confex.com/ash/2024/webprogram/Paper193644.html

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lower pulmonary gas exchange in Long COVID patients associated with impaired cognitive function: Study

In patients with long COVID, lower pulmonary gas exchange may be associated with impaired cognitive function, according to a study being presented next week at the annual meeting of the Radiological Society of North America (RSNA).

According to the National Center for Health Statistics, approximately 17.6% of adults in the U.S. have experienced a post-COVID condition commonly referred to as long COVID. People with long COVID may exhibit a wide variety of symptoms, including difficulty concentrating (“brain fog”), change in sense of smell or taste, fatigue, joint or muscle pain, dyspnea (shortness of breath), digestive symptoms, and more. These symptoms may persist for weeks, months, or even years after COVID-19 infection.

Researchers from the University of Iowa in Iowa City set out to assess associations between pulmonary MRI gas exchange, structural and functional brain MRI, and cognition in long COVID patients. In pulmonary gas exchange, oxygen moves from the lungs to the bloodstream, while carbon dioxide moves from the bloodstream to the lungs.

“This is the first time that MRI has been used to jointly assess lung and brain function to investigate their relationship in long COVID,” said the study’s lead author Keegan Staab, B.S., graduate research assistant in the Department of Radiology at the University of Iowa in Iowa City. “This research is new in that it combines multiple unique imaging types to study a multiorgan relationship in a disease population.”

Senior study author Sean B. Fain, Ph.D., professor and vice chair for research in the Department of Radiology at the University of Iowa, added, “If these findings can be generalized to the long COVID population, the study suggests that there may be a causative relationship between cognitive dysfunction and lung dysfunction, suggesting a potential treatment strategy using methods that target improved gas exchange.”

For the study, 10 female and 2 male patients (median age: 59 years) who had persistent dyspnea and/or fatigue following the resolution of acute COVID-19 infection were recruited from a post-COVID-19 clinic. Hyperpolarized Xe pulmonary MRI, structural and functional brain MRI, pulmonary function tests and cognitive tests were acquired.

“129Xe MRI allows for advanced measurements of ventilation and gas exchange,” Staab said. “The literature also indicates that 129Xe may be more sensitive to pulmonary injury compared to standard breathing tests, making it better suited to study long COVID in which patients typically have normal breathing tests.”

Perceived cognitive difficulties were measured using Patient-Reported Outcomes Measurement Information System, and objective cognitive performance was assessed using the National Institutes of Health Toolbox V3 Cognition Battery.

“There was a range of cognitive difficulties among the patients in the study,” Staab said. “Some were mild and indicated slight dysfunction, while others were more serious and indicated that some patients have slow thinking and trouble concentrating several times per day.”

The results showed that lower pulmonary gas exchange may be associated with cognitive dysfunction, as well as lower gray matter and white matter volumes in patients with long COVID. In addition, the researchers observed significant relationships suggesting that increased cerebral blood flow is associated with decreased gas exchange in long COVID patients.

Staab said larger studies are needed to investigate the association between gas exchange and cerebral blood flow in long COVID.

“This relationship could be a compensatory mechanism where lower lung function is compensated by higher cardiac output and higher brain perfusion,” he said. “It’s also a possibility that the disease mechanism that impairs pulmonary gas exchange also leads to higher brain perfusion through downstream vascular injury in both lung and brain.”

Based on the findings of this study, gas exchange abnormalities may help identify long COVID patients who require additional treatment or long-term management.

Reference:

Long COVID brain fog linked to lung function, Radiological Society of North America, Meeting: 110th Scientific Assembly and Annual Meeting of the Radiological Society of North America.

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Air pollution linked to rising depression rates, study finds

A groundbreaking study published in Environmental Science and Ecotechnology has revealed a strong connection between long-term air pollution exposure and an increased risk of depression. The research, led by Harbin Medical University and Cranfield University, analyzed data from over 12,000 participants in the China Health and Retirement Longitudinal Study (CHARLS).

The study identifies sulfur dioxide (SO₂) as the most significant contributor to depression risk, with fine particulate matter (PM2.5) and carbon monoxide (CO) also linked to depressive symptoms. These pollutants were found to have a compounded impact when combined, highlighting the dangers of multi-pollutant exposure.

The research also explored potential mechanisms, finding that cognitive and physical impairments partially mediate the link between pollution and depression. The findings emphasize the mental health risks posed by environmental pollutants and call for urgent action to reduce their levels.

“Our findings underscore the critical need for integrated air quality management to improve both physical and mental health,” the authors noted. Targeting SO₂ and other key pollutants could significantly alleviate the public health burden of depression, particularly among vulnerable populations like middle-aged and older adults.

With millions exposed to unsafe air quality levels worldwide, this study highlights the intersection of environmental and mental health challenges, calling for stricter pollution controls and targeted interventions.

Reference:

Yuqing Hao, Longzhu Xu, Meiyu Peng, Zhugen Yang, Weiqi Wang, Fanyu Meng, Synergistic air pollution exposure elevates depression risk: A cohort study, Environmental Science and Ecotechnology, https://doi.org/10.1016/j.ese.2024.100515.

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MELT-300 Demonstrates Successful Procedural Sedation for cataract extraction in new research

Melt Pharmaceuticals a clinical-stage pharmaceutical company developing novel approaches for procedural sedation, today announced positive topline results of its pivotal Phase 3 study evaluating the safety and efficacy of its lead product candidate, MELT‑300, a non-IV, non-opioid tablet for procedural sedation during cataract surgery. Based on a Special Protocol Assessment agreement reached with the U.S. Food and Drug Administration (“FDA”) earlier this year, this study design and these positive results support the necessary objectives required for a regulatory submission.

MELT-300 uniquely combines a fixed dose of midazolam (3mg) and ketamine (50mg) in one tablet that is administered sublingually using Catalent’s proprietary Zydis® delivery technology which dissolves in as little as 3 seconds allowing absorption of the active ingredients across the sublingual mucosa.

The MELT-300 Phase 3 clinical trial was a randomized, double-blind, three-arm study comparing, at a 4:1:1 ratio, MELT-300, sublingual midazolam, and sublingual placebo, respectively, for procedural sedation in patients undergoing cataract surgery. The study was conducted at 13 clinical sites in the United States and enrolled over 530 patients.

In commenting on the topline results, Dr. Larry Dillaha, Chief Executive Officer of Melt, said, “We are extremely excited with this robust topline data from our pivotal Phase 3 study. These overwhelmingly positive results support our belief that MELT-300, if approved by the FDA, would be a safe and effective non-IV, non-opioid alternative to current IV-based cataract surgery sedation protocols, which generally involve the administration of opioids. With the number of cataract surgeries performed each year in the U.S. expected to exceed 5 million in the coming years, we believe offering patients and physicians the ability to achieve an adequate sedation level without the need to start an IV or administer opioids is a very attractive proposition.”

MELT-300 co-inventor, Melt Pharmaceuticals board member, and board-certified ophthalmologist John Berdahl, M.D., commented, “A proprietary compounded combination of midazolam and ketamine, which was the inspiration for the development of the MELT-300 product candidate, has been used by hundreds of ophthalmologists, including myself – in hundreds of thousands of cataract surgeries. I am thrilled at the prospect of the FDA approving MELT-300, which I believe would greatly enhance the confidence of healthcare professionals in considering the adoption of this groundbreaking sedation method.”

George Magrath, M.D., a board-certified ophthalmologist and a MELT-300 Phase 3 study principal investigator, commented, “These Phase 3 data show the superiority of the combination of midazolam and ketamine compared with midazolam alone. If approved, I believe MELT-300 will be a safe and effective alternative to current sedation methods used for cataract surgery. As an ophthalmologist, I am excited about the prospect of using MELT-300 to enhance the overall experience for my cataract surgery patients.”

Dr. Dillaha continued, “In addition to supporting a regulatory submission, these MELT-300 Phase 3 data should further strengthen our already strong patent portfolio, both domestically and internationally. Further, with these data now confirming and complementing our robust Phase 2 efficacy and safety results, we believe we are well positioned to elevate the procedural sedation standard of care for cataract surgery and, through lifecycle management, eventually expand the potential use of MELT-300 to over 100 million annual procedures in various medical specialties, including dermatology, plastic surgery, dentistry, gastroenterology, and emergency care.

“Melt Pharmaceuticals is profoundly grateful to the Phase 3 MELT-300 study participants, whose involvement has been invaluable. This includes the ophthalmologists, optometrists, anesthesiologists, certified registered nurse anesthetists, staff, and patients at the 13 U.S. clinical sites.”

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