Whether left ventricular noncompaction (LVNC) is a distinct cardiomyopathy or a morphologic trait shared by different cardiomyopathies remains controversial. Current guidelines from professional ...organizations recommend different strategies for diagnosing and treating patients with LVNC. This state-of-the-art review discusses new insights into the basic mechanisms leading to LVNC, its clinical manifestations, treatment modalities, anatomy and pathology, embryology, genetics, epidemiology, and imaging. Three markers currently define LVNC: prominent left ventricular trabeculae, deep intertrabecular recesses, and a thin compacted layer. Although new genetic data from mice and humans supports LVNC as a distinct cardiomyopathy, evidence for LVNC as a shared morphological trait is not ruled out. Criteria supporting LVNC as a shared morphological trait may depend on consensus guidelines from the multiple professional organizations. Enhanced imaging and increased use of genetics are both predicted to significantly impact our overall understanding of the basic mechanisms causing LVNC and its optimal management.
In this study involving household contacts of persons with laboratory-confirmed Covid-19, the risk of household transmission was 40 to 50% lower among household contacts of index patients who had ...received one dose of vaccine 21 days or more before testing positive than among contacts of unvaccinated index patients.
Recent published studies have provided increasing evidence that lipoprotein(a) Lp(a) may be a potential causal, genetic, independent risk factor for cardiovascular disease (CVD). Lp(a) levels >25 ...mg/dl are present in ∼30% of Caucasians and 60% to 70% of Blacks. Lp(a) is composed of apolipoprotein B-100 and apolipoprotein (a) (apo(a). Circulating Lp(a) levels are primarily influenced by the LPA gene without significant dietary or environmental effects, mediating CVD risk throughout the patient's lifetime. Recent clinical outcomes studies, meta-analyses, and Mendelian randomization studies, in which randomization of Lp(a) levels is achieved through the random assortment of LPA gene variants thereby removing confounders, have shown that genetically determined Lp(a) levels are continuously and linearly related to risk of CVD. Currently, Lp(a) pathophysiology is not fully understood, and specifically targeted therapies to lower Lp(a) are not available. We provide a rationale for increased basic and clinical investigational efforts to further understand Lp(a) pathophysiology and assess whether reducing Lp(a) levels minimizes CVD risk. First, a detailed understanding of Lp(a) synthesis and clearance has not been realized. Second, several mechanisms of atherogenicity are known to varying extent, but the relative contributions of each are not known. Lp(a) may be atherothrombotic through its low-density lipoprotein moiety, but also through apo(a), including its ability to be retained in the vessel wall and mediate pro-inflammatory and proapoptotic effects including those potentiated by its content of oxidized phospholipids, and antifibrinolytic effects. Finally, development of specific Lp(a)-lowering agents to potently lower Lp(a) will allow testing of mechanistic hypotheses in animal models and the design of randomized clinical trials to assess reduction in CVD. A convergence of academic, scientific, pharmaceutical, and National Institutes of Health priorities and efforts can make this a reality in the next decade.
Stroke is the fifth-highest cause of death in the US and a leading cause of serious long-term disability with particularly high risk in Black individuals. Quality risk prediction algorithms, free of ...bias, are key for comprehensive prevention strategies.
To compare the performance of stroke-specific algorithms with pooled cohort equations developed for atherosclerotic cardiovascular disease for the prediction of new-onset stroke across different subgroups (race, sex, and age) and to determine the added value of novel machine learning techniques.
Retrospective cohort study on combined and harmonized data from Black and White participants of the Framingham Offspring, Atherosclerosis Risk in Communities (ARIC), Multi-Ethnic Study for Atherosclerosis (MESA), and Reasons for Geographical and Racial Differences in Stroke (REGARDS) studies (1983-2019) conducted in the US. The 62 482 participants included at baseline were at least 45 years of age and free of stroke or transient ischemic attack.
Published stroke-specific algorithms from Framingham and REGARDS (based on self-reported risk factors) as well as pooled cohort equations for atherosclerotic cardiovascular disease plus 2 newly developed machine learning algorithms.
Models were designed to estimate the 10-year risk of new-onset stroke (ischemic or hemorrhagic). Discrimination concordance index (C index) and calibration ratios of expected vs observed event rates were assessed at 10 years. Analyses were conducted by race, sex, and age groups.
The combined study sample included 62 482 participants (median age, 61 years, 54% women, and 29% Black individuals). Discrimination C indexes were not significantly different for the 2 stroke-specific models (Framingham stroke, 0.72; 95% CI, 0.72-073; REGARDS self-report, 0.73; 95% CI, 0.72-0.74) vs the pooled cohort equations (0.72; 95% CI, 0.71-0.73): differences 0.01 or less (P values >.05) in the combined sample. Significant differences in discrimination were observed by race: the C indexes were 0.76 for all 3 models in White vs 0.69 in Black women (all P values <.001) and between 0.71 and 0.72 in White men and between 0.64 and 0.66 in Black men (all P values ≤.001). When stratified by age, model discrimination was better for younger (<60 years) vs older (≥60 years) adults for both Black and White individuals. The ratios of observed to expected 10-year stroke rates were closest to 1 for the REGARDS self-report model (1.05; 95% CI, 1.00-1.09) and indicated risk overestimation for Framingham stroke (0.86; 95% CI, 0.82-0.89) and pooled cohort equations (0.74; 95% CI, 0.71-0.77). Performance did not significantly improve when novel machine learning algorithms were applied.
In this analysis of Black and White individuals without stroke or transient ischemic attack among 4 US cohorts, existing stroke-specific risk prediction models and novel machine learning techniques did not significantly improve discriminative accuracy for new-onset stroke compared with the pooled cohort equations, and the REGARDS self-report model had the best calibration. All algorithms exhibited worse discrimination in Black individuals than in White individuals, indicating the need to expand the pool of risk factors and improve modeling techniques to address observed racial disparities and improve model performance.
It is widely accepted that maternal healthcare is vital for improving maternal and neonatal mortality rates. Furthermore, the continuum of care-the integrated delivery of antenatal, delivery and ...postnatal care-has been shown to be particularly important. Sub-Saharan Africa has the highest neonatal and maternal mortality rates in the world; significant improvements in the provision and utilisation of the continuum are urgently needed, therefore the barriers preventing access need to be better understood. This study aimed to identify key factors associated with the utilisation of maternal healthcare, in the Mchinji District of Malawi.
4,244 pregnant women from the Mchinji District of Malawi were interviewed between March and December 2013. The overall utilisation of maternal healthcare was calculated by combining the use of antenatal, delivery and postnatal care into one variable-continuum of care. Univariate and multivariate logistic regressions were performed to determine the factors associated with utilisation of maternal healthcare.
Utilisation of maternal healthcare in the Mchinji District was inadequate; only 24% of women received the recommended package. Being further from a healthcare facility (OR = 0.2, 95%CI = 0.04-0.96), having at least one live child (OR = 0.87, 95%CI = 0.84-0.99), previous experience of miscarriage (OR = 0.64, 95%CI = 0.50-0.82) or abuse (OR = 0.81, 95%CI = 0.69-0.95) reduced utilisation, whereas being in the richest 20% (OR = 1.33 95%CI = 1.08-1.65), having a planned pregnancy (OR = 1.3, 95%CI = 1.11-1.51) or more control over decisions (OR = 1.09, 95%CI = 0.80-1.49) increased utilisation.
Seven groups of women were identified as having an increased risk of low utilisation of maternal healthcare; women living >5km from a healthcare facility, within the poorest socio-economic group, experiencing an unplanned pregnancy, with at least one live child, experience of a previous miscarriage, no control over their healthcare decisions or experience of abuse. Policy makers should pay extra attention to these high-risk groups when designing and delivering strategies to improve maternal healthcare utilisation.
Introduction
Previous systematic reviews concluded that rigorous research on the relationships between pregnancy intentions and pregnancy outcomes is limited. They further noted that most studies ...were conducted in high-income countries and had methodological limitations. We aim to assess the current evidence base for the relationship between pregnancy intention and miscarriage, stillbirth, low birthweight (LBW) and neonatal mortality. In March 2015 Embase, PubMed, Scopus and PsychInfo were searched for studies investigating the relationship between pregnancy intention and the outcomes of interest.
Methods
Studies published since 1975 and in English, French or Spanish were included. Two reviewers screened titles and abstracts, read the full text of identified articles and extracted data. Meta-analyses were conducted where possible.
Results
Thirty-seven studies assessing the relationships between pregnancy intention and LBW were identified. A meta-analysis of 17 of these studies found that unintended pregnancies are associated with 1.41 times greater odds of having a LBW baby (95%CI 1.31, 1.51). Eight studies looking at miscarriage, stillbirth or neonatal death were found. The limited data concerning pregnancy loss and neonatal mortality precluded meta-analysis but suggest these outcomes may be more common in unintended pregnancies.
Discussion
While there seems to be an increased risk of adverse pregnancy outcome in unintended pregnancies, there has been little improvement in either the quantity of evidence from low-income countries or in the quality of evidence generally. Longitudinal studies of pregnancy intention and pregnancy outcome, where pregnancy intention is assessed prospectively with a validated measure and where analyses include confounding or mediating factors, are required in both high- and low-income countries.
Despite growing evidence of pregnancy preparation benefits, there is little knowledge on how women in developing countries prepare for pregnancy and factors influencing their preparedness for ...pregnancy. Here, we determine how women in Malawi prepare for pregnancy and factors associated with pregnancy preparation.
We used data from a previous cohort study comprising 4,244 pregnant mothers, recruited between March and December 2013 in Mchinji district, Malawi. Associations of pregnancy preparation with socio-demographic and obstetric factors were tested for using mixed effects ordinal regression, with the likelihood ratio and Wald's tests used for variable selection and independently testing the associations.
Most mothers (63.9%) did not take any action to prepare for their pregnancies. For those who did (36.1%), eating more healthily (71.9%) and saving money (42.8%) were the most common forms of preparation. Mothers who were married (adjusted odds-ratio (AOR 7.77 (95% CI 5.31, 11.25) or with no or fewer living children were more likely to prepare for pregnancy (AOR 4.71, 95% CI 2.89,7.61. Mothers with a period of two to three years (AOR 2.51, 95% CI 1.47, 4.22) or at least three years (AOR 3.67, 95%CI 2.18, 6.23) between pregnancies were more likely to prepare for pregnancy than women with first pregnancy or shorter intervals. On the other hand, teenage and older (≥ 35 years old) mothers were less likely to prepare for pregnancy (AOR 0.61, 95%CI 0.47, 0.80) and AOR 0.49 95%CI 0.33, 0.73, respectively).
While preconception care may not be formally available in Malawi, our study has revealed that over a third of mothers took some action to prepare for pregnancy before conception. Although this leaves around two thirds of women who did not make any form of pregnancy preparation, our findings form a basis for future research and development of a preconception care package that suits the Malawian context.
Cardiovascular disease is a leading cause of death worldwide and accounts for >17.3 million deaths per year, with an estimated increase in incidence to 23.6 million by 2030. Cardiovascular death ...represents 31% of all global deaths—with stroke, heart attack, and ruptured aneurysms predominantly contributing to these high mortality rates. A key risk factor for cardiovascular disease is hypertension. Although treatment or reduction in hypertension can prevent the onset of cardiovascular events, existing therapies are only partially effective. A key pathological hallmark of hypertension is increased peripheral vascular resistance because of structural and functional changes in large (conductive) and small (resistance) arteries. In this review, we discuss the clinical implications of vascular remodeling, compare the differences between vascular smooth muscle cell remodeling in conductive and resistance arteries, discuss the genetic factors associated with vascular smooth muscle cell function in hypertensive patients, and provide a prospective assessment of current and future research and pharmacological targets for the treatment of hypertension.
Proteins bind the surfaces of nanoparticles, and biological materials in general, immediately upon introduction of the materials into a physiological environment. The further biological response of ...the body is influenced by the nanoparticle–protein complex. The nanoparticle's composition and surface chemistry dictate the extent and specificity of protein binding. Protein binding is one of the key elements that affects biodistribution of the nanoparticles throughout the body. Here we review recent research on nanoparticle physicochemical properties important for protein binding, techniques for isolation and identification of nanoparticle-bound proteins, and how these proteins can influence particle biodistribution and biocompatibility. Understanding the nanoparticle–protein complex is necessary for control and manipulation of protein binding, and allows for improved engineering of nanoparticles with favorable bioavailability and biodistribution.
In 2012 there were around 85 million unintended pregnancies globally. Unintended pregnancies unnecessarily expose women to the risks associated with pregnancy, unsafe abortion and childbirth, thereby ...contributing to maternal mortality and morbidity. Studies have identified a range of potential determinants of unplanned pregnancy but have used varying methodologies, measures of pregnancy intention and analysis techniques. Consequently there are many contradictions in their findings. Identifying women at risk of unplanned pregnancy is important as this information can be used to help with designing and targeting interventions and developing preventative policies.
4,244 pregnant women from Mchinji District, Malawi were interviewed at home between March and December 2013. They were asked about their pregnancy intention using the validated Chichewa version of the London Measure of Unplanned Pregnancy, as well as their socio-demographics and obstetric and psychiatric history. A conceptual hierarchical model of the determinants of pregnancy intention was developed and used to inform the analysis. Multiple random effects linear regression was used to explore the ways in which factors determine pregnancy intention leading to the identification of women at risk of unplanned pregnancies.
44.4% of pregnancies were planned. On univariate analyses pregnancy intention was associated with mother and father's age and education, marital status, number of live children, birth interval, socio-economic status, intimate partner violence and previous depression all at p<0.001. Multiple linear regression analysis found that increasing socio-economic status is associated with increasing pregnancy intention but its effect is mediated through other factors in the model. Socio-demographic factors of importance were marital status, which was the factor in the model that had the largest effect on pregnancy intention, partner's age and mother's education level. The effect of mother's education level was mediated by maternal reproductive characteristics. Previous depression, abuse in the last year or sexual abuse, younger age, increasing number of children and short birth intervals were all associated with lower pregnancy intention having controlled for all other factors in the model. This suggests that women in Mchinji District who are either young, unmarried women having their first pregnancy, or older, married women who have completed their desired family size or recently given birth, or women who have experienced depression, abuse in the last year or sexual abuse are at higher risk of unintended pregnancies.
A simple measure of pregnancy intention with well-established psychometric properties was used to show the distribution of pregnancy planning among women from a poor rural population and to identify those women at higher risk of unintended pregnancy. An analysis informed by a conceptual hierarchical model shed light on the pathways that lead from socio-demographic determinants to pregnancy intention. This information can be used to target family planning services to those most at risk of unplanned pregnancies, particularly women with a history of depression or who are experiencing intimate partner violence.
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