Forward Model Selection Research Articles

Ultrasound biomicroscopy in dogs suggests postoperative ocular hypertension may be associated with ciliary cleft changes related to cataract surgery.

To determine whether novel pre- and postsurgical ultrasound biomicroscopy (UBM) measurements of the canine ciliary cleft (CC) are associated with postoperative ocular hypertension (POH) following cataract surgery and to explore the relationship between intraocular pressure and CC UBM measurements. Following pharmacologic mydriasis, UBM images were obtained from 31 client-owned dogs before elective cataract surgery, immediately postsurgery, and 4 to 6 hours following surgery or while experiencing POH ≥ 25 mm Hg. Presurgery and the pre- to postsurgery change in CC measurements were assessed for association with POH using individual mixed-effects logistic regression models and forward variable selection models. Linear mixed-effects models were used to evaluate the relationship of intraocular pressure to UBM measurements within the same eye across multiple time points. Presurgical measurements were not predictive of POH development. An increase in pectinate ligament distance and CC area from presurgical baseline to immediate postsurgical measurement was associated with reduced odds of developing POH, while increasing CC length (from apex to mid point on the pectinate ligament) from pre- to postsurgery and immature cataracts was associated with increased odds of POH. The change in CC morphology following cataract surgery appears more impactful in the development of POH than individual variations in presurgery CC measurements. Several changes in the CC dimensions following surgery appear associated with POH risk. This understanding of a potential mechanism of POH development opens new avenues for researching preventative measures associated with modifying surgical techniques to influence CC morphology following cataract surgery.

Effect of Open Market Operations on Income Inequality

Inequality is particularly relevant for public debates on the disaggregate implications of economic policies since they might have distinct effects across different segments of the population. Impact of monetary easing on inequality have recently attracted increasing attention especially in developing countries. This article examined the effect of open market operations on income inequality in Kenya. A quantitative research design method was adopted. The study utilized a quantitative cross-sectional data from the Kenya Continuous Household Survey Programme (KCHSP) for the years 2020 and 2021. Stepwise regression, forward selection model was executed with a threshold of 0.2. Further, the study was supported by Permanent Income Hypothesis, Kuznets Hypothesis and the modernization theory. Income inequality, measured by the Gini coefficient, was the dependent variable. Open market operations (repo, and reverse repo) was the independent variable in the model. The male headed households had a Gini coefficient of 0.58 while a Gini coefficient of 0.59 was attributed to female headed households, across the 47 counties. The results showed that open market operations (reverse repo) had a coefficient of 0.022, p=0.026< 0.05 which was positive and statistically significant at 5% level. The findings indicate that in order to effectively manage income inequality in the country, policymakers should adopt an interdisciplinary and multifaceted approach. This approach should take into account the differential impacts of various policy instruments on income distribution, with a particular focus on demographic segmentation. Additionally, policymakers should combine careful adjustments to monetary policy with targeted social and fiscal measures. These measures should be continuously informed by rigorous data analysis, with the aim of fostering a more inclusive and equitable economy.

Estimating highest capacity propulsion performance using backward-directed force during walking evaluation for individuals with acquired brain injury

There are over 5.3 million Americans who face acquired brain injury (ABI)-related disability as well as almost 800,000 who suffer from stroke each year. To improve mobility and quality of life, rehabilitation professionals often focus on walking recovery soon after hospital discharge for ABI. Reduced propulsion capacity (force output of the lower limbs to counteract ground reaction forces) negatively impacts walking ability and complicates recovery during rehabilitation for brain injured people. We describe a method, using backward-directed resistance (BDR) in a robotic-based treadmill device, to allow measurement of maximum walking propulsion force (MWPF) that is not otherwise possible during overground walking assessment. Our objective was to test the construct validity of a maximum walking propulsion force (MWPF) measure that reflects a person’s propulsive strength against applied BDR, while walking on a robotic treadmill-based device for participants with acquired brain injury (ABI). Our study enrolled 14 participants with ABI at an in inpatient rehabilitation in Galveston, TX from 8/1/21 − 4/31/22. The range of weight-adjusted MWPF was 2.6–27.1% body weight (%BW), mean 16.5 ± 8.4%BW, reflecting a wide range of propulsive force capability. The strongest correlation with overground tests was between the 6-minute walk test (6-MWT) distance and the MWPF values (r = 0.83, p < 0.001) with moderate correlations between the 10-meter walk tests at comfortable (CWS) and fast speeds (FWS). The Five Times Sit-to-Stand (used as a standard clinical measure of functional lower extremity strength) and MWPF tests were poorly correlated (r = 0.26, p = 0.4). Forward model selection included 6-MWT distance, age, and overground CWS as significant partial predictors of MWPF. We conclude that this novel MWPF measure is a valid representation of maximum propulsive force effort during walking for people post-ABI. Additional research could help determine the impact of interventions designed to increase propulsive force generation during rehabilitation training to improve overground walking performance.

Bikeshare–Metrorail Integration in Washington, D.C.: What are the Characteristics of Neighborhoods that Encourage Capital Bikeshare Trips to and from the Metrorail?

Bikeshare has gained popularity worldwide and can serve as a first mile/last mile feeder for public transport. In many bikeshare systems, docking stations near a metrorail station are popular trip origins and destinations and bikeshare can help increase the ridership of the metrorail system as well. The goal of this study is to identify the determinants of bikeshare trips between neighborhood stations and bikeshare docking stations near the metrorail in Washington, D.C. For this study, we divided the bikeshare stations in Washington, D.C., into two categories: docking stations near a metrorail station (defined as bikeshare docking stations within a quarter mile radius of metrorail stations) and neighborhood stations (bikeshare docking stations outside the quarter mile radius of metrorail stations). We used two stepwise linear regression models of bikeshare trips between neighborhoods and metrorail stations stratifying the analysis by the determinants of neighborhood docking stations into four categories: socio-demographic conditions, transportation related, land use, and points of interests. In the backward elimination model, expanding the bike trail supply by an additional 100 m was associated with an increase in 70 annual bikeshare trips between a neighborhood station and a docking station near the metrorail. The forward selection model showed that a 1% increase in the poverty rate of the neighborhood stations was associated with 52 fewer annual such bikeshare trips. This study also found that adding bikeshare docking stations near national parks and neighborhoods with higher population density can promote bikeshare that starts/ends near metrorail stations.

Maternal satisfaction with reduced postnatal length of stay in Brussels: evidence from the KOZI&Home program

BackgroundReducing the length of stay (LOS) after childbirth is a trend, including cost savings, a more family-centered approach and lower risk for nosocomial infection. Evaluating the impact of reduced LOS is important to improve the outcomes of care, which include maternal satisfaction. The aim of this study was to compare the maternal satisfaction, before and after the reduced LOS.MethodsThis study was conducted in the University Hospital Brussels, before and after implementing the KOZI&Home program (intervention). This KOZI&Home program consisted of a reduced length of stay of at least one day for both vaginal delivery and caesarean section. It also included three extra antenatal visits with the midwife, preparing for discharge and postnatal home care by an independent midwife. Women completed a questionnaire, including the Maternity Satisfaction Questionnaire (MSQ) and Home Satisfaction Questionnaire (HSQ), respectively at discharge and two weeks postpartum. Satisfaction was split into five dimensions: ‘Midwives time investment’, ‘Provision of information’, ‘Physical environment’, ‘Privacy’ and ‘Readiness for discharge’. A combination of forward and backward model selection (both directions) was used for statistical analysis.ResultsIn total, 585 women were included in this study. 332 women in the non-intervention group and 253 women in the intervention group. Satisfaction with ‘provision of information’ at home had a higher mean score of 4.47/5 in the intervention group versus 4.08/5 in the non-intervention group (p < 0.001). Women in the KOZI&Home group were more satisfied regarding ‘privacy at home’ (mean 4.74/5 versus 4.48/5) (p < 0.001) and ‘readiness for discharge’ (p = 0.02).ConclusionThe intervention was associated with a higher score in some of dimensions of satisfaction. Our study concludes that this integrated care program is acceptable for postpartum women and associated with some favourable outcomes.

Model selection for component network meta-analysis in connected and disconnected networks: a simulation study

BackgroundNetwork meta-analysis (NMA) allows estimating and ranking the effects of several interventions for a clinical condition. Component network meta-analysis (CNMA) is an extension of NMA which considers the individual components of multicomponent interventions. CNMA allows to “reconnect” a disconnected network with common components in subnetworks. An additive CNMA assumes that component effects are additive. This assumption can be relaxed by including interaction terms in the CNMA.MethodsWe evaluate a forward model selection strategy for component network meta-analysis to relax the additivity assumption that can be used in connected or disconnected networks. In addition, we describe a procedure to create disconnected networks in order to evaluate the properties of the model selection in connected and disconnected networks. We apply the methods to simulated data and a Cochrane review on interventions for postoperative nausea and vomiting in adults after general anaesthesia. Model performance is compared using average mean squared errors and coverage probabilities.ResultsCNMA models provide good performance for connected networks and can be an alternative to standard NMA if additivity holds. For disconnected networks, we recommend to use additive CNMA only if strong clinical arguments for additivity exist.ConclusionsCNMA methods are feasible for connected networks but questionable for disconnected networks.

Addressing HIV Misconceptions among Heterosexual Black Men and Communities in Ontario

Black males accounted for 19.7% of all the new HIV diagnoses in Canada in 2020, yet Black people make up only 4.26% of the population. Persistent misconceptions about modes of HIV transmission need to be addressed to reduce the relatively high HIV prevalence among Black men. We described the HIV misconceptions held by some HBM in Ontario. We also identified the social determinants that are protective versus risk factors for HIV misconceptions among heterosexual Black men (HBM) in Ontario with a view to building evidence-based strategies for strengthening HIV prevention and stigma reduction among HBM and their communities in Ontario. We report quantitative findings of the weSpeak study carried out among HBM in four cities (Ottawa, Toronto, London, and Windsor) in Ontario. Sample size was 866 and sub-samples were: Ottawa (n = 210), Toronto (n = 343), London (n = 157), and Windsor (n = 156). Data were collected with survey questionnaire. The outcome variable, HIV misconception score ranging from 1 to 18, was measured by the number of statements on the HIV Knowledge Questionnaire with incorrect answers. We included three categories of independent variables in the analysis based on a stepwise and forward model selection approach. The variable categories include (i) sociodemographic background; (ii) personalised psychosocial attributes (levels of HIV misconceptions, negative condom attitude, age at sexual debut, and resilience); and (iii) socially ascribed psychosocial experiences (everyday discrimination and pro-community attitudes). After preliminary univariate and bivariate analyses, we used a hierarchical linear regression model (HLM) to predict levels of HIV misconceptions while controlling for the effect of the city of residence. More than 50% of participants in all study sites were aged 20-49 years, married, and have undergone a college or university undergraduate education. Yet, a significant proportion (27.2%) held varying levels of misconceptions about HIV. In those with misconceptions, the two most common misconceptions were: (i) people are likely to get HIV by deep kissing, putting their tongue in their partner's mouth, if their partner has HIV (40.1%); and (ii) taking a test for HIV one week after having sex will tell a person if she or he has HIV (31.6%). Discrimination (β = 0.23, p < 0.05, 95% CI = 0.01, 0.46), negative condom attitudes (β = 0.07, p < 0.05, 95% CI = 0.01, 0.12), and sexual debut at an older age (β = 0.06, p < 0.05, 95% CI = 0.01, 1) were associated with more HIV misconceptions. Being born in Canada (β = -0.96, p < 0.05, 95% CI = -1.8, -0.12), higher education (β = -0.37, p < 0.05, 95% CI = -0.52, -0.21), and being more resilient (β = -0.04, p < 0.05, 95% CI = -0.08, -0.01) were associated with fewer HIV misconceptions. HIV misconceptions are still common, especially among HBM. These misconceptions are associated with structural and behavioural factors. We recommend structural and policy-driven interventions that promote more accessible and equity-driven healthcare, education, and social integration of HBM in Ontario. We also recommend building capacity for collective resilience and critical health and racial literacy as well as creating culturally safe spaces for intergenerational dialogues among HBM in their communities.

The Effect of Body Mass Index and Residence in Food Priority Areas on Patterns-of-Care and Cancer Outcomes in Patients With Stage III Non-Small Cell Lung Cancer

Patients living in food priority areas (FPAs), where access to healthy meals is challenging, may be at greater risk of nutritional deficits, leading to poorer cancer outcomes. Currently, there are no published data analyzing how FPAs affect patterns-of-care or outcomes for patients with locally advanced non-small cell lung cancer (NSCLC). We aimed to analyze the effect of residing in an FPA on treatments rendered and cancer outcomes in patients with stage III NSCLC treated at a single institution. This is a retrospective study of 573 patients with locally advanced NSCLC consecutively treated from January 2000 to January 2020. χ2 and Mann-Whitney U tests were performed to determine differences between select variables. Kaplan-Meier analysis and Cox proportional hazard models were used to analyze overall survival (OS) and freedom from recurrence. Cox regression with forward model selection was used for multivariate analysis. Thirty-two percent of patients resided in an FPA (n=183) and were more likely to self-identify as Black (P < .0001), single (P < .001), <60 years of age (P=.001), and uninsured (P < .0001), with a lower median income (P < .001). Patients in FPAs also had lower mean pre-chemoradiation (CRT) albumin (P=.002), lower pre-CRT body mass index (BMI) (P=.026), and were less likely to receive trimodality therapy (P ≤ .001) compared with patients not living in FPAs. There was no difference in OS or freedom from recurrence between the 2 cohorts. However, in patients with a normal BMI, either pre-CRT (median OS, 18.4 vs 25.0 months; P=.005) or after CRT (15.1 vs 28.1 months, P=.002), residing in an FPA resulted in an OS detriment. We demonstrated a clear socioeconomic divide in our patient population with stage III NSCLC, where residing in FPAs was associated with less-aggressive therapy and an OS detriment for patients with a normal-weight BMI. We are currently conducting a prospective study characterizing the nutritional needs of patients, particularly those who live in FPAs.

1169. Derivation And Validation of an International Clinical Prognostication Model for 28-day Sepsis Mortality.

Abstract Background Survival prediction models have largely been derived and validated only in high-resource Western countries or in single center studies. We sought to create a prediction model for 28-day mortality using laboratory and physiologic parameters from 3 international sepsis cohorts and externally validated the model. Methods During 2014 to 2021, adult hospitalized patients with suspected infection were enrolled in Durham, United States (N=180) and those with suspected infection and ≥2 SIRS (Systemic Inflammatory Response Syndrome) criteria in Takeo, Cambodia (N=200), and Kumasi, Ghana (N=187). Twenty-five clinical laboratory and physiologic parameters were candidate covariates and sepsis screening scores included as comparators. First, bivariate Cox regression models were performed to determine risk of individual parameters. Then, a 10-fold cross-validated forward stepwise model selection technique was used to eliminate nonsignificant variables using a p-value &amp;lt; 0.10 and the cross-validated C-statistic was estimated. Lastly, this model was applied to an external cohort of hospitalized adults with suspected infection and ≥2 SIRS in Fort Portal, Uganda (N=331 with 9.3% 28-day mortality). Results Among 567 participants, overall mortality was 16.4% at 28-days. Mortality rate highest in Ghana (31.0%), followed by Cambodia (11.0%) and the United States (7.2%). Bivariate analyses identified hypernatremia ( &amp;gt;145 mEq/L) being associated with the highest risk of death (hazard ratio: 7.42; 95% CI: 3.65 to 15.10; Figure 1). On multivariable analysis, a 28-day mortality model including mean arterial pressure, Glasgow Coma score, blood sodium, lactate, and blood urea nitrogen (Table 1) resulted in a 10-fold cross-validated C-statistic of 0.80 (95% CI: 0.61 to 0.88). This model predicted mortality accurately in the validation cohort with a C-statistic of 0.74 (95%CI: 0.69 to 0.79). Figure 1.Forest plot for bivariate analyses for one month survival across United States, Cambodia, and Ghana cohorts. Conclusion Hypotension, altered mental status, serum sodium, serum BUN, and plasma lactate accurately identified risk of death by 28-days among those with suspected sepsis in 3 international derivation cohorts and in a validation cohort in Uganda. Our findings emphasize the importance of clinical laboratory results for sepsis risk stratification. Disclosures Ephraim L. Tsalik, MD PhD, Danaher Diagnostics, Predigen, and Biomeme: In the past 3 years, I have had held equity and consulted for Predigen and Biomeme. Currently, I am an employee of Danaher Diagnostics. Christopher W. Woods, MD MPH, Predigen, Inc: Co-founder.

The Impact of Body Mass Index and Residence in Food Priority Areas on Patterns-of-Care and Cancer Outcomes in Patients with Stage III Non-Small Cell Lung Cancer

<h3>Purpose/Objective(s)</h3> Nutritional deficiencies have been linked to poor prognosis in multiple cancer sites. Patients living in food priority areas (FPAs) where access to healthy meals is scarce may be at higher risk of nutritional deficits, leading to poor cancer outcomes. Currently, there is no published data analyzing how FPA residence impacts treatments rendered or outcomes for patients with locally advanced non-small cell lung cancer (LA-NSCLC). We aim to characterize socioeconomic and cancer demographics of LA- NSCLC patients living in zip code-designated FPAs treated with curative intent at a single institution. We hypothesize that living in a FPA will impact treatments rendered, patterns of failure, and cancer outcomes. <h3>Materials/Methods</h3> This is an IRB-approved retrospective study of 573 LA-NSCLC patients curatively treated January 2000-January 2020. Chi-square tests were done to compare variables stratified by residence in FPAs. Mann-Whitney U-test was used to compare differences between continuous variables. Kaplan-Meier analysis and cox proportional hazard models were used to analyze overall survival (OS) and freedom from recurrence (FFR) for whole cohort and stratified by BMI. Cox regression with forward model selection was used for multivariate analysis (MVA). <h3>Results</h3> Of the 32% of patients living in FPAs (N=183), more were black (80%, p<0.0001), single (p<0.001), <60yo (p=0.001), uninsured (p< 0.0001), and had a lower median income (p< 0.001). Patients in FPAs had lower mean pre-chemoradiation (CRT) albumin (p=.002) and pre-CRT BMI (p= 0.026) and were less likely to receive trimodality therapy (p=<0.001) or consolidative immunotherapy (p=0.012). There was no difference in OS (21.8m vs. 26.2m, p=0.207) or FFR (11.2m vs 11.3m, p=0.739) between FPA vs No FPA groups. In the subset with pre- and post-CRT normal BMI, there was a significant difference in OS for patients living in an FPA (Median OS 18.4m vs 25.0m, p=0.005 and 15.1m vs. 28.1m, p=0.002; respectively) but no difference in FFR (11.0m in pre (p=0.463) and post-CRT (p=0.526)) There was no significant difference in OS or FFR for obese, underweight, or overweight patients. In all patients, nutritional aspects predictive of OS on MVA were pre-CRT albumin (HR 0.753, p=0.010) and post-CRT BMI (Obese as REF; Underweight: HR 1.737, p=0.043). In patients with post-CRT normal BMI (N=152), living in a FPA (HR 1.888, p=0.008) and pre-CRT albumin (HR 0.645, p=0.004) were predictors of OS on MVA. <h3>Conclusion</h3> In this institutional analysis examining impact of FPAs in patients with LA- NSCLC, we demonstrate a socioeconomic divide in this population, where residing in FPAs reflects distinct patient demographics and receipt of less aggressive therapy. Patients with normal BMI before therapy and particularly after CRT had worse OS if living in a FPA but there was no difference in FFR in this group. To overcome limitations of a retrospective analysis, we are currently characterizing nutritional needs of our patients in a prospective study.

A transcriptomic map of EGFR-induced epithelial-to-mesenchymal transition identifies prognostic and therapeutic targets for head and neck cancer

BackgroundEpidermal growth factor receptor (EGFR) is both a driver oncogene and a therapeutic target in advanced head and neck squamous cell carcinoma (HNSCC). However, response to EGFR treatment is inconsistent and lacks markers for treatment prediction. This study investigated EGFR-induced epithelial-to-mesenchymal transition (EMT) as a central parameter in tumor progression and identified novel prognostic and therapeutic targets, and a candidate predictive marker for EGFR therapy response.MethodsTranscriptomic profiles were analyzed by RNA sequencing (RNA-seq) following EGFR-mediated EMT in responsive human HNSCC cell lines. Exclusive genes were extracted via differentially expressed genes (DEGs) and a risk score was determined through forward feature selection and Cox regression models in HNSCC cohorts. Functional characterization of selected prognostic genes was conducted in 2D and 3D cellular models, and findings were validated by immunohistochemistry in primary HNSCC.ResultsAn EGFR-mediated EMT gene signature composed of n = 171 genes was identified in responsive cell lines and transferred to the TCGA-HNSCC cohort. A 5-gene risk score comprising DDIT4, FADD, ITGB4, NCEH1, and TIMP1 prognosticated overall survival (OS) in TCGA and was confirmed in independent HNSCC cohorts. The EGFR-mediated EMT signature was distinct from EMT hallmark and partial EMT (pEMT) meta-programs with a differing enrichment pattern in single malignant cells. Molecular characterization showed that ITGB4 was upregulated in primary tumors and metastases compared to normal mucosa and correlated with EGFR/MAPK activity in tumor bulk and single malignant cells. Preferential localization of ITGB4 together with its ligand laminin 5 at tumor-stroma interfaces correlated with increased tumor budding in primary HNSCC tissue sections. In vitro, ITGB4 knock-down reduced EGFR-mediated migration and invasion and ITGB4-antagonizing antibody ASC8 impaired 2D and 3D invasion. Furthermore, a logistic regression model defined ITGB4 as a predictive marker of progression-free survival in response to Cetuximab in recurrent metastatic HNSCC patients.ConclusionsEGFR-mediated EMT conveyed through MAPK activation contributes to HNSCC progression upon induction of migration and invasion. A 5-gene risk score based on a novel EGFR-mediated EMT signature prognosticated survival of HNSCC patients and determined ITGB4 as potential therapeutic and predictive target in patients with strong EGFR-mediated EMT.

Use and perceived usefulness of a just-in-time resonance breathing intervention adjunct for substance use disorder: Contextual and physiological predictors.

Craving for alcohol and other drugs is often described as a momentary hyperarousal state that interferes with one's ability to use top-down strategies. As such, it may be best interrupted ‘in the moment' through bottom-up modulation. We recently reported that episodic resonance paced breathing (eRPB) delivered via mobile phone app as an add-on to outpatient treatment for substance use disorder (SUD) was effective at dampening craving over the course of an 8-week intervention (NCT#02579317). However, not all participants engaged with the eRPB app and there was high intra- and inter-individual variability in weekly ratings of usefulness. Here we examined baseline demographic, physiological, and psychiatric measures as well as time-varying exposure to positive, negative, and temptation craving triggers as predictors of frequency of eRPB app use and ratings of usefulness. Seventy-seven outpatient women were randomized to an eRPB (0.1 Hz) or a faster paced breathing sham (0.23 Hz) condition. Baseline measures were assessed within the first 3 weeks of treatment entry prior to randomization. App use frequency, ratings of usefulness, and trigger exposure were measured weekly throughout the intervention. Variables were entered into marginal means models with forward stepwise model selection and examined as predictors of use and usefulness. Frequent app use was associated with a lifetime alcohol use disorder (AUD) diagnosis (p = 0.026), higher ratings of usefulness (p < 0.001), and fewer exposures to positive triggers (e.g., celebration, socialization; p < 0.001). There was a trend-level association between frequency of app use and greater cardiovascular capacity at baseline (p = 0.088). Higher ratings of usefulness were associated with greater exposure to negative triggers (e.g,. loneliness, frustration; p < 0.001) and parasympathetic dysregulation at baseline (p = 0.05). A positive relationship between app use frequency and ratings of usefulness was present only in the eRPB group (p = 0.045). Matching ideal candidates and moments to an arousal modulation anti-craving intervention can help streamline screening and implementation of eRPB in the treatment of SUD.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT02579317, identifier NCT02579317.

Psychological distress reported by healthcare workers in Saudi Arabia during the COVID-19 pandemic: A cross-sectional study.

IntroductionFew studies have considered the impact of COVID-19 on the mental health of healthcare workers (HCWs) in the Kingdom of Saudi Arabia (KSA). We estimated the prevalence and severity of psychological distress and characterized predisposing risk factors among HCWs in KSA during the COVID-19 pandemic.MethodsWe conducted a cross-sectional online survey of 1,985 HCWs from 6 hospitals across the country designated with caring for COVID-19 patients between April 16 and June 21, 2020. Our data analysis was performed using logistic regressions. Ordered logistic regressions were also performed using forward stepwise model selection to explore the effects of risk factors on psychological distress.ResultsThe prevalence of psychological distress reported by HCWs in KSA was high, ranging from mild-moderate to severe in severity. Younger HCWs, women, those in contact with COVID-19 patients, and those who either had loved ones affected or who were themselves affected by COVID-19 were the most at-risk of psychological distress. Risk factors such as insomnia, loneliness, fear of transmission, and separation from loved ones most significantly predicted elevated levels of distress among HCWs.ConclusionsIncreasing psychological distress was commonly reported by HCWs during the early months of COVID-19 pandemic in KSA. Public health policy makers and mental health professionals must give special attention to risk factors that predispose HCWs in KSA to psychological distress.

162-LB: Cardiovascular Outcomes in People with Type 2 Diabetes and Acute Coronary Syndrome—The ELIXA Biomarker Study

Adding novel protein biomarkers to routine clinical risk factors may identify people with type 2 diabetes and acute coronary syndrome who are at highest risk for cardiovascular (CV) outcomes and death. Methods: Bio-banked baseline serum from 5128 of 6069 ELIXA (Evaluating Lixisenatide in Acute Coronary Syndrome) trial (NCT 01147250) participants was analyzed to identify independent risk factors for incident major adverse CV events (MACE, defined as a nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) , and death. A multiplex analysis of 1.8 ml of serum measured the concentration of 49 proteins. Forward-selection Cox models that identified proteins that independently predicted these outcomes were compared to previously validated biomarkers identified in the Outcomes Reduction with an Initial Glargine Intervention (ORIGIN) trial data (NCT00069784) . Results: Forty-two proteins were analyzed in 4957 participants who had 630 (12.7%) MACE outcomes and 349 (7.0%) deaths during a median follow-up period of 2.1 years. When added to clinical risk factors, the independent hazard ratios (HR; 95% confidence intervals) of MACE per standard deviation (SD) were NT-proBNP (1.54; 1,41, 1.68) , osteoprotegerin (1.18; 1.08, 1.30) and trefoil factor 3 (1.18, 1.08, 1.29) . HRs per SD for death were NT-proBNP (2.01; 1.78, 2.29) , osteoprotegerin (1.34; 1.18, 2.52) and angiopoietin-2 (1.28; 1.15, 1.44) . C statistics for MACE and death were 0.70 (0,68, 0.72) and 0.79 (0.76, 0.81) respectively compared to 0.63 (0.61, 0.65) and 0.66 (0.63, 0.69) for clinical variables alone. These proteins had all been previously identified and validated in ORIGIN. Notably, NT-proBNP alone plus clinical risk factors yielded C statistics of 0.69 (0.67, 0.71) and 0.78 (0.75, 0.80) for MACE and death respectively. Conclusion: NT-proBNP and other proteins independently predict CV outcomes in people with type 2 diabetes following acute coronary syndrome. Adding other biomarkers only marginally increased NT-proBNP's prognostic value. Disclosure H. C. Gerstein: Advisory Panel; Abbott, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Novo Nordisk, Pfizer Inc., Sanofi, Viatris Inc., Consultant; Kowa Company, Ltd., Other Relationship; DKSH, Eli Lilly and Company, Sanofi, Zuellig Pharma Holdings Pte. Ltd., Research Support; AstraZeneca, Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk, Sanofi. S. Hess: Employee; Sanofi. B. Claggett: Consultant; Amgen Inc., Biogen, Cardurion, Corvia, MyoKardia, Novartis AG. J. Tardif: Consultant; AstraZeneca, DalCor Pharmaceuticals, HLS Therapeutics Inc., Pendopharm, Other Relationship; DalCor Pharmaceuticals, Research Support; Amarin Corporation, AstraZeneca, Ceapro Inc., DalCor Pharmaceuticals, ESPERION Therapeutics, Inc., Ionis Pharmaceuticals, Novartis Pharmaceuticals Corporation, Pfizer Inc., REGENXBIO Inc., Sanofi. M. A. Pfeffer: Consultant; AstraZeneca, Boehringer Ingelheim and Eli Lilly Alliance, Corvidia Therapeutics, GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Peerbridge, Sanofi, Other Relationship; DalCor Pharmaceuticals, National Heart, Lung, and Blood Institute, Research Support; Novartis Pharmaceuticals Corporation. Funding Sanofi

Brain differential gene expression and blood cross-validation of a molecular signature of patients with major depressive disorder.

IntroductionThe agreement between clinicians diagnosing major depressive disorder (MDD) is poor. The objective of this study was to identify a reproducible and robust gene expression marker capable of differentiating MDD from healthy control (HC) subjects.Materials and methodsBrain and blood gene expression datasets were searched, which included subjects with MDD and HC. The largest database including different areas of brain samples (GSE80655) was used to identify an initial gene expression marker. Tests of robustness and reproducibility were then implemented in 13 brain and 7 blood independent datasets. Correlations between expression in brain and blood samples were also examined. Finally, an enrichment analysis to explore the marker biological meaning was completed.ResultsTwenty-eight genes were differentially expressed in GSE80655, of which 23 were critical to differentiate MDD from HC. The accuracy obtained using the 23 genes was 0.77 and 0.8, before and after the forward selection model, respectively. The gene marker’s robustness and reproducibility were between the range of 0.46 and 0.63 in the other brain datasets and between 0.45 and 0.78 for the blood datasets. Brain and blood expression tended to correlate in some samples. Thirteen of the 23 genes were related to stress and immune response.ConclusionA 23 gene expression marker was able to distinguish subjects with MDD from HC, with adequate reproducibility and low robustness in the independent databases investigated. This gene set was similarly expressed in the brain and blood and involved genes related to stress and immune response.

Predictors and risk-adjusted outcomes of new-onset postoperative atrial fibrillation in repeat surgical and valve-in-valve transcatheter aortic valve replacement

Aim: New-onset postoperative atrial fibrillation/flutter (POAF/AFL) complications have not been well studied for repeat aortic valve replacements (r-AVR); this study identified risk factors predisposing to POAF/AFL and POAF/AFL’s effect upon risk-adjusted outcomes. Methods: Using New York State’s Statewide Planning and Research Cooperative System records (2005-2018), multivariable forward selection models identified risks predictive of POAF/AFL. To identify POAF/AFL’s impact upon risk-adjusted mortality/morbidity (MM) and 30-day readmission (READMIT), forward selection logistic regression models applied Firth bias correction to address data sparsity. Results: Of the 242 r-AVR patients, 147 underwent repeat surgical aortic valve replacements (r-SAVR) and 95 underwent valve-in-valve transcatheter aortic valve replacements (ViV-TAVR); 39.46% of r-SAVR and 43.16% of ViV-TAVR patients had POAF/AFL. R-SAVR patients with POAF/AFL were older (69.7 ± 11.1 vs. 56.7 ± 13.2 years, P &lt; 0.01) compared to R-SAVR patients without POAF/AFL. Multivariable models identified an enhanced POAF/AFL risk for elderly (OR: 1.05, 95%CI: 1.03-1.07, P &lt; 0.01) and cerebral vascular disease (OR: 2.18, 95%CI: 1.05-4.55, P = 0.04) patients. Bivariately, POAF/AFL was associated with READMIT, but not MM. Correspondingly, multivariable models found POAF/AFL increased READMIT (OR: 3.12, 95%CI: 1.46-6.65, P &lt; 0.01), but not MM. However, black race (OR: 4.97, 95%CI: 1.61-15.37, P &lt; 0.01) and Elixhauser score (OR: 1.05, 95%CI: 1.02-1.08, P &lt; 0.01) increased risk for MM. Conclusion: More common in older and cerebrovascular disease patients, 41% of r-AVR patients with POAF/AFL had increased READMIT risk; thus, future investigations should focus on improving POAF/AF r-AVR patients’ post-discharge continuity of care.

Perinatal morbidity prediction utilizing ultrasonographic central adiposity measures compared to BMI in patients with BMI≥40

We observed that a 3-variable model of late 3rd trimester ultrasonographic (US) measures of central adiposity is superior to BMI alone in predicting cesarean delivery (CD) in patients with BMI≥40 kg/m2. As these patients are more likely to experience maternal and neonatal morbidity, we evaluated the predictive ability of these measurements as well as a new primary model for adverse perinatal outcomes and compared these to BMI alone. Planned secondary analysis of a single center prospective cohort study of patients with BMI≥40 at >36 weeks’ GA and viable singletons. Patients underwent a single study visit >36 weeks’ (blinded to clinicians) at which BMI and 19 US/anthropometric central adiposity measures were obtained by trained personnel. Exclusions were contraindications to vaginal birth or prior CD. For this analysis, the primary outcome was composite perinatal morbidity (maternal puerperal infection, umbilical cord arterial pH< 7.1, NICU admission and other neonatal morbidities, Table). Receiver operator characteristics (ROC) curves with area under the curve (AUC) assessed the original 3-variable model’s predictive ability for the composite; AUCs for BMI, the 3-variable model from the primary analysis, and a new best-fit forward selection (α =0.05) model for the composite were compared. From 2017-2020, 149 women (mean BMI 45.4±5.2) were enrolled. The rate of perinatal morbidity was 18%. Multivariable logistic regression retained only one measurement, minimum pre-peritoneal subxiphoid fat depth, that was significantly associated with the perinatal composite (Model 1), but was poorly predictive (AUC 0.64 95%CI 0.52-0.76). BMI had no predictive ability (AUC 0.49 [0.37-0.61]), while our original 3-variable model (Model 2) had poor prediction, similar to Model 1 (Table). In patients with BMI≥40, maternal US fat depth measurements are no more predictive of adverse perinatal outcome than BMI alone, itself a poor predictor. As perinatal outcome may reflect other maternal and labor characteristics, incorporating these into models may improve prediction.

Designing a Scoring System for Differential Diagnosis From Reactive Thrombocytosis and Essential Thrombocytosis.

Background: Thrombocytosis is a common finding in hospitalized patients and is of two main types, essential thrombocytosis (ET) and reactive thrombocytosis (RT). It is important to distinguish the two due to increased risk of developing marrow fibrosis, acute leukemia, and thrombosis in the former. Molecular studies are the main tools to differentiate the two but are not available in all hospitals. We aimed to design a highly sensitive scoring system using routine lab data to classify thrombocytosis as essential or reactive.Methods: A total of 145 patients were enrolled in this study. Potential predictors included patient demographics and clinical laboratory parameters. Receiver operating characteristic curve analysis was used to decide the optimal cutoff level. Multivariate logistic regression with forward model selection method was performed to decide the predictors.Results: The risk scores by multivariate analysis were as follows: 1 point for WBC > 13,500/μL; 2.5 points for Hb > 10.9 g/dL; 3 points for platelet count > 659,000/μL; and 2 points for MPV > 9.3 fL. The cut off value was set as 4.5 points, and sensitivity of 91.1% and specificity of 75.8% were noted.Conclusion: In this study, we investigated lab data and developed a high-sensitivity convenient-to-use scoring system to differentiate ET from RT. The scoring system was assigned to the resulting model to make it more economical, simple, and convenient for clinical practice.

Novel Tools for Adjusting Spatial Variability in the Early Sugarcane Breeding Stage.

The detection of spatial variability in field trials has great potential for accelerating plant breeding progress due to the possibility of better controlling non-genetic variation. Therefore, we aimed to evaluate a digital soil mapping approach and a high-density soil sampling procedure for identifying and adjusting spatial dependence in the early sugarcane breeding stage. Two experiments were conducted in regions with different soil classifications. High-density sampling of soil physical and chemical properties was performed in a regular grid to investigate the structure of spatial variability. Soil apparent electrical conductivity (ECa) was measured in both experimental areas with an EM38-MK2® sensor. In addition, principal component analysis (PCA) was employed to reduce the dimensionality of the physical and chemical soil data sets. After conducting the PCA and obtaining different thematic maps, we determined each experimental plot’s exact position within the field. Tons of cane per hectare (TCH) data for each experiment were obtained and analyzed using mixed linear models. When environmental covariates were considered, a previous forward model selection step was applied to incorporate the variables. The PCA based on high-density soil sampling data captured part of the total variability in the data for Experimental Area 1 and was suggested to be an efficient index to be incorporated as a covariate in the statistical model, reducing the experimental error (residual variation coefficient, CVe). When incorporated into the different statistical models, the ECa information increased the selection accuracy of the experimental genotypes. Therefore, we demonstrate that the genetic parameter increased when both approaches (spatial analysis and environmental covariates) were employed.

Predictive Factors of Detectable Viral Load in HIV-Infected Patients.

Despite availability of effective antiretroviral therapy (ART), many HIV patients still have a detectable viral load (VL). Predictive factors of detectable VL are not well documented. This study was done at two large multidisciplinary HIV outpatient clinics at the Centre hospitalier de l'Université de Montréal (CHUM) and the McGill University Health Centre (MUHC). This is a retrospective case-control study of patients treated between 2016 and 2018. Cases had a VL ≥50 copies/mL in 2018. Controls had an undetectable VL from 2016 to 2018. Matching was based on gender and year of HIV diagnosis. Primary objective was to identify predictive factors of detectable VL. Secondary objectives included to identify predictive factors of virologic failure, low persistent viremia, and viral blip. A forward stepwise model selection by the Akaike Information Criterion of the conditional logistic regression was used to identify predictive factors. Two hundred cases were identified and matched with 200 controls. The cohort was mostly male (68.0%) with a median age of 54 years (21-83 years). Among cases, viral blip was the most common type of detectable VL (43.0%). The strong predictive factors for a detectable VL were adherence to ART and seeking health care services. Asylum seekers were less at risk of detectable VL. Adherence to ART was the only strong predictive factor for virologic failure. Three main predictive factors of detectable VL were identified in two ambulatory clinic hospitals in Montreal. Ascertaining these factors will allow for identification of patients more at risk of detectable VL.