Study finds cognitive deficits even in fully recovered survivors of mild COVID

UK: A recent study published in the New England Journal of Medicine revealed similar small deficits in memory, thinking, or concentrating (“brain fog”) among COVID-19 patients recovering from short-term symptoms versus those with longer-term symptoms.

“Subjects with resolved persistent symptoms after COVID-19 had objectively measured cognitive function comparable to that in participants with shorter-duration symptoms,” the researchers wrote. Although short-duration COVID-19 was still linked with small cognitive deficits after recovery. The longer-term persistence of cognitive deficits and clinical implications remain uncertain.

Coronavirus disease 2019 (Covid-19) is a disease cause by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cognitive symptoms after COVID-19 are well recognized, however, there is no clarity on whether objectively measurable cognitive deficits exist and how long they persist.

In this observational study, Adam Hampshire, Imperial College London, London, UK, and colleagues’ primary hypothesis was that there would be measurable cognitive deficits after COVID-19 that would scale with covariates of illness duration and severity. Secondarily, they speculated that objective impairments in memory and executive functions would be observable in persons with prolonged symptoms, especially poor memory or brain fog.

They addressed these hypotheses by analyzing cognitive-task performance data that were obtained in the Real-Time Assessment of Community Transmission (REACT) cohort in England.

800,000 adults were invited to a study in England to complete an online assessment of cognitive function. The researchers estimated a global cognitive score across eight tasks. Of the 141,583 participants who started the online cognitive assessment, 112,964 completed it.

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

  • In a multiple regression analysis, participants who had recovered from Covid-19 in whom symptoms had resolved in less than four weeks or at least 12 weeks had similar small deficits in global cognition as compared with those in the no-Covid-19 group, who had not been infected with SARS-CoV-2 or had unconfirmed infection (-0.23 SD and -0.24 SD, respectively); larger deficits as compared with the no-Covid-19 group were seen in participants with unresolved persistent symptoms (-0.42 SD).
  • Larger deficits were in participants who had SARS-CoV-2 infection during periods in which the original virus or the B.1.1.7 variant was predominant than in those infected with later variants (e.g., -0.17 SD for the B.1.1.7 variant vs. the B.1.1.529 variant) and in participants who had been hospitalized than in those who had not been hospitalized (e.g., intensive care unit admission, -0.35 SD).
  • The results of the analyses were similar to those of propensity-score-matching analyses.
  • In a comparison of the group that had unresolved persistent symptoms with the no-Covid-19 group, memory, reasoning, and executive function tasks were associated with the largest deficits (-0.33 to -0.20 SD); these tasks correlated weakly with recent symptoms, including poor memory and brain fog.
  • There were no adverse events.

Based on the results, the researchers found objectively measurable cognitive deficits that may persist for a year or more after COVID-19. They also found that participants with resolved persistent symptoms had small deficits in cognitive scores versus the no–COVID–19 group, which were similar to those in participants with shorter-duration illness.

“Early periods of the pandemic, longer illness duration, and hospitalization had the strongest associations with global cognitive deficits,” they wrote. “There is no clarity on the implications of the longer-term persistence of cognitive deficits and their clinical relevance and warrants ongoing surveillance.”

Reference:

Hampshire A, Azor A, Atchison C, Trender W, Hellyer PJ, Giunchiglia V, Husain M, Cooke GS, Cooper E, Lound A, Donnelly CA, Chadeau-Hyam M, Ward H, Elliott P. Cognition and Memory after Covid-19 in a Large Community Sample. N Engl J Med. 2024 Feb 29;390(9):806-818. doi: 10.1056/NEJMoa2311330. PMID: 38416429.

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People in urban areas with more green space have better mental health, suggests study

A new study from the Texas A&M University School of Public Health suggests that city dwellers who have more exposure to urban green spaces require fewer mental health services.

The study, published in the International Journal of Environmental Research and Public Health, was conducted by Jay Maddock, Ph.D., Regents Professor of environmental and occupational health at Texas A&M, and colleagues from the Center for Health and Nature, a collaboration between Texas A&M Health, Houston Methodist and Texan by Nature. Maddock also directs the center.

The researchers measured urban greenness with NatureScore, which uses numerous data sets related to factors such as air, noise and light pollution, parks and tree canopies to calculate the amount and quality of natural elements for any known address in the United States and several other countries. Scores range from 0-19 points for Nature Deficient to 80-100 for Nature Utopia.

For addresses, they used data on mental health visits aggregated at the ZIP code level from Texas Hospital Outpatient Public Use Data Files from 2014 to mid-2019. The data contained information about patient encounters, including a patient’s age, gender, race/ethnicity, educational attainment, employment status, poverty level, principal diagnosis and ZIP code, although no patients were identified.

“The association between exposure to nature and better mental health is well established in the United States and elsewhere, but most studies use just one or two measurements of this exposure,” Maddock said. “Our study was the first to use NatureScore, which provides more complex data, to study the correlation between urban nature exposure and mental health.”

A total of 61,391,400 adult outpatient encounters in Texas cities for depression, bipolar disorders, stress and anxiety were selected. The sample included data from 1,169 ZIP codes in urban Texas, with a median NatureScore of 85.8. About half of the sample had high NatureScores (80+), and about 22 percent had NatureScores below 40.

Of these encounters, 63 percent were women, 30 percent were 65 years old or older, 54 percent were non-Hispanic white, and 15 percent were Hispanic. At the ZIP code level, 27 percent of the total population had a bachelor’s degree, 58 percent were employed, 14 percent lived under poverty, and 17 percent lacked health insurance coverage. The percentage of those 65 years old and older, white, Hispanic and employed were higher in areas with a higher NatureScore. In addition, the ZIP codes with a higher NatureScore had lower percentages of people who were Black, living in poverty or without insurance.

The trend for various mental health encounters decreased as the NatureScore of a neighborhood increased, and the rates of mental health encounters were about 50 percent lower in neighborhoods with NatureScores over 60. Those who lived in neighborhoods with the two highest NatureScore categories-Nature Rich and Utopia-had significantly lower rates of mental health encounters compared to neighborhoods with the lowest NatureScore category.

“We found that a NatureScore above 40-considered Nature Adequate-seems to be the threshold for good mental health,” Maddock said. “People in these neighborhoods have a 51 percent lower likelihood of developing depression and a 63 percent lower likelihood for developing bipolar disorders.”

The study’s lead author, Omar M. Makram, noted that these findings could have important implications for urban planning.

“Increasing green space in cities could promote well-being and mental health, which is critically important given that more than 22 percent of the adult population in the United States with a mental health disorder,” he said.

Reference:

Makram OM, Pan A, Maddock JE, Kash BA. Nature and Mental Health in Urban Texas: A NatureScore-Based Study. International Journal of Environmental Research and Public Health. 2024; 21(2):168. https://doi.org/10.3390/ijerph21020168.

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Transoesophageal Echocardiography Proves Vital for assessing residual lesions during Pediatric Heart Surgery

A recent study published in the recent edition of Archives of Cardiovascular Diseases unveiled the pivotal role of pediatric transoesophageal echocardiography probes in the perioperative evaluation of congenital heart disease surgeries. This innovative approach promises the enhanced safety and precision of echocardiography in pediatric cardiac interventions.

This study was conducted over the span of four years at a leading tertiary center and evaluated the efficacy of perioperative transoesophageal echocardiography in assessing residual lesions post-heart surgery in pediatric patients. The retrospective analysis encompassed 323 procedures after involving 310 young patients, with the median age of 13.8 months. The residual lesions were classified as mild, moderate or severe and were meticulously scrutinized using transoesophageal echocardiography. Also, 6.5% of cases revealed severe residual lesions necessitating immediate reintervention.

The critical findings highlight the severe right ventricular outflow tract obstruction that emerged as a predominant concern which prompts swift corrective measures in 12 cases. Additionally, instances of severe aortic regurgitation, superior vena cava stenosis and moderate residual ventricular septal defects underlined the significance of real-time perioperative evaluation.

Also, three neonates encountered ventilation difficulties due to the transoesophageal echocardiography probe, albeit without any lasting consequences. The findings of this study concludes that perioperative transoesophageal echocardiography represents a safe and invaluable adjunct in pediatric congenital heart disease surgeries. Its ability to promptly identify and address severe residual lesions has the potential to revolutionize the landscape of pediatric cardiac care by offering hope to young patients and their families. The integration of innovative technologies like transoesophageal echocardiography promises to elevate the standards of care and transform the outlook for pediatric cardiac patients worldwide. 

Reference:

Pyra, P., Hadeed, K., Guitarte Vidaurre, A., Vincent, R., Dulac, Y., Chausseray, G., Calvaruso, D. F., Acar, P., & Karsenty, C. (2024). Usefulness of perioperative transoesophageal echocardiography during paediatric cardiac surgery. In Archives of Cardiovascular Diseases. Elsevier BV. https://doi.org/10.1016/j.acvd.2023.12.006

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Endoscopic gallbladder stenting prevents recurrent cholecystitis among patients with deferred cholecystectomy: Study

According to a study published in Gastroenterology, Endoscopic transpapillary gallbladder stenting or ETGS can help prevent recurrent cholecystitis in acute cholecystitis patients with Common bile duct stones who have deferred cholecystectomy for three months. Most recurrences occurred within three months in those who did not receive ETGS.

Endoscopic transpapillary gallbladder stenting (ETGS) has been proposed as one of the adjunctive treatments, apart from antibiotics, before surgery in patients with acute cholecystitis whose cholecystectomy could not be performed or deferred.

ETGS has emerged as an alternative treatment for acute cholecystitis patients who cannot undergo or delay cholecystectomy. Although ETGS has been suggested as an adjunct to antibiotics, there is currently no data comparing its outcomes in patients who receive it versus those who do not. The objective of the present study is to evaluate the recurrent cholecystitis rates at 3 and 6 months in these two groups.

Between 2020-2023, eligible acute-calculous-cholecystitis patients (n=120) with a high probability of CBD stone, who were surgical candidates but could not have an early cholecystectomy during COVID-19 surgical lockdown, were randomized into groups A and B with 60 patients each. Group A received ETGS, and B did not. A definitive cholecystectomy was performed at three months or later in both groups.
Group A’s technical and clinical success rates were 90% and 100%, respectively. Based on intention-to-treat analysis, group A had a lower recurrence rate than group B at three months. At 3-6 months, group A showed a non-significantly lower rate of recurrent cholecystitis than group B.
Endoscopic transpapillary gallbladder stenting (ETGS) can effectively prevent recurrent cholecystitis in acute cholecystitis patients with CBD stones who have deferred cholecystectomy for three months. It is worth noting that most recurrences occur within the first three months after the procedure in patients who do not receive ETGS.
Reference:
Ridtitid, W., Karuehardsuwan, J., Faknak, N., Piyachaturawat, P., Vongwattanakit, P., Kulpatcharapong, S., Angsuwatcharakon, P., Mekaroonkamol, P., Kongkam, P., & Rerknimitr, R. (2024). Endoscopic gallbladder stenting to prevent recurrent cholecystitis in deferred cholecystectomy: a randomized trial. Gastroenterology. https://doi.org/10.1053/j.gastro.2024.02.007

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More schooling linked to slowed aging and increased longevity: JAMA

Participants in the Framingham Heart Study who achieved higher levels of education tended to age more slowly and went on to live longer lives as compared to those who did not achieve upward educational mobility, according to a new study at Columbia University Mailman School of Public Health and The Robert N. Butler Columbia Aging Center. Upward educational mobility was significantly associated with a slower pace of aging and lower risk of death. The results are published online in JAMA Network Open.

The Framingham Heart Study is an ongoing observational study first initiated in 1948 that currently spans three generations.

The Columbia analysis is the first to connect educational mobility with pace of biological aging and mortality.

“We’ve known for a long time that people who have higher levels of education tend to live longer lives. But there are a bunch of challenges in figuring out how that happens and, critically, whether interventions to promote educational attainment will contribute to healthy longevity,” said Daniel Belsky, PhD, associate professor of Epidemiology at Columbia Mailman School and the Aging Center and senior author of the paper.

To measure pace of aging, the researchers applied an algorithm known as the DunedinPACE epigenetic clock to genomic data collected by the Framingham Heart Study. The latest findings showed that, according to the yardstick of the DunedinPACE epigenetic clock, two years of additional schooling translated to a two- to three percent slower pace of aging. This slowing in the pace of aging corresponds to a roughly 10 percent reduction in risk of mortality in the Framingham Heart Study, according to previous research by Belsky on the association of DunedinPACE with risk of death.

DunedinPACE was developed by the Columbia researchers and colleagues and reported in January 2022. Based on an analysis of chemical tags on the DNA contained in white blood cells, or DNA methylation marks, DunedinPACE is named after the Dunedin Study birth cohort used to develop it. DunedinPACE (stands for Pace of Aging Computed from the Epigenome), is measured from a blood test and functions like a speedometer for the aging process, measuring how fast or slow a person’s body is changing as they grow older.

Biological aging refers to the accumulation of molecular changes that progressively undermine the integrity and resilience capacity of our cells, tissues and organs as we grow older.

The Columbia researchers used data from 14,106 Framingham Heart Study spanning three generations to link children’s educational attainment data with that of their parents. They then used data from a subset of participants who provided blood samples during data collection to calculate the pace of biological aging using the DunedinPACE epigenetic clock. In primary analysis, the researchers tested associations between educational mobility, aging, and mortality in a subset of 3,101 participants for whom educational mobility and pace of aging measures could be calculated.

For 2,437 participants with a sibling, the researchers also tested whether differences in educational attainment between siblings was associated with a difference in the pace of aging.

“A key confound in studies like these is that people with different levels of education tend to come from families with different educational backgrounds and different levels of other resources,” explained Gloria Graf, a PhD candidate in the Department of Epidemiology supervised by Belsky, and first author of the study. “To address these confounds, we focused on educational mobility, how much more (or less) education a person completed relative to their parents, and sibling differences in educational attainment – how much more (or less) education a person completed relative to their siblings. These study designs control for differences between families and allow us to isolate the effects of education.”

By combining these study designs with the new DunedinPACE epigenetic clock, the researchers were able to test how education affects the pace of aging. Then, by linking the education and pace of aging data with longitudinal records of how long participants lived, the team was able to determine if a slower pace of aging accounted for increased longevity in people with more education.

“Our findings support the hypothesis that interventions to promote educational attainment will slow the pace of biological aging and promote longevity,” noted Graf. “Ultimately, experimental evidence is needed to confirm our findings,” added Belsky. “Epigenetic clocks like DunedinPace have potential to enhance such experimental studies by providing an outcome that can reflect impacts of education on healthy aging well before the onset of disease and disability in later life.”

“We found that upward educational mobility was associated both with a slower pace of aging and decreased risk of death,” said Graf. “In fact, up to half of the educational gradient in mortality we observed was explained by healthier aging trajectories among better-educated participants.” This pattern of association was similar across generations and held within family sibling comparisons: siblings with higher educational mobility tended to have a slower pace of aging as compared with their less educated siblings.

Reference:

Graf GHJ, Aiello AE, Caspi A, et al. Educational Mobility, Pace of Aging, and Lifespan Among Participants in the Framingham Heart Study. JAMA Netw Open. 2024;7(3):e240655. doi:10.1001/jamanetworkopen.2024.0655.

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Passive video use among toddlers can negatively affect language development

A new study from SMU psychologist Sarah Kucker and colleagues reveals that passive video use among toddlers can negatively affect language development, but their caregiver’s motivations for exposing them to digital media could also lessen the impact.

Results show that children between the ages of 17 and 30 months spend an average of nearly two hours per day watching videos – a 100 percent increase from prior estimates gathered before the COVID pandemic. The research reveals a negative association between high levels of digital media watching and children’s vocabulary development.

Children exposed to videos by caregivers for their calming or “babysitting” benefits tended to use phrases and sentences with fewer words. However, the negative impact on language skills was mitigated when videos were used for educational purposes or to foster social connections – such as through video chats with family members.

“In those first couple years of life, language is one of the core components of development that we know media can impact,” said Kucker, assistant professor of psychology in SMU’s Dedman College of Humanities & Sciences. “There’s less research focused on toddlers using digital media than older ages, which is why we’re trying to understand better how digital media affects this age group and what type of screen time is beneficial and what is not.”

Published in the journal Acta Paediatrica, the study involved 302 caregivers of children between 17 and 30 months. Caregivers answered questions about their child’s words, sentences, and how much time they spend on different media activities each day. Those activities included video/TV, video games, video chat, and e-books, with caregivers explaining why they use each activity with their child. Print book reading was also compared.

Researchers looked at the amount of media use and the reasons provided by caregivers for their children’s media use. These factors were then compared to the children’s vocabulary and length using two or more words together (the mean length of utterance).

Kucker suggests that caregivers need to consider what kind of videos their children are watching (whether for learning or fun) and how they interact with toddlers watching videos. She acknowledges that parents often use digital media to occupy children while they complete tasks. Kucker recommends caregivers consider how much digital media they allow young children and if they can interact with them while using it.

The study’s findings underscore the need for parents, caregivers, and educators to be aware of the potential effects of digital media on language development in children 30 months and under. By understanding the types of digital media children are exposed to and the reasons behind its usage, appropriate measures can be taken to ensure more healthy language development.

Future research by Kucker and her colleagues will continue to explore the types of videos young children watch, how they use screens with others, and if young children watching digital media for two hours is the new normal and, if so, how that impacts language development.

Reference:

Sarah C. Kucker, Lynn K. Perry, Rachel Barr, Variability and patterns in children’s media use and links with language development, Acta Paediatrica, https://doi.org/10.1111/apa.17100.

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Epinephrine nasal spray reversed allergic reactions minutes after administration, results significant for quest to win FDA approval

USA: A small observational study showed that administering one intranasal epinephrine dose immediately after observing a grade 2 allergic reaction led to skipping a second dose of epinephrine within 15 minutes in all 15 pediatric patients.

“Neffy appears to be an effective needle-free option for treating anaphylactic symptoms,” the researchers wrote. 

The intranasal epinephrine spray ARS-1 (also known as neffy), despite being eluded from FDA approval, continues to build its case with findings of resolved allergic symptoms in children and teenagers undergoing an oral food challenge, and a separate study showed that it maintained its potency under extreme temperatures.

It took a median of 16 minutes to fully resolve grade 2 reactions to grade 0. Following the intranasal administration, respiratory, gastrointestinal, skin and mucosal symptoms all began to decrease within the first 5 minutes, reaching full resolution in a median of 15, 15.5, and 35 minutes, respectively, Motohiro Ebisawa, MD, PhD, of the Clinical Research Center for Allergy and Rheumatology at NHO Sagamihara National Hospital in Kanagawa, Japan, said at the American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting.
Gastrointestinal, respiratory, and skin and mucosal symptoms all began to decrease within the first 5 minutes following the intranasal administration, reaching full resolution in a median of 15, 15.5, and 35 minutes, respectively, reported Motohiro Ebisawa, MD, PhD, of the Clinical Research Center for Allergy and Rheumatology at NHO Sagamihara National Hospital in Kanagawa, Japan.
one patient did develop a biphasic allergic reaction about 2 hours and 45 minutes following administration — they were subsequently treated with epinephrine, Ebisawa reported.
The study marks another step in the quest for epinephrine nasal spray to win FDA approval.
The study included 15 pediatric patients experiencing grade 2 or higher allergic symptoms induced by an oral food challenge, leading to 18 observed reactions. Patients’ ages ranged from 6 to 17 years. Participants received a 2.0-mg dose of the intranasal product if they weighed below 30 kg (n=6), otherwise a 2.0-mg dose (n=9).
The one patient with grade 2 cardiovascular (CV) symptoms resolved to grade 0 at 32 minutes after intranasal administration (no grade 1 exists for these symptoms).
Regarding safety, ten patients had a treatment-emergent adverse event: six were deemed nasal spray-related, and four were judged to be a result of the oral food challenge and unrelated to treatment.
Developer ARS Pharmaceuticals tried last year to get FDA approval as the first non-injectable treatment for type 1 allergic reactions such as anaphylaxis but failed. Despite a favourable endorsement from the FDA’s Pulmonary-Allergy Drugs Advisory Committee for use in adult and pediatric patients, the agency ultimately requested that an additional premarket study — on repeat doses under allergen-induced allergic rhinitis conditions — be performed before approval may be considered again.
ARS Pharmaceuticals stated that it would submit a request for a formal dispute resolution to appeal the agency’s decision and resubmit the application to the agency likely in the first half of 2024.
If the intranasal product gets approval on the second try, it would be the first needle-free form of epinephrine.
While allergen avoidance is used for preventing type I allergic reactions, epinephrine remains the first-line emergency treatment in the event of a reaction. Barriers to use include, however, a fear of needles or issues surrounding correct administration that can delay or prevent crucial treatment.
ARS has investigated other factors that might deter patients from epinephrine use, and AAAAI presented other research demonstrating that its nasal spray maintains its potency following prolonged exposure to different temperatures.; 6 months at 40° C (104° F): -13.9%, -27.5%, and -17.2%, respectively, and 3 months at 50° C (122° F): -8.6%, -41.6%, and -56.6%.
Under room temperature conditions for six months, the intranasal product dropped in potency (7.7%), while the autoinjector’s potency dropped by 4.9%, and the prefilled syringe formulation dropped by 10%, the study showed.
Current regulatory specifications for the shelf life of an epinephrine product allow for a 20% reduction in potency.
According to Richard Lowenthal, president and CEO of ARS Pharmaceuticals, while allowing the intranasal product to freeze isn’t ideal, as it will not be available for immediate use, it can still be thawed for use later on.

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Extended anaerobic coverage in aspiration pneumonia not associated with additional mortality benefit: Study

Aspiration pneumonia, a serious condition resulting from the inhalation of oral or gastric contents into the lungs, often requires antibiotic treatment. However, the optimal choice of antibiotics, particularly regarding anaerobic coverage, remains debated.

A recent study aimed to compare outcomes between antibiotic therapy with limited anaerobic coverage (LAC) versus extended anaerobic coverage (EAC) in patients with community-acquired aspiration pneumonia. This study was published in the journal Chest by Anthony D Bai and colleagues. Current guidelines do not recommend extended anaerobic coverage for aspiration pneumonia, yet it is still commonly prescribed.

A multicenter retrospective cohort study across 18 hospitals in Ontario, Canada, analyzed data from 3,999 patients diagnosed with community-acquired aspiration pneumonia between 2015 and 2022. Patients were categorized into LAC or EAC groups based on the antibiotics prescribed within 48 hours of admission. The primary outcome was in-hospital mortality, with Clostridioides difficile colitis incidence as a secondary outcome. Propensity score weighting was used to balance baseline factors between the two groups.

The key findings of the study were:

  • Of the included patients, 2,683 received LAC and 1,316 received EAC.

  • In-hospital mortality rates were 30.3% in the LAC group and 32.1% in the EAC group.

  • Clostridioides difficile colitis occurred in ≤0.2% of the LAC group and 0.8% to 1.1% of the EAC group.

  • After adjusting for baseline factors, the difference in in-hospital mortality between the EAC and LAC groups was 1.6%, with a 1.0% difference in Clostridioides difficile colitis risk.

The study suggests that extended anaerobic coverage does not provide additional benefits in terms of in-hospital mortality for patients with community-acquired aspiration pneumonia. However, it is associated with an increased risk of Clostridioides difficile colitis. These findings highlight the importance of aligning antibiotic therapy with evidence-based guidelines to optimize patient outcomes and minimize the risk of adverse events.

Reference:

Bai, A. D., Srivastava, S., Digby, G. C., Girard, V., Razak, F., & Verma, A. A. Anaerobic antibiotic coverage in aspiration pneumonia and the associated benefits and harms: A retrospective cohort study. Chest,2024. https://doi.org/10.1016/j.chest.2024.02.025

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IV fosphenytoin appears to be a promising alternative treatment for acute zoster-associated pain: Study

Japan: A placebo-controlled randomized trial published in The Journal of Dermatology has shed light on the safety and efficacy of intravenous (IV) fosphenytoin for patients with acute herpes zoster-associated pain (ZAP).

The researchers revealed a rapid analgesic effect of a single dose of IV fosphenytoin for acute ZAP in patients with HZ for whom nonopioid drugs had shown an insufficient analgesic effect. “Therefore, IV fosphenytoin is promising as a potential alternative treatment for acute ZAP,” they wrote.

Herpes zoster (HZ) is a common viral disease caused by reactivation of the varicella-zoster virus, which lies latent in the dorsal root ganglia of the cranial and spinal nerves after primary varicella-zoster virus infection. Most patients with herpes zoster develop acute zoster-associated pain. Nonopioid analgesics are usually used for treating acute ZAP but are frequently ineffective.

Masako Iseki, Department of Anesthesiology and Pain Medicine, Juntendo University Faculty of Medicine, Bunkyo-ku, Tokyo, Japan, and colleagues administered IV fosphenytoin, the prodrug of phenytoin, to patients with acute ZAP to investigate its analgesic safety and efficacy.

They conducted a phase II, double-blind, placebo-controlled, randomized trial at 13 medical institutions in Japan of IV fosphenytoin in Japanese inpatients with acute zoster-associated pain for whom nonopioid analgesics had shown an insufficient analgesic effect.

The patients were randomly assigned in a 1:1:1 ratio to receive a single IV dose of fosphenytoin at 18 mg/kg (high dose), a single intravenous dose of fosphenytoin at 12 mg/kg (low dose), or a placebo.

The study’s primary endpoint was the mean change per hour (slope) in the numerical rating scale score from the baseline score until 120 min following the dosing.

The study led to the following findings:

  • Seventeen patients were assigned randomly to the low-dose fosphenytoin group (n = 6, median age 62.5 years), high-dose fosphenytoin group (n = 5, median age 69.0 years), and placebo group (n = 5, median age 52.0 years). One patient was excluded because of investigational drug dilution failure.
  • This study was discontinued due to the influences of coronavirus disease 2019.
  • The slope was significantly lower in the high- and low-dose fosphenytoin groups than in the placebo group.
  • Responsiveness to intravenous fosphenytoin (≥2-point reduction in the numerical rating scale score from baseline to 120 min after dosing) was inferred at plasma total phenytoin concentrations of 10–15 μg/mL.
  • Treatment-emergent adverse events caused no safety concerns in the clinical setting, and intravenous fosphenytoin was well tolerated.

“Intravenous fosphenytoin appears to be a promising and effective alternative treatment for acute zoster-associated pain,” the researchers wrote. “A further confirmatory clinical study is required.”

Reference:

Iseki, M., Yamamoto, T., Ogawa, Y., Majima, Y., Abe, Y., Watanabe, D., Amaya, F., Hasegawa, T., Inafuku, K., Kosugi, T., Nomura, Y., Deguchi, T., Hamada, T., Shimizu, K., Arai, S., Takahashi, M., Hamada, I., Ishikawa, Y., & Kawashima, M. (2024). Efficacy and safety of intravenous fosphenytoin for patients with acute herpes zoster-associated pain: A placebo-controlled randomized trial. The Journal of Dermatology, 51(2), 234-242. https://doi.org/10.1111/1346-8138.17054

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Fezolinetant Shows Promise in Alleviating Menopausal Vasomotor Symptoms

Menopausal vasomotor symptoms (VMS), including hot flashes and night sweats, can significantly impact the quality of life of women transitioning through menopause. Fezolinetant, a novel therapeutic agent, has shown potential in alleviating these bothersome symptoms. A recent meta-analysis aims to evaluate the efficacy and safety of fezolinetant in treating moderate-to-severe VMS and associated sleep disturbances in postmenopausal women.

VMS are common during menopause and can lead to discomfort, sleep disturbances, and decreased quality of life. Hormone therapy has traditionally been used to manage VMS, but concerns regarding safety have prompted the search for alternative treatments. Fezolinetant offers a promising option with its mechanism of action targeting neurokinin receptors. This study was published in the journal of Obstetrics and Gynaecology by Bonga K and colleagues.

A comprehensive literature search identified five randomized clinical trials comprising 2,168 participants that compared fezolinetant with placebo in postmenopausal women experiencing moderate-to-severe VMS. The efficacy and safety of fezolinetant were evaluated using various outcome measures, including VMS frequency, Menopause-Specific Quality of Life (MENQOL) scores, and sleep quality assessments.

The key findings of the study were:

  • Fezolinetant demonstrated significant efficacy in reducing VMS frequency, with a pooled mean difference of 2.62 (95% CI, 1.84–3.41).

  • The MENQOL scores also showed improvement with fezolinetant compared to placebo, with a pooled mean difference of −0.60 (95% CI, −0.92 to −0.28).

  • Moreover, fezolinetant was associated with a mean percentage improvement in VMS frequency of 22.51% (95% CI, 15.35–29.67).

  • Additionally, fezolinetant showed improvement in sleep quality compared to placebo.

This meta-analysis provides strong evidence supporting the efficacy of fezolinetant in reducing moderate-to-severe VMS frequency and improving sleep disturbances in postmenopausal women. Fezolinetant offers a promising alternative for women seeking relief from menopausal symptoms without the concerns associated with traditional hormone therapy. Further research and long-term safety evaluations are warranted to confirm these findings and establish fezolinetant as a standard treatment option for menopausal VMS.

Reference:

Bonga, K. N., Mishra, A., Maiti, R., Padhy, B. M., Meher, B. R., & Srinivasan, A. Efficacy and safety of fezolinetant for the treatment of menopause-associated vasomotor symptoms: A meta-analysis. Obstetrics and Gynecology,2024;143(3):393–402. https://doi.org/10.1097/aog.0000000000005508

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