Archive for month: August, 2024

A new study published in the Journal of the American College of Cardiology found that strong siRNA that lowers lipoprotein(a) (Lp(a)) over an extended period of time is olpasiran. Nearly a year after the previous dosage, the individuals receiving doses over 75 mg Q12W saw a ∼40% to 50% drop in Lp(a) levels. Apolipoprotein(a) (apo(a)) is covalently bonded to apoB100 within a modified low-density lipoprotein (LDL) particle to form lipoprotein(a) (Lp(a)). A substantial amount of data points to Lp(a) as a causative factor in the processes that encourage calcific aortic valve disease and atherogenesis. Based on Mendelian randomization studies, a significant decrease in Lp(a) could be necessary in order to provide a significant therapeutic effect.

Olpasiran is a small interfering RNA (siRNA) molecule linked to N-acetylgalactosamine (GalNAc) that obstructs the expression of the LPA gene by causing the messenger RNA encoding apo(a) to break down, thereby stopping the hepatocyte from assembling the Lp(a) particle. Olpasiran is a small interfering RNA (siRNA) that inhibits the translation of apolipoprotein(a) mRNA, hence blocking the formation of lipoprotein(a) (Lp(a)). This research by Michelle O’Donoghue and colleagues evaluated both the longer-term safety and the timing of Lp(a) returning to baseline following olpasiran withdrawal.

In the phase 2 dose-finding trial OCEAN(a)-DOSE (Olpasiran Trials of Cardiovascular Events And LipoproteiN[a] Reduction–DOSE Finding Study), a total of 281 participants with atherosclerotic cardiovascular disease and Lp(a) >150 nmol/L were enrolled to receive one of four active doses of olpasiran versus placebo (10 mg, 75 mg, 225 mg Q12W, or an exploratory dose of 225 mg Q24W administered subcutaneously). Week 36 was the last dosage of olpasiran, and after week 48, there was a minimum 24-week prolonged off-treatment follow-up period.

276 individuals (98.2%) of the total study population started the post-treatment follow-up phase. The mean duration of the trial encompassed both treatment and non-treatment periods, was 86 weeks (Q1-Q3: 79-99 weeks). At 60, 72, 84, and 96 weeks, the off-treatment placebo-adjusted mean percent decrease from baseline in Lp(a) for the 75 mg Q12W dosage were −76.2%, −53.0%, −44.0%, and −27.9%, respectively (all P < 0.001).

For the 225 mg Q12W dosage, the corresponding off-treatment decreases in Lp(a) were −84.4%, −61.6%, −52.2%, and −36.4% (all P < 0.001). In the follow-up phase of the extension, no additional safety issues were found. Overall, the RNA interference of Olpasiran causes a significant decrease in Lp(a), with long-term pharmacodynamic effects that last for many months after therapy is stopped.

Source:

O’Donoghue, M. L., Rosenson, R. S., López, J. A. G., Lepor, N. E., Baum, S. J., Stout, E., Gaudet, D., Knusel, B., Kuder, J. F., Murphy, S. A., Wang, H., Wu, Y., Shah, T., Wang, J., Wilmanski, T., Sohn, W., Kassahun, H., & Sabatine, M. S. (2024). The Off-Treatment Effects of Olpasiran on Lipoprotein(a) Lowering. In Journal of the American College of Cardiology (Vol. 84, Issue 9, pp. 790–797). Elsevier BV. https://doi.org/10.1016/j.jacc.2024.05.058

A new meta-analysis published in the Journal of Pediatric Urology discovered a strong correlation between maternal chronic hypertension (CH) and the higher risk of hypospadias in the offspring. Hypospadias is a complicated congenital disorder which is typified by the abortive development of ventral urethral spongiosum and is sometimes accompanied by incomplete foreskin and ventral chordee. Hypertensive disorders of pregnancy (HDP) are among the maternal-placental variables that have been associated with a number of birth abnormalities, including the finding that HDP may be a stand-alone risk factor for hypospadias. Although earlier research has indicated that pregnancy-related hypertensive diseases raise the incidence of hypospadias, no studies have examined the impact of maternal chronic hypertension yet. Thus, this study evaluated the relationship with maternal CH and the risk of hypospadias by conducting a systematic review and meta-analysis of the observational data that are currently available.

EMBASE, Pubmed, SCOPUS, and manual techniques were searched in accordance with PRISMA 2020 standards and the MOOSE checklist. The Newcastle-Ottawa Scale (NOS) was used to rate the quality of the eligible papers that were included in the research. DerSimonian and Laird model pooled analysis for unadjusted and adjusted effect sizes was used to calculate OR and 95% CI. The I2 test was used to test for heterogeneity, while funnel plots were used to look at publication bias and to deal with uncertainty, sensitivity assessments are carried out.

The results of the study included a total of 1,130 publications through searches and 6 relevant studies with a high NOS quality score (6–9) were chosen. Among the 6 studies that qualified for analysis, a total of 519 hypospadias patients had maternal CH. One research is eliminated following sensitivity analysis because its definition of hypospadias is different. According to pooled unadjusted and adjusted OR, there is an increased risk of hypospadias in the setting of maternal CH among the five remaining trials. In the unadjusted pooled analysis, heterogeneity was considerable (I2= 73% P=0.005), but in the adjusted analysis, it was minimal (I2= 0% P=0.40). In all studies, the funnel plots were symmetrical which suggested no publication bias. Overall, results from both unadjusted and adjusted effect size models support the relationship between maternal CH and an increased incidence of hypospadias in children that is highlighted by this meta-analysis.

Source:

Situmorang, G. R., Hasan, Wahyudi, I., Abbas, T., Rodjani, A., & Raharja, P. A. R. (2024). Hypospadias Risk Associated with Chronic Hypertension During Pregnancy: A Systematic Review and Meta-analysis. In Journal of Pediatric Urology. Elsevier BV. https://doi.org/10.1016/j.jpurol.2024.07.029

Tracheal extubation marks a crucial phase in transitioning the child to the post-anesthetic phase and is frequently accompanied by an elevated perioperative risk. Recent research paper titled “A randomised controlled trial to compare tracheal extubation quality in lateral and supine positions after general anaesthesia in children” published in J Anaesthesiol Clin Pharmacology aimed to compare the quality of tracheal extubation in lateral and supine positions in children undergoing elective surgeries under general anaesthesia. The study found that positioning children in the lateral position during extubation resulted in improved extubation quality, as evidenced by lower cough scores with fewer incidents of complications compared to the supine position. The primary objective of the study was to compare tracheal extubation quality as judged by the Modified Minogue cough score, while the secondary objectives included assessment of the incidence of oxygen desaturation, laryngospasm, bronchospasm, and upper airway obstruction during emergence from general anaesthesia. The study involved a single-blinded randomised trial with 110 children in the age group of 2–12 years enrolled to be positioned in either the lateral (group L) or supine (group S) position during extubation at the end of surgery. The patients received a standardised anaesthesia regimen, and vital parameters, extubation quality, sedation score, and the incidence of adverse respiratory events were recorded every 5 minutes till 30 minutes post extubation. The findings revealed that children in the lateral position had a significantly lower cough score at the 15th minute post extubation compared to those in the supine position. Additionally, children in the lateral position had a lower incidence of adverse respiratory events (18%) compared to those in the supine position (30%) with a relative risk of 1.67. The study concluded that positioning children in the lateral position during extubation resulted in improved extubation quality.

Study Findings

The paper discussed various factors influencing tracheal extubation, such as the risks of respiratory complications, the lack of clear clinical protocols, and the decision-making process based on clinician experience. The study highlighted the importance of airway patency and the potential advantages of lateral positioning during extubation. It also recognized the need for further research on the impact of lateral positioning in different patient populations and identified limitations in blinding and the subjective nature of defining adverse events.

Discussion of Factors and Implications

In conclusion, the study provides valuable insights into the impact of lateral positioning on tracheal extubation quality in children, emphasizing the potential benefits of the lateral position in reducing respiratory complications and improving extubation outcomes. This detailed summary accurately conveys the main points and findings of the original research paper in 400 words.

Key Points

1. The research aimed to compare the quality of tracheal extubation in lateral and supine positions in children undergoing elective surgeries under general anesthesia. It found that positioning children in the lateral position during extubation resulted in improved extubation quality, as evidenced by lower cough scores with fewer incidents of complications compared to the supine position.

2. The primary objective of the study was to compare tracheal extubation quality as judged by the Modified Minogue cough score. Secondary objectives included assessment of the incidence of oxygen desaturation, laryngospasm, bronchospasm, and upper airway obstruction during emergence from general anesthesia.

3. The study involved a single-blinded randomized trial with 110 children in the age group of 2–12 years. The patients received a standardized anesthesia regimen, and vital parameters, extubation quality, sedation score, and the incidence of adverse respiratory events were recorded every 5 minutes till 30 minutes post extubation.

4. Findings revealed that children in the lateral position had a significantly lower cough score at the 15th minute post-extubation compared to those in the supine position. Additionally, children in the lateral position had a lower incidence of adverse respiratory events (18%) compared to those in the supine position (30%) with a relative risk of 1.67.

5. The study discussed factors influencing tracheal extubation, such as the risks of respiratory complications, the lack of clear clinical protocols, and the decision-making process based on clinician experience. It highlighted the importance of airway patency and the potential advantages of lateral positioning during extubation, while also recognizing the need for further research on the impact of lateral positioning in different patient populations and identifying limitations in blinding and the subjective nature of defining adverse events.

6. In conclusion, the study provides valuable insights into the impact of lateral positioning on tracheal extubation quality in children, emphasizing the potential benefits of the lateral position in reducing respiratory complications and improving extubation outcomes.

Reference –

Ganigara, Anuradha; Bhavana, D.A1; Chandrika, Y.R; Sharma, Trishi. A randomised controlled trial to compare tracheal extubation quality in lateral and supine positions after general anaesthesia in children. Journal of Anaesthesiology Clinical Pharmacology ():10.4103/joacp.joacp_506_23, June 27, 2024. | DOI: 10.4103/joacp.joacp_506_23

A new study published in the journal of Diabetes Care and Clinical Practice showed that nutritional insulin administered after meals instead of before decreased the risk of hypoglycemia in hospitalized patients without appreciably lengthening their stay or causing severe hyperglycemia.

Hypoglycemia is a frequent occurrence on the patient days in intensive care units (10%) and non-intensive care units (3.5%), at least one hypoglycemic incident was seen. Hypoglycemia is associated with a considerable morbidity and mortality risk, particularly in the older population, with some studies suggesting a 3.4-fold greater risk of death. Insulin dosage errors are the most frequent cause of hypoglycemia in hospitalized patients when such patients have reduced calorie intake. While postprandial administration of most rapid-acting insulin analogs is allowed, they are often provided before meal consumption to enable enough time for absorption and an increase in plasma insulin levels to counteract postprandial blood sugar spikes. Thereby, Merit George and colleagues thus set out to investigate whether alterations in glycemic control or length of stay (LOS) might be brought about by a hospital-wide strategy that switched nutritional insulin delivery from pre-meal to post-meal.

This retrospective cohort research investigated the association between glycemia measurements and when nutritional insulin was administered to patients admitted to the Johns Hopkins Howard County Medical Center in Columbia, Maryland. This retrospective research, conducted over three time periods in a community hospital, assessed adult inpatients receiving nutritional insulin as Pre-intervention, post-intervention right away, and post-intervention later. These results encompassed the daily mean glucose level, LOS, severe hypoglycemia (≤ 40 mg/dL), moderate hypoglycemia (< 54 mg/dL) and severe hyperglycemia (≥ 300 mg/dL).

Between the three cohorts, the total number of patient-days studied were 1948, 1751, and 3244, respectively. The likelihood of experiencing severe hypoglycemia and any hypoglycemia reduced with time after multivariate correction. Over time, the daily mean glucose increased (194.6 ± 62.5 vs 196.8 ± 65.5 vs 199.3 ± 61.5 mg/dL; p = 0.003), despite the incidence of severe hyperglycemia (p = 0.10) and LOS (p = 0.74) did not change significantly.

By adopting a postprandial nutritional insulin delivery strategy throughout the whole hospital lowered the incidence of hypoglycemia while keeping the rate of severe hyperglycemia at bay. This implies a viable approach to enhance patient safety and more prospective randomized controlled studies are imperative to validate these results.

Source:

George, M., Zilbermint, M., Sokolinsky, S., Batty, K., Motevalli, M., Stanback, C., Gonzales, E., Miller, C., Sequeira, L., & Demidowich, A. P. (2024). Effects of preprandial versus postprandial nutritional insulin administration in the inpatient setting. In Diabetes Research and Clinical Practice (Vol. 214, p. 111785). Elsevier BV. https://doi.org/10.1016/j.diabres.2024.111785

Maternal depression affects approximately 1 in 7 pregnancies and is associated with pregnancy complications and adverse fetal outcomes. However, there are significant gaps in identifying and treating this condition. Recent study focused on examining the impact of maternal depression and anxiety during pregnancy on child executive functioning at 4.5 years of age. The research involved 323 mother-child dyads from the Ontario Birth Study, an open pregnancy cohort in Toronto, Canada. The study aimed to determine whether the timing and severity of maternal depression and/or anxiety during pregnancy affect child executive functioning, which is crucial for school readiness and long-term quality of life.

Impact of Maternal Depression and Anxiety

The results indicated that greater maternal depressive symptoms at 12 to 16 weeks of gestation were associated with impaired executive functioning in children at age 4.5 years. The study found that children of mothers meeting screening criteria for major depression in early pregnancy scored 11.3% lower on the Flanker test (a measure of attention) and 9.8% lower on the Dimensional Change Card Sort (a measure of cognitive flexibility) compared to children of mothers without maternal depressive symptoms in early pregnancy. The study also demonstrated that mild depressive symptoms had no significant effect on executive function scores. However, there was no significant effect of anxiety symptoms or maternal antidepressant use in early pregnancy or at later pregnancy stages.

Urgent Need for Maternal Depression Treatment

The study emphasized the urgent need to improve the recognition and treatment of maternal major depression, particularly in early pregnancy, to minimize its negative impact on child cognitive development. The findings suggested that fetal exposure to maternal major depression, but not milder forms of depression, at 12 to 16 weeks of gestation is associated with impaired executive functioning in the preschool years. The study provided detailed insights and nuanced findings related to the specific timing and severity of maternal depressive symptoms during pregnancy and their impact on child executive functioning. It analyzed the association between maternal depression and child executive functioning using standardized computerized assessments of attention and cognitive flexibility, highlighting the significance of early recognition and treatment of maternal major depression to minimize its negative effects on child cognitive development. The study results have implications for guiding clinical interventions and emphasizing the importance of addressing maternal mental health during pregnancy to optimize child neurodevelopment.

Key Points

– The study examined the impact of maternal depression and anxiety during pregnancy on child executive functioning at 4.5 years of age using a sample of 323 mother-child dyads from the Ontario Birth Study in Toronto, Canada.

– Greater maternal depressive symptoms at 12 to 16 weeks of gestation were found to be associated with impaired executive functioning in children at age 4.5 years. Children of mothers meeting screening criteria for major depression in early pregnancy scored significantly lower on measures of attention and cognitive flexibility compared to children of mothers without maternal depressive symptoms in early pregnancy.

– The study found no significant effect of anxiety symptoms or maternal antidepressant use in early pregnancy or at later pregnancy stages on child executive functioning. – The findings emphasized the urgent need to improve the recognition and treatment of maternal major depression, particularly in early pregnancy, to minimize its negative impact on child cognitive development. It was suggested that fetal exposure to maternal major depression at 12 to 16 weeks of gestation is associated with impaired executive functioning in the preschool years.

– The study provided detailed insights into the specific timing and severity of maternal depressive symptoms during pregnancy and their impact on child executive functioning through standardized computerized assessments of attention and cognitive flexibility.

– The results have implications for guiding clinical interventions and emphasize the importance of addressing maternal mental health during pregnancy to optimize child neurodevelopment. The study’s findings underscore the critical need for early recognition and treatment of maternal major depression in pregnancy to mitigate its adverse effects on child cognitive development, particularly in relation to executive functioning. These findings are crucial for informing clinical interventions and supporting the prioritization of maternal mental health during pregnancy to enhance child neurodevelopment.

Reference –

Levitan RD, Atkinson L, Knight JA, et al. Maternal major depression during early pregnancy is associated with impaired child executive functioning at 4.5 years of age. Am J Obstet Gynecol 2024;231:246.e1-10