Daytime Light Exposure Crucial for Better Sleep in Parkinson’s Disease, confirms study

Parkinson’s disease (PD) is associated with significant sleep disturbances, impacting patients’ overall well-being. Recent research suggests that light exposure plays a critical role in regulating sleep patterns. This study was published in the journal Sleep.

PD patients often experience circadian rhythm disruptions and sleep difficulties, which can exacerbate their symptoms and decrease their quality of life. Previous studies have highlighted the importance of light exposure in modulating circadian rhythms and improving sleep quality.

The study led by Kenji Obayashi, MD, PhD, investigated the association between light exposure and objective sleep measures in PD patients compared to controls. The study involved 189 PD patients and 1101 community-dwelling older adults as controls, assessing daytime and nighttime light exposure and their impact on sleep efficiency, wake after sleep onset, sleep onset latency, total sleep time, and fragmentation index.

The key findings of the study were:

• PD patients exhibited lower levels of daytime light exposure, with a mean light intensity of 201.1 lux (interquartile range [IQR], 101.2 – 305.7), compared to controls with 337.7 lux (IQR, 165.6 – 719) (P < .001).

• Furthermore, patients with PD had higher nighttime exposure, with light intensities of 2.0 (IQR, 0.5 – 7.8) than controls with 0.7 lux (IQR, 0.1 – 3.3) (P < .001).

• Higher daytime light exposure was significantly associated with better sleep efficiency and shorter wake after sleep onset in PD patients.

• The highest quartile of light exposure to ≥ 1000 lux light during the daytime was associated with an 8% greater sleep efficiency (95% CI, 2.1 – 13.4; P = .008) and a shorter short wake after sleep onset by 36.9 minutes (95% CI, 13.4 – 60.3; P = .002) than the lowest quartile.

• Conversely, higher nighttime light intensity was linked to poorer sleep outcomes in PD patients.

• The highest quartile of mean light intensity had significantly reduced sleep efficiency by 6.8% (95% CI, 1.3 – 12.3; P = .016) and had a longer short wake after sleep onset by 24.1 minutes (95% CI, 1.8 – 46.4; P = .034), longer sleep onset latency by 0.7 minutes (95% CI, 0.3 – 1.0; P < .001), and a greater fragmentation index by -0.3 log units (95% CI, 0.0 – 0.5; P = .006).

The study underscores the importance of optimizing daytime light exposure and minimizing nighttime light exposure for improving sleep quality in PD patients. These findings suggest that interventions targeting light exposure could potentially alleviate sleep disturbances in PD patients, thereby enhancing their overall well-being and quality of life.

Reference:

Obayashi K, Saeki K, Tai Y, et al. Daily light exposure profiles and the association with objective sleep quality in patients with Parkinson’s disease: The PHASE study. Sleep. Published online February 8, 2024. doi:10.1093/sleep/zsae036

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Lebrikizumab demonstrates efficacy in atopic dermatitis and skin of color patients in first of its kind study

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with limited treatment options for adolescents with moderate-to-severe disease.

Lebrikizumab is a monoclonal antibody targeting interleukin (IL)-13. Researchers have found in first of its kind study that Lebrikizumab was associated with clinical benefit among patients atopic dermatitis and skin of color.

In this study, treatment with lebrikizumab, an investigational medicine, showed improvement in skin clearance and itch relief. These late-breaking results from a Phase 3 study are being presented today at the American Academy of Dermatology (AAD) Annual Meeting.

The lebrikizumab efficacy results from this trial are consistent with data in other Phase 3 studies, which further reinforces lebrikizumab’s potential to be a first-line biologic treatment following topical prescription therapies for people across a range of skin tones with moderate-to-severe atopic dermatitis.

“People with skin of color are disproportionately affected by atopic dermatitis, often experiencing more severe symptoms, a delay in diagnosis and a lengthier timeframe to find appropriate treatment. They also have been historically underrepresented in clinical trials, which means we have lacked data pertaining to the treatment of patients with skin of color,” said Andrew Alexis, M.D., M.P.H., Professor of Clinical Dermatology and Vice Chair for Diversity and Inclusion in the Department of Dermatology at Weill Cornell Medicine, a dermatologist at New York-Presbyterian/Weill Cornell Medical Center, and lead study investigator. “With these initial results, Lilly is taking a step toward investigating the needs of people with skin of color affected by atopic dermatitis.”

The initial 16-week data from this study evaluated 50 patients with moderate-to-severe atopic dermatitis and darker skin tones as measured by the Fitzpatrick scale, including people who self-identify as Black or African American (80%), Asian (14%), American Indian or Alaska Native (6%). Of the 50 patients, 11 also self-identified as Hispanic/Latinx (22%) with the remaining 39 self-identifying as non-Hispanic/Latinx (78%). All patients received lebrikizumab 500-mg subcutaneously initially and at two weeks followed by 250-mg subcutaneously every two weeks to Week 16. Results at 16 weeks were consistent with the 16-week results from the ADhere and ADvocate 1 & 2 studies.

  • 68% of people experienced significant improvement of at least 75% in disease extent and severity (EASI-75)*.
  • 46% of people experienced at least 90% improvement in disease extent and severity (EASI-90)†.
  • 39% of people achieved clear or almost clear skin (IGA 0,1)‡ with a reduction of at least two points from baseline.
  • 56% of people experienced clinically meaningful itch relief (PNRS ≥4-point improvement)§.

No new safety signals were observed and there were no serious adverse events reported. The study also included a physician assessment of changes in post-inflammatory pigmentation using the newly developed PDCA-Derm™ scale. Full efficacy and safety results from the study will be shared at future congresses.

“Lebrikizumab is the first investigative treatment for atopic dermatitis to disclose robust efficacy data specifically for people with skin of color, who may experience barriers to treatment or inequitable care,” said Mark Genovese, M.D., senior vice president of Immunology Development at Lilly. “Through clinical trials like this, we hope to deliver more breakthroughs to make life better for people who have been underserved.”

Lilly is committed to finding solutions to elevate care and improve treatment outcomes for all people living with dermatologic conditions, including addressing the unmet needs of people with skin of color. The company’s work to advance health equity in dermatology is focused on engaging in impactful research that improves patient care, supporting health care providers with education to increase awareness of dermatologic diseases in patients with skin of color, and empowering the patient voice so patients can make their needs known and actively partner to find meaningful solutions.

Specific to clinical research, Lilly continues to engage in efforts to involve a more diverse range of participants in clinical trials and establish clear, measurable goals to drive progress.

Lilly has exclusive rights for development and commercialization of lebrikizumab in the U.S. and the rest of the world outside Europe. Lilly’s partner Almirall S.A. has licensed the rights to develop and commercialize lebrikizumab for the treatment of dermatology indications, including eczema, in Europe.

*EASI=Eczema Area and Severity Index, EASI-75=75 percent reduction in EASI from baseline to Week 16

† Eczema Area and Severity Index ≥ 90 percent Reduction

‡ IGA=Investigator’s Global Assessment 0 or 1 (“clear” or “almost clear”)

§ PNRS=Pruritus Numeric Rating Scale in participants with a baseline PNRS of ≥ 4

¶ Fitzpatrick phototype describes the amount of melanin pigment in the skin by determining constitutional color and the effect of exposure to ultraviolet radiation and “darker skin tone” is defined as IV-VI on the scale

About ADmirable

ADmirable (NCT05372419) is a Phase 3b, open-label, 24-week study, evaluating the safety and efficacy of lebrikizumab in adult and adolescent patients with skin of color and moderate-to-severe atopic dermatitis and defining innovative objective measures of pigment, erythema, and post-inflammatory hyper and hypopigmentation. Patients enrolled in the ADmirable study received lebrikizumab 500-mg subcutaneously initially and at two weeks followed by 250-mg every two weeks until Week 16.2 These interim data, which were analyzed before the completion of the 24-week study, represent primary and secondary endpoints from the study at 16 weeks.

About Lebrikizumab and Clinical Development Program

Lebrikizumab is an investigational, monoclonal antibody that targets IL-13 with high binding affinity and slow dissociation rate, to specifically prevent the formation of the IL-13Rα1/IL-4Rα heterodimer complex and subsequent signaling, thereby inhibiting the biological effects of IL-13. The cytokine IL-13 is key in atopic dermatitis, driving the type-2 inflammatory loop in the skin, leading to skin barrier dysfunction, itch, skin thickening and infection.

The lebrikizumab Phase 3 program consists of five key global studies evaluating over 1,300 patients, including two monotherapy studies (ADvocate 1 and 2), a combination study with topical corticosteroids (ADhere), as well as long-term extension (ADjoin) and adolescent open label (ADore) studies. Further data results from a study dedicated to people with skin of color (ADmirable) and patients previously treated with dupilumab (ADapt) are expected to be shared in late 2024.

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Liraglutide 3 mg per day Shows Efficacy in Weight Loss for Individuals with Bipolar Disorder: Study

Obesity is prevalent among individuals with bipolar disorder (BD), posing significant health risks. Liraglutide, a medication indicated for chronic weight management, has shown promise in reducing body weight with minimal neuropsychiatric effects. A recent study aimed to evaluate the efficacy and safety of liraglutide 3 mg/d in individuals with stable BD who were obese or overweight.

This study was published in the Journal of Clinical Psychopharmacology by McElroy and colleagues. Individuals with BD face a higher risk of obesity due to various factors, including medication side effects and lifestyle factors. Effective weight management strategies are crucial to mitigate associated health risks and improve overall well-being in this population.

The objective of the study was to assess the effects of liraglutide 3 mg/d on body weight, metabolic factors, and eating psychopathology in individuals with stable BD who were obese or overweight. The study was a 40-week, randomized, placebo-controlled clinical trial involving 60 participants with stable BD and obesity or overweight. Participants were randomized in a 1:1 ratio to receive either liraglutide 3 mg/d or placebo, in combination with a reduced-calorie diet and increased physical activity.

• The primary outcome measure was the percent change in body weight from baseline to the end of the study.

• Secondary outcomes included the percentage of participants who lost ≥5% of baseline body weight and changes in metabolic variables and measures of eating psychopathology.

• Compared to placebo, liraglutide recipients experienced significantly greater reductions in body weight, BMI, hemoglobin A1c levels, binge eating, and hunger.

• Liraglutide was well tolerated, with no significant differences in baseline characteristics between the liraglutide and placebo groups.

The study findings suggest that liraglutide 3 mg/d may be an effective and safe option for weight loss in individuals with stable BD who are obese or overweight. This medication could potentially address the significant health risks associated with obesity in this population.

Reference:

McElroy, S. L., Guerdjikova, A. I., Blom, T. J., Mori, N., & Romo-Nava, F. Liraglutide in obese or overweight individuals with stable bipolar disorder. Journal of Clinical Psychopharmacology,2024;44(2):89–95. https://doi.org/10.1097/jcp.0000000000001803

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High cholesterol twice as prevalent among American Indian teens and young adults, reveals study

Young American Indians, ages 15-39, had cholesterol levels more than two times higher than the general U.S. population, according to new research published in the Journal of the American Heart Association , an open access, peer-reviewed journal of the American Heart Association.

The researchers noted that previous research has estimated thatapproximately 25% of adolescents and approximately 30% of young adults in the U.S. have high cholesterol.

“This is the first study of total cholesterol levels in American Indian adolescents and young adults, and we were surprised by the levels of high cholesterol, especially in adolescents,” said principal investigator Ying Zhang, M.D., Ph.D., an associate professor of biostatistics and director of the Center for American Indian Health Research at the University of Oklahoma Health Sciences Center in Oklahoma City. “The high cholesterol in this population will likely lead to subtle damage in blood vessels and to premature heart disease. There is a need for care including early screening and treatment for high cholesterol levels.”

Researchers reviewed data from the Strong Heart Family Study-a study of risk factors for cardiovascular diseases among tribal communities in central Arizona, southwest Oklahoma, North Dakota and South Dakota. High cholesterol and its role in the development of heart disease and stroke was assessed among 1,440 American Indian teens and adults in the study.

The analysis found:

  • The prevalence of high cholesterol was 55.2% for American Indian adolescents, ages 15-19; 73.6% for American Indian young adults, ages 20-29; and 78% for American Indian adults, ages 30-39 years old.
  • Roughly 2.8% of all study participants had LDL-C, also known as “bad cholesterol,” higher than 160 mg/dL, which is above the recommended threshold for adults ages 20-39 years old.
  • During the follow-up examination in 2006-2009, 9.9% of participants had arterial plaque, 11% had plaque progression, and 9% had cardiovascular disease events. Arterial plaque are fatty deposits that accumulate on the inside of arteries, narrowing the vessels, which increase the risk of a number of health conditions, including peripheral artery disease, coronary heart disease and chronic kidney disease.
  • Participants with total cholesterol higher than 200 mg/dL had more than twice the risk of arterial plaque compared to participants with cholesterol lower than 200 mg/DL, as well as greater plaque buildup.
  • Despite the high prevalence of an imbalance of blood lipid levels (dyslipidemia) and the recommended cholesterol thresholds for intervention, none of the participants who were younger than age 20 were taking lipid-lowering medication during the study’s initial examination or 6-8 years later at the follow-up examination. (Dyslipidemia is an imbalance of blood lipid levels that can include high levels of low-density lipoproteins  (“bad” cholesterol) or triglycerides (the most common type of fat in the body) or low levels of high-density lipoproteins (“good” cholesterol).)
  • 1.8% of the participants were taking lipid-lowering medications during the baseline exam, from 2001-2003. The use of lipid-lowering medication remained low at the follow-up examination, from 2006-2009, with 8% of participants taking medication to help lower cholesterol.

“It is our hope that our study’s results attract attention within the health care community,” Zhang said. “It would be beneficial for American Indian youth and young adults to get recommendations from their physicians about regularly checking cholesterol levels and following the AHA’s Life’s Essential 8to help improve their cardiovascular health and prevent heart disease and stroke.”

Study details, background or design:

  • The Strong Heart Study is focused on genetic and conventional cardiovascular risk factors among American Indians.
  • The study was conducted between 2001-2003 through 2020 and included American Indian teens and adults ages 15-39 at the time of enrollment. Roughly 57% of the study’s participants self-identified as female, and 43% of participants self-identified as male.
  • Cardiovascular events were identified through 2020, with a median follow-up of 18.5 years.
  • Cholesterol levels were measured once, after a 12-hour fast at a follow-up exam.
  • Ultrasounds of the carotid artery were used to detect arterial plaque at enrollment and follow-up, with median follow-up of 5.5 years.

Study limitations include that the results may only be generalizable to other populations with a high prevalence of cardiometabolic risk factors, such as Type 2 diabetes, prediabetes, high cholesterol and abdominal obesity, similar to American Indian populations.

According to the Association’s 2020 scientific statement, Cardiovascular Health in American Indians and Alaska Natives, heart disease rates are noted as approximately 50% higher among the 5.2 million Americans who self-identify as American Indian and/or Alaska Native, compared to white Americans. In addition, Type 2 diabetes affects American Indian and Alaska Native adults at three times the rate of white adults in the U.S., and American Indian and Alaska Native adults develop cardiovascular diseases at younger ages in comparison to white adults.

Reference:

Jessica A. Reese, Mary J. Roman, Jason F. Deen, Tauqeer Ali, Shelley A. Cole, Richard B. Devereux, Amanda M. Fretts, Wm. James Howard, Elisa T. Lee, Kimberly Malloy, Jason G. Umans and Ying Zhang, Dyslipidemia in American Indian Adolescents and Young Adults: Strong Heart Family Study, Journal of the American Heart Association, https://doi.org/10.1161/JAHA.123.031741.

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Nirsevimab found Effective in Preventing RSV-Associated Hospitalizations Among Infants in new research

In a
significant development in pediatric healthcare, nirsevimab, a long-acting
monoclonal antibody, has demonstrated robust real-world effectiveness in
protecting infants against respiratory syncytial virus (RSV)-associated
hospitalizations, according to an analysis by the New Vaccine Surveillance
Network during the period of October 1, 2023, to February 29, 2024.


The
report was published in CDC Morbidity and Mortality Weekly Report.

Also Read: Statins may have role in tuberculosis prevention in patients with bronchiectasis, suggests study

RSV is a
major cause of infant hospitalization in the U.S. Nirsevimab, a long-acting
antibody, is recommended by CDC for infants and at-risk children. Clinical
trials show high efficacy. This analysis provides the first U.S. estimate of
post-introduction nirsevimab effectiveness in infants’ first RSV season.

The
CDC’s Advisory Committee on Immunization Practices had earlier recommended
nirsevimab for infants under the age of 8 months and for children aged 8–19
months at an increased risk for severe RSV disease. This groundbreaking
antibody, known for its extended duration of action, emerged from phase 3
clinical trials with an 81% efficacy against RSV-associated lower respiratory
tract infections leading to hospitalization within 150 days after receipt.


In the
real-world setting, the New Vaccine Surveillance Network’s analysis focused on
699 infants hospitalized with acute respiratory illness during the specified
period. Among them, 8% (59 infants) had received nirsevimab at least 7 days
before the onset of symptoms.

Findings:

  • The
    findings revealed an impressive 90% effectiveness of nirsevimab against
    RSV-associated hospitalizations (95% CI = 75%–96%).

  • Notably,
    the median time from receipt to symptom onset was 45 days (IQR = 19–76 days).


  • Despite
    the limited number of infants in the analysis who received nirsevimab and the
    restricted interval data, the early estimate strongly supports the current
    recommendation for nirsevimab’s use in preventing severe RSV disease in
    infants.

The data
underscore the importance of timely intervention with nirsevimab, either
through maternal RSV vaccination or direct administration to infants.

It is
essential to note that the number of infants in the analysis who received
nirsevimab was relatively low, making it impractical to stratify the data by
the duration from receipt. However, the analysis acknowledges that nirsevimab
effectiveness is anticipated to decline with increasing time after receipt due
to antibody decay. Continued monitoring and further research will be crucial to
refining recommendations and understanding the long-term efficacy of nirsevimab
in preventing RSV-associated hospitalizations.

Also Read: New research sheds light on mycophenolate and azathioprine efficacy in interstitial lung disease


This
breakthrough in pediatric healthcare offers a promising avenue for safeguarding
infants against the leading cause of hospitalization in the United States. As
the medical community awaits additional data and comprehensive assessments, the
current findings affirm the potential of nirsevimab to reshape the landscape of
RSV prevention, offering hope for a healthier start in life for countless
infants.

Further reading: Moline HL, Tannis A, Toepfer AP, et al. Early Estimate of Nirsevimab Effectiveness for Prevention of Respiratory Syncytial Virus–Associated Hospitalization Among Infants Entering Their First Respiratory Syncytial Virus Season — New Vaccine Surveillance Network, October 2023–February 2024. MMWR Morb Mortal Wkly Rep 2024;73:209–214. DOI: http://dx.doi.org/10.15585/mmwr.mm7309a4

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MRI-Guided Focal Therapy Shows Promising 2-Year Outcomes for Intermediate-Risk Prostate Cancer: Study

Prostate cancer is a common malignancy affecting men worldwide, and intermediate-risk prostate cancer (PCa) presents a challenging treatment scenario. MRI-guided focal therapy (FT) has emerged as a promising approach, allowing for targeted treatment while preserving healthy prostate tissue. However, long-term outcomes of this technique remain underexplored.

A recent study aimed to evaluate the 2-year oncological and functional outcomes of men with localized unifocal intermediate-risk PCa treated with MRI-guided FT. This study was published in the journal Radiology by Sangeet G. and colleagues.

In this single-center prospective phase II trial, 44 participants with intermediate-risk PCa underwent transrectal MRI-guided focused ultrasound between July 2016 and July 2019. Treatment success, adverse events, oncological outcomes, and quality-of-life measures were assessed over a 2-year follow-up period. Multiparametric MRI and biopsies were performed at 24 months to evaluate treatment response.

Key Findings:

• Treatment was successfully completed in all 44 participants, with no major adverse events recorded.

• After 2 years, 91% of participants had no clinically significant prostate cancer (csPCa) at the treatment site, and 84% had no cancer in the entire gland.

• There were no significant changes in quality-of-life measures, including International Index of Erectile Function-15 score and International Prostate Symptom Score, during the 2-year follow-up period.

This study demonstrates promising 2-year outcomes of MRI-guided FT for intermediate-risk PCa. The majority of participants had negative results for csPCa at biopsy, and there was no significant decline in quality of life. These findings support the potential efficacy and safety of MRI-guided FT as a treatment option for intermediate-risk PCa. Further research with longer follow-up periods is warranted to confirm these results and assess the durability of treatment response.

Reference:

Ghai, S., Finelli, A., Corr, K., Lajkosz, K., McCluskey, S., Chan, R., Gertner, M., van der Kwast, T. H., Incze, P. F., Zlotta, A. R., Kucharczyk, W., & Perlis, N. MRI-guided focused ultrasound focal therapy for intermediate-risk prostate cancer: Final results from a 2-year phase II clinical trial. Radiology,2024;310(3). https://doi.org/10.1148/radiol.231473

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How Effective isSingle Lung Ventilation with Double endotracheal tubes?

Recently published research paper discusses the effectiveness of single lung ventilation (SLV) using a double lumen tube (DLT) for providing surgical exposure in the thoracic cavity. It emphasizes the protective benefits of SLV for a healthy lung, highlighting the types of unhealthy lung fluids it protects from, such as blood, lavage fluid, malignant, or purulent secretions. Correct placement is emphasized and confirmed by endotracheal tubes (FOB).

The paper presents an alternative technique to the DLT in SLV without the use of a FOB, which involves inserting two endotracheal tubes (ETT) in the trachea. The study found that this technique can be effective in achieving lung separation and selective lung ventilation. The benefits of this technique include its flexibility, ease of use, and potential availability in low-resource settings where DLT and FOB may not be readily available.

Challenging Cases and Successful Utilization of New Technique –

The paper provides detailed descriptions of two challenging cases where this new technique was utilized, demonstrating successful lung isolation with no adverse consequences and maintaining oxygen saturation above 90%. The authors also mention the potential advantages of this technique in facilitating surgical procedures and managing difficult cases, such as patients with severe airway obstruction or frailty.

Potential Concerns with the New Technique –

However, the paper acknowledges potential concerns with the new technique, such as an increased risk of bleeding and airway trauma, as well as potential challenges in patients with anticipated difficult airways. The authors suggest that further clinical studies with larger sample sizes are needed to determine the value and potential applications of this technique, including in the ICU setting.

Paper’s Overall Insights and Conclusion –

Overall, the paper provides valuable insights into an alternative approach for selective lung ventilation without the use of a fiberoptic bronchoscope, highlighting its potential benefits and areas for further investigation.

Key Points –

– The paper discusses the effectiveness of single lung ventilation (SLV) using a double lumen tube (DLT) for providing surgical exposure in the thoracic cavity, emphasizing the protective benefits of SLV for a healthy lung and correct DLT placement confirmed by a fiberoptic bronchoscope.

– An alternative technique to DLT in SLV without a fiberoptic bronchoscope is presented, involving the insertion of two endotracheal tubes (ETT) in the trachea, with the study finding this technique effective in achieving lung separation and selective lung ventilation. The technique’s benefits include flexibility, ease of use, and potential availability in low-resource settings.

– The paper provides detailed descriptions of challenging cases where the new technique was utilized successfully, mentions potential concerns such as increased risk of bleeding and airway trauma, and suggests the need for further clinical studies with larger sample sizes to determine the value and potential applications of the technique.

Reference –

Alsamman H, Bui A, Howard J, et al. (April 25, 2023) An Alternative Approach for Selective Lung Ventilation. Cureus 15(4): e38126. DOI 10.7759/cureus.38126

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Once-weekly administration of apraglutide reduces dependency on parenteral support in short bowel syndrome: Phase 3 trial

USA: Findings from phase 3 STARS trial demonstrate the potential for apraglutide to improve the standard of care for all adult patients with short bowel syndrome with intestinal failure (SBS-IF) dependent on parenteral support as the only GLP-2 with once-weekly administration, if approved. 

The study showed that treatment with apraglutide was associated with a reduction in dependency on parenteral support in patients with short bowel syndrome with intestinal failure. 

SBS-IF, a rare and severe organ failure condition in which patients are dependent on PS, affects an estimated 18,000 adult patients in the U.S., Europe, and Japan. Based on these results, Ironwood plans to submit a new drug application (NDA) and other regulatory filings for apraglutide for use in adult patients with SBS who are dependent on PS.

The global, multicenter, double-blind, randomized, placebo-controlled trial evaluated the efficacy and safety of weekly subcutaneous injections of apraglutide in adult patients with SBS-IF. The trial met its primary endpoint of relative change from baseline in actual weekly PS volume at week 24, comparing apraglutide versus placebo (-25.5% vs. -12.5%; p=0.001).

“Reducing dependency on parenteral support and easing treatment burden are important goals for every patient with SBS-IF,” said Kishore R Iyer, MBBS, FRCS (Eng), FACS, Director of Adult and Pediatric Intestine Rehabilitation & Transplantation at The Mount Sinai Hospital in New York, Coordinating Principal Investigator of the trial, paid scientific advisor to Ironwood and chair of the scientific steering committee for the STARS Trial. “The STARS topline results are significant as this is the first successful Phase III placebo-controlled study in SBS-IF patients with a GLP-2 analog with once-weekly dosing.”

In addition, there were four key secondary endpoints evaluated in statistical hierarchy. Apraglutide demonstrated statistical significance for the first two key secondary endpoints, with more patients in the combined population achieving at least one day/week off PS relative to baseline at week 24 versus placebo (43.0% vs. 27.5%; p=0.040) and more patients treated with apraglutide versus placebo demonstrating improvement in relative change from baseline in actual weekly PS volume at week 24 in the stoma population (-25.6% vs. -7.8%; p<0.001). The third and fourth key secondary endpoints were specific to colon-in-continuity patients in assessing at least one day/week off PS versus baseline and reaching enteral autonomy at week 48, both of which were not achieved. Apraglutide was numerically favorable but not statistically significant relative to placebo for improving days off PS (51.8% versus 44.4%) and reaching enteral autonomy in seven out of 56 (12.5%) patients versus two out of 27 (7.4%) patients on placebo.

Apraglutide was generally well-tolerated. Topline safety results were generally consistent with the safety profile demonstrated in apraglutide studies to date.

“Patients with SBS-IF bear the dual burden of a devastating condition and a complex treatment regimen that includes hours of parenteral support, which significantly impacts their quality of life and carries a risk of severe complications such as infection,” said Michael Shetzline, M.D., Ph.D., chief medical officer, senior vice president and head of research and drug development at Ironwood Pharmaceuticals. “We believe these results demonstrate the potential for apraglutide to improve the standard of care for all adult patients with SBS dependent on parenteral support as the only GLP-2 with once-weekly administration, if approved. We are thankful to the patients and clinical investigators involved in the largest study of a GLP-2 analog in SBS-IF and will work with regulators on next steps with the goal of making apraglutide available to those living with this severe condition.”

Ironwood looks forward to presenting additional data from the STARS study at upcoming medical conferences later this year.

About STARS

The STARS (STudy of ApRaglutide in SBS) pivotal Phase III trial represents the largest Phase III trial in SBS-IF to date.

This global, multicenter, double-blind, randomized, placebo-controlled trial evaluated the efficacy and safety of weekly subcutaneous injections of apraglutide in adult patients with SBS-IF. STARS enrolled 164 patients and dosed 163 stratified approximately 50/50 (stoma vs. colon-in continuity), then evaluated them over 24 weeks (stoma and colon-in-continuity populations) and 48 weeks (colon-in-continuity population only). Patients were randomized 2:1 to either once weekly apraglutide or placebo. The primary endpoint was relative change from baseline in actual weekly PS volume at week 24. Key secondary endpoints included patients who achieved a reduction from baseline of at least 1 day/week of PS at week 24 (all patients); relative change from baseline in actual weekly PS volume at week 24 (stoma population); patients who achieved a reduction from baseline of at least 1 day/week of PS at week 48 (colon-in-continuity population); and patients reaching enteral autonomy at week 48 (colon-in-continuity population).

The study was conducted in 18 countries with 68 active sites.

About Short Bowel Syndrome (SBS)

SBS is a serious and chronic condition where there is diminished absorptive capacity for fluids and/or nutrients, sometimes requiring dependence on parenteral support to maintain health. Short bowel syndrome typically occurs because of extensive intestinal resection, and patients with SBS who are chronically dependent on parenteral support, also referred to as SBS with intestinal failure (SBS-IF), often experience significant quality of life impact and are at risk of severe complications such as infection. An estimated 18,000 adult patients suffer from SBS-IF in the U.S., Europe and Japan, and have chronic dependence on PS, which significantly impacts quality of life and carries the risk of severe complications such as infection. Those with the most severe SBS-IF require PS infusions for up to 10 to 15 hours per day. SBS-IF is associated with frequent complications, significant morbidity and mortality, high economic burden and an impaired quality of life.

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FDA approves semaglutide for major heart disease prevention among obese

The US Food and Drug Administration (FDA) has approved semaglutide (Wegovy) for reducing risk of cardiovascular death, heart attack, and stroke in adults with cardiovascular disease and either obesity or overweight.

Wegovy should be used in addition to a reduced calorie diet and increased physical activity. Cardiovascular disease is a group of diseases of the heart and blood vessels.

“Wegovy is now the first weight loss medication to also be approved to help prevent life-threatening cardiovascular events in adults with cardiovascular disease and either obesity or overweight,” said John Sharretts, M.D., director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research. “This patient population has a higher risk of cardiovascular death, heart attack and stroke. Providing a treatment option that is proven to lower this cardiovascular risk is a major advance for public health.”

Obesity or overweight affect approximately 70% of American adults. Obesity and overweight are serious health issues that increase the risk for premature death and a variety of health problems, including heart attack and stroke.

Wegovy contains semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist. Therefore, Wegovy should not be used in combination with other semaglutide-containing products or other GLP-1 receptor agonists.

Wegovy’s efficacy and safety for this new indication were studied in a multi-national, multi-center, placebo-controlled double-blind trial that randomly assigned over 17,600 participants to receive either Wegovy or placebo. Participants in both groups also received standard-of-care medical treatment (e.g., management of blood pressure and cholesterol) and healthy lifestyle counseling (including diet and physical activity). Wegovy significantly reduced the risk of major adverse cardiovascular events (cardiovascular death, heart attack and stroke), which occurred in 6.5% of participants who received Wegovy compared to 8% of participants who received placebo.

The prescribing information for Wegovy contains a boxed warning to inform health care professionals and patients about the risk of thyroid C-cell tumors. Because of this risk, Wegovy should not be used in patients with a personal or family history of medullary thyroid carcinoma or in patients with a rare condition called Multiple Endocrine Neoplasia syndrome type 2.

Wegovy should not be used in patients with a history of a severe allergic reaction to semaglutide or to any of the other ingredients. Patients should stop Wegovy immediately and seek medical help if a severe allergic reaction is suspected.

Wegovy also contains warnings for inflammation of the pancreas (pancreatitis), gallbladder problems (including gallstones), low blood sugar, acute kidney injury, hypersensitivity reactions, diabetic retinopathy (damage to the eye’s retina), increased heart rate and suicidal behavior or thinking. Patients should discuss with their health care provider if they have symptoms of pancreatitis or gallstones. If Wegovy is used with insulin or with a medication that causes insulin secretion, patients should speak to their health care provider about the risk of low blood sugar. Healthcare professionals should monitor patients for kidney disease, diabetic retinopathy and depression or suicidal behaviors or thoughts.

The most common side effects of Wegovy include nausea, diarrhea, vomiting, constipation, abdominal (stomach) pain, headache, fatigue, dyspepsia (indigestion), dizziness, abdominal distension, eructation (belching), hypoglycemia (low blood sugar) in patients with diabetes, flatulence (gas buildup) and gastroesophageal reflux disease (heartburn).

Wegovy received Priority Review designation for this indication.

The FDA granted the approval to Novo Nordisk A/S.

Wegovy is also approved to reduce excess weight and maintain weight reduction long term in certain adults with obesity or overweight and certain children with obesity, for use in addition to a reduced calorie diet and increased physical activity.

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Higher intake of nuts in early pregnancy enhances neuropsychological development and reduces peer problems in children: Study

It is already known that Maternal diet during pregnancy is associated with child development. Nuts are nutrient-dense foods and provide fatty acids, vitamins, fibre, minerals and proteins.

Pregnant women who consume nuts may potentially reduce the likelihood of their 5-year-old children experiencing peer problems, according to a study published in the Journal of Pediatric Gastroenterology and Nutrition.
This study determined the association between maternal nut intake during pregnancy and childhood risk of behavioural problems in 5-year-old Japanese children.
One thousand one hundred ninety-nine mother-child pairs participated in the study, and their dietary intake was assessed using a diet history questionnaire. The Strengths and Difficulties Questionnaire was used to evaluate emotional, conduct, hyperactivity, peer, and low prosocial behaviour problems, with adjustments made for confounding factors, including potentially related dietary factors.
Pregnant women who ate nuts had a reduced risk of peer problems in children, with an adjusted odds ratio of 0.64, compared with mothers who did not consume nuts during pregnancy. There were no measurable associations between maternal consumption of nuts during pregnancy and the risk of problems like emotional conduct, hyperactivity, and low prosocial behaviour.
Nut, when consumed in pregnancy, reduces the risk of peer problems in children, according to this study.
We confirmed our hypothesis of a relation between maternal consumption of nuts during pregnancy and childhood behavioural problems. To the best of our knowledge, the present pre-birth cohort study was the first to show an independent inverse association of maternal nut intake during pregnancy with the risk of peer problems in children. 21
prebirth prospective cohort design, large sample size, extended follow-up were the strengths of this study.
Reference:
Nguyen, Mai Quynh, et al. “Nut Consumption During Pregnancy Is Associated With Decreased Risk of Peer Problems in 5-year-old Japanese Children.” Journal of Pediatric Gastroenterology and Nutrition, 2024.

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