Nevin Manimala

Respir Med. 2023 Aug 26:107393. doi: 10.1016/j.rmed.2023.107393. Online ahead of print.

ABSTRACT

AVANT was a Phase 3, 24-week, randomized, parallel-group, double-blind, double-dummy, placebo-controlled study to assess the efficacy and safety of aclidinium/formoterol 400 μg/12 μg combination vs monotherapies and placebo (1:1:1:1) in Asian patients (∼70% of whom were Chinese) with moderate-to-severe stable chronic obstructive pulmonary disease (COPD). Endpoints were analyzed hierarchically to incorporate type I error control. At Week 24, aclidinium/formoterol demonstrated improvements from baseline in 1-h morning post-dose forced expiratory volume in 1 s (FEV₁) vs aclidinium (least squares [LS] mean 92 mL; 95% confidence interval [CI] 60, 124; p < 0.001), and in trough FEV₁ vs formoterol (LS mean 85 mL; 95% CI 53, 117; p < 0.001). Furthermore, aclidinium monotherapy provided improvements in trough FEV₁ vs placebo (LS mean 134 mL; 95% CI 103, 166; p < 0.001). There was an improvement in transition dyspnea index focal score at Week 24 for aclidinium/formoterol vs placebo (LS mean 0.8; 95% CI 0.2, 1.3; p = 0.005) but not aclidinium vs placebo (LS mean 0.4; 95% CI -0.1, 1.0; p = 0.132). Improvements in St George’s Respiratory Questionnaire total scores occurred for aclidinium/formoterol vs placebo (LS mean -4.0; 95% CI -6.7, -1.4; p = 0.003) and aclidinium vs placebo (LS mean -2.9; 95% CI -5.5, -0.3; p = 0.031). Aclidinium/formoterol and aclidinium monotherapy were well tolerated and safety findings were consistent with known profiles; rates of treatment-emergent (TE) adverse events (AEs) (aclidinium/formoterol: 54.8%; aclidinium: 47.4%; placebo: 53.9%), serious AEs (7.2, 7.9, and 7.8%, respectively) and AEs leading to discontinuation of study medication (2.3,1.5, and 2.2%, respectively) were similar between groups.

PMID:37640273 | DOI:10.1016/j.rmed.2023.107393

Am J Med Sci. 2023 Aug 26:S0002-9629(23)01317-4. doi: 10.1016/j.amjms.2023.08.008. Online ahead of print.

ABSTRACT

BACKGROUND: Congestion is the main cause of morbidity and a prime determinant of survival in patients with heart failure (HF). However, the assessment of congestion is subjective and estimation of plasma volume (ePV) has been suggested as a more objective measure of congestion. This study aimed to explore the relationships and interactions between ePV, the severity of congestion and survival using a nationwide registry.

METHODS: Of the 1054 patients with HF enrolled in the registry, 769 had sufficient data to calculate ePV (using the Duarte, Kaplan, and Hakim equations) and relative plasma volume status (rPVS), and these patients were subsequently included in the present analysis. The severity of congestion was assessed using a 6-point congestion score (CS). Patients were divided into three groups according to the degree of congestion.

RESULTS: Out of four equations tested, only ePV_Duarte and rPVS were statistically higher in patients with severe congestion as compared to patients with no congestion (p<0.001 for both). Both ePV_Duarte (r=0.197, p<0.001) and rPVS (r=0.153, p<0.001) showed statistically significant correlations with CS and both had a modest accuracy (70.4% for ePV_Duarte and 69.4% for rPVS) to predict a CS ≥3. After a median follow up of 496 days, both ePV_Duarte (OR:1.14,95%CI:1.03-1.26, p=0.01) and rPVS (OR:1.02, 95%CI:1.00-1.03, p=0.03) were associated with all-cause mortality after adjusting for demographic and clinical variables. However, none of the indices were associated with mortality following the introduction of CS to the models (p>0.05 for both).

CONCLUSIONS: Elevated ePV_Duarte and rPVS were indicators of congestion but with a limited robustness, and either parameter could be clinically useful when a comprehensive clinical evaluation of congestion is not feasible.

PMID:37640264 | DOI:10.1016/j.amjms.2023.08.008

J Ethnopharmacol. 2023 Aug 26:117090. doi: 10.1016/j.jep.2023.117090. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Anxiety disorders leads to a decline in quality of life and increased risk of morbidity and mortality. The Baihe Dihuang decoction (BDD) is a classic Chinese medical formula that has been widely used to treat anxiety disorders for thousands of years in China. However, the pharmacodynamic material that is responsible for the antianxiety of BDD remains unclear.

AIM OF THE STUDY: To screen the main ingredients of anti-anxiety in BDD based on the establishment of spectrum-effect relationship and verified experiment.

METHODS: The UPLC-Q-TOF/MS technique was utilized to establish fingerprints of various fractions of BDD and identify the main compounds. The anti-anxiety effects of BDD were comprehensively evaluated through multiple assessments, including the open field test, elevated plus maze test, and neurotransmitters tests. Then, the spectrum-effect relationship was established through Pearson correlation analysis, gray correlation analysis, orthogonal partial least squares regression analysis. The spectrum-effect relationship results were confirmed through various measures on an anxiety condition cell model, induced by a corticosterone and lipopolysaccharide intervention. These measures included assessing neuronal cell viability, morphology, apoptosis, synaptic damage, and the expression of neurotransmitters and inflammatory factors.

RESULTS: In the UPLC-Q-TOF-MS fingerprint, 46 common peaks were identified. The pharmacological results indicated that different fractions of BDD have strong effects on improving anxiety-like behavior and regulating neurotransmitters. Among them, butanol fraction has the highest comprehensive evaluation score of anti-anxiety efficacy, which is main active fraction of BDD for anti-anxiety. The analysis of the spectrum-effect relationship revealed that the 46 peaks exhibited varying degrees of correlation with the anti-anxiety efficacy indicators of BDD. Among them, 14 components have a high correlation with the anti-anxiety efficacy indicators, which may be the potential anti-anxiety efficacy components of BDD. The in vitro activity verification of active components verified our prediction, regaloside A, B, C, D, H, acteoside, and isoacteoside improved neuronal cell viability, cell morphology, apoptosis, and synaptic damage. Additionally, regaloside A, B, C, D, H and acteoside regulated the neurotransmitter levels, while regaloside A, B, C, D, acteoside and isoacteoside inhibited the levels of inflammatory cytokines.

CONCLUSION: The butanol fraction was found to be the main active fraction of BDD, and 14 compounds were the major anxiolytic active components. The results of verifying the major active components were consistent with the predicted results of the spectrum-effect analysis. The developed spectrum-effect analysis in this study demonstrates high accuracy and reliability for screening active components in TCMs.

PMID:37640258 | DOI:10.1016/j.jep.2023.117090

J Oral Maxillofac Surg. 2023 Aug 13:S0278-2391(23)00800-5. doi: 10.1016/j.joms.2023.08.004. Online ahead of print.

ABSTRACT

BACKGROUND: Condylar adaptations following orthognathic surgery remain an area of interest. Prior studies do not use 3-dimensional imaging modalities and lack standardization in the choice of osteotomy and movement when assessing condylar changes.

PURPOSE: The purpose of this study was to use 3-dimensional cephalometry to measure the association between osteotomy type (sagittal split osteotomy [SSO] vs vertical ramus osteotomy [VRO]) and changes in condylar volume and position.

STUDY DESIGN, SETTING, AND SAMPLE: This is a retrospective cohort study from January 2021 through December 2022 of patients at Bellevue Hospital in New York City, New York who were treated with either SSO or VRO for the correction of Class III skeletal malocclusion.

PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: The primary predictor was the type of mandibular osteotomy, sagittal split osteotomy, and vertical ramus osteotomy.

MAIN OUTCOME VARIABLES: The primary outcomes were changes in condylar volume (change measured in mm³) and relative position (anterior-posterior change utilizing the Pullinger and Hollinder method).

COVARIATES: Covariates included patient age, sex, setback magnitude, temporomandibular joint symptoms, and fixation method for SSO patients.

ANALYSES: Univariate comparisons were performed between independent variables and study outcomes. Volume changes were compared within each predictor using paired t-tests. Position changes were compared within each predictor using χ² tests. If there were multiple significant univariate predictors, multiple regression models were created to predict volume and position changes. A P < .05 value was considered statistically significant.

RESULTS: The final sample comprised 30 condyles derived from 30 subjects. Mean age was 22.7 years (SD = 5.7) and mean setback was 3.9 mm (SD = 0.9). Twenty two condyles (73.3%) were subject to SSO with fixation, while the remaining 8 (26.7%) condyles were subject to intraoral VRO without fixation. When compared to VRO, condyles manipulated with SSO had greater volume loss (-177.2 vs -60.9 mm³; P = .03) and positional change (68.2 vs 12.5%; P < .01). Self-reported measures of postoperative pain, internal derangement, and myofascial symptoms were not significantly associated with either volume or positional changes.

CONCLUSIONS AND RELEVANCE: The SSO resulted in greater postoperative condylar volume loss and positional changes. These volume and positional changes were not correlated with self-reported temporomandibular disorder symptoms.

PMID:37640238 | DOI:10.1016/j.joms.2023.08.004

J Pediatr. 2023 Aug 26:113700. doi: 10.1016/j.jpeds.2023.113700. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the ability of the Bayley-III cognitive and language composite scores at 18-22 months corrected age to predict WISC-IV Full Scale IQ (FSIQ) at 6-7 years in infants born extremely preterm.

STUDY DESIGN: Children in this study were part of the Neuroimaging and Neurodevelopmental Outcome (NEURO) cohort, a secondary study to the SUPPORT trial and born 24 to 27.6 weeks gestational age. Bayley-III cognitive and language scores and WISC-IV FSIQ were compared with pairwise Pearson correlation coefficients and adjusted for medical and socio-economic variables using linear mixed effect regression models.

RESULTS: Bayley-III cognitive (r=0.33) and language scores (r=0.44) were mildly correlated with WISC-IV FSIQ score. Of the children with Bayley-III cognitive scores less than 70, 67% also had FSIQ <70. There was less consistency for children with Bayley-III scores in the 85-100 range as 43% had FSIQ <85 and 10% FSIQ <70. Among those with Bayley-III language scores >100, about 1 in 5 had FSIQ <85. A cut point of 92 for the cognitive composite score resulted in sensitivity (0.60), specificity (0.64). A cut point of 88 for the language composite score produced sensitivity (0.61), specificity (0.70).

CONCLUSION: Findings indicate the Bayley-III cognitive and language scores correlate with later IQ but may fail to predict delay or misclassify children who are not delayed at school age. The Bayley-III can be a useful tool to help identify children born extremely preterm who have below average cognitive scores and may be at the greatest risk for ongoing cognitive difficulties.

PMID:37640232 | DOI:10.1016/j.jpeds.2023.113700

Environ Pollut. 2023 Aug 26:122465. doi: 10.1016/j.envpol.2023.122465. Online ahead of print.

ABSTRACT

The estimated health effects of air pollution vary between studies, and this variation is caused by factors associated with the study location, hereafter termed regional heterogeneity. This heterogeneity raises a methodological question as to which studies should be used to estimate risks in a specific region in a health impact assessment. Should one use all studies across the world, or only those in the region of interest? The current study provides novel insight into this question in two ways. Firstly, it presents an up-to-date analysis examining the magnitude of continent-level regional heterogeneity in the short-term health effects of air pollution, using a database of studies collected by Orellano et al. (2020). Secondly, it provides in-depth simulation analyses examining whether existing meta-analyses are likely to be underpowered to identify statistically significant regional heterogeneity, as well as evaluating which meta-analytic technique is best for estimating region-specific estimates. The techniques considered include global and continent-specific (sub-group) random effects meta-analysis and meta-regression, with omnibus statistical tests used to quantify regional heterogeneity. We find statistically significant regional heterogeneity for 4 of the 8 pollutant-outcome pairs considered, comprising NO₂, O₃ and PM_2.5 with all-cause mortality, and PM_2.5 with cardiovascular mortality. From the simulation analysis statistically significant regional heterogeneity is more likely to be identified as the number of studies increases (between 3 and 30 in each region were considered), between region heterogeneity increases and within region heterogeneity decreases. Finally, while a sub-group analysis using Cochran’s Q test has a higher median power (0.71) than a test based on the moderators’ coefficients from meta-regression (0.59) to identify regional heterogeneity, it also has an inflated type-1 error leading to more false positives (median errors of 0.15 compared to 0.09).

PMID:37640226 | DOI:10.1016/j.envpol.2023.122465

Chemosphere. 2023 Aug 26:139956. doi: 10.1016/j.chemosphere.2023.139956. Online ahead of print.

ABSTRACT

The incorrect disposal of textile dyes, such as Reactive Black 5 (RB5), causes several problems for living beings and the quality of the environment. Nanobiocomposites (NBC) produced from endophytic fungi (potentially remediation dyes-agents) and magnetic nanoparticles have high biotechnological potential due to their superparamagnetic behavior, which would allow their recovery through the magnetic field after the bioremediation process. This work aimed to obtain a new nanobiocomposite from the interaction of magnetite nanoparticles (Fe₃O₄) with the endophyte Aspergillus flavus (Af-CL-7) to evaluate its bioremediation capacity and to reduce the toxicity of RB5 and its reuse. Before obtaining the NBC, Af-CL-7 showed discoloration of RB5 and it was tolerant to all tested concentrations of this dye. The discovery of the nanobiocomposite textile dye bioremediator product presents a significant environmental advantage by addressing the issue of water pollution caused by textile dyes. The NBC called Af-Fe₃O₄ was successfully obtained with the magnetized endophyte, and their magnetic properties were verified by VSM analysis and by action of magnetic fields generated by Nd-Fe-B magnets SEM analyzes showed that the nanoparticles did not cause any damage to the hypha morphology, and TEM analyzes confirmed the presence of nanoparticles in the fungus wall and also inside the cell. The NBC Af-Fe₃O₄ and Af-CL-7 showed, respectively, 96.1% and 92.2% of RB5 discoloration in the first use, 91.1% e 86.2% of discoloration in the validation test, and 89.0% in NBC reuse. In the toxicological bioassay with Lactuca sativa seeds, NBC showed a positive reduction in the toxicity of RB5 after treatment, allowing the hypocotyl growth to be statistically similar to the control with water. Thus, we highlight the promising obtaining process of NBC that could be applied in bioremediation of contaminated waters, wherein the industrial economic cost will depend on the fermentation efficiency, biomass production and nanoparticle synthesis.

PMID:37640209 | DOI:10.1016/j.chemosphere.2023.139956

Photodiagnosis Photodyn Ther. 2023 Aug 27:103766. doi: 10.1016/j.pdpdt.2023.103766. Online ahead of print.

ABSTRACT

PURPOSE: To compare the peripapillary retinal nerve fiber layer thickness, macular thickness, ganglion cell layer thickness, and inner plexiform layer thickness determined by Optic Coherence Tomography in the patient group diagnosed with a generalized anxiety disorder who did not receive any psychiatric medication with the healthy control group.

METHODS: Forty newly diagnosed, drug-free Generalized Anxiety Disorder patients and 43 healthy age- and gender-matched control subjects were included in the study. Macular thickness, ganglion cell layer thickness, inner plexiform layer thickness, and peripapillary retinal nerve fiber layer thickness were measured using optical coherence tomography. Structured Clinical Interviews and a state-trait anxiety scale were applied to both groups.

RESULTS: Gender distributions (P=0.965) and mean ages were similar between the groups (P=0.340). Retinal nerve fiber layer thickness measurements were not significantly different between the groups. We observed statistically significant thinning in the inner superior, inner nasal, inner temporal, inner inferior, and outer inferior quadrants of the macula in the patient group compared to the control group (P=0.046, P=0.046, P=0.020, P=0.007, P=0.014) in the patient group. We found thinning at the Ganglion cell layer in the inner inferior and outer temporal quadrants (Respectively P=0.018, P=0.049), inner plexiform layer in the inner nasal, inner temporal, and inner inferior quadrants (Respectively P=0.046, P=0.044, P=0.011) compared to the control group.

CONCLUSIONS: This is the first study to reveal thinning in the macula, ganglion cell layer, and inner plexiform layer in newly diagnosed, drug-free Generalized Anxiety Disorder patients compared to the control group.

PMID:37640207 | DOI:10.1016/j.pdpdt.2023.103766

Photodiagnosis Photodyn Ther. 2023 Aug 26:103774. doi: 10.1016/j.pdpdt.2023.103774. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the long-term effect of systemic sclerosis on the optic disc and retinal capillary network and to see whether the drugs used in the treatment of SSc affected optical coherence tomography angiography (OCTA) parameters.

MATERIALS AND METHODS: This cross-sectional case-control study included 40 systemic sclerosis patients and 40 healthy individuals. We included only one eye of each patient in the study. Macular layers and angiography scanning were performed with a Zeiss Cirrus 5000 OCTA system. Such values as macular thickness, retinal nerve fiber layer (RNFL), ganglion cell inner plexiform layer (GC-IPL) were obtained. For central vessel and perfusion density (VD, PD), central 6 mm were obtained and were evaluated by dividing it into 3 groups as inner, outer, and full. The FAZ was evaluated through 3 parameters: area, perimeter, circularity index.

RESULTS: Statistically significant difference was found between the groups in terms of the mean and foveal macular thickness values (p=0.008, p=0.033). Significant differences were also found between the two groups in terms of the VD and PD parameters in all regions except for 1 mm center (p<0.05). There were no significant differences in RNFL and GC-IPL values between two groups. Also, a positive correlation was observed between parapapillary perfusion density values and RNFL and GC-IPL thicknesses in SSc group. When the subgroups were compared in terms of vasodilator drug use, the subgroup using vasodilators was seen to have higher mean RNFL and inferior RNFL thicknesses (p=0.045 and p=0.035, respectively). In addition, there was a significant positive correlation between parapapillary VD and RNFL values in the SSc subgroup treated with vasodilators.

CONCLUSIONS: The results of this study demonstrate microvascular loss in individuals with systemic sclerosis, compared with healthy subjects. Also, it has been determined that OCTA is an important test for screening retinal and optic disc microvascular changes over time in cases of systemic sclerosis and may be used to evaluate the response to vasodilator drugs used in the treatment of SSc disease.

PMID:37640203 | DOI:10.1016/j.pdpdt.2023.103774

Photodiagnosis Photodyn Ther. 2023 Aug 26:103771. doi: 10.1016/j.pdpdt.2023.103771. Online ahead of print.

ABSTRACT

BACKGROUND: Investigation of the effects of conventional strabismus surgeries on corneal densitometry (CD).

METHODS: Patients who had strabismus surgery between May 2022 and July 2022 were included in the study. CD software with a Pentacam device was used to determine corneal backward light scattering. CD data were analysed preoperatively and 1 month postoperatively. Patients were classified as those who had single muscle and two-muscle surgery.

RESULTS: The study included 33 eyes of 28 patients. The mean age of the patients was 20.51±8.22 (5-35) years. Of the eyes, 19 underwent single muscle recession surgery. Two-muscle surgeries (recession and resection combination) were performed in 14 eyes. In the 1st month postoperative, the mean CD value decreased statistically significantly only in the total cornea apical 0-2 mm zone among the layers examined (p = 0.039). There was no significant change in the other layers (p > 0.05 for all). Single-muscle and two-muscle surgery groups were similar in the amount of CD reduction, except for one layer.

CONCLUSIONS: CD did not change in most of the corneal layers examined in the first month postoperatively. Single muscle and two-muscle horizontal rectus surgeries did not impair corneal clarity in the postoperative 1st month.

PMID:37640202 | DOI:10.1016/j.pdpdt.2023.103771