ABSTRACT
Background: Nervous system post-acute sequelae of COVID-19 (NS-PASC) include cognitive and mental health symptoms. To further define these, we applied a Research Domain Criteria (RDoC) approach to examine motor, positive valence (PV) and negative valence (NV) systems, and social processing data in The COVID Mind Study of NS-PASC. Method(s): NS-PASC participants (>3 months after COVID-19) referred from a NeuroCOVID Clinic and non-COVID controls from New Haven, CT and Baltimore, MD completed an RDoC test battery for cognition (language, declarative and working memory, cognitive control, perception), motor, PV, NV, and social processes. To date, 3T MRI with diffusion tensor imaging was performed in 11 NS-PASC to assess white matter integrity (global white matter fractional anisotropy [FA]) as a contributor to alterations identified on the RDoC tests. Analysis of Covariance examined group differences after adjusting for sex, race, ethnicity, age, and years of education. Result(s): 25 NS-PASC participants (age 43.4+/-11.3 yrs, 76% female, 402 days after COVID-19 symptom onset) and 29 controls (age 46.2.6+/-13.1 yrs, 66% female) completed the battery. Controls were more racially diverse and less educated than NS-PASC (43% vs. 12% Black, p=0.005;14.5 vs. 16.1 yrs of education, p< 0.05). Means and statistics for RDoC between NS-PASC and controls are shown in Table. NS-PASC performed worse in language, verbal working and declarative memory, and perception and reported greater cognitive control difficulties (e.g., behavioral inhibition, set shifting) without issues on performance-based metrics (Stroop, Trail Making Test-Part B), and had slower motor function. NS-PASC reported more NV issues including greater symptoms of depression, rumination in response to depressive mood, apathy, childhood trauma, anxiety, and perceived stress. There were no differences in PV and social processing. In a subset of NS-PASC participants who underwent MRI, there was a dynamic range of FA values with a mean of 0.509 (IQR 0.481 - 0.536). Conclusion(s): Our findings extend previous PASC studies characterizing cognitive and mental health alterations, indicating that additional RDoC assessments warrant focus, including alterations in motor and the negative valence system. In future analyses, we will examine white matter integrity as a pathophysiologic contributor to these RDoC systems.
ABSTRACT
Background: The United Nations' 2030 Sustainable Development Goals (SDGs) target an end to preventable newborn deaths and a reduction in neonatal mortality rate (< 28 d, NMR) to 12/1,000 live births for all countries. Understanding concurrent trends in country-level, multisectoral factors associated with NMR trends may illuminate opportunities for intervention strategies. Our objective was to explore country-specific trends in NMR from 1990-2019 and identify those countries which contribute to the largest percentage of neonatal deaths in order to focus efforts on reducing NMRs in those specific countries. Unfortunately, due to the COVID-19 pandemic, the 2030 SDGs have been severely impacted. Methods: We created a comprehensive global database of NMR and associated variables that were selected based on literature review and categorized into Population Health, Health Systems, Maternal, Neonatal, and Social factors from 1990 to 2019. Data were compiled from publicly available sources including UNICEF, World Bank, WHO, and OECD. Data were collected and analyzed for 195 countries. NMR trends were analyzed from 1990 to 2019 with more targeted analysis of trends in the last 2 decades from 2000 to 2019. We then performed statistical analyses using the selected variables to compare variable means using t-tests, identify bivariate associations, and generate multivariable regression models. Results: In terms of total deaths, 20 countries contributed 75% of the total 2.5 million neonatal deaths. All of these 20 countries showed decreases in NMR since 1990 (Figure 1). However, only China and Egypt accomplished the UN goal of reducing NMR to 12/1,000 live births. We compared variables associated with NMR in our 20 target countries to the remaining countries and found significant differences between the means for most variables (Table 1). Bivariate regression analyses showed statistically significant associations between NMR trends and changes over time in median income, health care spending, literacy level, maternal mortality ratio, and low birthweight rate. Ultimately the variables maternal mortality ratio change and median income change were selected for multivariable analysis based on collinearity. The multivariate regression model generated using NMR, maternal mortality ratio change, median income change resulted in an r-squared value of 0.54, explaining 54% of the variance in NMR trends. Conclusion: Since 20 countries contribute 75% of the neonatal deaths worldwide, we propose that targeting these 20 countries would have the greatest impact on global neonatal deaths. Future research will focus on identification of country specific barriers and evaluating the countries with greatest NMR improvements to propose effective focused strategies for reducing NMRs in high burden countries. The disparate impact that COVID-19 has had on countries with the highest neonatal mortality burden should be a primary focus of continued public health invention efforts, and is a specific focus of our ongoing research.
ABSTRACT
Purpose of Study Parents of infants admitted to NICUs often experience significant psychosocial stress and have higher risks for depression, anxiety, and disturbed parent-child bonding. Analyses of parental stress often use either a predominantly biomedical or qualitative approach. The current study integrates these domains, using parental demographic and psychosocial assessments, stress-related salivary biomarkers, measures of illness severity, and open-ended question interviews for a more complete assessment of parental NICU experience and stressors. We detail a novel use of theme-coded qualitative analysis of open-ended interviews to explore parents' perceptions of the NICU experience, sources of stress and well-being, and associations with stress/depression measurements. Methods Used Inclusion criteria: parents of infants admitted to a Level IV NICU born £34 weeks gestation or having a predicted length of stay >2 weeks. At weeks 1 and 6 and before discharge, we collected parental salivary cortisol and α-amylase (AM, PM) and the Edinburgh Postpartum Depression Scale, Perceived Stress Scale, and Social Provisions Scale. Infant data and the Neonatal Acute Physiology Perinatal Extension-II and Neonatal therapeutic Intervention Scoring System were recorded. Parents individually participated in recorded openended question interviews. Interviews were transcribed and annotated using qualitative content analysis based on a grounded theory approach. Investigators affixed codes (with inter-rater checks) to transcripts using an iterative approach, highlighting common phrasing and themes. Transcripts were entered into NVivo qualitative data analysis software to sort and label categories and themes. Summary of Results Results are available for 15 interviews. We identified patterns, themes, subgroup differences, and common phrasing to develop an interactive model of the complex interplay among social supports, NICU environment, COVID- 19-related stressors, and parental experience [figure]. The model facilitates evaluating multiple components which influence parental experience and clarifies parental-perceived barriers and facilitators. Voiced resiliency was compared to subjects' stress and depression salivary biomarkers and the validated scales. Conclusions Parent interviews revealed feelings of isolation, fear, and resilience among NICU parents. Textual analysis of open-ended interviews informed construction of a conceptual model describing the NICU experience. Integration of biomedical and qualitative methods more comprehensively reveals experiences of parents and points to strategies for fostering support and resilience.
ABSTRACT
Gene environment interactions (GxE) are key to better understanding PD. We are testing pesticides for their effects in the dish, and in the context of mutations in the synuclein and GBA genes that are also being analyzed in Dr Ritzs epidemiologic cohort. Our experiments will enable us to answer whether key genetic risk factors create sensitivities in patients to particular toxicants and we will ascertain whether gene-toxicant interactions play out specifically at the level of the dopamine neuron. To date, we have generated a unique set of reagents from patients with PD caused by synuclein and GBA mutations and observed differential effects to PD-linked pesticides and toxicants with respect to survival, neurite outgrowth and calcium signaling. From the PEG cohort data and leveraging agricultural pesticide application records (CA-PUR database (discussed below), 1974-2018), we have established long-term exposure profiles for over 200 widely used agricultural pesticides for 1,870 PD patients and population-based controls. Using this data for analysis, we have generated a list of 33 pesticide toxicants that are both significantly associated with PD (FDR less than 0.01) and have exposure in both alpha-syn SNPs and GBA variant carriers. This epidemiologic analysis agnostically highlighted, out of pesticides widely used agriculturally in California over the study period, the most significantly associated with PD. In synergy, the lab-based teams (Rubin and Khurana) will in the next phase of research test these epidemiologically derived pesticides in in vitro cell lines in the context of mutations in the synuclein and GBA mechanisms. Validated hits from these screens will then be used in conjunction with SNCA and GBA genetic data to assess GxE interactions with pathway relevant SNPs in the PEG study.