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- Smerdon, J. E., et al.
(författare)
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Comparing proxy and model estimates of hydroclimate variability and change over the Common Era
- 2017
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 13:12, s. 1851-1900
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Tidskriftsartikel (refereegranskat)abstract
- Water availability is fundamental to societies and ecosystems, but our understanding of variations in hydroclimate (including extreme events, flooding, and decadal periods of drought) is limited because of a paucity of modern instrumental observations that are distributed unevenly across the globe and only span parts of the 20th and 21st centuries. Such data coverage is insufficient for characterizing hydroclimate and its associated dynamics because of its multidecadal to centennial variability and highly regionalized spatial signature. High-resolution (seasonal to decadal) hydroclimatic proxies that span all or parts of the Common Era (CE) and paleoclimate simulations from climate models are therefore important tools for augmenting our understanding of hydroclimate variability. In particular, the comparison of the two sources of information is critical for addressing the uncertainties and limitations of both while enriching each of their interpretations. We review the principal proxy data available for hydroclimatic reconstructions over the CE and highlight the contemporary understanding of how these proxies are interpreted as hydroclimate indicators. We also review the available last-millennium simulations from fully coupled climate models and discuss several outstanding challenges associated with simulating hydroclimate variability and change over the CE. A specific review of simulated hydroclimatic changes forced by volcanic events is provided, as is a discussion of expected improvements in estimated radiative forcings, models, and their implementation in the future. Our review of hydroclimatic proxies and last-millennium model simulations is used as the basis for articulating a variety of considerations and best practices for how to perform proxy-model comparisons of CE hydroclimate. This discussion provides a framework for how best to evaluate hydroclimate variability and its associated dynamics using these comparisons and how they can better inform interpretations of both proxy data and model simulations. We subsequently explore means of using proxy-model comparisons to better constrain and characterize future hydroclimate risks. This is explored specifically in the context of several examples that demonstrate how proxy-model comparisons can be used to quantitatively constrain future hydroclimatic risks as estimated from climate model projections.
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- Cleland, J. G. F., et al.
(författare)
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Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials
- 2018
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 39:1, s. 26-35
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Tidskriftsartikel (refereegranskat)abstract
- Aims Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40-49% should be managed similar to LVEF >= 50%. We investigated the effect of beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials. Methods and results Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm (Clinicaltrials.gov: NCT0083244; PROSPERO: CRD42014010012). Primary outcomes were all-cause mortality and cardiovascular death over 1.3 years median follow-up, with an intention-to-treat analysis. For 14 262 patients in sinus rhythm, median LVEF was 27% (interquartile range 21-33%), including 575 patients with LVEF 40-49% and 244 >= 50%. Beta-blockers reduced all-cause and cardiovascular mortality compared to placebo in sinus rhythm, an effect that was consistent across LVEF strata, except for those in the small subgroup with LVEF >= 50%. For LVEF 40-49%, death occurred in 21/292 [7.2%] randomized to beta-blockers compared to 35/283 [12.4%] with placebo; adjusted hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.34-1.03]. Cardiovascular death occurred in 13/292 [4.5%] with beta-blockers and 26/283 [9.2%] with placebo; adjusted HR 0.48 (95% CI 0.24-0.97). Over a median of 1.0 years following randomization (n = 4601), LVEF increased with beta-blockers in all groups in sinus rhythm except LVEF >= 50%. For patients in atrial fibrillation at baseline (n = 3050), beta-blockers increased LVEF when < 50% at baseline, but did not improve prognosis. Conculations Beta-blockers improve LVEF and prognosis for patients with heart failure in sinus rhythm with a reduced LVEF. The data are most robust for LVEF < 40%, but similar benefit was observed in the subgroup of patients with LVEF 40-49%.
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- Kotecha, D., et al.
(författare)
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Heart Rate and Rhythm and the Benefit of Beta-Blockers in Patients With Heart Failure
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 69:24, s. 2885-2896
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The relationship between mortality and heart rate remains unclear for patients with heart failure with reduced ejection fraction in either sinus rhythm or atrial fibrillation (AF). OBJECTIVES This analysis explored the prognostic importance of heart rate in patients with heart failure with reduced ejection fraction in randomized controlled trials comparing beta-blockers and placebo. METHODS The Beta-Blockers in Heart Failure Collaborative Group performed a meta-analysis of harmonized individual patient data from 11 double-blind randomized controlled trials. The primary outcome was all-cause mortality, analyzed with Cox proportional hazard ratios (HR) modeling heart rate measured at baseline and approximately 6 months post-randomization. RESULTS A higher heart rate at baseline was associated with greater all-cause mortality for patients in sinus rhythm (n = 14,166; adjusted HR: 1.11 per 10 beats/min; 95% confidence interval [CI]: 1.07 to 1.15; p < 0.0001) but not in AF (n = 3,034; HR: 1.03 per 10 beats/min; 95% CI: 0.97 to 1.08; p = 0.38). Beta-blockers reduced ventricular rate by 12 beats/min in both sinus rhythm and AF. Mortality was lower for patients in sinus rhythm randomized to beta-blockers (HR: 0.73 vs. placebo; 95% CI: 0.67 to 0.79; p < 0.001), regardless of baseline heart rate (interaction p = 0.35). Beta-blockers had no effect on mortality in patients with AF (HR: 0.96, 95% CI: 0.81 to 1.12; p = 0.58) at any heart rate (interaction p = 0.48). A lower achieved resting heart rate, irrespective of treatment, was associated with better prognosis only for patients in sinus rhythm (HR: 1.16 per 10 beats/min increase, 95% CI: 1.11 to 1.22; p < 0.0001). CONCLUSIONS Regardless of pre-treatment heart rate, beta-blockers reduce mortality in patients with heart failure with reduced ejection fraction in sinus rhythm. Achieving a lower heart rate is associated with better prognosis, but only for those in sinus rhythm. (C) 2017 by the American College of Cardiology Foundation.
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- Kotecha, D., et al.
(författare)
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Effect of age and sex on efficacy and tolerability of beta blockers in patients with heart failure with reduced ejection fraction: individual patient data meta-analysis
- 2016
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Ingår i: Bmj-British Medical Journal. - : BMJ. - 1756-1833. ; 353
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES To determine the efficacy and tolerability of beta blockers in a broad age range of women and men with heart failure with reduced ejection fraction (HFrEF) by pooling individual patient data from placebo controlled randomised trials. Prospectively designed meta-analysis of individual patient data from patients aged 40-85 in sinus rhythm at baseline, with left ventricular ejection fraction < 0.45. The primary outcome was all cause mortality; the major secondary outcome was admission to hospital for heart failure. Analysis was by intention to treat with an adjusted one stage Cox proportional hazards model. Compared with placebo, beta blockers were effective in reducing mortality across all ages: hazard ratios were 0.66 (95% confidence interval 0.53 to 0.83) for the first quarter of age distribution (median age 50); 0.71 (0.58 to 0.87) for the second quarter (median age 60); 0.65 (0.53 to 0.78) for the third quarter (median age 68); and 0.77 (0.64 to 0.92) for the fourth quarter (median age 75). There was no significant interaction when age was modelled continuously (P=0.1), and the absolute reduction in mortality was 4.3% over a median follow-up of 1.3 years (number needed to treat 23). Admission to hospital for heart failure was significantly reduced by beta blockers, although this effect was attenuated at older ages (interaction P=0.05). There was no evidence of an interaction between treatment effect and sex in any age group. Drug discontinuation was similar regardless of treatment allocation, age, or sex (14.4% in those give beta blockers, 15.6% in those receiving placebo). Irrespective of age or sex, patients with HFrEF in sinus rhythm should receive beta blockers to reduce the risk of death and admission to hospital.
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