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Recent research paper which is a phase III, prospective, multi-centric, observer-blind, randomized controlled trial that compares the efficacy and safety of a generic remifentanil with fentanyl and Ultiva during general anesthesia in the Indian population. The study was conducted at 13 centers in India and included 314 subjects scheduled for elective therapeutic and diagnostic surgical procedures. The primary efficacy endpoint was the haemodynamic response during specific activities such as endotracheal intubation, skin incision, skin closure, and extubation. The results of the study indicated that there were no significant differences in demographic and baseline characteristics across the study groups. Heart rate was found to be similar between the remifentanil and Ultiva groups during the specific activities, whereas the fentanyl group exhibited significantly higher heart rates during these activities. The need for vasopressor and anti-cholinergic drugs was similar across the groups, and no subjects required naloxone administration. The study concluded that generic remifentanil is non-inferior to fentanyl and equivalent to Ultiva for general anesthesia in Indian patients undergoing various surgical and diagnostic procedures. Moreover, it was found that remifentanil offered advantages in terms of optimum haemodynamic stability, fast equilibrating analgesia, and rapid emergence from sedation, making it a suitable alternative to fentanyl.

Research Methodology

The study utilized a robust, observer-blind, multi-center design with rigorous monitoring of haemodynamic parameters. It employed ANOVA, paired t-test, and chi-square/Fisher’s exact test for statistical analysis. The study findings were consistent with earlier research, suggesting that remifentanil effectively attenuates the sympathetic response during intubation and aids in stable haemodynamic control during surgical stress. Despite some limitations, including the limited age range of the subjects and the single geographic focus on India, the study support the non-inferiority of generic remifentanil compared to fentanyl and its equivalence with Ultiva, establishing it as an alternative analgesic component for general anesthesia for various surgical procedures in the Indian population.

Conclusion and Disclosures

In conclusion, the study demonstrated the non-inferiority of generic remifentanil to fentanyl and its equivalence to Ultiva for general anesthesia in the Indian population, making remifentanil a suitable alternative analgesic option during induction and maintenance of general anesthesia in Indian patients. The authors indicated that de-identified data may be requested from the corresponding author and acknowledged the support of Themis Medicare Limited, Mumbai, India, as the study’s sponsor. The authors disclosed their potential conflicts of interest related to the study.

Key Points

– The research paper is a phase III, prospective, multi-centric, observer-blind, randomized controlled trial conducted at 13 centers in India, comparing the efficacy and safety of generic remifentanil with fentanyl and Ultiva during general anesthesia in the Indian population. It included 314 subjects scheduled for elective therapeutic and diagnostic surgical procedures.

– The primary efficacy endpoint was the haemodynamic response during specific activities such as endotracheal intubation, skin incision, skin closure, and extubation. The study found no significant differences in demographic and baseline characteristics across the study groups. Heart rate was similar between the remifentanil and Ultiva groups during specific activities, while the fentanyl group exhibited significantly higher heart rates.

– The need for vasopressor and anti-cholinergic drugs was similar across the groups, and no subjects required naloxone administration. The study concluded that generic remifentanil is non-inferior to fentanyl and equivalent to Ultiva for general anesthesia in Indian patients undergoing various surgical and diagnostic procedures. Remifentanil offered advantages in terms of optimum haemodynamic stability, fast equilibrating analgesia, and rapid emergence from sedation, making it a suitable alternative to fentanyl.

– The study utilized a robust, observer-blind, multi-center design with rigorous monitoring of haemodynamic parameters. It employed ANOVA, paired t-test, and chi-square/Fisher’s exact test for statistical analysis. The findings were consistent with earlier research, supporting the non-inferiority of generic remifentanil compared to fentanyl and its equivalence with Ultiva as an alternative analgesic component for general anesthesia for various surgical procedures in the Indian population.

– In conclusion, the study demonstrated the non-inferiority of generic remifentanil to fentanyl and its equivalence to Ultiva for general anesthesia in the Indian population. The authors indicated that de-identified data may be requested from the corresponding author and acknowledged the support of Themis Medicare Limited, Mumbai, India, as the study’s sponsor. The authors disclosed their potential conflicts of interest related to the study.

Reference –

Hemantkumar I, Swain AK, Mishra M, Singh S, Gurudatt CL, Giridhar JB. Efficacy and safety of a generic remifentanil formulation versus fentanyl and Ultiva during general anaesthesia: A phase III, prospective, multi‑centric, observer‑blind, randomised controlled trial. Indian J Anaesth 2024;68:985‑95

A new study published in the Graefe’s Archive for Clinical and Experimental Ophthalmology found that ciclosporin A (CsA) 0.1% cationic emulsion may be safe, efficient, and well-tolerated when used in clinical settings to treat severe dry eye disease. It can be difficult to identify and treat dry eye disease (DED), often referred to as keratoconjunctivitis sicca, in clinical practice. DED is a chronic, multifactorial, and complicated ocular disorder that requires long-term care. The effectiveness, safety, and tolerability of ciclosporin A (CsA) 0.1% cationic emulsion (CE) in regular clinical practice as a remedy for adults with severe keratitis and dry eye disease that continued inadequately controlled with artificial tears were assessed in the PERSPECTIVE study. Thus, Ines Lanzl and colleagues analyzed the data from German ophthalmology clinics to offer additional detailed information on CsA 0.1% CE.

Adults beginning CsA 0.1% CE (one drop in each eye before bed) were the subjects of the study, and they were monitored at Weeks 4, 12, and 24 as well as Month 12. Mean shift from baseline in corneal fluorescein staining (CFS) score (Oxford Grade Scale) at Month 12 was the main outcome. Secondary endpoints looked at adverse events (AEs) and the intensity of ocular signs and symptoms.

A total of 236 patients from 20 German ophthalmology clinics took part in the PERSPECTIVE research. After receiving CsA 0.1% CE, CFS scores of patients significantly decreased starting in Week 4 and continued to do so until Month 12 (P<0.0001). By Month 12, 81.6% of patients had improved their CFS score from baseline.

Significant improvements in the intensity of subjective ocular symptoms (all P ≤ 0.015) and eyelid and conjunctival erythema at month 12 were seen with CsA 0.1% CE (P < 0.001) when compared to baseline. The safety statistics aligned with the established safety profile of 0.1% CE CsA. 95.7% of patients and 97.2% of doctors assessed tolerability as “satisfactory,” “good,” or “very good.”

Overall, a country-level sub-analysis of the PERSPECTIVE study data from German ophthalmology clinics revealed results that are comparable to those reported for the entire study population which are indicative of the treatment outcomes that ophthalmologists may look forward with CsA 0.1% CE treatment in real-life clinical practice. Beginning with Week 4 and continuing through Month 12, CsA 0.1% CE significantly decreased the severity of keratitis and DED signs and symptoms.

Source:

Lanzl, I., Deuter, C. M. E., Lorenz, K., & Geerling, G. (2024). Real-world insights and outcomes related to ciclosporin A 0.1% cationic emulsion for the long-term treatment of dry eye disease in Germany: Country-level sub-analysis of the PERSPECTIVE study. In Graefe’s Archive for Clinical and Experimental Ophthalmology (Vol. 262, Issue 10, pp. 3261–3271). Springer Science and Business Media LLC. https://doi.org/10.1007/s00417-024-06414-z

Researchers at the University of Massachusetts Amherst and UMass Chan Medical School have demonstrated in mice a new method to combat pancreatic cancer. The study, published in Science Translational Medicine, outlines the synergistic effects of a novel nanoparticle drug-delivery system to activate an immune pathway in combination with tumor-targeting agents.

Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer. With a dismal,13% five-year survival rate, it is the third leading cause of cancer deaths.

One major challenge is the microenvironment surrounding the tumor. This environment is characterized by dense tissue creating a barrier around the tumor that inhibits blood vessel formation and blocks immune infiltration.

“Drug delivery is a huge challenge due to the architecture of these difficult-to-treat tumors’ microenvironment,” says Prabhani Atukorale, assistant professor of biomedical engineering at UMass Amherst and one of the corresponding authors of the paper. She adds that the environment also blocks the activation of the body’s immune cells and their penetration into the tumor.

“Pancreas cancer, unfortunately, doesn’t respond to most conventional therapies like chemotherapy, or even immunotherapy, which has revolutionized a lot of cancer therapy in the last 10 years,” says Marcus Ruscetti, assistant professor of molecular, cell and cancer biology at UMass Chan Medical School, and the other corresponding author.

Ruscetti’s previous research demonstrated that two cancer drugs (MEK inhibitor trametinib and CDK4/6 inhibitor palbociclib, or T/P) can promote blood vessel development, enabling greater T cell (as well as chemotherapy) delivery into the tumor. However, the cancer “tricks” the immune system into thinking that the tumor is just a regular, healthy clump of cells. Since the T cells aren’t activated, simply having more of them present won’t clear the cancer.

Here’s where the researchers want to implement a trick of their own. The first pathway is called the stimulator of interferon genes (STING) pathway. STING recognizes viral infections in the body. “If we can trick the immune system into thinking that there is a viral-type infection, then we harness a very robust anti-tumor immune response to bring in for tumor immunotherapy,” Atukorale explains.

The researchers also wanted to activate the TRL4 pathway because it boosts the effects of STING activation. They use agonists, which are any chemicals that can trigger a biological response; in this case, in immune stimulatory pathways. But getting these immunity-triggering chemicals through the tumor’s microenvironment is still a challenge.

The researchers’ solution: encapsulating the STING and TRL4 agonists in a novel design of lipid-based nanoparticles. The nanoparticles have several benefits. First, the research demonstrated that they are highly effective at delivering the agonists into the challenging tumor microenvironment.

The design also allows both of the agonists to be packaged together-a challenge since these two mix as well as oil and water. “It ensures that they are carried within the blood circulation together, they reach the same target cell together and are taken up together by the same target cell,” says Atukorale.

“We’re using biocompatible, lipid-based materials to encapsulate drugs that functionally work together, but don’t like to be next to each other, and then we are able to use engineering capabilities to build in various functionalities to direct them where they need to go,” she says.

The synergistic effect of the two agonists plus the T/P therapy proved effective: eight out of nine of the mice saw tumor necrosis and shrinkage. “And we had two mice that had complete responses, meaning the tumors completely went away, which is pretty striking,” says Ruscetti. “We’ve never seen that in this model before.”

There is still work to be done because the tumors returned after the mice were taken off of the treatment, but Ruscetti says it is still a very encouraging step toward a cure.

“If you go beyond pancreas cancer to other cancer types, you need a combination therapy to target the tumor and to target the immune system,” he adds. “This is a strategy to be able to do that.” Treatments for cancers like PDAC that could be derived from this study include mutations of colon cancer, lung cancer, liver cancer and cholangiocarcinoma (cancer of the bile ducts).

Prabhani adds that the modular nature of this design allows for therapies that can be easily personalized for patients. “It’s sort of plug and play,” she says. “We can tailor the agonist ratios, the drug combinations, the targeting molecules, but keeping essentially the same platform. This is what will make it hopefully translational, but also tunable on a per patient basis, because many of these cancer therapies need to be personalized.”

Finally, she nods to the power of collaboration between the two UMass institutions, saying, “This type of system is easily built when you have complementary, but multidisciplinary and cross-disciplinary, expertise.” 

Reference:

Loretah Chibaya et al. ,Nanoparticle delivery of innate immune agonists combined with senescence-inducing agents promotes T cell control of pancreatic cancer.Sci. Transl. Med.16,eadj9366(2024).DOI:10.1126/scitranslmed.adj9366.

Lateral ankle sprain (LAS) is the most common sports-related injury. However, there are currently no published evidence-based criteria to guide the patient’s return to sport (RTS) and this decision is generally time-based.

Picot et al conducted a study to assess the psychometric properties of a new score (Ankle-GO) and its predictive ability for RTS at the same level of play after LAS. The article has been published in ‘Sport health’ journal.

The Ankle-GO was administered to 30 healthy participants and 64 patients at 2 and 4 months after LAS. The score was calculated as the sum of 6 tests for a maximum of 25 points. Construct validity, internal consistency, discriminant validity, and test-retest reliability were used to validate the score. The predictive value for the RTS was also validated based on the receiver operating characteristic (ROC) curve.

Ankle-GO is a composite score based on the sum of 7 components for an objective evaluation of the main deficits associated with LAS or CAI and which can result in a risk of reinjury.It was calculated from 4 functional tests: the single leg stance test (SLS) on a firm surface, the modified star excursion balance test (mSEBT), the side hop test (SHT), and the figure-of-8 test (F8T). In addition, 2 patient self-reported questionnaires were used: the Foot and Ankle Ability Measure, involving 2 subscales evaluating activities in daily life (FAAM adl) and sports (FAAMsport ), and the Ankle Ligament Reconstruction- Return to Sport after Injury (ALR-RSI).

Key findings of the study were:

• The internal consistency of the score was good (Cronbach’s alpha coefficient of 0.79) with no ceiling or floor effect.

• Test-retest reliability was excellent (intraclass coefficient correlation = 0.99) with a minimum detectable change of 1.2 points.

• The 2-month scores were significantly lower than 4-month and control group scores (7.7 ± 4, 13.9 ± 4.6, and 19.6 ± 3.4 points, respectively, P < 0.01).

• Ankle-GO values were also significantly higher in patients who returned to their preinjury level at 4 months compared with those who did not (P < 0.01).

• The predictive value of the 2-month Ankle-GO score was fair for a RTS at the same or higher than preinjury level at 4 months (area under ROC curve, 0.77; 95% CI, 0.65-0.89; P < 0.01).

Clinical Relevance: Ankle-GO is the first objective score to help in the decision-making of the RTS after LAS. At 2 months, patients with an Ankle-GO score <8 points are unlikely to RTS at the same preinjury level.

The authors concluded that – “Ankle-GO is a valid and reliable score when assessing patients after LAS during the RTS continuum. This inexpensive clinical tool composed of functional test and self-reported questionnaires seems relevant to discriminate and predict the level of RTS. At 2 months after injury, a patient exhibiting an Ankle-GO score <8 points are unlikely to resume at the same preinjury level at 4 months.”

Prospective diagnostic study

Level of Evidence: Level 2.

Key Words: ankle sprain, decision, functional testing, psychological readiness, return to sport, Picot et al, SPORTS HEALTH, Ankle-GO Score.

Further reading:

Development and Validation of the Ankle-GO Score for Discriminating and Predicting Return-to-Sport Outcomes After Lateral Ankle Sprain

Picot et al

SPORTS HEALTH

DOI: 10.1177/19417381231183647

Adolescents who meet the recommended guidelines of nine to 11 hours of sleep per day were shown to have a significantly lower risk of hypertension, according to a new study from UTHealth Houston.

Recently published in the Journal of the American Heart Association, the research revealed that adolescents had a 37% lower risk of developing incidents of high blood pressure by meeting healthy sleep patterns, and underscoring the importance of adequate sleep behavior. The research further explored the impact of environmental factors potentially impacting sleep.

“Disrupted sleep can lead to changes in the body’s stress response, including elevated levels of stress hormones like cortisol, which in turn can increase blood pressure,” said first author Augusto César Ferreira De Moraes, PhD, assistant professor in the Department of Epidemiology at UTHealth Houston School of Public Health.

Utilizing the Adolescent Brain Cognitive Development study, which tracks adolescents’ biological and behavioral development, De Moraes and his team analyzed data from 3,320 adolescents across the U.S. to investigate incidents of high blood pressure during nighttime sleep cycles. Scientists identified a rise in hypertension incidents over two data periods, 2018-2020 and 2020-2022, showing an increase from 1.7% to 2.9%. The data included blood pressure readings and Fitbit assessments, which measured total sleep time and REM sleep duration at night.

The study’s design analyzed covariates such as Fitbit-tracked sleep, blood pressure, and neighborhood noise by residential geocodes, allowing for a thorough examination of environmental noise exposure for each participant.

Scientists investigated the impact of neighborhood/community noise but did not find a significant association with the incidence of hypertension. Environmental factors, such as neighborhood noise, point to the need for longer-term studies to investigate the relationship between sleep health and hypertension, particularly in relation to socioeconomic status, stress levels, and genetic predispositions.

The study emphasizes the importance of improved sleep behaviors and meeting recommendations. “Consistent sleep schedules, minimizing screen time before bed, and creating a calm, quiet sleep environment can all contribute to better sleep quality,”Martin Ma, MPH, second author of the study and recent graduate of the school. “Although environmental noise didn’t directly affect hypertension in this study, maintaining a quiet and restful sleep environment is still important for overall well-being.”

Additional authors included Marcus Vinicius Nascimento-Ferreira, PhD, with the Universidade Federal do Tocantins; and School of Public Health faculty Ethan Hunt, PhD, assistant professor in Health Promotion and Behavioral Sciences; and Deanna Hoelscher, PhD, RDN, LD, regional dean in Austin and professor in Health Promotion and Behavioral Sciences.