Restricted Maximum Likelihood Research Articles

Real-time exposure to negative news media and suicidal ideation intensity among LGBTQ young adults in a high-stigma US state

Abstract Background With a recent surge in anti-LGBTQ policies and associated news/media coverage worldwide, there is a crucial need to study the role of LGBTQ negative news/media on proximal risk for suicide among LGBTQ youth, especially in high-stigma contexts. Methods Using a smartphone-based protocol, participants responded to brief self-report surveys 3x per day for 28 consecutive days. LGBTQ young adults (ages 18-24 years old) residing in Tennessee with recent suicidal ideation were recruited. At each assessment, participants reported real-time exposure to negative news/media, whether the news/media was related to LGBTQ topics, expectations of anti-LGBTQ rejection, and current intensity of passive suicidal ideation, active suicidal ideation, and self-harm ideation. Statistical analyses employed multilevel path analyses with restricted maximum likelihood estimation. Results 31 participants completed 2189 assessments (90.5% median compliance). Within-person effects showed that real-time exposure to LGBTQ - but not general - negative news/media was positively associated with suicidal ideation intensity. Significant indirect effects were present from exposure to LGBTQ negative news/media to higher suicidal ideation intensity through expectations of rejection. Mediation through expectations of rejection accounted for 25% and 39% of the total effect for active and passive suicidal ideation, respectively. Conclusions Findings have important public health implications related to media reporting, policy, and clinical intervention. Interventions targeting media organizations should promote responsible reporting practices and increase awareness of the potential suicidogenic impact of negative LGBTQ news coverage. This study joins numerous others in documenting the potential mental health harms of policies that restrict LGBTQ visibility and rights. Mental health professionals play a vital role in promoting coping in the face of exposure to LGBTQ negative news/media content.

Adherence to the ABC pathway improves prognosis in patients with AF: preliminary findings from an updated meta-analysis of 360,000 patients

Abstract Background With the increasing complexity of patients with Atrial Fibrillation (AF), the ‘Atrial Fibrillation Better Care’ (ABC) pathway was proposed to streamline a holistic approach for the comprehensive management of patients with AF. The ABC pathway is based on three main pillars: ‘A’ Avoid stroke (through optimal anticoagulant use); ‘B’ Better symptom control; and ‘C’ Cardiovascular and Comorbidity management optimization. Such a holistic and integrated approach is currently recommended by international guidelines, including the ones from the European Society of Cardiology (ESC); a previous meta-analysis showed sub-optimal adherence to such approach in real-world cohorts, with an overall reduction in the risk of major outcomes in patients treated according to the ABC pathway. We hereby performed an updated systematic review and meta-analysis of the current evidence on the implementation of the ABC pathway in patients with AF. Methods We performed a systematic review and meta-analysis according to PRISMA Guidelines. MEDLINE and EMBASE were searched for all studies reporting data on the prevalence of ABC pathway adherent management in patients with AF, and/or the association between ABC pathway management and the incidence of major outcomes, including all-cause death, cardiovascular death, thromboembolism, and major bleeding. Data on the prevalence of ABC pathway management were pooled using a generalized linear mixed model; number of events and total number of patients were pooled using a random-effect model. Pooled estimates were reported as odds ratios (OR) and 95% Confidence Intervals (95%CI); heterogeneity was estimated using the restricted maximum-likelihood estimator, and the Inconsistency index (I2) was also reported. Results 4,059 articles were retrieved from the literature search; after duplicates removal, title and abstract screening and full-text evaluation, 16 studies were included, for a total of more than 360,000 patients. Pooled prevalence of adherence to the ABC pathway was 28.5% (95%CI: 21.1-37.3%, I2=100%; Figure 1). Adherence to the ABC pathway was associated with a significant lower risk of all-cause death (pooled OR: 0.47, 95%CI: 0.40-0.56, I2=97%), cardiovascular death (pooled OR: 0.43, 95%CI: 0.33-0.56, I2=95%) and stroke (pooled OR: 0.61, 95%CI: 0.47-0.79, I2=91%; Figure 1). Patients treated adherent to the ABC pathway also showed a lower risk of major bleeding (pooled OR: 0.77, 95%CI: 0.66-0.90, I2=85%). Conclusions In this updated systematic review and meta-analysis, adherence to the ABC pathway was found in less than one-third of patients with AF. Implementation of the ABC pathway was associated with lower risk of all major adverse events in patients with AF, including all-cause death, and thromboembolic and bleeding events. These data further reinforce the need for routine implementation of the ABC pathway for the management of AF in clinical practice.Figure 1

Mortality effects of beta-blockers on myocardial infarction in patients without reduced ejection fraction or heart failure in the contemporary reperfusion era : a systematic review and meta-analysis

Abstract Background The 2023 ESC and AHA/ACC guidelines note that contemporary data are heterogenous regarding the use of beta-blockers (BB) post-myocardial infarction (MI) in patients without reduced ejection fraction (EF) or heart failure (HF). Purpose We performed a systematic review and meta-analysis to address the heterogeneity in existing literature around BB post-MI in patients without HF. Methods We searched 6 databases from Jan 1, 2000 to Jan 12, 2024 to identify modern randomized controlled trials (RCTs) or observational studies enrolling MI patients without reduced EF or history of HF who received BB at index MI, and comparing outcomes between BB users and non-users. Reduced EF was defined as EF ≤40%. The primary outcome was all-cause death. Subgroup analyses and meta-regression were conducted to explore heterogeneity. Meta-analysis was conducted using the restricted maximum likelihood method. Results There were 22 studies, including 1 RCT, involving 281,631 patients enrolled between 1997 and 2020. BB did not confer a significant reduction in all-cause death in patients with a 1-year event-free period (HR, 0.99; 95% CI, 0.94 to 1.06; I2 = 0%; Figure 1A), defined as no death, recurrent MI, or HF while on BB following index MI. In patients with a 3-year event-free period, a non-significant trend towards increased all-cause mortality was observed in BB users (HR, 1.39; 95% CI, 0.81 to 2.40; I2 = 0%; Figure 1A). For patients without a stable period, meta-regression showed BB morality benefits were modified by study inclusion period (P = 0.01; R2 = 51%; Figure 1B), indicating a temporal trend of decreasing mortality benefits of BB over time. Of note, BB exhibited no mortality benefits in patients enrolled after 2010 (HR, 0.97; 95% CI, 0.90 to 1.04; I2 = 0%; Figure 1C). Subgroup analysis showed BB led to a significantly lower all-cause death in patients with mildly-reduced EF (HR, 0.79; 95% CI, 0.68 to 0.91; I2 = 0%; Figure 2A). No mortality benefit of BB was observed in patients with preserved EF (HR, 0.83; 95% CI, 0.68 to 1.02; I2 = 66%; Figure 2A), however, with high statistical heterogeneity. Further exploration of this heterogeneity via meta-regression revealed a pronounced temporal trend of decreasing BB mortality benefits in patients with preserved EF (P <.0001; R2 = 100%; Figure 2B). The R2 value rising from 51% to 100% suggests that unexplained 49% heterogeneity is attributed to mildly-reduced EF patients. Similarly, BB's mortality benefit was not significant in patients enrolled after 2010 (HR, 1.02; 95% CI, 0.95 to 1.09; I2 = 0%; Figure 2C). Conclusion In the contemporary reperfusion era, BB do not confer additional mortality benefits beyond a 1-year event-free period post-MI in patients without reduced EF. Moreover, given the temporal decreases in observed mortality benefits, especially in studies post-2010, BB may not remain an essential medication in post-MI care for patients with preserved EF in modern practice.Patients with/without a stable periodMildly-reduced and preserved EF patients

A meta-analysis of the effects of sacubitril-valsartan on surrogate markers of systemic right ventricular dysfunction in congenital heart disease

Abstract Introduction Dysfunction of systemic right ventricle (sRV) in adult congenital heart disease (ACHD) patients is expectable and often associated with heart failure and other dismal cardiovascular events. Despite limited evidence, several neurohormonal modulators approved for heart failure with reduced ejection fraction (HFrEF) have been used off-label in patients with RV dysfunction1. Sacubitril-valsartan (ARNI) effects on sRV remains poorly studied, with current evidence being limited to small cohorts. Purpose Review and summarize current evidence about the effects of ARNI in ACHD patients with sRV. Methods We performed a systematic review on MEDLINE, EMBASE, COCHRANE, and SCOPUS for articles that included "systemic right ventricle" and "sacubitril valsartan" until January 2024. Two investigators screened the literature and extracted data. Treatment effects were measured by Cohen's d effect-size (EZ) pre and post-ARNI, with a 95% confidence interval (CI), using a restricted maximum likelihood model. Results From 197 publications screened, five studies fulfilled our criteria, comprising a total of 135 patients. Follow-up after ARNI therapy ranged from 12 to 27 months. No randomized clinical trials were found, and only two studies had a prospective design. Dextro-transposition of the great arteries (D-TGA) after atrial switch operation was the most common type of congenital heart disease with sRV (n=95; 70%). Meta-analysis demonstrates that ARNI reduced NT-proBNP levels during follow-up (EZ= -0.34, CI -0.59 to 0.08; p=0.01; I2=4.0%). Regarding RV function, ARNI improved RV fractional area change (RVFAC) (EZ= 0.75, CI 0.01 to 1.50; p= 0.048; I2=85.0%). A trend for RV global longitudinal strain improvement was also observed with ARNI (EZ= 1.74, CI -0.05 to 3.54; p=0.06; I2=95.9%) but not for tricuspid annular plane systolic excursion (EZ= -0.07, CI -0.33 to 0.20; p=0.62; I2=0.0%). RV diastolic diameter did not change significantly with ARNI (EZ= 0.07, CI -0.43 to 0.56; p=0.79; I2=68.2%). A trend for improvement on the 6-minute walk test was observed (EZ= 1.89, CI -0.13 to 3.91; p=0.07; I2=96.3%), but no effect on exercise oxygen consumption (VO2) (EZ= -0.09, CI -1.32 to 1.15; p=0.89; I2=91.4%). During follow-up ARNI did not change significantly systolic blood pressure (EZ= -0.32, CI -0.74 to 0.11; p=0.15; I2=58.4%) or serum creatinine (EZ= 0.23, CI -0.04 to 0.49; p=0.09; I2=0.0%). Conclusions Despite heterogeneity among these studies, this meta-analysis demonstrates that ARNI might improve NT-proBNP levels and RV function. ARNI seems safe and well tolerated, with no significant effect on blood pressure and renal function. More well-powered studies are needed to confirm the beneficial effects of ARNI in ACHD with sRV.

Prevalence of anemia among coronavirus disease 2019 patients in Ethiopia: A meta-analysis

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2, impacting various systems in the human body, including the hematological and reticuloendothelial systems, which can alter blood production. Consequently, severe anemia-associated complications could occur in COVID-19 patients. At present, there is a lack of pooled prevalence data on anemia among COVID-19 patients in Ethiopia. This systematic review and meta-analysis aimed to determine the overall prevalence of anemia in this population. Following PRISMA guidelines, we conducted a literature search across PubMed/MEDLINE, Cochrane Library, Google Scholar, HINARI, and the Ethiopian Journal of Health Development for articles published before 2024. Additional manual searches were performed to identify relevant studies. Study selection, data extraction, and quality assessment were conducted independently by the authors. The I2 test statistics were used to assess heterogeneity among studies, and the overall prevalence was calculated using a random-effect restricted maximum likelihood model. Out of 860 studies obtained, 11 articles were included in the meta-analysis. The pooled prevalence of anemia among COVID-19 patients in Ethiopia was found to be 22.81% (95% CI [confidence interval]: 14.76 – 30.85%). Specifically, the prevalence of anemia in Addis Ababa and Amhara was 27.13% (95% CI: 14.59 – 39.66%) and 22.50% (95% CI: 11.04 – 33.96%), respectively. This study indicates that anemia is a moderate public health problem among COVID-19 patients in Ethiopia. Consequently, it is imperative to implement preventative interventions and management strategies for anemia in this population.

Oral anticoagulants or antiplatelets for cryptogenic stroke: a systematic review and meta-analysis

Abstract Background Cryptogenic strokes comprise 20 to 30% of ischemic strokes and include a substantial proportion classified as embolic stroke of undetermined source (ESUS). However, the optimal antithrombotic strategy for cryptogenic stroke remains contentious. Purpose We conducted a systematic review and meta-analysis to compare the efficacy and safety of oral anticoagulants (OAC) versus antiplatelets in patients with cryptogenic stroke. Methods Six electronic databases of PubMed, Embase, Web of Science, the Cochrane Library, Google Scholar and ClinicalTrials.gov were searched from inception to Feb 15, 2024 to identify relevant randomized controlled trials (RCTs) comparing stroke recurrence and major bleeding rates between OAC and antiplatelets in cryptogenic stroke patients. We included trials adhering to a stringent diagnostic work-up for cryptogenic stroke, defined as cerebral infarction not attributed to definite sources of cardioembolism, large artery atherosclerosis, or small artery disease despite undergoing comprehensive investigations. The primary outcome was recurrent ischemic stroke, and the secondary outcome was major bleeding based on International Society of Thrombosis and Hemostasis criteria. Subgroup analysis was conducted for ESUS patients with an increased risk of cardiac emboli, such as patent foramen ovale (PFO) and atrial cardiopathy, defined as lead V1 terminal P-wave > 5000 μV × ms in electrocardiogram, serum N-terminal pro-B-type natriuretic peptide level > 250 pg/mL, and left atrial diameter (LAE) > 4 cm, or LAE index ≥ 3 cm/m2 on echocardiogram. Hazard ratio (HR) with 95% confidence (CI) was used as a measure of the effect estimates for aforementioned outcomes. Random-effects meta-analysis was performed using a restricted maximum likelihood model given between-study variance is inevitable. Results Our meta-analysis included 9 RCTs with a total of 15,139 patients (OAC = 7,343; antiplatelets = 7,796). ARCADIA, RE-SPECT ESUS, and NAVIGATE ESUS Trial investigated apixaban, dabigatran, and rivaroxaban, respectively, while warfarin was primarily used as OAC in the remaining six trials. Aspirin was predominantly utilized for antiplatelet therapy. There was no significant difference in recurrent ischemic stroke between OAC and antiplatelets (HR, 0.90; 95% CI, 0.78 to 1.04; I2 = 0%). However, OAC use was associated with a significantly higher risk of major bleeding (HR, 1.66; 95% CI, 1.07 to 2.56; I2 = 36%). Subgroup analysis in ESUS patients revealed comparable rates of recurrent ischemic stroke in those with atrial cardiopathy (HR, 0.91; 95% CI, 0.65 to 1.29; I2 = 0%) and PFO (HR, 0.72; 95% CI, 0.49 to 1.07; I2 = 0%). Conclusions Our meta-analysis suggests that OAC use does not decrease the risk of recurrent ischemic stroke compared with antiplatelet use but is associated with a significantly higher risk of major bleeding in patients with cryptogenic stroke.Primary (A) and secondary (B) outcomesSubgroup analysis for recurrent stroke

Genetic determinism of sensitivity to environmental challenges using daily feed intake records in three lines of pigs.

In pig breeding, environmental challenges can affect the welfare and productivity of animals. Resilient animals have the capacity to be minimally affected by these environmental challenges. Understanding the genetic basis of sensitivity to these environmental challenges is crucial for selecting more resilient animals, thereby enhancing welfare and productivity. The aims of this study were to: (1) estimate the probability of the occurrence of an unrecorded environmental challenge at a given day using daily feed intake (DFI) data, and (2) evaluate the genetic determinism of environmental sensitivity in three pig lines bred in real selection conditions. Data comprised of 100,799, 186,247, and 304,826 DFI records from 1,618, 2,517, and 3,788 Landrace (LA), Large White (LW) and Piétrain (PI) male pigs, respectively. The pedigree included 3,730, 5,649, and 9,293 animals for LA, LW, and PI, respectively. The probabilities of the occurrence of an unrecorded environmental challenge at a given day were estimated via a mixture model. The probabilities (p) of being "high CV days" were then taken as reference and used in genetic analysis as an environmental descriptor to describe the environment. DFI records were analysed using two linear models: a linear reaction norm animal model (RNAM) and the animal model. (Co)variance components were estimated using average-information restricted maximum likelihood (AI-REML). The means of the probabilities of the occurrence of an environmental challenge for LA, LW, and PI were 0.24, 0.10, and 0.22, respectively, indicating that the probability of an environmental challenge was low for most of the days. The genetic correlations between the intercept and the slope obtained from the RNAM for LA, LW, PI were -0.52, 0.06, and -0.36, respectively. These findings suggest that selecting hypothetically for decreased DFI in non-stressful conditions would result in pigs with increased DFI in stressful conditions in the LA and PI lines, whereas it would have a minor impact on the environmental sensitivity of LW. The proportion of resilient animals for LA, LW, and PI was 75.0, 74.2, and 72.2%, respectively, implying that most of the animals were resilient. The study demonstrated that the slope of DFI is heritable and can effectively be used as an indicator of sensitivity to environmental challenges. These results are valuable in improving the resilience of livestock species to environmental challenges through genetic selection.

A Comparison between Methods for Estimating the Restricted Gamma Ridge Regression Model Using the Simulation

In this paper, we discuss estimating the parameters of the restricted gamma ridge regression model by combining gamma ridge regression with restricted maximum likelihood. The characteristics of the new estimator and its superiority over the restricted gamma ridge regression estimator and restricted maximum likelihood will be identified, using several formulas for the shrinkage factor k, and it will also be Using the Monte Carlo simulation method to generate data that suffers from the problem of multicollinearity with different sizes (n=25,50,100,250) in light of other influential factors (degree of correlation, number of explanatory variables), and subjecting the parameters to linear restrictions, to get rid of the problem of multicollinearity in light of the subjection of the parameters to the model has linear constraints and the model parameters will be estimated using four estimation methods that rely on the mean square error (MSE) as a standard for comparison between the estimation methods, Through the results of the simulation experiment it was shown that the compound estimator method is the best way to estimate the parameters of the finite gamma regression model . Paper type : Research paper

Genetic assessment of productive and reproductive traits in Friesian, native, and crossbred cattle in Egypt

This study utilized a dataset comprising 3023 lactation records for Friesian cows, 596 records for Native cows (Baladi), and 1189 records for Crossbred cows spanning from 1994 to 2015. The objective was to estimate and assess genetic and phenotypic parameters and breeding values for 305-day milk yield (305-DMY), lactation period (LP), calving interval (CI), and days open (DO) within the Egyptian dairy context. The motivation for this research stemmed from the need to understand the genetic potential of different cattle genotypes in Egypt and identify opportunities for enhancing dairy production. Data were analyzed using the linear mixed model least squares and maximum likelihood (LSMLMW) and multiple-trait derivative-free restricted maximum likelihood (MTDFREML) programs. The analytical model included fixed effects such as season and year of calving, parity, and genotype groups, while random effects included animal and error. Unadjusted means for 305-DMY, LP, CI, and DO were calculated for each genotype group. Genotype groups significantly impacted all studied traits. Heritability estimates varied across genotype groups, with higher estimates observed in Crossbred (0.32, 0.26, 0.25, 0.23) and Native cows (0.26, 0.28, 0.28) compared to Friesian cows (0.24, 0.22, 0.16, 0.17) for productive and reproductive traits, respectively. Genetic correlations among traits ranged from 0.10 to 0.86 for the three genotype groups, while corresponding phenotypic correlations were generally small to moderate and positive. Regarding breeding values, the accuracy estimates suggested that both sires and cows could contribute to genetic improvement. This indicates the potential for enhancing dairy production through selective breeding strategies.

Sub- and supratherapeutic efavirenz plasma concentrations with risk for HIV therapy failure are mainly genetically explained in Ugandan children: The prospective GENEFA cohort study.

Interindividual variations in efavirenz (EFV) plasma concentrations are extensive, but paediatric data on its consequences for viral control are scarce. The aim of this study was to explore the role of genetic variation in achieving therapeutic efavirenz plasma concentrations in a cohort of Ugandan children and the linkage between genetic CYP2B6 variants, EFV plasma variability, viral resistance and viral outcome. Ninety-nine treatment-naïve children, aged 3-12 years and living with HIV, were followed for 24 weeks after ART initiation assessing mid-dose efavirenz plasma concentrations, HIV RNA, HIV drug resistance and adherence. Polymorphisms in genes coding for drug-metabolizing enzymes were genotyped. Efavirenz concentrations were determined by liquid chromatography coupled with high-resolution tandem mass spectrometry. Metabolizer phenotype was predicted from composite genotypes of CYP2B6 (c.516G>T and c.983 T>C). A mixed effects restricted maximum likelihood regression model was used to identify important factors for efavirenz exposure. Efavirenz plasma concentrations were below the therapeutic interval (1000-4000 mg/mL) in 12-17% and above in 21-24% of measurements. Eight children had persisting subtherapeutic concentrations, five of which failed virologically and three acquired at least one new resistant mutation. Multivariate modelling explained 70% of interindividual variation in plasma concentration, with treatment duration, adherence, CYP2B6c.136A>G, and metabolizer phenotype as independent predictors of EFV concentration. In univariate analysis, metabolizer phenotype explained 50% of interindividual variation. Metabolizer phenotype explained 50% of interindividual variation in efavirenz plasma concentration. Autoinduction was not confirmed and >33% of the concentrations were outside the therapeutic interval. Subtherapeutic concentrations worsened virological resistance and outcomes. Genotype-based dosing may help avert both sub- and supratherapeutic efavirenz plasma concentrations in Ugandan children.

Role of Embolic Protection in Percutaneous Coronary Intervention without Saphenous Venous graft lesions in ST-elevation myocardial infarction - a systematic review and meta-analysis.

Embolic protection devices are catheter-based devices that can be used to capture atherosclerotic remnants released during percutaneous coronary intervention (PCI). We aim to study the efficacy and safety of EPDs in PCIs without saphenous vein grafts (SVG) in ST-elevation myocardial infarction(STEMI). 3 electronic databases of MEDLINE, Web of Science, and Embase were searched from inception to Apr 10, 2024, to identify relevant randomized controlled trials (RCTs) that compared outcomes of patients subjected to EPD during PCI with control group where EPDs were not utilized. The primary outcome was 30-day all-cause mortality. Secondary outcomes were major adverse cardiovascular and cerebrovascular events (MACCE) at 30 days, post-PCI Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow attainment, ST-segment resolution at 90 minutes post-procedure and post-procedure angiographically detectable signs of distal embolization. The effect estimates of outcomes were assessed using risk ratio (RR) with a 95% confidence interval (CI). Random-effects meta-analysis was conducted using the restricted maximum likelihood method given the inter-study variance was inevitable. We included 3 RCTs enrolling 741 patients (age 61.6 ± 12.15 years, 22% females) undergoing PCI without SVG lesions. As opposed to the control group, the use of EPD did not yield a significant effect on all-cause mortality (RR, 0.76; 95% CI, 0.31-1.86; I2 = 0%), MACCE (RR, 0.66; 95% CI, 0.34-1.27; I2 = 0%), post-PCI TIMI 3 flow (RR, 1.18; 95% CI, 0.86-1.62; I2 = 77%) and ST segment resolution at 90 minutes post-procedure (RR, 1.05; 95% CI, 0.90-1.22; I2 = 0%). However, EPD significantly decreased angiographically detectable signs of distal embolization (RR, 0.60; 95% CI, 0.36 to 0.99; I2 = 0%). EPD significantly reduced angiographically detectable signs of distal embolization in PCI without SVG lesions in STEMI, though there were no clinical signs of improved flow or mortality. Further trials are necessary to thoroughly evaluate the potential benefits and requirements of EPD usage in such procedures.

Estimates of Genetic Parameters and Genetic Trends for Growth Traits in Menz Sheep under Community-based Breeding Programs

The main objectives of this study were to estimate genetic and phenotypic parameters for growth traits in Menz sheep under community-based breeding programs (CBBPs). Data used in the study were collected from five Menz CBBPs villages during 15-year period (2009 to 2023). Studied growth traits were birth weight (BW), weaning weight (WW), six-month weight (6MW), yearling weight (YW), Average daily gain from birth to weaning (ADG1), average daily gain from weaning to six months (ADG2) and average daily gain from six months to yearling (ADG3). Fixed effects were estimated using the GLM procedure of SAS 9.4. Genetic parameters were estimated fitting different univariate animal models using Average Information Restricted Maximum Likelihood (AI-REML) procedure using WOMBAT software. The most appropriate model for each trait was determined applying likelihood ratio tests. Model including only direct additive genetic effect was the most appropriate model for BW, YW, ADG2 and ADG3, whereas model including direct additive and maternal additive genetic effect without taking into account covariance between them was the most appropriate for WW, 6MW and ADG1. Based on the most appropriate models, direct heritability of BW, WW, 6MW, YW, ADG1, ADG2 and ADG3 were 0.29 ± 0.01, 0.45 ± 0.01, 0.46 ± 0.02, 0.42 ± 0.02, 0.44 ± 0.01, 0.75 ± 0.02 and 0.21 ± 0.02, respectively. The estimated maternal heritability were 0.04 ± 0.01, 0.02 ± 0.01 and 0.02 ± 0.01 for WW, 6MW and ADG1, respectively. Additive coefficient of variance were ranged from 9.53% for BW to 33.02% for ADG2. Moderate to higher estimates of direct heritability and additive coefficient of variation (CVA) in the current study indicates higher potential for genetic improvement of studied traits through direct selection. The genetic trends for WW, 6MW, and YW showed a positive improvement a rate of 0.02, 0.038 and 0.03kg over years, respectively. Optimizing the ongoing breeding program into specializing-sire producer groups and applying intensive selection on the sub-nucleus flock could improve the efficiency of the breeding program. Genetic correlations among the studied traits were ranged from -0.50 for ADG-ADG2 to 0.98 for WW-ADG1. Genetic correlation between 6MW and other studied traits was positive and moderate in magnitude. To achieve optimum genetic gain, the implemented selection criteria for Menz sheep (6MW) should be continued.

Urea to Treat Hyponatremia Due to Syndrome of Inappropriate Antidiuretic Hormone Secretion: A Systematic Review and Meta-Analysis

Rationale & ObjectiveThe use of urea to treat hyponatremia related to the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) has not been universally adopted due to questions about effectiveness, safety, and tolerability. This systematic review and meta-analysis of observational studies aimed to address these questions. Study DesignThis PRISMA-guided study examined published research across four electronic databases. Study PopulationsPatients with SIADH-related hyponatremia. Selection CriteriaClinical trials and observational studies reporting at least one outcome related to serum sodium concentration, symptom resolution, or adverse effects after oral or nasogastric urea administration. Data ExtractionData extraction was performed independently by two reviewers using a standardized form recording study characteristics, participant demographics, intervention details, and treatment outcomes. Analytical ApproachA meta-analysis was conducted using the restricted maximum likelihood method for the random-effects model to assess the effect of urea treatment on serum sodium and serum urea compared to other treatment modalities. Subgroup analyses were conducted based on treatment duration and SIADH severity. ResultsUrea treatment significantly increased serum sodium [mean difference (MD) = 9.08 (95%CI 7.64-10.52), p < 0.01] and urea [MD = 31.66 (95%CI 16.05-47.26), p < 0.01] in patients with SIADH albeit with significantly high heterogeneity. Subgroup analysis based on the treatment duration showed a significant rise in the serum sodium level after 24 hours, two, five, seven, and fourteen days, as well as after one year of treatment. Greater increases in serum sodium levels after treatment with urea occurred in patients with severe (<120 mEq/L) [MD = 18.04 (95%CI 13.68-22.39)] than with moderate (120-129 mEq/L [MD = 7.86 (95%CI 6.78-8.94)] or mild (130-135 mEq/L) [MD = 8.00 (95%CI 7.31-8.69)] SIADH induced hyponatremia. Urea treatment was comparable to fluid restriction [MD = 0.81 (95%CI: -0.93-2.55), p = 0.36) and vaptans [MD = -1.96 (95%CI: -4.59-0.66, p = 0.14) but superior to no treatment [MD = 7.99 (95%CI 6.25-9.72), p < 0.01]. Urea was associated with minor adverse events, with poor palatability being most common. LimitationsAs no RCTs investigating urea as a treatment for hyponatremia were identified for inclusion, these analyses were based on observational studies. ConclusionsUrea is safe and effective for managing SIADH-induced hyponatremia. These finding suggest that urea may be a useful treatment modality in resource-limited settings or when other treatments are contraindicated or poorly tolerated.

Association between low-calorie sweetener consumption during pregnancy and child health: A systematic review and meta-analysis.

We examined the association between low-calorie sweeteners (LCS) consumption during preconception, pregnancy, and breastfeeding and child health outcomes. A systematic search of electronic databases in PubMed, Embase, Cumulated Index to Nursing and Allied Health Literature, the Cochrane Library, Scopus, Web of Science, PsycINFO, ProQuest Health and Medical, ClinicalTrials.gov, and Google Scholar was conducted up to 21 September 2023. A random effects model with restricted maximum likelihood estimation was used for the meta-analysis. Seventeen eligible studies were included. The standardised mean difference (SMD) and 95% confidence interval (CI) in birth weight between those who frequently consumed LCS (≥1 serve/day) during pregnancy and those who did not consume LCS was 0.04 (0.00, 0.08) (four cohort studies). Any LCS consumption during pregnancy compared with no consumption was not associated with birth weight [SMD (95% CI) = 0.03 (-0.03, 0.08)] (four cohort studies). Any LCS consumption during pregnancy was not associated with body mass index z-scores. The weighted mean difference (95% CI) was 0.00 (-0.05, 0.06) at birth, 0.06 (-0.29, 0.40) at 6 months, -0.04 (-0.19, 0.10) at 1 year, 0.00 (-0.16, 0.17) at 3 years, and 0.10 (-0.15, 0.34) at 7 years of the child age, compared with no intake (five cohort studies). The odds of being overweight at 1 year among children exposed to LCS during pregnancy was 1.19 (OR [95% CI]: 1.19 [0.81, 1.58]) compared with unexposed children (two cohort studies). The effect sizes were not precise for all the outcomes as the 95% CI indicated the effect estimates could range from small protective to a higher risk. The effect of LCS consumption on child behaviour and cognition was inconsistent. There is not enough evidence to confirm LCS consumption during pregnancy affects birth weight and risk of overweight in children. However, frequent consumption increased birth weight and the risk of overweight at different ages, though the effects were imprecise. More robust research evidence is required as the quality of evidence is low.

Evaluating animal models comprising additive genetic and maternal effects on growth traits in German Angora rabbit

This investigation was carried out to estimate the genetic parameters for German Angora rabbits using most appropriate animal model comprising additive and maternal effects. The pedigree information and data on growth traits were collected from 5221 rabbits, which descended from 699 does and 294 bucks over a period of 21 yr (2001–2021) kept at Northern Temperate Regional Station, Garsa, Kullu (Himachal Pradesh), India. The average daily gain (ADG) and Kleiber ratio (KR) were calculated at different age intervals. Analyses were carried out by restricted maximum likelihood procedure fitting six animal models with various combinations of direct and maternal effects. The best model was evaluated on the basis of a likelihood ratio test. Analysis revealed that the model including both direct and maternal genetic effects along with permanent effect of the dam was most suitable for all traits except for body weight (BW) at 6th wk of age, ADG from 6th to 12th wk of age and KR associated to ADG from 12th to 18th wk of age. The direct heritability estimates from the best model were ranged from, 0.34±0.05 to 0.49±0.05 for BW; 0.19±0.04, to 0.46±0.06 for ADG and 0.21±0.04 to 0.41±0.05 for KR, respectively. Direct heritability estimates were overestimated when maternal effects were ignored. Maternal effects on BW declined from 0.49±0.04 at weaning to 0.06±0.03 at 12th wk of age and 0.09±0.04 at 18th wk of age. Correlations between direct and maternal effects ranged from −0.44±0.15 to−0.52±0.14 for body weights, indicating biological antagonism between these effects. Genetic correlations among various growth traits were positive and high, indicating scope for correlated response in later expressed traits. Analysis revealed that maternal additive influences were only important until weaning, whereas permanent environmental maternal influences were present in all growth traits considered in this study. The moderate estimates of heritability for growth traits and Kleiber ratio of rabbit in this study indicate that rates of genetic progress may be possible for these traits by selection under the standard management system.

Genetic variability and diversity analysis for some agronomic traits of a sweet potato (Ipomoea batatas L.) collection: Insights for breeding superior genotypes

A study was conducted during the 2017 cropping season to assess the genetic variability of selected agronomic traits in sweet potato. A total of 355 sweet potato genotypes (351 from different countries of the world and four check varieties) were evaluated at Tuber Crops Research Sub Centre, Bangladesh Agricultural Research Institution, Bogura, Bangladesh. The experiment was conducted using an augmented randomized complete block design. Findings revealed positive correlations among five agronomic traits, namely the weight of marketable storage root per plant (MRW), weight of storage root per plant (RW), fresh weight of foliage per plant (FW), number of marketable storage root per plant (MRN) and number of storage root per plant (RN) suggesting their suitability for phenotypic selection. There was a positive skewness in most studied traits (FW, MRW, MRW and RW), indicating the presence of a few genotypes with exceptionally high values for those traits. By employing principal component analysis, the most influential traits in sweet potato genotypes were identified for first two components (Dim) showing significant contributions to Dim-1 and Dim-2 collectively accounting for 84.7 % of the total variance. Through cluster analysis, two main clusters (Cluster I and Cluster II) were identified among the studied genotypes, each characterized by distinct trait patterns. Cluster I demonstrated superior performance in all traits, while Cluster II exhibited lower values for all traits. Further sub-clustering within Cluster II (sub-clusters IIA and IIB) revealed additional variations of the collection. The Euclidean distance for inter-cluster (ranging from 7.94 to 11.39) and intra-cluster (ranging from 3.17 to 10.38) were determined utilizing the complete distance method. In restricted maximum likelihood (REML) model, all the traits were significantly influenced by genetic effects, with broad-sense heritability ranging from 32 % to 70 %. The REML displayed high selection accuracy, with values exceeding 91 % for studied traits. The Multi-Trait Genotype-Ideotype Distance Index (MGIDI) identified 18 genotypes, with Moz1.15 emerging as the best-performing genotype under a 5 % selection pressure. Among the selected genotypes, trait uniqueness was highest for FW (54 %), followed by RN (50 %), MRN (18 %), MRW (14 %), and RW (5 %). The selection gain for these top-ranked genotypes varied between 23.2 % and 69.2 %. Findings established the existence of useful genetic variability for selected agronomic traits of sweet potato that could be exploited for breeding, genetics study and conservation.

Improved quality of life in head and neck cancer patients treated with modern arc radiotherapy techniques - A prospective longitudinal analysis.

The present longitudinal study aimed to evaluate the potential impact of modern radiotherapy (RT) techniques on quality of life (QOL) in patients with head and neck (HNC) cancer. In this single-center prospective study, participants were asked to complete QOL questionnaires that included the EORTC QLQ-C30, QLQ-H&N 35 and utility score by time trade-off (TTO) at three time points (2 weeks, 3 months and 6 months) after completion of RT. All patients were treated by modern RT techniques [volumetric modulated arc therapy (VMAT) or helical tomotherapy (HT)]. Patients who developed recurrence or died before the 6-month follow-up were excluded. Linear mixed models with random intercepts for participants and restricted maximum likelihood estimates were used to assess the effect of our study variables (age, sex, primary site, cancer stage, treatment, radiation dose and radiation method). Overall changes in QOL, utility scores and symptom burdens at different time points were tested using paired t tests. A total of 45 patients were recruited from 2022 to 2023. Those who completed the surveys at 2 weeks with at least 1 follow-up (30 patients, 67%) were enrolled in the final analysis. The majority of these 30 patients were men (76.7%), had oral cancer (40%), had stage III or IV disease (60%), received surgical intervention (63%) and were treated with chemoradiation (80%). A curative total dose of 66 to 70 Gy was delivered to 23 (76.7%) patients, half of whom received HT. Patients who received chemotherapy had significantly lower global QoL scales (mean difference, 27.94; 95% CI, 9.33-46.55; p=0.005). Global QOL, physical function, symptoms of sticky saliva, cough, feelings of illness and weight loss improved significantly between 2 weeks and 3 months. There was no significant difference between 3 and 6 months. Interestingly, improvements in social function, social contact, pain and nutrition reached significance at 6 months. Subgroup analysis revealed greater pain relief over time for patients who underwent HT (p=0.030). Moreover, patients who participated in swallowing rehabilitation programs had a greater decrease in nausea and vomiting (p=0.036). HNC patients treated with modern RT techniques experience improved QOL and physical function over time. The most significant improvement occurs between 2 weeks and 3 months, after which the improvement plateaus. However, social function, social contact, pain and nutrition may require longer recovery intervals after treatment. HT with daily image guidance could provide a therapeutic opportunity for improving pain relief in patients with HNC.

Date SMART’s Impact on Aggression in System Involved Girls: Does Victimization Moderate Effects?

ABSTRACT Aggression and victimization increase negative outcomes for legal system involved girls. While aggression is often enacted against multiple targets (e.g. peers, dating partners), most interventions only target one violence type (e.g. teen dating violence [TDV]). However, TDV shares risk factors with other violence forms; therefore, TDV-specific interventions may reduce other types of violence (e.g. general aggression). The current study explored the effects of a TDV intervention, Date SMART, on general physical and verbal aggression (i.e. aggression not tied to dating) in legal system involved girls (N = 239, Mage = 15.57) and how victimization history (including sexual abuse) moderated treatment effects compared to a Knowledge Only (KO) group. Hierarchical restricted maximum likelihood linear mixed effect models evaluated differences in aggression from baseline to post-intervention and 3-, 6-, and 9-month follow-ups. Findings indicated that from baseline to post-intervention, verbal and physical aggression initially increased in Date SMART relative to KO, but then decreased at a greater rate in the Date SMART group than the KO group throughout follow-ups. Exploratory analyses indicated that victimization history moderated response to Date SMART and KO. Findings suggest that rates of multiple forms of violence can be reduced by Date SMART but may benefit from tailoring for peer relationships and victimization histories.

Abstract C005: Predictors of advance care planning documentation in female patients with breast cancer: A multilevel model analysis

Abstract Background: Advance care planning (ACP) is a process that supports adults at any age or stage of health in understanding and sharing their personal values, life goals, and preferences regarding future medical care. Likewise, ACP is associated with multiple benefits, such as lower rates of hospitalizations and reduced futile, aggressive cancer treatment at the end of life. However, ACP rates remain low in the U.S., especially for patients with advanced cancer. Despite being more likely to be diagnosed at advanced stages and hospitalized due to advanced cancer with poor prognosis, the Black and Hispanic/Latino populations continue to have meager rates of ACP. Research has shown that both individual-level and systems-level factors contribute to these racial disparities in ACP. Considering these disparities among vulnerable populations, interventions that increase ACP among minority patients with cancer are needed. Objective: To analyze using multilevel model analysis the predictors of ACP documentation in female patients with breast cancer over 5 years in the UChicago Health System. Methods: Using the Clinical Data Research Warehouse, this study included women diagnosed with breast cancer (N=7,814) from 2016 to 2021. Descriptive statistics were performed to characterize ACP, and potential differences in ACP rates among control variables were assessed using odds ratio (OR) estimations. Significantly correlated variables were included as covariates in the multivariate analyses through a logistic regression model. The multilevel random-effects (mixed-effects) model, using restricted maximum likelihood estimation, examined the pattern of ACP documentation; in the multilevel model, level 1 modeled the changes in individual ACP documentation, and level 2 included the between-subjects effects of the predictors of documentation. Results: 13.76% of women with breast cancer filled out at least one type of ACP documentation, 4.25% filled out the Power of Attorney, 5.75% filled out the Advance Directive, and 8.92% filled out the Code Status. Increasing age and being black/African-American seem to be related to an increased likelihood of completion of at least one type of ACP documentation. While increasing BMI and outpatient services seem to be related to a decrease in the likelihood of completing at least one type of ACP documentation. Conclusion: Understanding the factors related to ACP documentation will allow us to manage them and improve their completion. These results will help to inform the development of tools to increase the integration of ACP into care, especially those that are technology-based. Further work could include designing a predictive model to prioritize patients requiring ACP. Providing knowledge about ACP in nonclinical areas can lead to increased education about ACP and its benefits to families and communities. Citation Format: Andres Mauricio Garcia Sierra, Marcia Tan. Predictors of advance care planning documentation in female patients with breast cancer: A multilevel model analysis [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C005.

Beta-Blockers for Secondary Prevention following Myocardial Infarction in Patients Without Reduced Ejection Fraction or Heart Failure: An Updated Meta-Analysis.

The 2023 ESC guidelines for acute coronary syndrome note that contemporary data are heterogenous regarding beta-blockers (BB) use post-myocardial infarction (MI) in patients without reduced ejection fraction (EF) or heart failure (HF). We aimed to address the heterogeneity in contemporary data around BB post-MI in this population. We searched 6 databases from Jan 1, 2000 to Sep 1, 2024 to identify contemporary studies enrolling MI patients without reduced EF (≤40%) or history of HF receiving BB at index MI, and comparing outcomes between BB users and non-users. The primary outcome was all-cause mortality. Secondary outcomes included major adverse cardiac and cerebrovascular events (MACCE) and cardiovascular (CV) mortality. Random-effects meta-analysis was conducted using the restricted maximum likelihood method. There were 24 studies including 290,349 patients enrolled in the contemporary era. Overall, BB use was associated with a significant 11% reduction in all-cause mortality (HR, 0.89; 95% CI, 0.81 to 0.97; I2 = 40%; Figure 1), however with moderate-to-high statistical heterogeneity. Prespecified subgroup analyses demonstrate comparable all-cause mortality (HR, 0.99; 95% CI, 0.94 to 1.06; I2 = 0%), CV mortality (HR, 0.99; 95% CI, 0.85 to 1.15; I2 = 0%), and MACCE (HR, 1.24; 95% CI, 1.01 to 1.52; I2 = 0%) in patients with a 1-year event-free period, defined as no death, recurrent MI, or HF while on BB following index MI. In patients with no event-free period, meta-regression revealed that BB mortality benefits were modified by the study inclusion period (P = 0.01), reflecting a temporal trend of decreasing BB mortality benefits over time. Based on the temporal trend, in patients with preserved EF post-2010, BB exhibited no reduction in all-cause mortality (HR, 0.97; 95% CI, 0.90 to 1.04; I2 = 0%), but a non-significant trend towards increased CV mortality (HR, 1.29; 95% CI, 0.96 to 1.72; I2 = 0%) and a significant increase in MACCE (HR, 1.24; 95% CI, 1.01 to 1.52; I2 = 0%). In the contemporary reperfusion era, BB may not confer additional mortality benefits beyond a 1-year event-free period post-MI in patients without reduced EF. Moreover, post-MI BB use was associated with detrimental effects in patients with preserved EF.