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Background: In GALACTIC-HF (Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure) (n = 8,256), the cardiac myosin activator, omecamtiv mecarbil, significantly reduced the primary composite endpoint (PCE) of time-to-first heart failure event or cardiovascular death in patients with heart failure and reduced ejection fraction (EF) (≤35%).Objectives: The purpose of this study was to evaluate the influence of baseline EF on the therapeutic effect of omecamtiv mecarbil.Methods: Outcomes in patients treated with omecamtiv mecarbil were compared with placebo according to EF.Results: The risk of the PCE in the placebo group was nearly 1.8-fold greater in the lowest EF (≤22%) compared with the highest EF (≥33%) quartile. Amongst the pre-specified subgroups, EF was the strongest modifier of the treatment effect of omecamtiv mecarbil on the PCE (interaction as continuous variable, p = 0.004). Patients receiving omecamtiv mecarbil had a progressively greater relative and absolute treatment effect as baseline EF decreased, with a 17% relative risk reduction for the PCE in patients with baseline EF ≤22% (n = 2,246; hazard ratio: 0.83; 95% confidence interval: 0.73 to 0.95) compared with patients with EF ≥33% (n = 1,750; hazard ratio: 0.99; 95% confidence interval: 0.84 to 1.16; interaction as EF by quartiles, p = 0.013). The absolute reduction in the PCE increased with decreasing EF (EF ≤22%; absolute risk reduction, 7.4 events per 100 patient-years; number needed to treat for 3 years = 11.8), compared with no reduction in the highest EF quartile.Conclusions: In heart failure patients with reduced EF, omecamtiv mecarbil produced greater therapeutic benefit as baseline EF decreased. These findings are consistent with the drug's mechanism of selectively improving systolic function and presents an important opportunity to improve the outcomes in a group of patients at greatest risk. (Registrational Study With Omecamtiv Mecarbil/AMG 423 to Treat Chronic Heart Failure With Reduced Ejection Fraction [GALACTIC-HF]; NCT02929329). [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy-induced diarrhea (CID) is a common symptom that occurs in 50 to 80% of patients. Given that the majority of the data on the occurrence and severity of CID is based on physician-rated toxicity criteria, this study's purposes were to identify subgroups of patients with distinct CID profiles and determine how these subgroups differ in terms of demographic and clinical characteristics; severity, frequency, and distress of CID; the co-occurrence of common GI symptoms; and QOL. Methods: Patients (n = 1133) completed the Memorial Symptom Assessment Scale six times over two cycles of chemotherapy. Latent profile analysis was used to identify subgroups of patients with distinct diarrhea profiles. Differences among these subgroups were evaluated using parametric and nonparametric statistics. Results: Four distinct diarrhea profiles were identified: none (58.3%), decreasing (22.0%), increasing (5.2%), and high (14.5%). Compared with the none class, patients in the high class had a lower functional status, a worse comorbidity profile, were more likely to have gastrointestinal cancer, and were more likely to receive chemotherapy on a 14-day cycle. No differences were found among the classes in the percentages of patients who received chemotherapy with a targeted therapy. Conclusion: Given that CID occurred in over 40% of the patients, clinicians should assess for this symptom and other common GI symptoms and initiate appropriate pharmacologic and dietary interventions. [ABSTRACT FROM AUTHOR]

Background: Long-term glycemic control reduces retinopathy risk, but transient worsening can occur with glucose control intensification. Glucagon-like peptide 1 receptor agonists (GLP-1RA) lower glucose, but the long-term impact on retinopathy is unknown. GLP-1RA cardiovascular outcome trials (CVOTs) provide long-term follow-up, allowing examination of retinopathy outcomes.Purpose: To examine the associations between retinopathy, HbA1c, systolic blood pressure (SBP), and weight in GLP-1RA CVOTs.Data Sources: Systematic review identified six placebo-controlled GLP-1RA CVOTs reporting prespecified retinopathy outcomes.Study Selection: Published trial reports were used as the primary data sources.Data Extraction: HbA1c, SBP, and weight data throughout follow-up by treatment group were extracted.Data Synthesis: Random-effects model meta-analysis showed no association between GLP-1RA treatment and retinopathy (odds ratio [OR] 1.10; 95% CI 0.93, 1.30), with high heterogeneity between studies (I2 = 52.2%; Q statistic P = 0.063). Univariate meta-regression showed an association between retinopathy and average HbA1c reduction during the overall follow-up (slope = 0.77, P = 0.007), but no relationship for SBP or weight. Sensitivity analyses for HbA1c showed a relationship at 3 months (P = 0.006) and 1 year (P = 0.002). A 0.1% (1.09 mmol/mol) increase in HbA1c reduction was associated with 6%, 14%, or 8% increased Ln(OR) for retinopathy at the 3-month, 1-year, and overall follow-up, respectively.Limitations: CVOTs were not powered to assess retinopathy outcomes and differed in retinopathy-related criteria and methodology. The median follow-up of 3.4 years is short compared with the onset of retinopathy.Conclusions: HbA1c reduction was significantly associated with increased retinopathy risk in meta-regression for GLP-1RA CVOTs. The magnitude of HbA1c reduction was correlated with retinopathy risk in people with diabetes and additional cardiovascular risk factors, but the long-term impact of improved glycemic control on retinopathy was unmeasured in these studies. Retinopathy status should be assessed when intensifying glucose-lowering therapy. [ABSTRACT FROM AUTHOR]

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is being tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and results: Adults with established HFrEF, New York Heart Association (NYHA) functional class ≥II, ejection fraction ≤35%, elevated natriuretic peptides and either current hospitalization for heart failure or history of hospitalization/emergency department visit for heart failure within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5, or 50 mg bid). A total of 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean ejection fraction 27%, ischaemic aetiology in 54%, NYHA class II 53% and III/IV 47%, and median N‐terminal pro‐B‐type natriuretic peptide 1971 pg/mL. Heart failure therapies at baseline were among the most effectively employed in contemporary heart failure trials. GALACTIC‐HF randomized patients representative of recent heart failure registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure <100 mmHg (n = 1127), estimated glomerular filtration rate <30 mL/min/1.73 m2 (n = 528), and treated with sacubitril/valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation. [ABSTRACT FROM AUTHOR]

Severe catastrophic natural disasters adversely affect housing stock and regional capacity to build and repair houses, with unfavorable impacts on the business continuity of industrial and business organizations resting on that affected community. Restoring industrial capacity and business continuity is crucial for the organizations’ survival in the aftermath of a disaster but the process takes time while the affected region faces an unexpected surge in the demand for housing. Modeling approaches largely used in the supply chain management realm may support humanitarian logistics and policy-making by providing a testbed in which supply chain elements of the recovery process can be examined before implementing. This research presents a system dynamics model that considers the problem of housing recovery from the demand and supply perspective and provides significant insights for policymakers into how the production of permanent housing depends upon the uncertainties and feedback effects of material and labor. In order to highlight its utility, a hypothetical scenario in which a hurricane hits the U.S. Hampton Roads region, which is a major population center along the mid-Atlantic coast, has been configured by using actual data collected from both governmental and academic sources. [ABSTRACT FROM AUTHOR]

• Examined how vulnerability and COVID-19 alter evacuation behavior. • People afraid of COVID-19 exposure may refuse to evacuate. • Web and phone surveys were conducted in the Hampton Roads area of U.S. Virginia. • Developed a multinomial order logit model on factors and intended decisions. • Race and risk perception influence the decision-making evacuation process. Historical data suggest that when a severe tropical storm or hurricane impacts a community, the vulnerable segment of the population suffers the most severe consequences. With an increased aging population, it is crucial to understand how vulnerability alters evacuation behavior. Emergent variables such as fear of COVID-19 require additional exploration. People afraid of COVID-19 exposure may refuse to evacuate, exposing themselves unnecessarily. Differentiation is critical to evacuation logistics since it is needed to determine what proportion would stay in a local shelter, public or other, rather than evacuating or staying in their home and guide the logistics resource allocation process. This research uses data from a web and phone survey conducted in the Hampton Roads area of U.S. Virginia, with 2,200 valid responses to analyze the influence of social and demographic vulnerability factors and risk perception on evacuation decisions. This research contributes to the existing literature by developing a multinomial order logit model based on vulnerability factors and intended evacuation decisions, including staying at home, looking for a shelter, or leaving the Hampton Roads area. Findings show that race and risk perception are the variables that influence the decision-making process the most. Fear of COVID-19 transmission is also associated with an increased likelihood of leaving homes during evacuation. The variations in findings from previous studies are discussed regarding their implications for logistics emergency managers. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is the leading cause of death and disability in Argentina. Because most of the patients who are aware of their diagnosis were receiving medications, increasing the rate of awareness would immediately translate into a higher rate of treated patients and, most likely, better rates of hypertension control. At 3 years, the rate of blood pressure control was high (82%), and patients were receiving 2.5 antihypertension drugs on average (unpublished data, 2018). [Extracted from the article]

Study Design: A case report.Objective: We describe a technique to drain a thoracic and cervical postoperative epidural hematoma causing paraplegia after anterior cervical discectomy and fusion.Summary Of Background Data: Postoperative compressive spinal epidural hematoma (SEH) is a devastating complication and early diagnosis and treatment is essential. The most commonly accepted treatment is decompression and drainage of hematoma.Methods: A 65-year-old male with a degenerative disc disease located at C4-C5, C5-C6, and C6-C7 levels with disc herniation underwent a standard anterior cervical decompression and fusion at C4-C5-C6-C7. Three hours after the procedure, the patient started complaining of progressive paraplegia and affectation of upper extremity. A magnetic resonance imaging (MRI) revealed a postoperative SEH extending from C3 to T6, causing compression.To resolve this unusual complication, a new surgery was performed. An anterior approach through the previous one was performed, and a C6 corpectomy was done. The anterior epidural hematoma was drained with an elastic urinary catheter. At the end of the surgery, a tricortical iliac crest autograft was placed between C5-C7 and the plate was placed as previously.Results: The patient recovered tactile and vibratory senses, as well as motor function in both hands 12 hours after the second procedure. The complete drainage of the hematoma was MRI-verified the first postoperative day.The patient was discharged from the hospital presenting a complete sensitive recovery and a 3/5 of muscle recovery. At one year, the patient made a full recovery and was able to walk unassisted.Conclusion: The treatment of choice in SEH is the early decompression as complete as possible, usually with the same approach or at the level of major compression. In rare cases like this, we recommend the use of an elastic catheter to complete hematoma drainage, distant from the surgical wound.Level Of Evidence: N/A. [ABSTRACT FROM AUTHOR]

Investment in transportation infrastructure has been widely utilized as an instrument for inducing economic growth. Such investment usually leads to job creation and an increase in per capita income that attracts population through migration to the region. This increases the utilization of the transport infrastructure over time, resulting in high levels of congestion. The congestion negatively impacts the attractiveness of the region and the gross regional product (GRP). Regions cyclically invest in transport infrastructure that temporally spurs economic activity and migration, and reduces congestion. This research employs a system dynamics simulation approach to capture and mimic the behavior of these complex and cyclical relationships over time. Our approach suggests the modeling of key demographic, transportation infrastructure, travel behavior, and economic activity components to determine the impact of infrastructure investments on regional growth. Given a set of prospective investment scenarios, the model replicates and projects levels of productivity, travel demand, congestion, GRP, and net migration patterns over time. The model also provides insights into the duration of critical cyclical patterns given these prospective infrastructure investments. The simulation model presented in this paper seeks to be utilized as guidance to support decision-making processes that lead to the execution of more exhaustive transportation studies that organize the execution of such investments. [ABSTRACT FROM AUTHOR]

Objectives: First, to test a model of the drivers of frequent emergency department utilization conceptualized as falling within predisposing, enabling, and need dimensions. Second, to extend the model to include social networks and service quality as predictors of frequent utilization. Third, to illustrate the variation in thresholds that define frequent utilization in terms of the number of emergency department encounters by the predictors within the model. Data Source: Primary data collection over an eight week period within a level-1 trauma urban hospital’s emergency department. Study Design: Representative randomized sample of 1,443 adult patients triaged ESI levels 4–5. Physicians and research staff interviewed patients as they received services. Relationships with the outcome variable, utilization, were tested using logistic regression to establish odds-ratios. Principal Findings: 70.6 percent of patients have two or more, 48.3 percent have three or more, 25.3 percent have four or more, and 14.9 percent have five or more emergency department visits within 12 months. Factors associated with frequent utilization include gender, race, poor mental health, mental health drugs, prescription drug abuse, social networks, employment, perceptions of service quality, seriousness of condition, persistence of condition, and previous hospital admittance. Conclusions: Interventions targeting associated factors will change global emergency department encounters, although the mutability varies. Policy interventions to address predisposing factors such as substance abuse or access to mental health treatment as well as interventions that speak to enabling factors such as promoting the resiliency of social networks may result in decreased frequency of emergency department utilization. [ABSTRACT FROM AUTHOR]

Chronic diseases are persistent ailments that are not preventable or curable with medication or vaccination. Many of the leading chronic conditions in industrialized societies may be related to lifestyle choices. The prevalence of these chronic conditions significantly affects the health, suffering, and longevity of patients. This paper demonstrates the utility of system dynamics as an approach to model and simulate the behavior of key cost factors in the implementation of population health management interventions. The study uses modeling and simulation as an evaluative method to identify potential savings stemming from an intervention within a well-defined population group. The model is flexible in that it allows policy-makers the ability to set saving targets that, in turn, generate knowledge about the cost structure adjustments necessary to reach these targets. The model provides useful insights into how the initial estimates of the cost of intervention, the resulting savings, and potential costs adjustments may change. The functionality of the model is demonstrated by means of scenarios implemented via sensitivity analysis. [ABSTRACT FROM AUTHOR]

Despite the non-trivial number of (non-institutionalized) residents with special needs – referred to as the medically fragile population in this paper – there is virtually no research available to guide the hurricane evacuation planning for this population group. One area is their evacuation time choice behavior that can have tremendous implications for their safety as well as the logistics of the evacuation process. In this paper, we fundamentally advance our understanding of the evacuation timing behavior of this heavily understudied, and potentially vulnerable, population group. Analysis indicates that key differences exist between the medically fragile and non-medically fragile population. [ABSTRACT FROM AUTHOR]

Background: This research offers two exploratory frameworks, one for medical regimen compliance and one for medical immediacy. The first classifies compliance awareness, compliance mitigation, and financial limitation for those patients that exhibit nonadherence with a medical regimen. The second classifies medical immediacy and characterizes avoidable utilization. Methods: Representative sampling of adult patients presenting at an emergency department (62,000/ppy) triaged as low acuity; emergency department physician assessment of noncompliance with medical regimen for those patients with a complaint related to a chronic condition; and emergency department physician assessment of medical immediacy and avoidable utilization. Results: Physicians report 48.3% (95% confidence interval (CI) 43.5% to 53.1%) of patients with at least a single chronic condition are presenting with symptoms or complaint related to a chronic condition, and 39.6% (CI 31.7% to 47.4%) of these exhibit noncompliance with the medical regimen associated with that chronic condition. 16.4% (CI 6.6% to 26.1%) of the patients exhibit pseudo compliance, a belief that the medical regimen is in compliance when in fact it is not. If the patient had been in compliance, 85.9% (CI 77.0% to 94.8%) of the presenting conditions may have been mitigated. Noncompliance cases (34.5% (CI 22.0% to 47.1%)) are partly attributable to financial constraints. Further, 19.1% (CI 15.7% to 22.5%) are assessed as requiring no medical intervention and 3.4% (CI 1.8% to 4.9%) require immediate stabilization. Conclusions: A large portion of low-acuity presentations are related to a chronic condition and noncompliance with the associated medical regimen contributes to the need to seek medical services. Interventions addressing literacy and financial constraints may increase compliance and decrease utilization. [ABSTRACT FROM AUTHOR]

This article discusses the dynamics inherent in modeling and simulation (M&S) standards development processes within the context of the competitive struggle for resources and market dominance. A conceptual framework is presented that provides the theoretical logic for the tension between inclusive, consensus-driven standards development processes and exclusive, preferential processes. Standards development is conceptualized as a porous process subject to both cooperative interests and competitive pressures. We elucidate how the tension between these two process ideals shapes the adoption and conformity of M&S standards and, in turn, how these processes facilitate broader system values. Normative questions are explicated about the proper tradeoffs among the desire to realize collective efficiencies gained through standards, the drive to create, own, and financially exploit new, emerging technologies through the concept of intellectual property, and the objective of economic development through fostering innovation. Both the organizational and individual incentives to engage in standards processes are discussed, together with how the politics of participation may shape standards development. This research contributes a compelling theoretical perspective not fully developed in the growing and changing discipline of M&S. The significance of exploring these questions is found in that there is a national interest in M&S standards development activities that contribute to our technological innovation and economic competitiveness. [ABSTRACT FROM PUBLISHER]

The article focuses on the status and management of verticillium wilt, considered to be a major threat to olive production. It says that verticillium wilt is olive is caused by Verticillium dahliae Kleb, a soilborne fungus, in which it states that the said fungus is the most soilborne disease the affect worldwide olive production. It discusses the syndromes and symptoms of the said olive plant disease, adding that the disease has two syndromes such as defoliating (D) and non- defoliating (ND).

Severity of Verticillium wilt in olive trees in Andalusia, southern Spain is associated with the spread of a highly virulent, defoliating (D) Verticil-Hum dahliae pathotype of vegetative compatibility group 1A (VCG1A) but the extent of this spread and the diversity of the pathogen population have never been documented. VCG typing of 637 V. dahliae isolates from 433 trees in 65 orchards from five olive-growing provinces in Andalusia indicated that 78.1% were of VCG1A, 19.8% of VCG2A, 0.6% of VCG2B, 1.4% of VCG4B, and one isolate was heterokaryon self-incompatible. A single VCG prevailed among isolates within most orchards but two and three VCGs were identified in 12 and 3 orchards, respectively, with VCG1A+VCG2A occurring in 10 orchards. VCG1A was the predominant VCG in the three most important olive-growing provinces, and was almost as prevalent as VCG2A in another one. Molecular pathotyping of the 637 isolates using specific polymerase chain reaction assays indicated that VCG1A isolates were of the D pathotype whereas isolates of VCG2A, -2B, and -4B were of the less virulent nondefoliating (ND) pathotype. The pathotype of isolates correlated with the disease syndrome affecting sampled trees. Only three (seql, seq2, and seq4) of the seven known sequences of the V. dahliae-specific 539- or 523-bp amplicon were identified among the 637 isolates. Distribution and prevalence of VCGs and seq sequences among orchards indicated that genetic diversity within olive V. dahliae in Andalusia is higher in provinces where VCG1A is not prevalent. Log-linear analysis revealed that irrigation management, source of irrigation water, source of planting stock, and cropping history of soil were significantly associated with the prevalence of VCG1A compared with that of VCG2A. Multivariate analyses using a selected set of agricultural factors as variables allowed development of a discriminant model for predicting the occurrence of D and ND pathotypes in the area of the study. Blind tests using this model correctly indentified the V. dahliae pathotype occurring in an orchard. The widespread occurrence and high prevalence of VCG IA/D pathotype in Andalusia have strong implications for the management of the disease. [ABSTRACT FROM AUTHOR]

Pulsed-field gel electrophoresis and 16S rRNA hybridization experiments showed that multichromosome genome structures and very large genome sizes (6.46 to 8.73 Mb) are prevalent in novel plant-associated Burkholderia species. 15N2 isotope dilution assays revealed unambiguous diazotrophy in these novel species. nifH gene sequence analysis, often used to determine phylogenetic relatedness among diazotrophs, showed tight clusters of Burkholderia species, which were clearly distinct from those of other diazotrophs. [ABSTRACT FROM AUTHOR]

This article presents the results of a study to determine the clinical benefit of glucose-insulin-potassium (GIK) infusion in patients with ST-segment elevation myocardial infarction (STEMI). Some smaller trials have suggested a benefit while the large Clinical Trial of Reviparin and Metabolic Modulation in Acute Myocardial Infarction Treatment and Evaluation (CREATE-ECLA) trial showed no benefit. This study looked at mortality rates at 30 days and 6 months for patients treated with GIK and found that the treatment provided no benefit and may even cause early harm in patients who have a STEMI. The authors suggest avoidance of the treatment until more studies can be performed.

This study examined the relationship between initimate partner violence (IPV) and HIV sexual risk behavior using a probability sample of 912 Latino gay and bisexual men from three U.S. cities. Prevalence estimates of psychological, physical, and sexual abuse are higher in our sample than usually found in the general population of gay and bisexual or heterosexual men, with 52% reporting some type of abuse, IPV also was associated with being HIV positive. Controlling for HIV status, age, and immigrant status, all three dimensions of IPV-psychological [RR = 2,42; 95% CI = 1,02, 5,78], physical, [RR = 2,86; 95% CI = 1,21, 6,74], and sexual abuse [RR = 4,63; 95% CI = 1.63, 13.18]-were, overall, associated with significantly greater likelihood of unprotected receptive anal intercourse with a non-monogamous partner. Sexual abuse [RR = 3,22; 95% CI = 1,00, 10,37], emerged as significant even while controlling for the other two dimensions of IPV. [ABSTRACT FROM AUTHOR]

Focuses on the Collaborative HIV Prevention Research in Minority Communities Program of the National Institutes of Health in the U.S. Purpose of the program; Elements of the program; Comparison on the health conditions between the white population and the communities of color.

Presents a study which explored behavioral self-regulation, private speech and speech-action coordination in behaviorally at-risk preschool children. Method; Results and discussion.

Aims Methods and results Conclusions Biologically active adrenomedullin (bio‐ADM) is a promising marker of residual congestion. The STRONG‐HF trial showed that high‐intensity care (HIC) of guideline‐directed medical therapy (GDMT) improved congestion and clinical outcomes in heart failure (HF) patients. The association between bio‐ADM, decongestion, outcomes and the effect size of HIC of GDMT remains to be elucidated.We measured plasma bio‐ADM concentrations in 1005 patients within 2 days prior to anticipated discharge (baseline) and 90 days later. Bio‐ADM correlated with most signs of congestion, with the exception of rales. Changes in bio‐ADM were strongly correlated with change in congestion status from baseline to day 90 (gamma −0.24; p = 0.0001). Patients in the highest tertile of baseline bio‐ADM concentrations were at greater risk than patients in the lowest tertile for the primary outcome of 180‐day all‐cause mortality or HF rehospitalization (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.42–3.22) and 180‐day HF rehospitalization (HR 2.33, 95% CI 1.38–3.94). Areas under the receiver‐operating characteristic curves were 0.5977 (95% CI 0.5561–0.6393), 0.5800 (95% CI 0.5356–0.6243), and 0.6159 (95% CI 0.5711–0.6607) for bio‐ADM, N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and their combination, respectively, suggesting that both bio‐ADM and NT‐proBNP provided similarly modest discrimination for this outcome. A trend towards better discrimination by combined bio‐ADM and NT‐proBNP than NT‐proBNP alone was found (p = 0.059). HIC improved the primary outcome, irrespective of baseline bio‐ADM concentration (interaction p = 0.37). In contrast to NT‐proBNP, the 90‐day change in bio‐ADM did not differ significantly between HIC and usual care.Bio‐ADM is a marker of congestion and predicts congestion at 3 months after a HF hospitalization. Higher bio‐ADM was modestly associated with a higher risk of death and early hospital readmission and may have added value when combined with NT‐proBNP. [ABSTRACT FROM AUTHOR]

Presents information on a study which explored the patterns of mother-child interaction, children's private speech use, and behavioral self-regulation among the preschool children with behavior problems. Association of task performance with the internalized private speech use among preschoolers; Quality of parent-child interaction; Results of the study; Conclusions.

This study examined four types of predictors of sexual risk within a sample of 110 predominantly English-speaking Latino gay/bisexual men residing in the city of San Francisco. More than one fourth of the sample reported at least one instance of unprotected anal intercourse in the last 30 days; one fifth of the sample reported unprotected anal intercourse with a nonmonogamous sexual partner within the same time period. Findings suggest that weak personal intentions for safer sex and low levels of perceived self-efficacy are associated with risky sexual practices. In addition, a history of sexual abuse in childhood, drug use during sexual activity, and frequency of sex in public cruising environments emerged as significant predictors of sexual risk. Multivariate analyses indicated that a four-predictor model (including a young age, low levels of intention/self-efficacy, a high frequency of sex under the influence of drugs, and a high frequency of sex with nonmonogamous partners) is the most parsimonious model to predict sexual risk in this population. A history of childhood sexual abuse correlated positively with all predictors of risk in the model, except age. [ABSTRACT FROM AUTHOR]

In this paper, we analyse the focus group discussions of approximately 300 Latino gaymen, when asked to explain the high rates of unprotected anal intercourse in their communities. Men's responses and discussions were mapped into three different categories, representing different ideologies of sexual risk: (1) ideologies about situations, circumstances and male characteristics that converge in a loss of sexual control; (2) ideologies about a basic incompatibility between safer sex and interpersonal trust, intimacy and love; and (3) fatalistic ideologies about the inevitability of HIV infection, where the fatalism evokes responses ranging from resignation to rebellion. The ideologies presented here should not be interpreted simplistically as 'causes' for unprotected sex; rather, they are windows offering views of socially-shared meaning that can help us understand the subjective experience of those who struggle with safer sex in the Latino gay community. [ABSTRACT FROM AUTHOR]

Studies bilingual cognitive development by testing Spanish-English bilingual children attending kindergarten and first grade bilingual education programs at two points in time, six months apart. Attribution of cognitive differences between second-language proficiency groups to group differences in socioeconomic variables; Positive relationship between degree of bilingualism and cognitive abilities.

An introduction is presented in which the authors discuss various reports within the issue on topics including the applications of modeling and simulations (M&S) and optimization heuristics, the flexible job shop scheduling problem (FJSP), and time-cost tradeoffs uncertainty for PERT-type projects.

Long-term glucose control reduces retinopathy risk. We examine the association between HbA1c change and retinopathy in the first year or at final follow-up in GLP-1 RA cardiovascular outcomes trials (CVOTs). A random-effects model meta-analysis included 6 CVOTs reporting retinopathy events, using within-trial event definitions. Univariate meta-regression analyses describe the association between HbA1c change and retinopathy events. Meta-analysis showed no significant effect of GLP-1 RA on retinopathy risk (odds ratio [OR] 1.10; 95% CI 0.93, 1.30), with moderate heterogeneity between studies (I2=52.2%; Q-statistic p-value=0.063). HbA1c change and retinopathy were significantly associated at 1-year (slope=1.40, p-value=0.002) and overall (Figure), with 0.1% HbA1c reduction associated with 15% increased OR in the first year, declining to 8.0% increase over longer follow-up. In these studies of varying duration (1.3 to 5.4 years), GLP-1 RA treatment was not significantly associated with increased retinopathy risk. HbA1c reduction rate is correlated with risk for retinopathy in people with diabetes and additional CV risk factors. Clinicians should consider retinopathy status when initiating any therapy that rapidly lowers HbA1c. Disclosure: A. Bethel: Employee; Self; Eli Lilly and Company. R. Diaz: None. N. Castellana: None. H.C. Gerstein: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Consultant; Self; Kowa Pharmaceuticals America, Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Other Relationship; Self; Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Sanofi. M. Lakshmanan: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. Funding: Eli Lilly and Company [ABSTRACT FROM AUTHOR]

Aims: A high‐intensity care (HIC) strategy with rapid guideline‐directed medical therapy (GDMT) up‐titration and close follow‐up visits improved outcomes, compared to usual care (UC), in patients recently hospitalized for acute heart failure (AHF). Hypotension is a major limitation to GDMT implementation. We aimed to assess the impact of baseline systolic blood pressure (SBP) on the effects of HIC versus UC and the role of early SBP changes in STRONG‐HF. Methods and results: A total of 1075 patients hospitalized for AHF with SBP ≥100 mmHg were included in STRONG‐HF. For the purpose of this post‐hoc analysis, patients were stratified by tertiles of baseline SBP (<118, 118–128, and ≥129 mmHg) and, in the HIC arm, by tertiles of changes in SBP from the values measured before discharge to those measured at 1 week after discharge (≥2 mmHg increase, ≤7 mmHg decrease to <2 mmHg increase, and ≥8 mmHg decrease). The primary endpoint was 180‐day heart failure rehospitalization or death. The effect of HIC versus UC on the primary endpoint was independent of baseline SBP evaluated as tertiles (pinteraction = 0.77) or as a continuous variable (pinteraction = 0.91). In the HIC arm, patients with increased, stable and decreased SBP at 1 week reached 83.5%, 76.2% and 75.3% of target doses of GDMT at day 90. The risk of the primary endpoint was not significantly different between patients with different SBP changes at 1 week (adjusted p = 0.46). Conclusions: In STRONG‐HF, the benefits of HIC versus UC were independent of baseline SBP. Rapid GDMT up‐titration was performed also in patients with an early SBP drop, resulting in similar 180‐day outcome as compared to patients with stable or increased SBP. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The cardiovascular benefits of low-dose colchicine have been demonstrated in patients with coronary disease. Its effects were evaluated in this prespecified analysis in patients with type 2 diabetes (T2D) from the Colchicine Cardiovascular Outcomes Trial (COLCOT). RESEARCH DESIGN AND METHODS: COLCOT was a randomized, double-blinded trial of colchicine, 0.5 mg daily, versus placebo initiated within 30 days after a myocardial infarction. RESULTS: There were 959 patients with T2D enrolled and monitored for a median of 22.6 months. A primary end point event occurred in 8.7% of patients in the colchicine group and in 13.1% in the placebo group (hazard ratio 0.65; 95% CI 0.44–0.96; P = 0.03). Nausea was reported in 2.7% and 0.8% in the study groups (P = 0.03), and pneumonia occurred in 2.4% and 0.4% (P = 0.008). CONCLUSIONS: Among patients with T2D and a recent myocardial infarction, colchicine, 0.5 mg daily, leads to a large reduction of cardiovascular events. These results support the conduct of the COLCOT-T2D trial in primary prevention. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lipoprotein(a) is a risk factor for cardiovascular events and modifies the benefit of PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors. Lipoprotein(a) concentration can be measured with immunoassays reporting mass or molar concentration or a reference measurement system using mass spectrometry. Whether the relationships between lipoprotein(a) concentrations and cardiovascular events in a high-risk cohort differ across lipoprotein(a) methods is unknown. We compared the prognostic and predictive value of these types of lipoprotein(a) tests for major adverse cardiovascular events (MACE). METHODS: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the PCSK9 inhibitor alirocumab with placebo in patients with recent acute coronary syndrome. We compared risk of a MACE in the placebo group and MACE risk reduction with alirocumab according to baseline lipoprotein(a) concentration measured by Siemens N-latex nephelometric immunoassay (IA-mass; mg/dL), Roche Tina-Quant turbidimetric immunoassay (IA-molar; nmol/L), and a noncommercial mass spectrometry-based test (MS; nmol/L). Lipoprotein(a) values were transformed into percentiles for comparative modeling. Natural cubic splines estimated continuous relationships between baseline lipoprotein(a) and outcomes in each treatment group. Event rates were also determined across baseline lipoprotein(a) quartiles defined by each assay. RESULTS: Among 11970 trial participants with results from all 3 tests, baseline median (Q1, Q3) lipoprotein(a) concentrations were 21.8 (6.9, 60.0) mg/dL, 45.0 (13.2, 153.8) nmol/L, and 42.2 (14.3, 143.1) nmol/L for IA-mass, IA-molar, and MS, respectively. The strongest correlation was between IA-molar and MS (r=0.990), with nominally weaker correlations between IA-mass and MS (r=0.967) and IA-mass and IA-molar (r=0.972). Relationships of lipoprotein(a) with MACE risk in the placebo group were nearly identical with each test, with estimated cumulative incidences differing by ≤0.4% across lipoprotein(a) percentiles, and all were incrementally prognostic after accounting for low-density lipoprotein cholesterol levels (all spline P≤0.0003). Predicted alirocumab treatment effects were also nearly identical for each of the 3 tests, with estimated treatment hazard ratios differing by ≤0.07 between tests across percentiles and nominally less relative risk reduction by alirocumab at lower percentiles for all 3 tests. Absolute risk reduction with alirocumab increased with increasing lipoprotein(a) measured by each test, with significant linear trends across quartiles. CONCLUSIONS: In patients with recent acute coronary syndrome, 3 lipoprotein(a) tests were similarly prognostic for MACE in the placebo group and predictive of MACE reductions with alirocumab at the cohort level. [ABSTRACT FROM AUTHOR]

Aim: In this subgroup analysis of STRONG‐HF, we explored the association between changes in renal function and efficacy of rapid up‐titration of guideline‐directed medical therapy (GDMT) according to a high‐intensity care (HIC) strategy. Methods and results: In patients randomized to the HIC arm (n = 542), renal function was assessed at baseline and during follow‐up visits. We studied the association with clinical characteristics and outcomes of a decrease in estimated glomerular filtration rate (eGFR) at week 1, defined as ≥15% decrease from baseline. Patients in the usual care group (n = 536) were seen at day 90. The treatment effect of HIC versus usual care was independent of baseline eGFR (p‐interaction = 0.4809). A decrease in eGFR within 1 week occurred in 77 (15.5%) patients and was associated with more rales on examination (p = 0.004), and a higher New York Heart Association class at the corresponding visit. Following the decrease in eGFR at 1 week, lower average optimal doses of GDMT were prescribed during follow‐up (p = 0.0210) and smaller reductions in N‐terminal pro‐B‐type natriuretic peptide occurred (geometrical mean 0.81 in no eGFR decrease vs 1.12 in GFR decrease, p = 0.0003). The rate of heart failure (HF) readmission or death at 180 days was 12.3% in no eGFR decrease versus 18.5% in eGFR decrease (p = 0.2274) and HF readmissions were 7.8% versus 16.6% (p = 0.0496). Conclusions: In the STRONG‐HF study, HIC reduced 180‐day HF readmission or death regardless of baseline eGFR. An early decrease in eGFR during rapid up‐titration of GDMT was associated with more evidence of congestion, yet lower doses of GDMT during follow‐up. [ABSTRACT FROM AUTHOR]

Aims: To assess the potential interaction between non‐cardiac comorbidities (NCCs) and the efficacy and safety of high‐intensity care (HIC) versus usual care (UC) in the STRONG‐HF trial, including stable patients with improved but still elevated natriuretic peptides. Methods and results: In the trial, eight NCCs were reported: anaemia, diabetes, renal dysfunction, severe liver disease, chronic obstructive pulmonary disease/asthma, stroke/transient ischaemic attack, psychiatric/neurological disorders, and malignancies. Patients were classified by NCC number (0, 1, 2 and ≥3). The treatment effect of HIC versus UC on the primary endpoint, 180‐day death or heart failure (HF) rehospitalization, was compared by NCC number and by each individual comorbidity. Among the 1078 patients, the prevalence of 0, 1, 2 and ≥3 NCCs was 24.3%, 39.8%, 24.5% and 11.4%, respectively. Achievement of full doses of HF therapies at 90 and 180 days in the HIC was similar irrespective of NCC number. In HIC, the primary endpoint occurred in 10.0%, 16.6%, 13.6% and 26.2%, in those with 0, 1, 2 and ≥3 NCCs, respectively, as compared to 19.1%, 25.4%, 23.3% and 26.2% in UC (interaction‐p = 0.80). The treatment benefit of HIC versus UC on the primary endpoint did not differ significantly by each individual comorbidity. There was no significant treatment interaction by NCC number in quality‐of‐life improvement (p = 0.98) or the incidence of serious adverse events (p = 0.11). Conclusions: In the STRONG‐HF trial, NCCs neither limited the rapid up‐titration of HF therapies, nor attenuated the benefit of HIC on the primary endpoint. In the context of a clinical trial, the benefit–risk ratio favours the rapid up‐titration of HF therapies even in patients with multiple NCCs. [ABSTRACT FROM AUTHOR]

Studies of adults who experienced sexual orientation change efforts (SOCE) have documented a range of health risks. To date, there is little research on SOCE among adolescents and no known studies of parents' role related to SOCE with adolescents. In a cross-sectional study of 245 LGBT White and Latino young adults (ages 21–25), we measured parent-initiated SOCE during adolescence and its relationship to mental health and adjustment in young adulthood. Measures include being sent to therapists and religious leaders for conversion interventions as well as parental/caregiver efforts to change their child's sexual orientation during adolescence. Attempts by parents/caregivers and being sent to therapists and religious leaders for conversion interventions were associated with depression, suicidal thoughts, suicidal attempts, less educational attainment, and less weekly income. Associations between SOCE, health, and adjustment were much stronger and more frequent for those reporting both attempts by parents and being sent to therapists and religious leaders, underscoring the need for parental education and guidance. [ABSTRACT FROM AUTHOR]

Aims: STRONG‐HF examined a high‐intensity care (HIC) strategy of rapid up‐titration of guideline‐directed medical therapy (GDMT) and close follow‐up after acute heart failure (AHF) admission. We assess the role of age on efficacy and safety of HIC. Methods and results: Hospitalized AHF patients, not treated with optimal GDMT were randomized to HIC or usual care. The primary endpoint of 180‐day death or HF readmission occurred equally in older (>65 years, n = 493, 74 ± 5 years) and younger patients (53 ± 11 years, adjusted hazard ratio [aHR] 1.02, 95% confidence interval [CI] 0.73–1.43, p = 0.89). Older patients received slightly lower GDMT to day 21, but same doses at day 90 and 180. The effect of HIC on the primary endpoint was numerically higher in younger (aHR 0.51, 95% CI 0.32–0.82) than older patients (aHR 0.73, 95% CI 0.46–1.15, adjusted interaction p = 0.30), partially related to COVID‐19 deaths. After exclusion of COVID‐19 deaths, the effect of HIC was similar in younger (aHR 0.51, 95% CI 0.32–0.82) and older patients (aHR 0.63, 95% CI 0.32–1.02, adjusted interaction p = 0.56), with no treatment‐by‐age interaction (interaction p = 0.57). HIC induced larger improvements in quality of life to day 90 in younger (EQ‐VAS adjusted‐mean difference 5.51, 95% CI 3.20–7.82) than in older patients (1.77, 95% CI −0.75 to 4.29, interaction p = 0.032). HIC was associated with similar rates of adverse events in older and younger patients. Conclusion: High‐intensity care after AHF was safe and resulted in a significant reduction of all‐cause death or HF readmission at 180 days across the study age spectrum. Older patients have smaller benefits in terms of quality of life. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to evaluate efficacy and safety of rapid up‐titration of guideline‐directed medical therapies (GDMT) in men and women hospitalized for acute heart failure (AHF). Methods and results: In STRONG‐HF, AHF patients were randomized just prior to discharge to either usual care (UC) or a high‐intensity care (HIC) strategy of GDMT up‐titration. In these analyses, we compared the implementation, efficacy, and safety of the HIC strategy between men and women. In the randomized AHF population, 416/1078 (39%) were women. By day 90, a higher proportion of both sexes in the HIC group had been up‐titrated to full doses of GDMT compared to UC. Overall, there were no differences in the primary endpoint between the sexes. The primary endpoint, 180‐day heart failure readmission or death, occurred in 15.8% HIC women versus 23.5% women in the UC group (adjusted hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.40–1.13) and in 14.9% HIC men versus 23.5% UC men (adjusted HR 0.57, 95% CI 0.38–0.88) (adjusted interaction p = 0.65). There was no significant treatment‐by‐sex interaction in quality‐of‐life improvement or in adverse events, including serious or fatal adverse events. Conclusion: The results of the current analyses suggest that a rapid up‐titration of GDMT immediately after an AHF hospitalization can and should be implemented similarly in men and women, as it results in reduction of 180‐day all‐cause death or heart failure readmission, quality‐of‐life improvement in both men and women with a similar safety profile. [ABSTRACT FROM AUTHOR]

An introduction is presented which discusses various articles within the issue on topics including modeling and simulation (M&S) optimization for designing the parameters of a power system stabilizer (PSS), an approach for cell formation, and a mathematical approach for reducing the vibrations.

Acute heart failure (AHF) is associated with a poor prognosis regardless of left ventricular ejection fraction (LVEF). STRONG-HF showed the efficacy and safety of a strategy of rapid uptitration of oral treatment for heart failure (HF) and close follow-up (high-intensity care), compared with usual care, in patients recently hospitalized for AHF and enrolled independently from their LVEF. In this study, we sought to assess the impact of baseline LVEF on the effects of high-intensity care vs usual care in STRONG-HF. The STRONG-HF trial enrolled patients hospitalized for AHF with any LVEF and not treated with full doses of renin-angiotensin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. High-intensity care with uptitration of oral medications was performed independently from LVEF. The primary endpoint was the composite of HF rehospitalization or all-cause death at day 180. Among the 1,078 patients randomized, 731 (68%) had LVEF ≤40% and 347 (32%) had LVEF >40%. The treatment benefit of high-intensity care vs usual care on the primary endpoint was consistent across the whole LVEF spectrum (interaction P with LVEF as a continuous variable = 0.372). Mean difference in the EQ-5D visual analog scale change from baseline to day 90 between treatment arms was slightly greater at higher LVEF values, but with no interaction between LVEF as a continuous variable and the treatment strategy (interaction P = 0.358). Serious adverse events were also independent from LVEF. Rapid uptitration of oral medications for HF and close follow-up reduce 180-day death and HF rehospitalization after AHF hospitalization independently from LVEF. (Safety, Tolerability and Efficacy of Rapid Optimization, Helped by NT-ProBNP Testing, of Heart Failure Therapies [STRONG-HF]; NCT03412201) [Display omitted] [ABSTRACT FROM AUTHOR]

Keywords: GLP-1 receptor agonists; lixisentatide; natriuretic peptides; randomized controlled trial EN GLP-1 receptor agonists lixisentatide natriuretic peptides randomized controlled trial 1125 1129 5 03/08/23 20230401 NES 230401 BACKGROUND Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) lower glucose, weight and blood pressure, and reduce cardiovascular and kidney outcomes in people with type 2 diabetes (T2D).[1], [2], [3] Although mechanisms for their effects remain unclear, small recent studies have reported that they may reduce natriuretic peptides.[4] B-type natriuretic peptide (BNP) and its inactive precursor N-terminal-pro BNP (NT-proBNP) were measured at baseline and follow-up in the Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial. GLP-1 receptor agonists, lixisentatide, natriuretic peptides, randomized controlled trial 2 Abbreviation: ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BNP, B-type natriuretic peptide; COPD, chronic obstructive pulmonary disease; GFR, glomerular filtration rate; NT-proBNP, N terminal, pro-hormone B-type natriuretic peptide. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials. [Extracted from the article]

Little is known about how adolescents cope with minority stressors related to sexual orientation. This study examined 245 lesbian, gay, and bisexual (LGB) young adult’s (ages 21–25) retrospective reports of coping in response to LGB minority stress during adolescence (ages 13–19) to test the reliability and validity of a measure of minority stress coping. Further, the study examined associations between LGB minority stress coping and young adult psychosocial adjustment and high school attainment. Validation and reliability was found for three minority stress coping strategies: LGB-specific strategies (e.g., involvement with LGBT organizations), alternative-seeking strategies (e.g., finding new friends), and cognitive strategies (e.g., imagining a better future). LGB-specific strategies were associated with better psychosocial adjustment and greater likelihood of high school attainment in young adulthood, whereas alternative-seeking and cognitive-based strategies were associated with poorer adjustment and less likelihood of high school attainment. [ABSTRACT FROM PUBLISHER]

Describes a practical regeneration of alcohols from their allylic ethers. Hydrolysis of bromo ether; High regioselectivity of the bromination.

Aim: N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) is predictive of both outcomes and response to treatment in patients with heart failure with reduced ejection fraction (HFrEF). The aim of this study was to examine the effect of the cardiac myosin activator omecamtiv mecarbil according to baseline NT‐proBNP level in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure trial (GALACTIC‐HF). Methods and results: The primary outcome was the composite of a worsening heart failure event (urgent clinic visit, emergency department visit, or hospitalization) or cardiovascular death. We prespecified analysis of the effect of treatment according to baseline NT‐proBNP (≤ median, > median), excluding individuals with atrial fibrillation/flutter (AF/AFL). Of the 8232 patients analysed, 8206 had an available baseline NT‐proBNP measurement. Among the 5971 patients not in AF/AFL, the median (Q1–Q3) NT‐proBNP level was 1675 (812–3579) pg/ml. Hazard ratios (HR) for the effect of omecamtiv mecarbil, compared with placebo, for the primary endpoint in patients without AF/AFL were: ≤ median 0.94 (95% confidence interval [CI] 0.80–1.09), > median 0.81 (0.73–0.90) (p‐interaction = 0.095); for the overall population (including patients with AF/AFL) the HRs were ≤ median 1.01 (0.90–1.15) and > median 0.88 (0.80–0.96) (p‐interaction = 0.035). There was an interaction between treatment and NT‐proBNP, examined as a continuous variable, with greater effect of omecamtiv mecarbil on the primary outcome in patients with a higher baseline NT‐proBNP (p‐interaction = 0.086). Conclusions: In GALACTIC‐HF, the benefit of omecamtiv mecarbil appeared to be larger in patients with higher baseline NT‐proBNP levels, especially in patients without AF/AFL. Clinical Trial Registration: ClinicalTrials.gov Identifier NCT02929329; EudraCT number, 2016‐002299‐28. [ABSTRACT FROM AUTHOR]