Respiratory syncytial virus has increased frequency of transplacental transmission in Pregnant Women: Study

A recent comprehensive study illuminated the transmission of respiratory viral infections from pregnant women to their offspring. This research uncovered significant disparities between the respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The key findings were published in the recent issue of American Journal of Respiratory and Critical Care Medicine.

This prospective cohort study was conducted to discern the frequencies of transplacental transmission of these viruses, analyze concentrations of inflammatory mediators in maternal and fetal blood and assess clinical consequences. The finding, spanning from October 2020 to June 2022, were published in a recent medical journal.

The study included a total of 103 mother–baby dyads and utilized droplet digital PCR to test blood mononuclear cells. Also, the results revealed that twice as many newborns were vertically infected with RSV when compared to SARS-CoV-2 where the rates stood at 25.2% and 11.9%, respectively. This sharp contrast underlines the differing transmission dynamics of these respiratory viruses during pregnancy.

Further analysis through multiplex ELISA showed significantly increased concentrations of various inflammatory cytokines and chemokines in both maternal and cord blood from newborns with evidence of viral exposure in utero. This suggests a strong link between prenatal infection and fetal inflammation with the distinct expression profiles contingent upon the virus type.

Moreover, this study unveiled consequential impacts on newborn health. Babies exposed to these viruses in utero experienced lower birth weights and exhibited compromised postnatal weight growth. These effects signify the potential pathological consequences of virus-induced inflammation on neonatal health, manifesting within the first days of life.

The study emphasized the importance of these findings in understanding the intricate dynamics of vertical transmission and its implications for maternal and neonatal health. This research elucidates the complexities of prenatal viral infections and the need for higher vigilance in managing respiratory illnesses during pregnancy

This study serves as a crucial milestone in elucidating the nuances of vertical transmission. Further research and clinical insights is mandated that could better help the healthcare professionals customize strategies to safeguard the health and well-being of both pregnant women and their offspring.

Research:

Trinh, I. V., Desai, S. P., Ley, S. H., Mo, Z., Satou, R., Pridjian, G. C., Longo, S. A., Shaffer, J. G., Robinson, J. E., Norton, E. B., & Piedimonte, G. (2024). Prenatal Infection by Respiratory Viruses Is Associated with Immunoinflammatory Responses in the Fetus. In American Journal of Respiratory and Critical Care Medicine (Vol. 209, Issue 6, pp. 693–702). American Thoracic Society. https://doi.org/10.1164/rccm.202308-1461oc

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Trigonelline supplementation has therapeutic potential for age-associated muscle decline in sarcopenia: Study

Switzerland: A research team, including researchers from Nestle Research, revealed that a compound found in fenugreek and coffee, but also made in the gut microbiome, can improve muscle function in aging mice, humans, and worms.

“Dietary trigonelline supplementation in male mice prevents fatigue and enhances strength during aging,” the researchers reported in Nature Metabolism. “We identified nutritional supplementation of trigonelline as a nicotinamide adenine dinucleotide (NAD+)-boosting strategy with therapeutic potential for age-associated muscle decline.”

Sarcopenia is the progressive loss of muscle strength and mass and affects many adults when they get older. The disease is thought to affect approximately 10%-16% of people over the age of 65, and prevalence is higher in people with other conditions, for example, diabetes and cancer.

The muscle mass loss can contribute to frailty, mobility problems, and subsequent reduction in independence for many older people. As such, it represents a significant disease burden in an aging population.

Mitochondrial dysfunction and low NAD+ levels are hallmarks of skeletal muscle aging and sarcopenia, however, there is no clarity on whether these defects result from local changes or can be mediated by dietary or systemic cues. Considering this, Jerome N. Feige, Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland, and colleagues report a functional link between circulating levels of the natural alkaloid trigonelline, which is structurally related to nicotinic acid, NAD+ levels, and muscle health in multiple species.

In humans, there is a reduction in serum trigonelline levels with sarcopenia and correlates positively with muscle strength and mitochondrial oxidative phosphorylation in skeletal muscle. The researchers using, naturally occurring and isotopically labeled trigonelline, demonstrated that trigonelline incorporates into the NAD+ pool and increases NAD+ levels in mice, Caenorhabditis elegant, and primary myotubes from healthy individuals, and individuals with sarcopenia.

Mechanistically, trigonelline did not activate GPR109A but is metabolized via the nicotinate phosphoribosyltransferase/Preiss–Handler pathway across models. In C. elegans, trigonelline, through an NAD+-dependent mechanism requiring sirtuin, improves biogenesis and mitochondrial respiration, reduces age-related muscle wasting, and increases mobility and lifespan.

Correcting for dietary caffeine and vitamin B3 intake did not impact the association between trigonelline and muscle strength. The targeted metabolomic profiling of human sarcopenia revealed trigonelline as a new metabolite associated with mitochondrial metabolism, muscle function, and NAD+.

In conclusion, clinical profiling revealed an association between trigonelline and human muscle health. The preclinical experiments showed that trigonelline is an NAD+ precursor that optimizes mitochondrial function to improve muscle strength and prevent fatigue during aging.

“Therefore, trigonelline is a nutritional geroprotector with therapeutic potential to manage sarcopenia and other age-related pathologies,” the researchers wrote.

Reference:

Membrez, M., Migliavacca, E., Christen, S., Yaku, K., Trieu, J., Lee, A. K., Morandini, F., Giner, M. P., Stiner, J., Makarov, M. V., Garratt, E. S., Vasiloglou, M. F., Chanvillard, L., Dalbram, E., Ehrlich, A. M., Luis, J., Canto, C., Karagounis, L. G., Treebak, J. T., . . . Feige, J. N. (2024). Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia. Nature Metabolism, 6(3), 433-447. https://doi.org/10.1038/s42255-024-00997-x

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Triple conventional synthetic DMARD therapy may lower disease activity in RA patients: Study

A recent study published in the Joint Bone Spine journal unveiled comparative insights into the effectiveness of conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) treatment strategies for rheumatoid arthritis (RA), focusing on patient retention rates between two popular treatment combinations. This study provides important data on the real-world application of triple therapy (methotrexate, sulfasalazine and hydroxychloroquine) against the double therapy (methotrexate and leflunomide) by offering valuable guidance for clinicians and patients who navigate RA treatment options.

The comprehensive research from the Ontario Best Practices Research Initiative (OBRI) included a total of 692 RA patients and grouped them based on their treatment regimen. 258 patients were on triple therapy and 434 patients were on double therapy and were followed up from enrollment. The primary goal was to analyze and compare the retention rates of these treatment strategies that provide insight into their long-term viability and effectiveness.

The study found a close competition between the two treatment approaches in terms of patient retention. The triple therapy group had a median treatment duration of 15.1 months a bit longer than the 9.6 months observed in the double therapy group. Despite this difference, the statistical analysis revealed no significant difference between the therapy groups which hints a comparable effectiveness between the two strategies.

The data showed that at 6 and 12 months, the patients on triple therapy expressed lower disease activity levels than the individuals on double therapy based on based on the erythrocyte sedimentation rate (DAS28-ESR) calculated by the 28-joint count Disease Activity Score. Also, mean DAS28 scores were lower for the triple therapy group at both intervals by illuminating the potential for enhanced quality of life and symptom management with this treatment combination.

This study explored reasons behind treatment discontinuation and identified risk factors by enriching the concern around patient oriented care and personalized treatment planning. This aspect of the research emphasizes the importance of understanding patient experiences and outcomes beyond mere statistical comparisons to foster a more precise approach to manage RA.

While these findings did not establish a statistically significant superiority of one treatment over the other and underline the nuanced landscape of RA treatment. The slight edge in retention time and reduced disease activity scores with triple therapy could influence the future clinical guidelines and patient preferences by highlighting the importance of tailored treatment strategies in managing RA.

Reference:

Bhavsar, S. V., Movahedi, M., Cesta, A., Pope, J. E., & Bombardier, C. (2024). Retention of triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine compared to combination methotrexate and leflunomide in rheumatoid arthritis. In Joint Bone Spine (p. 105732). Elsevier BV. https://doi.org/10.1016/j.jbspin.2024.105732

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Study compares patch test positivity: 24 versus 48 hours of occlusion time in allergic contact dermatitis patients

India: A recent prospective study published in Contact Dermatitis compared patch test positivity after 24 and 48 hours of occlusion time in patients with allergic contact dermatitis (ACD). 

The researchers reported no significant difference in patch test among ISS allergens after either occlusion time, 48 h occlusion performed significantly better versus 24 h when reactions of all allergens (ISS, parthenium acetone extract, and patient material) are analyzed together. 

Allergic contact dermatitis is a common skin disorder characterized by inflammation resulting from exposure to allergens. Patch testing is a valuable diagnostic tool used to identify the culprit allergens. However, the duration of occlusion during patch testing remains a subject of debate among dermatologists. 

Conventionally, the patches are applied for 48 hours, which causes excessive sweating in tropical weather conditions, leading to irritation, and sometimes the patches come off, making the test inconclusive. In a recent study, Kaushal Verma, Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi, India, and colleagues sought to compare the patch test positivity after 24 and 48 h of occlusion time in patients of allergic contact dermatitis, using standard allergen concentration.

The study involved clinically suspected allergic contact dermatitis patients and patch-tested using the Indian Standard Series, parthenium acetone extracts (1:50, 1:100, and 1:200 dilutions), and patient material. Using a random number table, patches were applied in duplicate on either side of the back. 

One set of patches was removed following 24-h occlusion, while the other set after 48-h. Two independent dermatologists performed the readings at 48- and 96-h, blinder to the duration of occlusion. 

The study revealed
the following findings:

  • 133 and 142 positive reactions were
    observed after 48 h occlusion at 48 and 96 h reading, respectively. Of these 87.9%
    and 92.9% patches were positive and concordant and noted at 24 h occlusion
    time.
  • The Cohen’s kappa coefficient was 0.94 for 48 h
    and 0.97 for 96 h reading, showing an almost complete agreement (ⱪ > 0.81) between patches occluded for 24 and
    48 h.

“A 24-hour occlusion period may be sufficient for some patch test series (such as the ISS); however, other patch series with different allergens require further assessment with this shorter occlusion time,” the researchers wrote. 

The implications of these findings are significant for ACD management. By optimizing patch testing protocols, clinicians can enhance diagnostic accuracy, leading to more precise identification of allergens and better management of the condition. This, in turn, facilitates the development of personalized treatment plans tailored to each patient’s specific sensitivities.

In conclusion, the comparative analysis of patch test positivity after 24 and 48 hours of occlusion time offers valuable insights into optimizing diagnostic approaches for allergic contact dermatitis.

By considering individual variations in occlusion duration and allergen reactivity, dermatologists can improve the accuracy of patch testing and enhance patient care in managing this common dermatological condition.

Reference:

Ahuja, R., Bhari, N., Sethuraman, G., Kalaivani, M., & Verma, K. Comparison of patch test positivity after 24 and 48 hours of occlusion time in patients of allergic contact dermatitis: A prospective study. Contact Dermatitis. https://doi.org/10.1111/cod.14543

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Transarterial chemoembolization and sorafenib combo improves survival in hepatocellular patients with PVTT: JAMA

China: A recent study showed a longer recurrence-free survival and overall survival with the combination of sorafenib and transarterial chemoembolization as postoperative adjuvant therapy among patients with hepatocellular carcinoma with portal vein tumor thrombus (PVTT).

“The randomized clinical trial comprising 158 patients showed that both the median recurrence-free survival and median overall survival were significantly longer with transarterial chemoembolization plus sorafenib versus sorafenib alone,” the researchers reported in JAMA Surgery.

The transarterial chemoembolization with the sorafenib group did not show additional toxicity versus the sorafenib monotherapy group.

Previous studies have shown that surgical resection might be beneficial in certain patients with hepatocellular carcinoma with portal vein tumor thrombus, and postoperative adjuvant therapy may lower the incidence of tumor recurrence. Zhenwei Peng, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, and colleagues aimed to compare the safety and efficacy of sorafenib plus transarterial chemoembolization versus sorafenib alone as postoperative adjuvant therapy for patients with hepatocellular carcinoma with PVTT.

For this purpose, the researchers conducted a phase 3, multicenter, randomized clinical trial in five hospitals in China. One hundred and fifty-eight patients were enrolled and randomized from October 2019 to March 2022, with a median follow-up of 28.4 months. PVTT grading was done by the Cheng classification.

The trial included eligible patients with hepatocellular carcinoma with Cheng grade I to III PVTT (ie, involving segmental or sectoral branches, right- or left-side branch, or main trunk of the portal vein).

Patients were randomly assigned in a 1:1 ratio to receive transarterial chemoembolization with sorafenib or sorafenib alone as postoperative adjuvant therapy. Of 158 included patients, the median age was 54 years and 88.6% were male.

The researchers reported the following findings:

  • The median recurrence-free survival was significantly longer in the transarterial chemoembolization with sorafenib group (16.8 versus 12.6 months; hazard ratio [HR], 0.57).
  • The median overall survival was also significantly longer with transarterial chemoembolization with sorafenib than with sorafenib alone (30.4 versus 22.5 months; HR, 0.57).
  • The most common grade 3/4 adverse event was hand-foot syndrome (23 of 79 patients in the transarterial chemoembolization with sorafenib group [29.1%] vs 24 of 79 patients in the sorafenib alone group [30.4%]).
  • There were no treatment-related deaths in either group.
  • The transarterial chemoembolization with the sorafenib group did not show additional toxicity compared with the sorafenib monotherapy group.

In conclusion, the study showed longer recurrence-free survival and overall survival with the combination of sorafenib and transarterial chemoembolization as postoperative adjuvant therapy versus sorafenib alone in patients with hepatocellular carcinoma with portal vein tumor thrombus. The combination treatment was also well tolerated.

Reference:

Peng Z, Fan W, Liu Z, et al. Adjuvant Transarterial Chemoembolization With Sorafenib for Portal Vein Tumor Thrombus: A Randomized Clinical Trial. JAMA Surg. Published online April 03, 2024. doi:10.1001/jamasurg.2024.0506

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Lower oxygenation target in ICU patients with COVID-19 tied to more days alive without life support: JAMA

Denmark: An arterial oxygen pressure (PaO2) target of 60 mm Hg versus 90 mm Hg led to more days alive without support in intensive care unit (ICU) patients with COVID-19 and severe hypoxemia, findings from HOT-COVID Randomized Clinical Trial have shown.

The randomized trial, including 726 patients, found that targeting a Pao2 of 60 mm Hg resulted in 80.0 days alive without support at 90 days versus 72.0 days when targeting a Pao2 of 90 mm Hg. This difference was statistically significant. The findings were published online in the Journal of the American Medical Association (JAMA) on March 19, 2024.

COVID-19 pneumonia may result in hypoxemic respiratory failure needing high levels of supplemental oxygen and intensive care. Supplemental oxygen is ubiquitously used in patients with COVID-19 and severe hypoxemia, but there remains uncertainty about the effects of higher versus lower oxygenation strategies.

To fill this knowledge gap, Frederik M. Nielsen, Aalborg University Hospital, Aalborg, Denmark, and colleagues aimed to assess the effects of targeting a Pao2 of 60 mm Hg versus 90 mm Hg in patients with COVID-19 and severe hypoxemia in the ICU.

For this purpose, the researchers conducted a multicenter randomized clinical trial comprising 726 adults with COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation across 11 ICUs in Europe from 2020 to 2023.

The trial was stopped prematurely before the outcome assessment due to slow enrollment. The end of the 90-day follow-up was June 1, 2023.

Patients were randomized in a 1:1 ratio to a Pao2 of 60 mm Hg (lower oxygenation group; n = 365) or 90 mm Hg (higher oxygenation group; n = 361) for up to 90 days in the ICU.

The primary outcome was the number of days alive without life support (kidney replacement therapy, circulatory support, or mechanical ventilation) at 90 days. Secondary outcomes included a proportion of patients with serious adverse events, mortality, and number of days alive and out of hospital, all at 90 days.

The following were the study’s key findings:

  • Of 726 randomized patients, primary outcome data were available for 697 (351 in the lower oxygenation group and 346 in the higher oxygenation group). The median age was 66 years, and 68% of patients were male.
  • At 90 days, the median number of days alive without life support was 80.0 days in the lower oxygenation group and 72.0 days in the higher oxygenation group.
  • Mortality at 90 days was 30.2% in the lower oxygenation group and 34.7% in the higher oxygenation group (risk ratio, 0.86).
  • There were no statistically significant differences in the proportion of patients with serious adverse events or the number of days alive and out of hospital.

“Targeting a Pao2 of 60 mm Hg resulted in more days alive without life support over 90 days than targeting a Pao2 of 90 mm Hg in adult patients in the ICU with COVID-19 and severe hypoxemia,” the researchers concluded.

Reference:

Nielsen FM, Klitgaard TL, Siegemund M, et al. Lower vs Higher Oxygenation Target and Days Alive Without Life Support in COVID-19: The HOT-COVID Randomized Clinical Trial. JAMA. 2024;331(14):1185–1194. doi:10.1001/jama.2024.2934

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Urine test halves painful procedures in bladder cancer follow up, new trial shows

A simple urine test can more than halve the number of cystoscopies necessary to follow up high-risk bladder cancer patients, new research has found.

Cystoscopies involve inserting a flexible probe through the urethra into the bladder, which allows a clinician to look at the bladder lining for signs of cancer. While they are predominantly safe procedures, cystoscopies do incur some risk of urinary infections and bleeding. They can also cause pain and discomfort.

Initial results from a two-year study, presented today [6 April 2024] at the European Association of Urology Congress in Paris, suggest that there is also no increased risk of recurrence in patients who had a urine biomarker test rather than a standard flexible cystoscopy. Full results on this aspect of the trial are expected in the summer.

The study was carried out in Denmark, where post-surgical follow up for high-risk bladder cancer recommends cystoscopies every four months for two years. In the UK, patients undergo even more frequent cystoscopies: every three months for two years.

High-risk patients with the most aggressive form of bladder cancer have a 60-70% likelihood of cancer returning within 5 years post-surgery, which is why follow up for these patients is so intensive.

The new research is the first time a urine biomarker test has been assessed in a randomised interventional controlled trial with high-risk patients. This trial design allowed the researchers to assess whether the test could reduce the number of cystoscopies patients had to undergo, as well as picking up any signs of returning cancer. Previous studies have only assessed biomarker tests observationally, adding the biomarker tests to existing standard of care.

Thomas Dreyer, a researcher at the Bladder Cancer Research Team, Dept of Urology, Aarhus University Hospital, who carried out the study for his PhD, explains: “There have been lots of studies of urine biomarker tests showing positive results, but no randomised trial to show what the impact would actually be in the clinic. We were confident the test was sensitive enough to not provide false negatives that put patients at risk. But would it provide false positives and actually result in equal or even higher numbers of cystoscopies being carried out? Our findings show that wasn’t the case.”

The researchers, from Aarhus University Hospital in Denmark, recruited 313 patients. Half were randomised to receive the standard three cystoscopies per year. The other half were randomised to receive just one cystoscopy per year, with their remaining two follow up cystoscopies replaced with the Xpert® Bladder Cancer Monitor test, a urine biomarker test. The test monitors for recurrence of bladder cancer by measuring levels of five target mRNAs, or genetic markers. The researchers chose to trial this particular biomarker test as it had previously shown promising results in high-risk bladder cancer patients.

Any patients who received a positive result on their urine test were called into hospital for a cystoscopy to check for evidence of the cancer returning. The urologists undertaking the cystoscopy were aware of the positive result, as they would be in normal practice.

After two years, for patients receiving primarily the urine test, just under 44% of follow up appointments involved a cystoscopy, compared to nearly 100% in those receiving standard treatment.

The researchers also found strong evidence that the urine test could pick up cancer recurrence before any disease was visible through the cystoscopy. For more than half of the patients who had a ‘false positive’ test-that is, the biomarker test showed positive but the cystoscopy was clear-the researchers found evidence of recurrence at a later visit.

“We know that many patients really dread their cystoscopy appointments, but are prepared to go through with them because they want to be sure they are free of the cancer,” said Thomas Dreyer. “However, if given the option of providing a urine sample instead of undergoing an uncomfortable medical procedure, most would choose that, so long as they were confident that it was just as effective.”

Joost Boormans, Professor of Urology at Erasmus University Medical Centre in Rotterdam and member of the EAU Scientific Congress Office said: “We know as urologists, we carry out too many cystoscopies, particularly during follow up of patients with non-muscle-invasive bladder cancer, so we need to find alternatives. Bladder cancer is a disease that particularly affects the elderly, and we foresee an increasing number of patients due to the ageing population, which could impact on the numbers able to access care.”

“This trial shows us a possible means of reducing cystoscopies. If the final results later this year do confirm that the urine test can pick up cancer recurrence as effectively as cystoscopies, then this is something we need to look at introducing into clinical practice as soon as possible, because it reduces demand on our resources and helps to make healthcare more accessible.”

Reference:

Urine test halves painful procedures in bladder cancer follow up, new trial shows, European Association of Urology, Meeting: EAU24 European Association of Urology Congress.

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Brepocitinib Demonstrates Promising Phase 2 Results in Uveitis Treatment

Priovant Therapeutics recently unveiled promising results from the NEPTUNE Phase 2 study by testing the efficacy of brepocitinib in patients with non-anterior non-infectious uveitis (NIU) which can lead to severe visual impairment. This study highlights the potential of brepocitinib to revolutionize treatment paradigms in autoimmunity by specifically targeting a condition with few effective treatments currently available.

The study evaluated a total of 26 subjects with active NIU and they were randomized to receive either 45 mg or 15 mg doses of brepocitinib. Remarkably, at week 24, the treatment failure rate was significantly lower in the 45 mg group (29%) when compared to the 15 mg group (44%) that indicates a substantial improvement in the disease management. Furthermore, the rate of treatment failure due to disease activity was reduced to 18% in the higher dose group which highlights the effectiveness of brepocitinib.

The NEPTUNE study marked brepocitinib 45 mg to have the most favorable treatment failure rates among active NIU studies and additionally highlights its positive impact across all secondary efficacy endpoints. Also, the patients experienced significant improvements in the prevention and treatment of uveitic macular edema that can lead to vision loss.

With over 1,400 subjects treated in clinical trials, brepocitinib demonstrated a consistent safety profile similar to the approved JAK inhibitors without the identification of new safety concerns. This positions brepocitinib as a potential therapy for the autoimmunity, specially with ongoing studies in dermatomyositis and the anticipated initiation of a pivotal NIU program.

A NEPTUNE investigator emphasized the urgent need for more effective treatments for non-infectious uveitis that remained as a significant cause of blindness in the U.S. The results on brepocitinib points to its potential as a transformative oral therapy for this debilitating disease. The dual inhibition mechanism of the drug offers a targeted approach to suppressing key cytokines involved in the autoimmunity.

The CEO of Priovant expressed excitement over the outcomes of the study and the dose-dependent benefits observed across various measures of disease activity. He highlighted the rigor of the NEPTUNE study design to minimize false positives by strengthening the confidence in moving forward to Phase 3. The pipeline of Priovant Therapeutics is to launch a Phase 3 program in NIU in late 2024, with the ongoing efforts in dermatomyositis that is expected to yield results by 2025.

Source:

Therapeutics, P. (2024, April 2). Priovant therapeutics announces positive phase 2 NEPTUNE study results for brepocitinib in non-infectious uveitis (NIU), showing strongest efficacy data in NIU observed to date. PR Newswire. https://www.prnewswire.com/news-releases/priovant-therapeutics-announces-positive-phase-2-neptune-study-results-for-brepocitinib-in-non-infectious-uveitis-niu-showing-strongest-efficacy-data-in-niu-observed-to-date-302105011.html

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FDA clears non invasive device for treatment of anxiety

The US Food and Drug Administration has cleared Modius Stress to treat generalized anxiety disorder.

Made by Neurovalens is a non-invasive electrical stimulation device for treatment of anxiety.

Modius Stress becomes company’s second product cleared for use in US

Neurovalens, a global leader in non-invasive neuro-technology, has received medical device clearance from the US Food & Drug Administration (FDA) to treat anxiety with its Modius Stress device.

Based in Belfast, Neurovalens is a health-tech company that specialises in combining neuroscience and technology to tackle a range of global health challenges.

The company’s medical devices have been designed to deliver non-invasive electrical stimulation to key areas of the brain and nervous system without the need for surgically implanted electrodes.

Modius Stress is designed to treat anxiety by delivering a small and safe electrical pulse to the head for a period of 30 minutes before bed, during which users can do other activities, such as watching TV or reading.

The FDA regulates the development, manufacturing, authorisation, distribution and sale of medical devices in the US across multiple product categories. Achieving regulatory approval via FDA 510(k) clearance means the Modius Stress device can now be sold directly to people suffering from Generalised Anxiety Disorder (GAD) across the US who have a prescription from their doctor.

GAD is a long-term condition that causes people to feel anxious most days about a wide range of situations and issues, rather than a specific event. GAD can cause both psychological and physical symptoms including feeling restless or worried, having trouble concentrating or sleeping, dizziness and heart palpitations.

The decision by the FDA was secured following two Phase III / Pivotal clinical trials carried out in mid-2023 in the UK and Ireland by Ulster University and in India by the Indian Center of Neurophysiology (ICN).

It follows the company receiving clearance from the FDA in October 2023 for its Modius Sleep device, which can be used to treat insomnia. The Modius Sleep is now available for sale and is being actively promoted by doctors.

Dr Jason McKeown, CEO of Neurovalens, said:

“Having the Modius Stress technology as a certified medical device for the treatment of generalised anxiety disorder is the next meaningful step for the company as we focus on continued growth in the US market.

“GAD affects an estimated 6.8 million adults in the US, over 3% of the population, with women twice as likely to be affected as men, according to the American Depression and Anxiety Association. Modius Stress is a non-invasive device that treats the underlying issue to improve the lives of patients.

“We believe that the low risk, non-invasive therapeutic intervention offered by Neurovalens technology will be truly transformative for a range of serious medical conditions and this latest clearance moves us further towards that goal.

”Neurovalens also announced today that it has closed a £2.1m ($2.65m) funding round with existing investors in preparation for a $40m-$50m Series B fundraising round, which the company expects to launch later this year.

Neurovalens has previously raised around £11m in equity funding from UK investors including Wharton Asset Management, IQ Capital, Techstart Ventures, Angel Co Fund, Beltrae Partners, Clarendon Fund Management and British Business Bank.

The company continues to run clinical trials on the effectiveness of its drug-free technology in treating other conditions and has approvals pending for the treatment of PTSD and obesity.

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Acetaminophen use during pregnancy not tied to children’s risk of autism, ADHD, and intellectual disability: JAMA

In the largest study to date on the subject, researchers found no evidence to support a causal link between acetaminophen use during pregnancy and increased risk of autism, ADHD and intellectual disability in children. The findings, using data from a nationwide cohort of over 2.4 million children born in Sweden, including siblings not exposed to the drug before birth, were published today in the Journal of the American Medical Association (JAMA) from researchers at Drexel’s Dornsife School of Public Health and Karolinska Institutet of Sweden.

Advertised as a pain reliever and fever reducer, the generic drug acetaminophen is the active ingredient in Tylenol and is an ingredient in versions of other drugs, such as Theraflu, Excedrin, and Mucinex, among others.

Following each child up to 26 years after birth, the team found a small increased risk of autism, ADHD and intellectual disability in the overall population – as seen in similar previous studies that reported such a link. However, the authors found no increased risk of any of the conditions when comparing full siblings when one sibling was exposed to acetaminophen while in the uterus before birth and the other sibling was not. Because siblings share a substantial portion of their genetic background, as well as similar exposure to many of the same environmental factors during development, comparing siblings helps to control for these shared factors that are otherwise hard to measure in epidemiological studies, the authors noted.

“Users of acetaminophen differ from non-users in a number of ways and standard statistical analyses without a sibling control can’t control for all of the differences,” said co-senior author Brian Lee, PhD, an associate professor in Drexel’s Dornsife School of Public Health, fellow at the A.J. Drexel Autism Institute, and research affiliate at the Karolinska Institutet. “Sibling comparisons allow us to control for familial characteristics that might explain an apparent relationship between acetaminophen use during pregnancy and risk of neurodevelopmental conditions.”

Using data from Sweden’s national health and prescription drug registers, the researchers gathered data on medication use throughout pregnancy for births from 1995 to 2019. Only about 7.5% of the study sample-185,909 children-were exposed to acetaminophen during pregnancy. In previous studies, acetaminophen use during pregnancy varied greatly depending on the study setting; a study in Denmark reported 6.2% use while one study in the U.S. reported 10-fold higher use. Previous studies suggested that many pregnant people, who may benefit from acetaminophen, do not take it for fear of side effects, such as a 2019 study that surveyed 850 pregnant Swedish persons, in which more than 60% considered medication use during early pregnancy to be “probably harmful” or “harmful.”

“This study’s findings may be welcome news for birthing people who use acetaminophen as a pain or fever management option, since there are few safe alternatives for relief available,” said co-senior author Renee M. Gardner, PhD, of Sweden’s Karolinska Institutet. “We hope that our results provide reassurance to expectant parents when faced with the sometimes fraught decision of whether to take these medications during pregnancy when suffering from pain or fever.”

The authors say all patients should follow the guidance from their physician on whether acetaminophen is safe for them and their future children.

The study authors said that the statistically increased risk of neurodevelopmental disorders in children exposed to acetaminophen in the womb is likely due to other factors.

“Our study and others suggest there are many different health and familial factors that are associated with both acetaminophen use and neurodevelopmental disorders,” said Lee. “Genetics likely play a role, but future work to elucidate this mechanism is crucial.”

In 2015, the U.S. Food and Drug Administration said that studies on over-the-counter pain medicines “are too limited to make any recommendations,” but noted that “severe and persistent pain that is not effectively treated during pregnancy can result in depression, anxiety, and high blood pressure in the mother.” A 2021 consensus statement in Nature Reviews Endocrinology by an international group of scientists and clinicians recommended that pregnant individuals “minimize exposure (to acetaminophen) by using the lowest effective dose for the shortest possible time” due to research suggesting that prenatal exposure to the drug could increase the risk of neurodevelopmental and other disorders.

Although the Drexel and Karolinska study used data on prescribed acetaminophen and reports from pregnant people to their midwives during prenatal care and may not capture all over-the-counter use in all patients, the findings represent data from a large representative sample and controls for many other factors that may be linked to neurodevelopmental disorders.

Reference:

Ahlqvist VH, Sjöqvist H, Dalman C, et al. Acetaminophen Use During Pregnancy and Children’s Risk of Autism, ADHD, and Intellectual Disability. JAMA. 2024;331(14):1205–1214. doi:10.1001/jama.2024.3172.

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