Category: Nevin Manimala

Obstet Gynecol. 2021 Apr 8. doi: 10.1097/AOG.0000000000004361. Online ahead of print.

ABSTRACT

Rigorous studies carried out by the National Center for Health Statistics show that previously reported increases in maternal mortality rates in the United States were an artifact of changes in surveillance. The pregnancy checkbox, introduced in the revised 2003 death certificate and implemented by the states in a staggered manner, resulted in increased identification of maternal deaths and in reported maternal mortality rates. This Commentary summarizes the findings of the National Center for Health Statistics reports, describes temporal trends and the current status of maternal mortality in the United States, and discusses future concerns. Although the National Center for Health Statistics studies, based on recoding of death certificate information (after excluding information from the pregnancy checkbox), showed that crude maternal mortality rates did not change significantly between 2002 and 2018, age-adjusted analyses show a temporal reduction in the maternal mortality rate (21% decline, 95% CI 13-28). Specific causes of maternal death, which were not affected by the pregnancy checkbox, such as preeclampsia, showed substantial temporal declines. However, large racial disparities continue to exist: Non-Hispanic Black women had a 2.5-fold higher maternal mortality rate compared with non-Hispanic White women in 2018. This overview of maternal mortality underscores the need for better surveillance and more accurate identification of maternal deaths, improved clinical care, and expanded public health initiatives to address social determinants of health. Challenges with ascertaining maternal deaths notwithstanding, several causes of maternal death (unaffected by surveillance artifacts) show significant temporal declines, even though there remains substantial scope for preventing avoidable maternal death and reducing disparities.

PMID:33831914 | DOI:10.1097/AOG.0000000000004361

Obstet Gynecol. 2021 Apr 8. doi: 10.1097/AOG.0000000000004356. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the role of prepregnancy obesity as a mediator in the association between race-ethnicity and severe maternal morbidity.

METHODS: We conducted an analysis on a population-based retrospective cohort study using 2010-2014 birth records linked with hospital discharge data in New York City. A multivariable logistic regression mediation model on a subgroup of the sample consisting of normal-weight and obese women (n=409,021) calculated the mediation effect of obesity in the association between maternal race-ethnicity and severe maternal morbidity, and the residual effect not mediated by obesity. A sensitivity analysis was conducted excluding the severe maternal morbidity cases due to blood transfusion.

RESULTS: Among 591,455 live births, we identified 15,158 cases of severe maternal morbidity (256.3/10,000 deliveries). The severe maternal morbidity rate among obese women was higher than that of normal-weight women (342 vs 216/10,000 deliveries). Black women had a severe maternal morbidity rate nearly three times higher than White women (420 vs 146/10,000 deliveries) and the severe maternal morbidity rate among Latinas was nearly twice that of White women (285/10,000 deliveries). Among women with normal or obese body mass index (BMI) only (n=409,021), Black race was strongly associated with severe maternal morbidity (adjusted odds ratio [aOR] 3.02, 95% CI 2.88-3.17) but the obesity-mediated effect represented only 3.2% of the total association (aOR 1.03, 95% CI 1.02-1.05). Latina ethnicity was also associated with severe maternal morbidity (aOR 2.01, 95% CI 1.90-2.12) and the obesity-mediated effect was similarly small: 3.4% of the total association (aOR 1.02, 95% CI 1.01-1.03). In a sensitivity analysis excluding blood transfusion, severe maternal morbidity cases found a higher mediation effect of obesity in the association with Black race and Latina ethnicity (15.3% and 15.2% of the total association, respectively).

CONCLUSION: Our findings indicate that prepregnancy obesity, a modifiable factor, is a limited driver of racial-ethnic disparities in overall severe maternal morbidity.

PMID:33831920 | DOI:10.1097/AOG.0000000000004356

Obstet Gynecol. 2021 Apr 8. doi: 10.1097/AOG.0000000000004343. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the association between individual-level and neighborhood-level risk factors and severe maternal morbidity.

METHODS: This was a retrospective cohort study of all pregnancies delivered between 2010 and 2017 in the University of Pennsylvania Health System. International Classification of Diseases codes classified severe maternal morbidity according to the Centers for Disease Control and Prevention guidelines. Logistic regression modeling evaluated individual-level risk factors for severe maternal morbidity, such as maternal age and preeclampsia diagnosis. Additionally, we used spatial autoregressive modeling to assess Census-tract, neighborhood-level risk factors for severe maternal morbidity such as violent crime and poverty.

RESULTS: Overall, 63,334 pregnancies were included, with a severe maternal morbidity rate of 2.73%, or 272 deliveries with severe maternal morbidity per 10,000 delivery hospitalizations. In our multivariable model assessing individual-level risk factors for severe maternal morbidity, the magnitude of risk was highest for patients with a cesarean delivery (adjusted odds ratio [aOR] 3.50, 95% CI 3.15-3.89), stillbirth (aOR 4.60, 95% CI 3.31-6.24), and preeclampsia diagnosis (aOR 2.71, 95% CI 2.41-3.03). Identifying as White was associated with lower odds of severe maternal morbidity at delivery (aOR 0.73, 95% CI 0.61-0.87). In our final multivariable model assessing neighborhood-level risk factors for severe maternal morbidity, the rate of severe maternal morbidity increased by 2.4% (95% CI 0.37-4.4%) with every 10% increase in the percentage of individuals in a Census tract who identified as Black or African American when accounting for the number of violent crimes and percentage of people identifying as White.

CONCLUSION: Both individual-level and neighborhood-level risk factors were associated with severe maternal morbidity. These factors may contribute to rising severe maternal morbidity rates in the United States. Better characterization of risk factors for severe maternal morbidity is imperative for the design of clinical and public health interventions seeking to lower rates of severe maternal morbidity and maternal mortality.

PMID:33831923 | DOI:10.1097/AOG.0000000000004343

J Environ Manage. 2021 Apr 5;289:112495. doi: 10.1016/j.jenvman.2021.112495. Online ahead of print.

ABSTRACT

This study quantifies the degree of pollution and assess the ecological risk of As, Ba, Cd, Co, Cr, Cu, Mo, Ni, Pb, V and Zn in sediments and soils of the Limoncocha Biological Reserve (Ecuador), identified as a Ramsar site with high ecological and socioeconomic value. The hydrologic system of the Reserve is mainly formed by two rivers that drain into the Limoncocha lagoon, which occupies only five percent of the protected area but support a high anthropic influence. Local statistical baseline of studied potentially toxic elements is established using cumulative frequency method, and Al is selected as reference element due to the good correlation with the studied elements. The grade of pollution and the potential ecological risk are evaluated applying three individual (Contamination Factor, Geo-accumulation Index and Enrichment Factor) and six integrated (Degree and modified degree of contamination, Pollution Load Index, Nemerow and modified Nemerow pollution indexes and potential ecological risk index) indices. Results analysis are based on the combined application of traditional statistics, multivariate data analysis and self organizing maps. Outcomes suggest to classify sediments and soils as “moderate contamination and enrichment” due mainly to the concentrations of Cu (66.4-110 mg/kg) and Cd (0.0262-0.808 mg/kg), derived from domestic wastewaters and agricultural activities, and in a lesser extent due to Mo (0.822-4.37 mg/kg), Ni (10.3-25.8 mg/kg), Co (7.27-24.8 mg/kg) and V (60.3-178 mg/kg), derived from oil field drilling activities. The distributions of As (0.328-8.83 mg/kg), Ba (143-1100 mg/kg), Pb (7.20-26.5 mg/kg), Zn (60.1-276 mg/kg) and Cr (10.1-48.6 mg/kg) are heterogeneous in the studied sampling sites. Sediments located next to the pier and at the central area of the Limoncocha lagoon, show moderate potential risk and according to sediment quality guidelines, the calculated mean Effect Range Median quotient (mERMq) classify the sites as medium-low priority risk level. A three-level classification of a mean quotient based on soil quality and soil potential uses is proposed. Soil sites with high anthropogenic activities show low to moderate potential ecological risk being classified as poor soil quality sites but with all potential soil uses allowed according to the legal limits for land uses in Ecuador.

PMID:33831761 | DOI:10.1016/j.jenvman.2021.112495

J Electrocardiol. 2021 Mar 31;66:79-83. doi: 10.1016/j.jelectrocard.2021.03.011. Online ahead of print.

ABSTRACT

INTRODUCTION: The clinical utility of inferolateral early repolarisation (ER) and late potentials (LP) in children with Brugada Syndrome (BrS) has not been previously evaluated. The aim of this study was to determine the prevalence of electrocardiographic (ECG) abnormalities in children with BrS, and to investigate their relationship with clinical outcomes.

METHODS: 43 patients with BrS and 47 controls aged ≤18 undergoing systematic clinical and ECG evaluation, including signal-averaged ECG (SAECG) and pharmacological provocation testing, between 2003 and 2019 were included.

RESULTS: Four patients with BrS (9%) presented with a spontaneous type 1 Brugada pattern; the remaining 39 (91%) were diagnosed following ajmaline provocation testing. Twelve BrS patients (28%) had late potentials (LP) on SAECG compared to 1 (2%) in controls (p = 0.001). LP were more common in 5 patients with a high-risk phenotype (60% vs 24%) but this was not statistically significant. Twelve patients with BrS (28%) had inferolateral early repolarisation (ER) and 2 (5%) had fractionated QRS (f-QRS), but there were no statistically-significant differences with controls in these parameters. A significant arrhythmia (non-sustained ventricular tachycardia or atrial fibrillation) was seen in 4 patients (9%).

CONCLUSIONS: This study shows a high prevalence of SAECG abnormalities in children with BrS compared with controls, but this was not significantly associated with a high-risk phenotype.

PMID:33831794 | DOI:10.1016/j.jelectrocard.2021.03.011

AIDS. 2021 Apr 6. doi: 10.1097/QAD.0000000000002900. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the effect on anthropometric, metabolic and adipose tissue parameters of switching ART-controlled persons living with HIV (PLWH) from a protease-inhibitor regimen to raltegravir/maraviroc.

DESIGN: Substudy of ROCnRAL-ANRS157 with investigation of subcutaneous abdominal adipose tissue (SCAT) biopsy at inclusion and study end.

METHODS: We performed lipoaspiration of paired SCAT samples, histology on fresh/fixed samples and examined the transcriptomic profile analyzed using Illumina microarrays after RNA extraction. Statistical analyses used Wilcoxon-paired test.

RESULTS: The patients (n = 8) were mainly male (7/8), aged (mean±SEM) 54.9 ± 1.2 years, BMI 26.1 ± 1.2 kg/m2, CD4: 699 ± 56 cells/mm3, all viral load (VL)<50 copies/mL. After a follow-up of 6 ± 0.5 months, all PLWH remained with VL<50 copies/mL. BMI, trunk and limb fat amounts were unchanged yet systemic insulin resistance increased. Adipose tissue histology was unchanged except for borderline increased adipocyte diameter (P = 0.1). Amongst the 16,094 RNA transcripts, 458 genes were up-regulated and 244 down-regulated. Analyses of the KEGG and GO databases, evaluating modifications in the main functional pathways, revealed that genes related to immune recognition/function were less expressed as were genes encoding T-cell receptor and receptor signaling pathways. The gene expression profiles indicated decreased inflammation but genes involved in adipogenesis and insulin resistance were overexpressed.

CONCLUSION: After 6 months of raltegravir/maraviroc, adipogenesis-related gene profile was enhanced in SCAT, in agreement with a tendency for increased adipocyte size. Enhanced SCAT insulin resistance-related profile was concordant with higher systemic insulin resistance. However, immune activation/inflammation profile was globally lowered. We propose that raltegravir/maraviroc might favor SCAT gain but reduce inflammation/immune activation.

PMID:33831906 | DOI:10.1097/QAD.0000000000002900

Gait Posture. 2021 Mar 26;86:278-286. doi: 10.1016/j.gaitpost.2021.03.029. Online ahead of print.

ABSTRACT

BACKGROUND: Common etiologies for post-traumatic ankle osteoarthritis are ankle fractures and chronic ankle instability. As the nature of trauma is different for these two etiologies, it might be expected that the two subtypes of post-traumatic ankle osteoarthritis would display different foot mechanics during gait.

RESEARCH QUESTION: The objective of this exploratory cross-sectional study was to compare the foot kinematics and kinetics of patients suffering from post-fracture ankle osteoarthritis with those of patients suffering from post-sprain ankle osteoarthritis.

METHODS: Twenty-nine subjects with end-stage post-traumatic ankle osteoarthritis and fifteen asymptomatic control subjects participated in this study. All patients suffered from post-traumatic ankle osteoarthritis secondary to ankle-related fracture (Group 1; n = 15) or to chronic ankle instability (Group 2; n = 14). A four-segment kinematic and kinetic foot model was used to calculate intrinsic foot joint kinematics and kinetics during gait. Vector field statistical analysis MANOVA was used to assess differences between groups for the entire three-component intrinsic foot joint angles and moments.

RESULTS: MANOVA showed significant differences between the groups. Post-hoc analyses suggested that the differences between post-fracture ankle osteoarthritis group and controls were caused by a combination of less adducted Shank-Calcaneus position and less plantarflexion at this joint. Post-hoc analyses also suggested that both pathological groups exhibited a decreased plantarflexion moment for Shank-Calcaneus, Chopart, Lisfranc joints compared to controls. Analyses of both pathological groups versus controls for power suggested lower Shank-Calcaneus and Lisfranc power generation during pre-swing phase.

SIGNIFICANCE: No significant differences were found between the two pathological groups in this exploratory study. Alterations in foot kinematics and kinetics were mainly found about the dorsi-/plantarflexion axis during the pre-swing phase of the stance phase for both pathological groups compared to controls. Observed differences were not limited to the painful ankle joint, but seem also to have affected the kinetics of the neighbouring foot joints.

PMID:33831743 | DOI:10.1016/j.gaitpost.2021.03.029

Cell Immunol. 2021 Mar 23;364:104345. doi: 10.1016/j.cellimm.2021.104345. Online ahead of print.

ABSTRACT

Previously, we generated IL233, a hybrid cytokine composed of interleukin (IL)-2 and IL-33, with better therapeutic potential than either cytokine in multiple inflammatory diseases, in part through promoting T-regulatory cells (Tregs). Here we test the potential of IL233 pretreatment in a murine model of excessive Th1 activation, the parent-into-F1 model of acute GVHD (aGVHD). Five days of IL233 pretreatment of the recipients blocked or delayed the aGVHD-linked loss of B cells as seen in either the peripheral blood (day-11) or lymph nodes (day-14). IL233 pretreatment also prevented the expansion of donor CD8 T-cells in blood and LN at day-14 and significantly reduced day-14 serum IFNγ and TNFα compared to saline treated GVHD mice although, the level of Tregs did not statistically differ between saline and IL233-treated mice. Overall, the current study provides support for the use of IL233 as a therapeutic option in excessive Th1/CD8-driven conditions.

PMID:33831754 | DOI:10.1016/j.cellimm.2021.104345

J Environ Manage. 2021 Apr 5;289:112474. doi: 10.1016/j.jenvman.2021.112474. Online ahead of print.

ABSTRACT

In this study, a sequencing batch reactor (SBR) with aerobic granular sludge (AGS) was operated with synthetic wastewater containing environmental relevant concentrations of 17β-estradiol (E2), 17α-ethinylestradiol (EE2) and sulfamethoxazole (SMX). Despite the presence of the studied PhAC, the granular fraction clearly predominated (TSS_gran/TSS ranging from 0.82 to 0.98) throughout the monitoring period, presenting aggregates with high organic fraction (VSS/TSS above 0.83) and good settling characteristics (SVI₅ ranging from 15 to 39 mL/gTSS). A principal component analysis (PCA) with quantitative image analysis (QIA) based data allowed to distinguish the different operational periods, namely with mature granules (CONT), and the E2, EE2, and SMX feeding periods. It further revealed a positive relationship between the biomass density, sludge settling ability, overall and granular biomass contents, granulation properties, granular biomass fraction and large granules fraction and size. Moreover, a discriminant analysis (DA) allowed to successfully discriminate not only the different operational periods, mainly by using the floccular apparent density, granular stratification and contents data, but also the PhAC presence in samples. The filamentous bacteria contents, sludge settling properties, settling properties stability and granular stratification, structure and contents parameters were found to be crucial for that purpose.

PMID:33831759 | DOI:10.1016/j.jenvman.2021.112474

Clin Transl Sci. 2021 Apr 8. doi: 10.1111/cts.12980. Online ahead of print.

ABSTRACT

The current success rate of a drug candidate, from the beginning of the clinical trial to receiving marketing approval, is about 10%-20%, and it has not changed during the past few decades. Therefore, pharmaceutical companies are under pressure to select one compound, among many others, with a high probability of success. The differences in drug features affect their probabilities of approval success. In this study, we examined the approval success rates of drug candidates, developed in the United States, the European Union, or Japan, by focusing on four parameters (“drug target,” “drug action,” “drug modality,” and “drug application”) and their combinations, and identified factors that conditioned the outcome of the drug development process. We obtained a total success rate of 12.8%, after evaluating 3999 compounds. Moreover, after analyzing the combinations of these parameters, the approval success rates of drugs that corresponded to the following categories-a stimulant in drug action or an enzyme in drug target and biologics (excluding monoclonal antibody) in drug modality-were high (34.1% and 31.3%, respectively). Univariate and multivariate logistic regression analyses revealed that stimulant in drug action, and “B” (blood and blood forming organs), “G” (genito-urinary system and sex), and “J” (anti-infectives for systemic use) in drug application were statistically associated with high approval success rates. We found several parameters and their combinations that affected drug approval success rates. Our results could assist pharmaceutical companies in evaluating the probability of success of their drug candidates and, thus, in efficiently conducting the clinical development process.

PMID:33831276 | DOI:10.1111/cts.12980