Nevin Manimala

Biomed Pharmacother. 2022 Oct;154:113661. doi: 10.1016/j.biopha.2022.113661. Epub 2022 Sep 7.

ABSTRACT

A causal relationship between ginsenoside Rb3 (G-Rb3) and improved inflammation and cardiac function has not been established. To determine which specific signaling pathways were involved in G-Rb3 improvement of inflammation and myocardial function. In vivo, we found that G-Rb3 decreased the levels of both nuclear factor κB (NF-κB p65) and CD45, an inflammatory marker. G-Rb3 also enhanced key proteins of the contraction unit (cardiac troponin protein I (cTnI) and α-actinin) to improve cardiac function. G-Rb3 inhibited NF-κB p65 nuclear translocation in vitro, as verified by western blot and IF. When NF-κB p65 was overexpressed, a decrease in cyclic nucleotide phosphodiesterase 3B (PDE3B) and SERCA2a expression, while no statistical significance was observed in the expressions of cAMP, PKA, and calcium/calmodulin-dependent protein kinase type II (CaMKⅡ) in each group. The NF-κB p65 plasmid blocked the SERCA2a promoter, as verified by the luciferase reporter system, and G-Rb3 truncated the NF-κB p65 block on the SERCA2a promoter. qPCR was also used to confirm that G-Rb3 increased the mRNA of SERCA2a. In conclusion, we confirmed that the mechanisms of G-Rb3 on ventricular systolic dysfunction causing inflammation are not via the cAMP/PKA pathway, but via suppressing the blockage of NF-κB p65 on the SERCA2a promoter and increasing the SERCA2a expression.

PMID:36942602 | DOI:10.1016/j.biopha.2022.113661

Transfus Med. 2023 Mar 21. doi: 10.1111/tme.12967. Online ahead of print.

ABSTRACT

INTRODUCTION: Platelet products are scarce and expensive resources to be used judiciously. However, inappropriate usage is common. Lack of physician awareness is an important issue. We implemented a physician education program (PEP) along with repeated WhatsApp reminders at our centre. We audited the platelet usage practise before and after the intervention.

METHODS: Charts of patients with acute myeloid leukaemia (AML) treated between January 2020 and August 2020 was reviewed, and the mean platelet usage per patient per day was calculated. Physician education was implemented between September 2020 and December 2020 (2 PowerPoint lectures of 20 min each and weekly WhatsApp messages containing the guidelines). Data of patients treated between Jan 2021 and August 2021 was prospectively audited to understand platelet usage and the indications for transfusions. The British Committee for the Standards in Haematology (BCSH) platelet transfusion guidelines were used as the adjudication tool to evaluate compliance. The mean platelet usage per day per kg body weight of a patient before and after the PEP was compared using the t-test.

RESULTS: Group A (before physician education) consisted of 22 patients, and group B (after physician education) consisted of 23 patients. The mean number of platelet transfusions for each patient in a day per kg body weight was 125.7 × 10⁸ in group A whereas, after the PEP, it had reduced to 73.9 × 10⁸ amounting to an absolute reduction of 51 × 10⁸ (58.8%) from the baseline with a statistical significance of P = 0.001. After implementing the PEP, the mean number of random donor platelets used reduced by 10.25 units (34% reduction), and the mean single donor platelets used reduced by 0.83 units (19% reduction). The 190 requests for platelet transfusion received during this period were classified as appropriate (157/190), which constituted 82.63% of the requests, or inappropriate (33/190), which accounted for 17.36%.

CONCLUSIONS: A short-duration education programme supplemented with weekly WhatsApp messages and an active feedback mechanism on the rationale of platelet transfusion by the treating physician and transfusion specialist could significantly reduce platelet consumption during the therapy of acute myeloid leukaemia patients. This is a measure that can be considered by all high-volume haematology centres, which can improve patient safety and reduce costs.

PMID:36942594 | DOI:10.1111/tme.12967

Stroke. 2023 Mar 21. doi: 10.1161/STROKEAHA.122.041026. Online ahead of print.

ABSTRACT

BACKGROUND: Mood disorders and strokes are often comorbid, and their health toll worldwide is huge. This study characterizes prognostic and causal roles of mood disorders in stroke.

METHODS: We tested if genetic susceptibilities for mood disorders were associated with all strokes, ischemic strokes in the Malmö Diet and Cancer cohort (24 631 individuals with a median follow-up of 21.3 (interquartile range: 16.6-23.2) years. We further examined the causal effects for mood disorders on all strokes and ischemic strokes using summary statistics from large genome-wide association studies of mood disorders (up to 609 424 individuals, Psychiatric Genomics Consortium), all strokes and ischemic strokes (up to 446 696 individuals, MEGASTROKE Consortium).

RESULTS: Among 24 366 stroke-free participants at baseline, 2632 individuals developed strokes, 2172 of them ischemic, during follow-up. After properly adjusting for well-known risk factors, participants in the highest quintile of polygenic risk scores for mood disorders had 1.45× (95% CI, 1.21-1.74) higher risk of strokes and 1.44× (95% CI, 1.18-1.76) higher risk of ischemic strokes compared with the lowest quintile in women. Mendelian randomization analyses suggested that mood disorders had a causal effect on strokes (odds ratio, 1.07 [95% CI, 1.03-1.11]) and ischemic strokes (odds ratio, 1.09 [95% CI, 1.04-1.13]).

CONCLUSIONS: Our results suggest a causal role of mood disorders in the risk of stroke. High-risk women could be identified early in life using polygenic risk scores to ultimately prevent mood disorders and strokes.

PMID:36942587 | DOI:10.1161/STROKEAHA.122.041026

Palliat Support Care. 2022 Dec;20(6):779-784. doi: 10.1017/S1478951521001814.

ABSTRACT

OBJECTIVE: The prevalence and effects of delirium in very old individuals aged ≥80 years have not yet been systematically evaluated. Therefore, this large single-center study of the one-year prevalence of delirium in 3,076 patients in 27 medical departments of the University Hospital of Zurich was conducted.

METHODS: Patient scores on the Delirium Observation Screening scale, Intensive Care Delirium Screening Checklist, Diagnostic and Statistical Manual, 5th edition, and electronic Patient Assessment-Acute Care (nursing tool) resulted in the inclusion of 3,076 individuals in 27 departments. The prevalence rates were determined by simple logistic regressions, odds ratios (ORs), and confidence intervals.

RESULTS: Of the 3,076 patients, 1,285 (41.8%) developed delirium. The prevalence rates in the 27 departments ranged from 15% in rheumatology (OR = 0.30) to 73% in intensive care (OR = 5.25). Delirious patients were more likely to have been admitted from long-term care facilities (OR = 2.26) or because of emergencies (OR = 2.24). The length of their hospital stay was twice as long as that for other patients. Some died before discharge (OR = 24.88), and others were discharged to nursing homes (OR = 2.96) or assisted living facilities (OR = 2.2).

CONCLUSION: This is the largest study to date regarding the prevalence of delirium in patients aged ≥80 years and the medical characteristics of these patients. Almost two out of five patients developed delirium, with a high risk of loss of independence and mortality.

PMID:36942581 | DOI:10.1017/S1478951521001814

J Health Commun. 2023 Mar 21:1-10. doi: 10.1080/10810730.2023.2193151. Online ahead of print.

ABSTRACT

The use of social media has changed since the outbreak of coronavirus disease 2019 (COVID-19). However, little is known about the gender disparity in social media use for nonspecific and health-specific issues before and during the COVID-19 pandemic. Based on a gender difference perspective, this study aimed to examine how the nonspecific and health-specific uses of social media changed in 2017-2020. The data came from the Health Information National Trends Survey Wave 5 Cycle 1-4. This study included 10,426 participants with complete data. Compared to 2017, there were higher levels of general use in 2019 and 2020, and an increased likelihood of health-related use in 2020 was reported among the general population. Female participants were more likely to be nonspecific and health-specific users than males. Moreover, the relationship of gender with general use increased in 2019 and 2020; however, concerning health-related use, it expanded in 2019 but narrowed in 2020. The COVID-19 global pandemic led to increased use of social media, especially for health-related issues among males. These findings further our understanding of the gender gap in health communication through social media, and contribute to targeted messaging to promote health and reduce disparities between different groups during the pandemic.

PMID:36942570 | DOI:10.1080/10810730.2023.2193151

Prehosp Disaster Med. 2023 Mar 21:1-6. doi: 10.1017/S1049023X23000341. Online ahead of print.

ABSTRACT

INTRODUCTION: Terrorist attacks against hospitals and health care providers have disproportionally increased during the last decades. A significant proportion of these attacks targeted abortion clinics and abortion providers. In the light of the overturning of Roe v. Wade in 2022, an increase of anti-abortion terrorist attacks is anticipated. Therefore, it becomes imperative to gain further insight into the risk and characteristics of past terrorist attacks. This study aimed to review terrorist attacks against health care targets providing abortion services from 1970 through 2020.

METHODS: Data collection was performed using a retrospective database search through the Global Terrorism Database (GTD). The GTD was searched using the internal database functions for all terrorist attacks against abortion health care providers from January 1, 1970 – December 31, 2020. Temporal factors, location, attack and weapon type, and number of casualties or hostages were analyzed using descriptive statistics.

RESULTS: In total, 262 terrorist attacks were identified in five different countries. The majority (96.6%) occurred in the United States, with the highest counts during the last 20 years of the 20th century. Facility and infrastructure attacks were the most common attack types, followed by bombings and explosions. The attacks resulted in 34 injuries and nine fatalities. Kidnapping took place in three incidents. Of all successful attacks, 96.9% resulted in property damage.

CONCLUSION: Abortion-related health care facilities and providers have repeatedly been the target of terrorists over the past decades. Nearly all of these attacks took place in the United States, with the highest counts during the last 20 years of the 20th century.

PMID:36942568 | DOI:10.1017/S1049023X23000341

J Neuroendocrinol. 2023 Mar 2:e13250. doi: 10.1111/jne.13250. Online ahead of print.

ABSTRACT

To assess the risk factors for polycystic ovary syndrome (PCOS) in women with epilepsy (WWE) and develop a practical approach for PCOS screening based on clinical characteristic, blood indicator, and anti-seizure medication (ASM) profiles. This cross-sectional study was conducted with 248 WWE who were consecutively enrolled from the Epilepsy Center of West China Hospital between April 2021 and March 2022. The epilepsy characteristics, blood indicators, and use of ASMs were compared between WWE with and without PCOS. Multivariate logistic regression was used to identify the factors independently associated with PCOS. The differential analysis showed that younger age at onset of epilepsy (<13 years), a history of birth hypoxia, obesity (BMI ≥25 kg/m² ), use of levetiracetam (LEV) (≥1 year), higher levels of cholesterol, luteinizing hormone (LH) and anti-Müllerian hormone (AMH), and lower levels of sex hormone-binding globulin were associated with PCOS (p < .05). Multivariate logistic regression identified that obesity (BMI ≥25 kg/m² ), use of LEV (≥1 year), and higher levels of AMH and LH were independently associated with PCOS in WWE (p < .05). Obesity (BMI ≥25 kg/m² ), LEV use (≥1 year), and elevated AMH and LH levels suggest an increased in the probability of occurrence of PCOS in WWE. The combination of these profiles provides a practical approach for screening PCOS in WWE.

PMID:36942563 | DOI:10.1111/jne.13250

JAMA. 2023 Mar 21. doi: 10.1001/jama.2023.3576. Online ahead of print.

NO ABSTRACT

PMID:36942555 | DOI:10.1001/jama.2023.3576

JAMA. 2023 Mar 21. doi: 10.1001/jama.2023.3651. Online ahead of print.

ABSTRACT

IMPORTANCE: Randomized clinical trials (RCTs) of therapeutic-dose heparin in patients hospitalized with COVID-19 produced conflicting results, possibly due to heterogeneity of treatment effect (HTE) across individuals. Better understanding of HTE could facilitate individualized clinical decision-making.

OBJECTIVE: To evaluate HTE of therapeutic-dose heparin for patients hospitalized for COVID-19 and to compare approaches to assessing HTE.

DESIGN, SETTING, AND PARTICIPANTS: Exploratory analysis of a multiplatform adaptive RCT of therapeutic-dose heparin vs usual care pharmacologic thromboprophylaxis in 3320 patients hospitalized for COVID-19 enrolled in North America, South America, Europe, Asia, and Australia between April 2020 and January 2021. Heterogeneity of treatment effect was assessed 3 ways: using (1) conventional subgroup analyses of baseline characteristics, (2) a multivariable outcome prediction model (risk-based approach), and (3) a multivariable causal forest model (effect-based approach). Analyses primarily used bayesian statistics, consistent with the original trial.

EXPOSURES: Participants were randomized to therapeutic-dose heparin or usual care pharmacologic thromboprophylaxis.

MAIN OUTCOMES AND MEASURES: Organ support-free days, assigning a value of -1 to those who died in the hospital and the number of days free of cardiovascular or respiratory organ support up to day 21 for those who survived to hospital discharge; and hospital survival.

RESULTS: Baseline demographic characteristics were similar between patients randomized to therapeutic-dose heparin or usual care (median age, 60 years; 38% female; 32% known non-White race; 45% Hispanic). In the overall multiplatform RCT population, therapeutic-dose heparin was not associated with an increase in organ support-free days (median value for the posterior distribution of the OR, 1.05; 95% credible interval, 0.91-1.22). In conventional subgroup analyses, the effect of therapeutic-dose heparin on organ support-free days differed between patients requiring organ support at baseline or not (median OR, 0.85 vs 1.30; posterior probability of difference in OR, 99.8%), between females and males (median OR, 0.87 vs 1.16; posterior probability of difference in OR, 96.4%), and between patients with lower body mass index (BMI <30) vs higher BMI groups (BMI ≥30; posterior probability of difference in ORs >90% for all comparisons). In risk-based analysis, patients at lowest risk of poor outcome had the highest propensity for benefit from heparin (lowest risk decile: posterior probability of OR >1, 92%) while those at highest risk were most likely to be harmed (highest risk decile: posterior probability of OR <1, 87%). In effect-based analysis, a subset of patients identified at high risk of harm (P = .05 for difference in treatment effect) tended to have high BMI and were more likely to require organ support at baseline.

CONCLUSIONS AND RELEVANCE: Among patients hospitalized for COVID-19, the effect of therapeutic-dose heparin was heterogeneous. In all 3 approaches to assessing HTE, heparin was more likely to be beneficial in those who were less severely ill at presentation or had lower BMI and more likely to be harmful in sicker patients and those with higher BMI. The findings illustrate the importance of considering HTE in the design and analysis of RCTs.

TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT02735707, NCT04505774, NCT04359277, NCT04372589.

PMID:36942550 | DOI:10.1001/jama.2023.3651

Neuroradiol J. 2023 Mar 21:19714009231166100. doi: 10.1177/19714009231166100. Online ahead of print.

ABSTRACT

OBJECTIVES: Histological studies have shown alterations of thalamic nuclei in patients with Down syndrome (DS). The correlation of these changes on MRI (magnetic resonance imaging) is unclear. Therefore, this study investigates volumetric differences of thalamic nuclei in children with DS compared to controls.

METHODS: Patients were retrospectively identified between 01/2000 and 10/2021. Patient inclusion criteria were: (1) 0-18 years of age, (2) diagnosis of DS, and (3) availability of a brain MRI without parenchymal injury and a non-motion-degraded volumetric T1-weighted sequence. Whole thalamus and thalamic nuclei (n = 25) volumes were analyzed bilaterally relative to the total brain volume (TBV). Two-sided t-tests were used to evaluate differences between groups. Differences were considered significant if the adjusted p-value was <0.05 after correction for multiple hypothesis testing using the Holm-Bonferroni method.

RESULTS: 21 children with DS (11 females, 52.4%, mean age: 8.6 ± 4.3 years) and 63 age- and sex-matched controls (32 females, 50.8%, 8.6 ± 4.3 years) were studied using automated volumetric segmentation. Significantly smaller ratios were found for nine thalamic nuclei and the whole thalamus on the right and five thalamic nuclei on the left. TBV was significantly smaller in patients with DS (p < 0.001). No significant differences were found between the groups for age and sex.

CONCLUSIONS: In this exploratory volumetric analysis of the thalamus and thalamic nuclei, we observed statistically significant volumetric changes in children with DS. Our findings confirm prior neuroimaging and histological studies and extend the range of involved thalamic nuclei in pediatric DS.

PMID:36942548 | DOI:10.1177/19714009231166100