Archive for month: July, 2024

This study was conducted in children below five years who had ARF and were on NIV. Clinical data were captured along with comfort scores at the initiation of NIV and at 3, 6, 12, 24, and 48 hours. The patient comfort was assessed on the COMFORT-behavior scale while the NIV failure was defined as endotracheal intubation.

Results

A total of 457 patients participated, with a median age of 3.3 months (IQR 1.3–16.1). Sedation was administered to 213 children (46.6%), who exhibited higher heart rates, higher COMFORT-B scores, and lower SpO2/FiO2 ratios compared to those not receiving sedation. Significant improvements were observed in the sedation group, including:

• COMFORT-B Scores: Improved at 3, 6, 12, and 24 hours.

• Heart Rate: Improved at 6 and 12 hours.

• SpO2/FiO2 Ratio: Improved at 6 hours.

• The overall NIV success rate was 95.6%, with intubation required in 6.1% of the sedation group and 2.9% of the non-sedation group (p = 0.092).

• Multivariate analysis identified the PRISM III score at NIV initiation (OR 1.408; 95% CI 1.230–1.611) and respiratory rate at 3 hours (OR 1.043; 95% CI 1.009–1.079) as independent predictors of NIV failure.

• Factors correlated with PICU length of stay included weight, PRISM III score, respiratory rate at 12 hours, SpO2 at 3 hours, FiO2 at 12 hours, NIV failure, and NIV duration.

• Sedation was not independently related to NIV failure or PICU length of stay.

The findings support sedation in children with ARF on NIV to improve comfort and some clinical parameters without reducing NIV success rates or increasing PICU stay. Though children who were receiving sedation were sicker at the time of the initiation of the technique, sedation remained a useful intervention.

In children with ARF treated by NIV, the use of sedation can improve clinical parameters and comfort without raising the rates of NIV failure or the length of stay in a PICU. The findings support sedation as a potentially useful adjunct in the management of paediatric ARF within a PICU setting.

Reference:

Bermúdez-Barrezueta, L., Mayordomo-Colunga, J., Miñambres-Rodríguez, M., Reyes, S., Valencia-Ramos, J., Lopez-Fernandez, Y. M., Mendizábal-Diez, M., Vivanco-Allende, A., Palacios-Cuesta, A., Oviedo-Melgares, L., Unzueta-Roch, J. L., López-González, J., Jiménez-Villalta, M. T., Cuervas-Mons Tejedor, M., Artacho González, L., Jiménez Olmos, A., Pons-Òdena, M., Brezmes Raposo, M., Pino Vázquez, M. A., … SEDANIV Study group of the Spanish Society of Pediatric Intensive Care. (2024). Implications of sedation during the use of noninvasive ventilation in children with acute respiratory failure (SEDANIV Study). Critical Care (London, England), 28(1). https://doi.org/10.1186/s13054-024-04976-2

The study found that regardless of the mode of diagnosis, endometriosis is associated with a marginally increased risk for mental health conditions. The increased risk, particularly evident in the years immediately after the diagnosis, underscores the need for proactive mental health screening among those with a new diagnosis of endometriosis.

Endometriosis, a chronic condition characterized by the growth of endometrial-like tissue outside the uterus, affects millions of women worldwide. Beyond the physical symptoms such as pelvic pain, infertility, and painful menstrual periods, the study delved into the psychological toll of living with endometriosis.

Although the physiological manifestations of endometriosis have been explored, its impact on mental health is less well-defined. Existing studies of endometriosis and mental health were conducted within diverse healthcare landscapes with varying access to care and primarily focused on surgically diagnosed endometriosis.

Against the above background, Ally Murji, Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada, and colleagues aimed to assess the association between endometriosis and the risk for mental health conditions. They also evaluated differences between patients diagnosed medically and those diagnosed surgically.

For this purpose, the researchers conducted a matched, population-based retrospective cohort study in Ontario and included patients 18 to 50 years of age with a first-time endometriosis diagnosis between 2010 and 2020. ‘

Either medical or surgical diagnostic criteria determined endometriosis exposure. A medical diagnosis was defined using corresponding International Classification of Disease diagnostic codes from in-hospital and outpatient visits. In contrast, a surgical diagnosis was identified through inpatient or same-day surgeries. Individuals with endometriosis were matched 1:2 on sex, age, and geography to unexposed individuals without an endometriosis history.

The primary outcome was the first occurrence of any mental health condition following an endometriosis diagnosis. It excluded individuals with a mental health diagnosis in the two years before study entry.

Cox regression models were used to generate hazard ratios with adjustment for salpingo-oophorectomy, hysterectomy, pregnancy history, infertility, qualifying surgery for study inclusion, history of asthma, immigration status, diabetes, abnormal uterine bleeding, fibroids, hypertension, migraines, irritable bowel disorder, and nulliparity.

The study led to the following findings:

• The study included 107,832 individuals, 35,944 with an endometriosis diagnosis (29.5% medically diagnosed, 60.5% surgically diagnosed, and 10.0% medically diagnosed with surgical confirmation), and 71,888 unexposed individuals.
• Over the study period, the incidence rate was 105.3 mental health events per 1000 person-years in the endometriosis group and 66.5 mental health events per 1000 person-years among unexposed individuals.
• Relative to the unexposed individuals, the adjusted hazard ratio for a mental health diagnosis was 1.28 among patients with medically diagnosed endometriosis, 1.33 among surgically diagnosed patients, and 1.36 among those diagnosed medically with subsequent surgical confirmation.
• The risk of receiving a mental health diagnosis was highest in the first year after an endometriosis diagnosis and declined in subsequent years.
• The cumulative incidence of a severe mental health condition requiring hospital visits was 7.0% among patients with endometriosis and 4.6% among unexposed individuals (hazard ratio, 1.56).

“Future research should investigate the potential benefits of mental health interventions for people with endometriosis to enhance their overall quality of life,” the researchers concluded.

Reference:

Thiel, P. S., Bougie, O., Pudwell, J., Shellenberger, J., Velez, M. P., & Murji, A. (2024). Endometriosis and mental health: A population-based cohort study. American Journal of Obstetrics and Gynecology, 230(6), 649.e1-649.e19. https://doi.org/10.1016/j.ajog.2024.01.023

Electroconvulsive therapy (ECT), wherein a generalized epileptic seizure is induced, is a treatment for major depressive disorder (MDD). Currently, it is unclear whether there is an association between seizure length and treatment outcome. A study was done to explore the association between seizure duration, potential confounding variables, and ECT treatment outcome. This population-based cohort study obtained data from the Swedish National Quality Register for ECT. Patients treated for unipolar MDD with unilateral electrode placement between January 1, 2012, and December 31, 2019, were included. The electroencephalographic (EEG) seizure duration from the first ECT treatment session for each patient was used for analysis. Data analyses were performed between March 2021 and May 2024. The primary outcome was remission, defined as a cutoff score of less than 10 points on the self-assessment version of the Montgomery-Åsberg Depression Rating Scale within 1 week after ECT. Multivariate logistic regression analysis was performed to calculate odds ratios (ORs) between different seizure duration groups. Furthermore, the associations between concomitant use of pharmacological treatments, seizure duration, and remission rate were explored. Results: Among the 6998 patients included, 4229 (60.4%) were female and the mean (SD) age was 55.2 (18.6) years. Overall, 2749 patients (39.3%) achieved remission after ECT. Patients with EEG seizure duration of 60 to 69 seconds had the highest remission rates compared with patients with seizure duration of less than 20 seconds (OR, 2.17; 95% CI, 1.63-2.88; P < .001). Anticonvulsant medications were associated with shorter seizure duration (eg, lamotrigine: β coefficient [SE], −6.02 [1.08]; P < .001) and lower remission rates (eg, lamotrigine: adjusted OR, 0.67; 95% CI, 0.53-0.84; P < .001). This study found an association between seizure length and remission from MDD. Use of anticonvulsant medication during ECT was associated with shorter seizure duration and lower remission rates after ECT.

Reference:

Gillving C, et al “Seizure duration and electroconvulsive therapy in major depressive disorder” JAMA Netw Open 2024; DOI: 10.1001/jamanetworkopen.2024.22738.

Keywords:

Longer, seizures, ECT, session, greater, chance, remission, major, depressive, disorder, Study

The findings, published in Frontiers in Immunology, indicate a marked upregulation of CTSS in both serum and renal tissues of patients with IgAN, suggesting that CTSS could be a valuable diagnostic and prognostic biomarker, as well as a promising target for developing effective therapies for IgAN.

IgA nephropathy is a prevalent form of glomerulonephritis globally that exhibits complex pathogenesis. Cathepsins, cysteine proteases within lysosomes, are implicated in various pathological and physiological processes, including renal conditions. Previous observational studies have indicated a potential link between cathepsins and IgAN, yet there is no clarity on the precise causal relationship.

Against the above background, Shaojie Fu, Department of Nephrology, The First Hospital of Jilin University, Changchun, China, and colleagues aimed to systematically explore the causal association between cathepsins and IgAN by conducting a comprehensive bidirectional and multivariable Mendelian randomization (MR) study using publicly available genetic data.

Enzyme-linked immunosorbent assay (ELISA) and immunohistochemical (IHC) staining were employed to evaluate cathepsin expression levels in renal tissues and serum of IgAN patients. They investigated the underlying mechanisms via gene set variation analysis (GSVA), immune cell infiltration analysis, and gene set enrichment analysis (GSEA). Additionally, virtual screening and molecular docking were performed to identify potential drug candidates through drug repositioning.

The study led to the following findings:

• Univariate MR analyses demonstrated a significant link between increased CTSS levels and a heightened risk of IgAN. This was evidenced by an odds ratio (OR) of 1.041, estimated using the inverse variance weighting (IVW) method.
• In multivariable MR analysis, even after adjusting for other cathepsins, elevated CTSS levels showed a strong correlation with an increased risk of IgAN (IVW P=0.020, OR=1.037).
• Reverse MR analyses did not establish a causal relationship between IgAN and various cathepsins.
• IHC and ELISA findings revealed significant overexpression of CTSS in both renal tissues and serum of IgAN patients compared to controls, and this high expression was unique to IgAN compared with several other primary kidney diseases such as membranous nephropathy, minimal change disease, and focal segmental glomerulosclerosis.
• Investigations into immune cell infiltration, GSEA, and GSVA showed the role of CTSS expression in the immune dysregulation observed in IgAN.
• Molecular docking and virtual screening highlighted Camostat mesylate, c-Kit-IN-1, and Mocetinostat as the top drug candidates for targeting CTSS.

The study revealed convincing evidence linking increased CTSS levels with an increased IgAN risk.

“We noted a significant CTSS upregulation in both the serum and renal tissues of IgAN patients. These findings could prove invaluable as markers for the IgAN diagnosis and prognosis. Furthermore, our exploration into inhibitors targeting CTSS could be a promising pathway for developing effective IgAN treatments,” the researchers concluded.

Reference:

Fu, S., Wu, M., Cheng, Y., Guan, Y., Yu, J., Wang, X., Su, S., Wu, H., Ma, F., Zou, Y., Wu, S., Xu, H., & Xu, Z. (2024). Cathepsin S (CTSS) in IgA nephropathy: An exploratory study on its role as a potential diagnostic biomarker and therapeutic target. Frontiers in Immunology, 15, 1390821. https://doi.org/10.3389/fimmu.2024.1390821

New Delhi: The Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organization (CDSCO) has approved AstraZeneca’s protocol amendment proposal to study the anti-cancer drug Capivasertib.

This came after AstraZeneca presented protocol amendment 5, version 6.0 dated 05 March 2024 protocol no. D361DC00001.

Capivasertib is a serine/threonine kinase inhibitor used to treat hormone receptor-positive, HER2-negative, locally advanced, or metastatic breast cancer.

Capivasertib is an inhibitor of all 3 isoforms of serine/threonine kinase AKT (AKT1, AKT2, and AKT3) and inhibits the phosphorylation of downstream AKT substrates. AKT activation in tumors is a result of activation of upstream signaling pathways, mutations in AKT1, loss of phosphatase and tensin homolog (PTEN) function, and mutations in the catalytic subunit alpha of phosphatidylinositol 3-kinase (PIK3CA).

At the recent SEC meeting for oncology held on July 9, 2024, the expert panel reviewed protocol amendment 5, version 6.0 dated 05 March 2024 protocol no. D361DC00001.

After detailed deliberation, the committee recommended the approval of the protocol amendment as presented by the firm.

Also Read: CDSCO Panel Approves Johnson and Johnson’s Protocol Amendment Proposal to Study JNJ-77242113