Previous systematic reviews and meta-analyses consistently show the positive effect of exercise-based rehabilitation for heart failure (HF) on exercise capacity; however, the direction and magnitude ...of effects on health-related quality of life, mortality and hospital admissions in HF remain less certain. This is an update of a Cochrane systematic review previously published in 2010.
To determine the effectiveness of exercise-based rehabilitation on the mortality, hospitalisation admissions, morbidity and health-related quality of life for people with HF. Review inclusion criteria were extended to consider not only HF due to reduced ejection fraction (HFREF or 'systolic HF') but also HF due to preserved ejection fraction (HFPEF or 'diastolic HF').
We updated searches from the previous Cochrane review. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue1, 2013) from January 2008 to January 2013. We also searched MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO) and PsycINFO (Ovid) (January 2008 to January 2013). We handsearched Web of Science, bibliographies of systematic reviews and trial registers (Controlled-trials.com and Clinicaltrials.gov).
Randomised controlled trials of exercise-based interventions with six months' follow-up or longer compared with a no exercise control that could include usual medical care. The study population comprised adults over 18 years and were broadened to include individuals with HFPEF in addition to HFREF.
Two review authors independently screened all identified references and rejected those that were clearly ineligible. We obtained full-text papers of potentially relevant trials. One review author independently extracted data from the included trials and assessed their risk of bias; a second review author checked data.
We included 33 trials with 4740 people with HF predominantly with HFREF and New York Heart Association classes II and III. This latest update identified a further 14 trials. The overall risk of bias of included trials was moderate. There was no difference in pooled mortality between exercise-based rehabilitation versus no exercise control in trials with up to one-year follow-up (25 trials, 1871 participants: risk ratio (RR) 0.93; 95% confidence interval (CI) 0.69 to 1.27, fixed-effect analysis). However, there was trend towards a reduction in mortality with exercise in trials with more than one year of follow-up (6 trials, 2845 participants: RR 0.88; 95% CI 0.75 to 1.02, fixed-effect analysis). Compared with control, exercise training reduced the rate of overall (15 trials, 1328 participants: RR 0.75; 95% CI 0.62 to 0.92, fixed-effect analysis) and HF specific hospitalisation (12 trials, 1036 participants: RR 0.61; 95% CI 0.46 to 0.80, fixed-effect analysis). Exercise also resulted in a clinically important improvement superior in the Minnesota Living with Heart Failure questionnaire (13 trials, 1270 participants: mean difference: -5.8 points; 95% CI -9.2 to -2.4, random-effects analysis) - a disease specific health-related quality of life measure. However, levels of statistical heterogeneity across studies in this outcome were substantial. Univariate meta-regression analysis showed that these benefits were independent of the participant's age, gender, degree of left ventricular dysfunction, type of cardiac rehabilitation (exercise only vs. comprehensive rehabilitation), mean dose of exercise intervention, length of follow-up, overall risk of bias and trial publication date. Within these included studies, a small body of evidence supported exercise-based rehabilitation for HFPEF (three trials, undefined participant number) and when exclusively delivered in a home-based setting (5 trials, 521 participants). One study reported an additional mean healthcare cost in the training group compared with control of USD3227/person. Two studies indicated exercise-based rehabilitation to be a potentially cost-effective use of resources in terms of gain in quality-adjusted life years (QALYs) and life-years saved.
This updated Cochrane review supports the conclusions of the previous version of this review that, compared with no exercise control, exercise-based rehabilitation does not increase or decrease the risk of all-cause mortality in the short term (up to 12-months' follow-up) but reduces the risk of hospital admissions and confers important improvements in health-related quality of life. This update provides further evidence that exercise training may reduce mortality in the longer term and that the benefits of exercise training on appear to be consistent across participant characteristics including age, gender and HF severity. Further randomised controlled trials are needed to confirm the small body of evidence seen in this review for the benefit of exercise in HFPEF and when exercise rehabilitation is exclusively delivered in a home-based setting.
The aim of this meta‐analysis was to quantify the effects of high‐intensity interval training (HIIT) on markers of glucose regulation and insulin resistance compared with control conditions (CON) or ...continuous training (CT). Databases were searched for HIIT interventions based upon the inclusion criteria: training ≥2 weeks, adult participants and outcome measurements that included insulin resistance, fasting glucose, HbA1c or fasting insulin. Dual interventions and participants with type 1 diabetes were excluded. Fifty studies were included. There was a reduction in insulin resistance following HIIT compared with both CON and CT (HIIT vs. CON: standardized mean difference SMD = −0.49, confidence intervals CIs −0.87 to −0.12, P = 0.009; CT: SMD = −0.35, −0.68 to −0.02, P = 0.036). Compared with CON, HbA1c decreased by 0.19% (−0.36 to −0.03, P = 0.021) and body weight decreased by 1.3 kg (−1.9 to −0.7, P < 0.001). There were no statistically significant differences between groups in other outcomes overall. However, participants at risk of or with type 2 diabetes experienced reductions in fasting glucose (−0.92 mmol L⁻¹, −1.22 to −0.62, P < 0.001) compared with CON. HIIT appears effective at improving metabolic health, particularly in those at risk of or with type 2 diabetes. Larger randomized controlled trials of longer duration than those included in this meta‐analysis are required to confirm these results.
The Current State of Peritoneal Dialysis Mehrotra, Rajnish; Devuyst, Olivier; Davies, Simon J ...
Journal of the American Society of Nephrology,
11/2016, Volume:
27, Issue:
11
Journal Article
Peer reviewed
Open access
Technical innovations in peritoneal dialysis (PD), now used widely for the long-term treatment of ESRD, have significantly reduced therapy-related complications, allowing patients to be maintained on ...PD for longer periods. Indeed, the survival rate for patients treated with PD is now equivalent to that with in-center hemodialysis. In parallel, changes in public policy have spurred an unprecedented expansion in the use of PD in many parts of the world. Meanwhile, our improved understanding of the molecular mechanisms involved in solute and water transport across the peritoneum and of the pathobiology of structural and functional changes in the peritoneum with long-term PD has provided new targets for improving efficiency and for intervention. As with hemodialysis, almost half of all deaths on PD occur because of cardiovascular events, and there is great interest in identifying modality-specific factors contributing to these events. Notably, tremendous progress has been made in developing interventions that substantially reduce the risk of PD-related peritonitis. Yet the gains have been unequal among individual centers, primarily because of unequal clinical application of knowledge gained from research. The work to date has further highlighted the areas in need of innovation as we continue to strive to improve the health and outcomes of patients treated with PD.
More than 30% of patients with pleural infection either die or require surgery. Drainage of infected fluid is key to successful treatment, but intrapleural fibrinolytic therapy did not improve ...outcomes in an earlier, large, randomized trial.
We conducted a blinded, 2-by-2 factorial trial in which 210 patients with pleural infection were randomly assigned to receive one of four study treatments for 3 days: double placebo, intrapleural tissue plasminogen activator (t-PA) and DNase, t-PA and placebo, or DNase and placebo. The primary outcome was the change in pleural opacity, measured as the percentage of the hemithorax occupied by effusion, on chest radiography on day 7 as compared with day 1. Secondary outcomes included referral for surgery, duration of hospital stay, and adverse events.
The mean (±SD) change in pleural opacity was greater in the t-PA-DNase group than in the placebo group (-29.5±23.3% vs. -17.2±19.6%; difference, -7.9%; 95% confidence interval CI, -13.4 to -2.4; P=0.005); the change observed with t-PA alone and with DNase alone (-17.2±24.3 and -14.7±16.4%, respectively) was not significantly different from that observed with placebo. The frequency of surgical referral at 3 months was lower in the t-PA-DNase group than in the placebo group (2 of 48 patients 4% vs. 8 of 51 patients 16%; odds ratio for surgical referral, 0.17; 95% CI, 0.03 to 0.87; P=0.03) but was greater in the DNase group (18 of 46 patients 39%) than in the placebo group (odds ratio, 3.56; 95% CI, 1.30 to 9.75; P=0.01). Combined t-PA-DNase therapy was associated with a reduction in the hospital stay, as compared with placebo (difference, -6.7 days; 95% CI, -12.0 to -1.9; P=0.006); the hospital stay with either agent alone was not significantly different from that with placebo. The frequency of adverse events did not differ significantly among the groups.
Intrapleural t-PA-DNase therapy improved fluid drainage in patients with pleural infection and reduced the frequency of surgical referral and the duration of the hospital stay. Treatment with DNase alone or t-PA alone was ineffective. (Funded by an unrestricted educational grant to the University of Oxford from Roche UK and by others; Current Controlled Trials number, ISRCTN57454527.).
Two large low-shear-velocity provinces (LLSVPs) in the deep mantle beneath Africa and the Pacific are generally interpreted as hot but chemically dense ‘piles’, which have remained isolated from ...mantle circulation for several hundred million years. This interpretation largely hinges on four seismic observations: (i) their shear wave velocity anomalies are considered too large for purely thermal structures; (ii) shear wave velocity gradients at their edges are sharp; (iii) their shear to compressional wave-speed anomaly ratios are high; and (iv) their shear and bulk-sound velocity anomalies appear to be anti-correlated. However, using compressible global mantle circulation models driven by 300Myr of plate motion history and thermodynamic methods for converting from physical to seismic structure, we show that observed lower mantle shear wave velocity anomalies do not require, and are most likely incompatible with, large-scale chemical ‘piles’. A prescribed core-mantle-boundary temperature of 4000K, which is consistent with current estimates, combined with anelastic seismic sensitivity to temperature, ensures that purely thermal LLSVPs, strongly focussed beneath Africa and the Pacific by subduction history, can reconcile observed shear wave velocity anomalies and gradients. By contrast, shear wave velocity anomalies from models that include dense chemical ‘piles’ at the base of Earth's mantle, where ‘piles’ correspond to only 3% of the mantle's volume, are substantially stronger than the tomographic model S40RTS, even after accounting for limited tomographic resolution. Our results also suggest that in the presence of post-perovskite, elevated ratios between shear and compressional wave-speed anomalies and the correlation between shear and bulk-sound velocity anomalies cannot be used to discriminate between thermal and compositional heterogeneity at depth: in all calculations, an anti-correlation only occurs within the post-perovskite stability field. Taken together, this implies that although there must be considerable chemical heterogeneity within Earth's mantle, large, coherent ‘piles’ are not required to reconcile the seismic observations examined here. Indeed, our results suggest that if chemical heterogeneity is present in these regions, its dynamical and seismic significance is far less than has previously been inferred.
► Synthetic seismic velocity structures of thermal and thermo-chemical pile models are compared. ► Temperature variations alone can reconcile observed deep mantle Vs anomalies and gradients. ► By contrast, thermo-chemical pile models substantially over predict deep mantle Vs anomalies. ► In the presence of post-perovskite, elevated d lnVs/d lnVp ratios do not imply chemical heterogeneity. ► Anti-correlated Vs and bulk-sound anomalies are not easily explained by compositional variations.
The American Diabetes Association and the European Association for the Study of Diabetes have briefly updated their 2018 recommendations on management of hyperglycemia, based on important research ...findings from large cardiovascular outcomes trials published in 2019. Important changes include:
) the decision to treat high-risk individuals with a glucagon-like peptide 1 (GLP-1) receptor agonist or sodium-glucose cotransporter 2 (SGLT2) inhibitor to reduce major adverse cardiovascular events (MACE), hospitalization for heart failure (hHF), cardiovascular death, or chronic kidney disease (CKD) progression should be considered independently of baseline HbA
or individualized HbA
target;
) GLP-1 receptor agonists can also be considered in patients with type 2 diabetes without established cardiovascular disease (CVD) but with the presence of specific indicators of high risk; and
) SGLT2 inhibitors are recommended in patients with type 2 diabetes and heart failure, particularly those with heart failure with reduced ejection fraction, to reduce hHF, MACE, and CVD death, as well as in patients with type 2 diabetes with CKD (estimated glomerular filtration rate 30 to ≤60 mL min
1.73 m
or urinary albumin-to-creatinine ratio >30 mg/g, particularly >300 mg/g) to prevent the progression of CKD, hHF, MACE, and cardiovascular death.
'Reactive oxygen species' (ROS) is a generic term that defines a wide variety of oxidant molecules with vastly different properties and biological functions that range from signalling to causing cell ...damage. Consequently, the description of oxidants needs to be chemically precise to translate research on their biological effects into therapeutic benefit in redox medicine. This Expert Recommendation article pinpoints key issues associated with identifying the physiological roles of oxidants, focusing on H
O
and O
. The generic term ROS should not be used to describe specific molecular agents. We also advocate for greater precision in measurement of H
O
, O
and other oxidants, along with more specific identification of their signalling targets. Future work should also consider inter-organellar communication and the interactions of redox-sensitive signalling targets within organs and whole organisms, including the contribution of environmental exposures. To achieve these goals, development of tools that enable site-specific and real-time detection and quantification of individual oxidants in cells and model organisms are needed. We also stress that physiological O
levels should be maintained in cell culture to better mimic in vivo redox reactions associated with specific cell types. Use of precise definitions and analytical tools will help harmonize research among the many scientific disciplines working on the common goal of understanding redox biology.
Malignant pleural effusion causes disabling dyspnea in patients with a short life expectancy. Palliation is achieved by fluid drainage, but the most effective first-line method has not been ...determined.
To determine whether indwelling pleural catheters (IPCs) are more effective than chest tube and talc slurry pleurodesis (talc) at relieving dyspnea.
Unblinded randomized controlled trial (Second Therapeutic Intervention in Malignant Effusion Trial TIME2) comparing IPC and talc (1:1) for which 106 patients with malignant pleural effusion who had not previously undergone pleurodesis were recruited from 143 patients who were treated at 7 UK hospitals. Patients were screened from April 2007-February 2011 and were followed up for a year.
Indwelling pleural catheters were inserted on an outpatient basis, followed by initial large volume drainage, education, and subsequent home drainage. The talc group were admitted for chest tube insertion and talc for slurry pleurodesis.
Patients completed daily 100-mm line visual analog scale (VAS) of dyspnea over 42 days after undergoing the intervention (0 mm represents no dyspnea and 100 mm represents maximum dyspnea; 10 mm represents minimum clinically significant difference). Mean difference was analyzed using a mixed-effects linear regression model adjusted for minimization variables.
Dyspnea improved in both groups, with no significant difference in the first 42 days with a mean VAS dyspnea score of 24.7 in the IPC group (95% CI, 19.3-30.1 mm) and 24.4 mm (95% CI, 19.4-29.4 mm) in the talc group, with a difference of 0.16 mm (95% CI, −6.82 to 7.15; P = .96). There was a statistically significant improvement in dyspnea in the IPC group at 6 months, with a mean difference in VAS score between the IPC group and the talc group of −14.0 mm (95% CI, −25.2 to −2.8 mm; P = .01). Length of initial hospitalization was significantly shorter in the IPC group with a median of 0 days (interquartile range IQR, 0-1 day) and 4 days (IQR, 2-6 days) for the talc group, with a difference of −3.5 days (95% CI, −4.8 to −1.5 days; P < .001). There was no significant difference in quality of life. Twelve patients (22%) in the talc group required further pleural procedures compared with 3 (6%) in the IPC group (odds ratio OR, 0.21; 95% CI, 0.04-0.86; P = .03). Twenty-one of the 52 patients in the catheter group experienced adverse events vs 7 of 54 in the talc group (OR, 4.70; 95% CI, 1.75-12.60; P = .002).
Among patients with malignant pleural effusion and no previous pleurodesis, there was no significant difference between IPCs and talc pleurodesis at relieving patient-reported dyspnea.
isrctn.org Identifier: ISRCTN87514420.
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