Does microcredit increase aspirational hope? Evidence from a group lending scheme in Sierra Leone:Evidence from a group lending scheme in Sierra Leone

Microcredit has received considerable attention due to its potential to help achieve the Sustainable Development Goals (SDGs), in particular through its effects on poverty alleviation, female empowerment and self-employment. To date, its effectiveness has largely been evaluated in terms of relieving external constraints of the poor, such as a lack of financial capital for business development. The current study examines whether, and to what extent, microcredit can change internal constraints, such as aspirational hope. We use a cross-sectional dataset of 1295 women in Sierra Leone, 854 of whom are active borrowers of a Microfinance Institution, BRAC. To assess the relationship between microcredit, aspirational hope and economic welfare, we rely on BRAC's eligibility criteria, that only allow access to finance for women living with-in 4 km of a BRAC branch. We find statistically significant and economically meaningful positive associations with both aspirational hope and economic welfare. Overall, this study suggests that microcredit could play an important role in reducing internal psychological constraints, and via this channel contributes to the realization of the SDGs.</p

Does Conflict affect Preferences? Results from Field Experiments in Burundi

We use experimental data from 35 randomly selected communities in Burundi to examine the impact of exposure to conflict on social-, risk- and time preferences. These types of preferences are important as they determine people’s propensity to invest and their ability to overcome social dilemmas, so that changes therein foster or hinder economic growth. We find that conflict affects preferences. Individuals that have been exposed to greater levels of violence display more altruistic behavior towards their neighbors, are more risk seeking, and have higher discount rates. Adverse, but temporary, shocks can thus alter savings and investments decisions, and potentially have long-run consequences.civil war, preferences, field experiments, Africa

Biomarker profiles of acute heart failure patients with a mid-range ejection fraction

OBJECTIVES: In this study, the authors used biomarker profiles to characterize differences between patients with acute heart failure with a midrange ejection fraction (HFmrEF) and compare them with patients with a reduced (heart failure with a reduced ejection fraction [HFrEF]) and preserved (heart failure with a preserved ejection fraction [HFpEF]) ejection fraction. BACKGROUND: Limited data are available on biomarker profiles in acute HFmrEF. METHODS: A panel of 37 biomarkers from different pathophysiological domains (e.g., myocardial stretch, inflammation, angiogenesis, oxidative stress, hematopoiesis) were measured at admission and after 24 h in 843 acute heart failure patients from the PROTECT trial. HFpEF was defined as left ventricular ejection fraction (LVEF) of ≥50% (n = 108), HFrEF as LVEF of &lt;40% (n = 607), and HFmrEF as LVEF of 40% to 49% (n = 128). RESULTS: Hemoglobin and brain natriuretic peptide levels (300 pg/ml [HFpEF]; 397 pg/ml [HFmrEF]; 521 pg/ml [HFrEF]; ptrend &lt;0.001) showed an upward trend with decreasing LVEF. Network analysis showed that in HFrEF interactions between biomarkers were mostly related to cardiac stretch, whereas in HFpEF, biomarker interactions were mostly related to inflammation. In HFmrEF, biomarker interactions were both related to inflammation and cardiac stretch. In HFpEF and HFmrEF (but not in HFrEF), remodeling markers at admission and changes in levels of inflammatory markers across the first 24 h were predictive for all-cause mortality and rehospitalization at 60 days (pinteraction &lt;0.05). CONCLUSIONS: Biomarker profiles in patients with acute HFrEF were mainly related to cardiac stretch and in HFpEF related to inflammation. Patients with HFmrEF showed an intermediate biomarker profile with biomarker interactions between both cardiac stretch and inflammation markers. (PROTECT-1: A Study of the Selective A1 Adenosine Receptor Antagonist KW-3902 for Patients Hospitalized With Acute HF and Volume Overload to Assess Treatment Effect on Congestion and Renal Function; NCT00328692)

Circumstellar Structure around Evolved Stars in the Cygnus-X Star Formation Region

We present observations of newly discovered 24 micron circumstellar structures detected with the Multiband Imaging Photometer for Spitzer (MIPS) around three evolved stars in the Cygnus-X star forming region. One of the objects, BD+43 3710, has a bipolar nebula, possibly due to an outflow or a torus of material. A second, HBHA 4202-22, a Wolf-Rayet candidate, shows a circular shell of 24 micron emission suggestive of either a limb-brightened shell or disk seen face-on. No diffuse emission was detected around either of these two objects in the Spitzer 3.6-8 micron Infrared Array Camera (IRAC) bands. The third object is the luminous blue variable candidate G79.29+0.46. We resolved the previously known inner ring in all four IRAC bands. The 24 micron emission from the inner ring extends ~1.2 arcmin beyond the shorter wavelength emission, well beyond what can be attributed to the difference in resolutions between MIPS and IRAC. Additionally, we have discovered an outer ring of 24 micron emission, possibly due to an earlier episode of mass loss. For the two shell stars, we present the results of radiative transfer models, constraining the stellar and dust shell parameters. The shells are composed of amorphous carbon grains, plus polycyclic aromatic hydrocarbons in the case of G79.29+0.46. Both G79.29+0.46 and HBHA 4202-22 lie behind the main Cygnus-X cloud. Although G79.29+0.46 may simply be on the far side of the cloud, HBHA 4202-22 is unrelated to the Cygnus-X star formation region.Comment: Accepted by A

Clinical Outcome Predictions for the VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) Trial

Background: The prediction of outcomes in patients with heart failure (HF) may inform prognosis, clinical decisions regarding treatment selection, and new trial planning. The VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction included high-risk patients with HF with reduced ejection fraction and a recent worsening HF event. The study participants had a high event rate despite the use of contemporary guideline-based therapies. To provide generalizable predictive data for a broad population with a recent worsening HF event, we focused on risk prognostication in the placebo group. Methods and Results: Data from 2524 participants randomized to placebo with chronic HF (New York Heart Association functional class II–IV) and an ejection fraction of less than 45% were studied and backward variable selection was used to create Cox proportional hazards models for clinical end points, selecting from 66 candidate predictors. Final model results were produced, accounting for missing data, and nonlinearities. Optimism-corrected c-indices were calculated using 200 bootstrap samples. Over a median follow-up of 10.4 months, the primary outcome of HF hospitalization or cardiovascular death occurred in 972 patients (38.5%). Independent predictors of increased risk for the primary end point included HF characteristics (longer HF duration and worse New York Heart Association functional class), medical history (prior myocardial infarction), and laboratory values (higher N-terminal pro-hormone B-type natriuretic peptide, bilirubin, urate; lower chloride and albumin). Optimism-corrected c-indices were 0.68 for the HF hospitalization/cardiovascular death model, 0.68 for HF hospitalization/all-cause death, 0.72 for cardiovascular death, and 0.73 for all-cause death. Conclusions: Predictive models developed in a large diverse clinical trial with comprehensive clinical and laboratory baseline data—including novel measures—performed well in high-risk patients with HF who were receiving excellent guideline-based clinical care. Clinical Trial Registration: Clinicaltrials.gov identifier, NCT02861534. Lay Summary: Patients with heart failure may benefit from tools that help clinicians to better understand a patient's risk for future events like hospitalization. Relatively few risk models have been created after the worsening of heart failure in a contemporary cohort. We provide insights on the risk factors for clinical events from a recent, large, global trial of patients with worsening heart failure to help clinicians better understand and communicate prognosis and select treatment options

Soluble guanylate cyclase stimulators in patients with heart failure with reduced ejection fraction across the risk spectrum

Patients with heart failure with reduced ejection fraction (HFrEF) have a high residual risk of adverse outcomes, even when treated with optimal guideline-directed medical therapy and in a clinically stable state. Soluble guanylate cyclase (sGC) stimulators have the potential to lower this risk by modifying the nitric oxide–sGC–cyclic guanosine monophosphate cascade – a pathophysiological pathway that has been targeted with limited success in HFrEF previously. Vericiguat, an sGC stimulator, was shown to improve outcomes in patients with HFrEF in the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial. However, this trial included patients with recently worsening disease. In this brief review, we discuss the rationale of evaluating sGC stimulators in lower-risk HFrEF patients. First, all key HFrEF medications have been evaluated in both higher- and lower-risk populations, and the treatment effect is not always consistent across the risk spectrum. Second, pre-clinical studies and post-hoc studies of the VICTORIA trial have suggested that sGC stimulators may have cardioprotective effects – these effects may be more apparent when the medication is initiated earlier in the disease process. Third, the effect of vericiguat on cardiovascular mortality remains uncertain and a trial with a longer follow-up in a lower-risk population may allow better assessment of its effect on cardiovascular mortality. Therefore, there is a pertinent need to investigate the effects of vericiguat in optimally treated, low-risk HFrEF patients (i.e. those without recently worsening heart failure).</p

Ejection Fraction, Biomarkers, and Outcomes and Impact of Vericiguat on Outcomes Across EF in VICTORIA

Background: Vericiguat reduced the risk of cardiovascular death (CVD) or hospitalization for heart failure (HF) in patients with worsening HF and reduced left ventricular ejection fraction (LVEF).Objectives: The authors assessed the association of LVEF with biomarker levels, risk of outcome, and whether the effect of vericiguat was homogeneous across LVEF in the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure With Reduced Ejection Fraction) trial.Methods: Patients were grouped by LVEF tertiles (≤24%, 25%-33%, and &gt;33%). Patient characteristics, clinical outcomes, and efficacy and safety of vericiguat were examined by tertile. Prespecified biomarkers including N-terminal pro–B-type natriuretic peptide, cardiac troponin T, growth differentiation factor 15, interleukin 6, high-sensitivity C-reactive protein, and cystatin C were examined.Results: The mean LVEF was 29% ± 8% (range: 5%-45%). A pattern of higher N-terminal pro–B-type natriuretic peptide, high-sensitivity C-reactive protein, and interleukin 6 was evident in patients in the lowest LVEF tertile vs the other tertiles. Patients with lower LVEF experienced higher rates of the composite outcome (41.7%, 36.3%, and 33.4% for LVEF ≤24, 25-33, and &gt;33; P &lt; 0.001). There was no significant treatment effect heterogeneity of vericiguat across LVEF groups (adjusted HR from lowest to highest tertiles: 0.79 [95% CI: 0.68-0.94]; 0.95 [95% CI: 0.82-1.11]; 0.94 [95% CI: 0.79-1.11]; P for interaction = 0.222), although the HR was numerically lower in the lowest tertile. There was also no heterogeneity of effect for CVD and HF hospitalization individually (P interaction for CVD = 0.964; HF hospitalization = 0.438). Discontinuation of treatment because of adverse events, symptomatic hypotension, or syncope was consistent across the range of LVEF.Conclusions: Patients with lower LVEF had a distinctive biomarker profile and a higher risk for adverse clinical outcomes vs those with a higher LVEF. There was no significant interaction for the benefit of vericiguat across LVEF tertiles, although the largest signal for benefit in both the primary outcome and HF hospitalizations was noted in tertile 1 (LVEF ≤24%).</p

Management of Worsening Heart Failure With Reduced Ejection Fraction:<i>JACC </i>Focus Seminar 3/3

Despite worsening heart failure (HF) being extremely common, expensive, and associated with substantial risk of death, there remain no dedicated clinical practice guidelines for the specific management of these patients. The lack of a management guideline is despite a rapidly evolving evidence-base, as a number of recent clinical trials have demonstrated multiple therapies to be safe and efficacious in this high-risk population. Herein, we propose a framework for treating worsening HF with reduced ejection fraction with the sense of urgency it deserves. This includes treating congestion; managing precipitants; and establishing a foundation of rapid-sequence, simultaneous, and/or in-hospital initiation of quadruple medical therapy for HF with reduced ejection fraction, with the top priority being at least low doses of all 4 medications. Moreover, to maximally reduce residual clinical risk, we further propose consideration of upfront simultaneous use of vericiguat (ie, quintuple medical therapy) and administration of intravenous iron for those who are iron deficient.</p

Assessment of Biomarkers of Myocardial injury, Inflammation, and Renal Function in Heart Failure With Reduced Ejection Fraction:The VICTORIA Biomarker Substudy

Background: Circulating biomarkers may be useful in understanding prognosis and treatment efficacy in heart failure with reduced ejection fraction. In the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial, vericiguat, a soluble guanylate cyclase stimulator, decreased the primary outcome of cardiovascular death or heart failure hospitalization in heart failure with reduced ejection fraction. We evaluated biomarkers of cardiac injury, inflammation, and renal function for associations with outcomes and vericiguat treatment effect. Methods and Results: High-sensitivity cardiac troponin T (hs-cTnT), growth differentiation factor-15 (GDF-15), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and cystatin C were measured at baseline and 16 weeks. Associations of biomarkers with the primary outcome and its components were estimated. Interaction with study treatment was tested. Changes in biomarkers over time were examined by study treatment. One or more biomarkers were measured in 4652 (92%) of 5050 participants at baseline and 4063 (81%) at 16 weeks. After adjustment, higher values of hs-cTnT, growth differentiation factor-15, and interleukin-6 were associated with the primary outcome, independent of N-terminal pro-B-type natriuretic peptide. Higher hs-cTnT values were associated with a hazard ratio per log standard deviation of 1.21 (95% confidence interval 1.14–1.27). A treatment interaction with vericiguat was evident with hs-cTnT and cardiovascular death (P = .04), but not HF hospitalization (P = .38). All biomarkers except cystatin C decreased over 16 weeks and no relationship between treatment assignment and changes in biomarker levels was observed. Conclusions: hs-cTnT, growth differentiation factor-15, and interleukin-6 levels were associated with risk of the primary outcome in VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction). Uniquely, lower hs-cTnT was associated with a lower rate of cardiovascular death but not HF hospitalization after treatment with vericiguat.</p

The Additive Prognostic Value of Serial Plasma Interleukin-6 Levels over Changes in Brain Natriuretic Peptide in Patients with Acute Heart Failure

Background: Elevated plasma interleukin-6 (IL-6) concentrations are frequently observed in patients with acute heart failure (AHF). However, the predictive value of serial IL-6 measurements beyond brain natriuretic peptide (BNP) remains poorly characterized. Methods and Results: This was a retrospective analysis of the PROTECT cohort (2033 patients with AHF). Plasma IL-6 and BNP levels were determined on days 1, 2, 7 and 14 after admission for AHF in 1591 (78.3%), 1462 (71.9%), 1445 (71.1%) and 1451 (71.4%) patients, respectively. The primary endpoint was 180-day all-cause mortality. The median day-1 IL-6 concentration was 11.1 pg/mL (IQR: 6.6, 20.9) and decreased to 10.1 pg/mL (IQR: 5.6-18.5) at day-7. Higher cross-sectional IL-6 concentrations at all time-points predicted the primary endpoint, independent of a risk model for this cohort and changes in BNP. Each doubling of IL-6 between day-1 and day-7 predicted the primary endpoint independent of baseline IL-6 concentrations, the risk model, baseline BNP and changes in BNP [HR (95% CI): 1.18 (1.07-1.30), p=0.0013]. Collectively, 214 (17%) patients experienced at least a doubling of their IL-6 concentrations between day-1 and day-7. Conclusions: We demonstrate that the temporal evolution patterns of IL-6 in patients with AHF have additive prognostic value independent of changes in BNP