Rationale for Prolonged Glucocorticoid Use in Pediatric ARDS: What the Adults Can Teach Us.

Based on molecular mechanisms and physiologic data, a strong association has been established between dysregulated systemic inflammation and progression of acute respiratory distress syndrome (ARDS). In ARDS patients, glucocorticoid receptor-mediated downregulation of systemic inflammation is essential to restore homeostasis, decrease morbidity and improve survival and can be significantly enhanced with prolonged low-to-moderate dose glucocorticoid treatment. A large body of evidence supports a strong association between prolonged glucocorticoid treatment-induced downregulation of the inflammatory response and improvement in pulmonary and extrapulmonary physiology. The balance of the available data from eight controlled trials (n = 622) provides consistent strong level of evidence for improving patient-centered outcomes and hospital survival. The sizable increase in mechanical ventilation-free days (weighted mean difference, 6.48 days; CI 95% 2.57-10.38, p < 0.0001) and intensive care unit-free days (weighted mean difference, 7.7 days; 95% CI, 3.13-12.20, p < 0.0001) by day 28 is superior to any investigated intervention in ARDS. For treatment initiated before day 14 of ARDS, the increased in hospital survival (70 vs. 52%, OR 2.41, CI 95% 1.50-3.87, p = 0.0003) translates into a number needed to treat to save one life of 5.5. Importantly, prolonged glucocorticoid treatment is not associated with increased risk for nosocomial infections (22 vs. 27%, OR 0.61, CI 95% 0.35-1.04, p = 0.07). Treatment decisions involve a tradeoff between benefits and risks, as well as costs. This low-cost, highly effective therapy is familiar to every physician and has a low risk profile when secondary prevention measures are implemented

Prolonged Glucocorticoid Treatment in ARDS: Impact on Intensive Care Unit-Acquired Weakness.

Systemic inflammation and duration of immobilization are strong independent risk factors for the development of intensive care unit-acquired weakness (ICUAW). Activation of the pro-inflammatory transcription factor nuclear factor-κB (NF-κB) results in muscle wasting during disuse-induced skeletal muscle atrophy (ICU bed rest) and septic shock. In addition, NF-κB-mediated signaling plays a significant role in mechanical ventilation-induced diaphragmatic atrophy and contractile dysfunction. Older trials investigating high dose glucocorticoid treatment reported a lack of a sustained anti-inflammatory effects and an association with ICUAW. However, prolonged low-to-moderate dose glucocorticoid treatment of sepsis and ARDS is associated with a reduction in NF-κB DNA-binding, decreased transcription of inflammatory cytokines, enhanced resolution of systemic and pulmonary inflammation, leading to fewer days of mechanical ventilation, and lower mortality. Importantly, meta-analyses of a large number of randomized controlled trials investigating low-to-moderate glucocorticoid treatment in severe sepsis and ARDS found no increase in ICUAW. Furthermore, while the ARDS network trial investigating methylprednisolone treatment in persistent ARDS is frequently cited to support an association with ICUAW, a reanalysis of the data showed a similar incidence with the control group. Our review concludes that in patients with sepsis and ARDS, any potential direct harmful neuromuscular effect of glucocorticoids appears outweighed by the overall clinical improvement and reduced duration of organ failure, in particular ventilator dependency and associated immobilization, which are key risk factors for ICUAW

Intake of 12 food groups and disability-adjusted life years from coronary heart disease, stroke, type 2 diabetes, and colorectal cancer in 16 European countries

Our aim was to estimate and rank 12 food groups according to disability-adjusted life years (DALYs) from coronary heart disease (CHD), stroke, type 2 diabetes (T2D), and colorectal cancer (CRC) in 16 European countries. De novo published non-linear dose–response meta-analyses of prospective studies (based on 297 primary reports), and food consumption data from the European Food Safety Authority Comprehensive European Food Consumption Database in Exposure Assessment, and DALY estimates from the Institute for Health Metrics and Evaluation were used. By implementing disease-specific counterfactual scenarios of theoretical minimum risk exposure level (TMRELs), the proportion of DALYs attributed to 12 food groups was estimated. In addition, a novel modelling approach was developed to obtain a single (optimized) TMREL across diseases. Four scenarios were analysed (A: disease-specific TMRELs/all food-disease associations; B: disease-specific TMRELs/only significant food-disease associations; C: single TMREL/all food-disease associations; D: single TMREL/only significant food-disease associations). Suboptimal food intake was associated with the following proportions of DALYs; Scenario A (highest-estimate) and D (lowest-estimate): CHD (A: 67%, D: 52%), stroke (A: 49%, D: 30%), T2D (A: 57%, D: 51%), and CRC (A: 54%, D: 40%). Whole grains (10%) had the highest impact on DALYs, followed by nuts (7.1%), processed meat (6.4%), fruit (4.4%) and fish and legumes (4.2%) when combining all scenarios. The contribution to total DALYs of all food groups combined in the different scenarios ranged from 41–52% in Austria to 51–69% in the Czech-Republic. These findings could have important implications for planning future food-based dietary guidelines as a public health nutrition strategy

Considering even-order terms in stochastic nonlinear system modeling with respect to broadband data communication

As a tradeoff between efficiency and costs modern communication systems contain a variety of components that can at least be considered weakly nonlinear. A critical element in evaluating the degree of nonlinearity of any underlying nonlinear system is the amount of undesired signal strength or signal power this system is introducing outside the transmission bandwidth. This phenomenon called spectral regrowth or spectral broadening is subject to stringent restrictions mainly imposed by the given specifications of the particular communication standard. Consequently, achieving the highest possible efficiency without exceeding the linearity requirements is one of the main tasks in system design. Starting from this challenging engineering problem there grows a certain need for specialized tools that are capable of predicting linearity and efficiency of the underlying design. Besides a multitude of methods aiming at the prediction of spectral regrowth a statistical approach in modeling and analyzing nonlinear systems offers the advantage of short processing times due to closed form mathematical expressions in terms of input and output power spectra and is therefore further examined throughout this article

Impact of long-term lifestyle programmes on weight loss and cardiovascular risk factors in overweight/obese participants: a systematic review and network meta-analysis

BACKGROUND: The aim of this meta-analysis was to compare the long-term efficacy of diet plus exercise (D + E) vs. diet (D), D + E vs. exercise (E) and D vs. E on anthropometric outcomes and cardiovascular risk factors in overweight and obese participants. METHODS: Electronic searches were performed in MEDLINE and the Cochrane Central Register of controlled trials. Inclusion criteria were as follows: body mass index ≥25 kg/m(2) and a minimum intervention period including follow-up of ≥12 months. Outcomes of interest were as follows: anthropometric parameters, blood lipids, blood pressure and cardiorespiratory fitness. Pooled effects were calculated using pairwise random effects and Bayesian random effects network meta-analysis. Results of the corresponding fixed effects models were compared in sensitivity analyses. RESULTS: Overall, 22 trials (24 reports) met the inclusion criteria and 21 (including 3,521 participants) of them were included in the quantitative analysis. As compared with D, D + E resulted in a significantly more pronounced reduction in body weight [mean differences (MD): -1.38 kg, 95% confidence interval (CI) -1.98 to -0.79], and fat mass (MD: -1.65 kg, 95% CI -2.81 to -0.49], respectively. When comparing D + E with E, MD in change of body weight (-4.13 kg, 95% CI -5.62 to -2.64), waist circumference (-3.00 cm, 95% CI -5.81 to -0.20), and fat mass (-3.60 kg, 95% CI -6.15 to -1.05) was in favour of combined diet and exercise, respectively. Comparing E vs. D, diet resulted in a significantly more pronounced decrease in body weight (MD: -2.93 kg, 95% CI -4.18 to -1.68), and fat mass (MD: -2.20 kg, 95% CI -3.75 to -0.66). D + E yielded also the greatest reductions with respect to blood lipids and blood pressure when compared to single applications of D and E, respectively. Results from the network meta-analyses confirmed these findings. CONCLUSIONS: Moderate-quality evidence from the present network meta-analysis suggests that D + E can be highly recommended for long-term obesity management. Furthermore, the evidence suggests a moderate superiority of D over E with respect to anthropometric outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD4201300390

Impact of Different Training Modalities on Anthropometric and Metabolic Characteristics in Overweight/Obese Subjects:A Systematic Review and Network Meta-Analysis

<div><p>Background</p><p>The aim of this systematic review of randomized controlled trials was to compare the effects of aerobic training (AET), resistance training (RT), and combined aerobic and resistance training (CT) on anthropometric parameters, blood lipids, and cardiorespiratory fitness in overweight and obese subjects.</p><p>Methods</p><p>Electronic searches for randomized controlled trials were performed in MEDLINE, EMBASE and the Cochrane Trial Register. Inclusion criteria were: Body Mass Index: ≥25 kg/m², 19+ years of age, supervised exercise training, and a minimum intervention period of 8 weeks. Anthropometric outcomes, blood lipids, and cardiorespiratory fitness parameters were included. Pooled effects were calculated by inverse-variance random effect pairwise meta-analyses and Bayesian random effects network meta-analyses.</p><p>Findings</p><p>15 trials enrolling 741 participants were included in the meta-analysis. Compared to RT, AET resulted in a significantly more pronounced reduction of body weight [mean differences (MD): -1.15 kg, p = 0.04], waist circumference [MD: -1.10 cm, p = 0.004], and fat mass [MD: -1.15 kg, p = 0.001] respectively. RT was more effective than AET in improving lean body mass [MD: 1.26 kg, p<0.00001]. When comparing CT with RT, MD in change of body weight [MD: -2.03 kg, p<0.0001], waist circumference [MD: -1.57 cm, p = 0.0002], and fat mass [MD: -1.88 kg, p<0.00001] were all in favor of CT. Results from the network meta-analyses confirmed these findings.</p><p>Conclusion</p><p>Evidence from both pairwise and network meta-analyses suggests that CT is the most efficacious means to reduce anthropometric outcomes and should be recommended in the prevention and treatment of overweight, and obesity whenever possible.</p></div

Generating the evidence for risk reduction : a contribution to the future of food-based dietary guidelines

A major advantage of analyses on the food group level is that the results are better interpretable compared with nutrients or complex dietary patterns. Such results are also easier to transfer into recommendations on primary prevention of non-communicable diseases. As a consequence, food-based dietary guidelines (FBDG) are now the preferred approach to guide the population regarding their dietary habits. However, such guidelines should be based on a high grade of evidence as requested in many other areas of public health practice. The most straightforward approach to generate evidence is meta-analysing published data based on a careful definition of the research question. Explicit definitions of study questions should include participants, interventions/exposure, comparisons, outcomes and study design. Such type of meta-analyses should not only focus on categorical comparisons, but also on linear and non-linear dose-response associations. Risk of bias of the individual studies of the meta-analysis should be assessed, rated and the overall credibility of the results scored (e.g. using NutriGrade). Tools such as a measurement tool to assess systematic reviews or ROBIS are available to evaluate the methodological quality/risk of bias of meta-analyses. To further evaluate the complete picture of evidence, we propose conducting network meta-analyses (NMA) of intervention trials, mostly on intermediate disease markers. To rank food groups according to their impact, disability-adjusted life years can be used for the various clinical outcomes and the overall results can be compared across the food groups. For future FBDG, we recommend to implement evidence from pairwise and NMA and to quantify the health impact of diet-disease relationships

Glycaemic control in the diabetes and lifestyle cohort twente: a cross-sectional assessment of lifestyle and pharmacological management on Hba1c target achievement

The majority of patients with type 2 diabetes do not reach target levels of glycated haemoglobin (HbA1c < 7%). We investigated the prevalence of HbA1c‐target achievement and opportunities afforded by lifestyle and pharmacological treatment to increase target achievement. We performed cross‐sectional analyses of baseline data from the Diabetes and Lifestyle Cohort Twente‐1 (DIALECT‐1). Patients were divided according to (1) HbA1c <53 and ≥53 mmol/mol (<7%) and (2) non‐insulin treatment and tertiles of daily insulin use. We found that 161 (36%) patients achieved the target HbA1c level. Patients with HbA1c ≥53 mmol/mol had a longer duration of diabetes (13 [8‐20] vs 9 [4‐14] years; P < .001) and more frequently were insulin‐users (76% vs 41%, P < .001). Patients in the highest tertile of insulin use had a higher body mass index than those in the lowest tertile (35.8 ± 5.5 vs 29.8 ± 5.5 kg/m2; P < .001). Achievement of target HbA1c is low in this type 2 diabetes population. High resistance to pharmacological treatment, paralleled with high body mass index, illustrates that increasing insulin sensitivity through lifestyle intervention is the best opportunity to improve HbA1c target achievement in this real‐life population

Responses to oral glucose challenge differ by physical activity volume and intensity : a pilot study.

Background: One hour postprandial hyperglycaemia is associated with increased risk of type 2 diabetes and cardiovascular disease. Physical activity has short-term beneficial effects on post-meal glucose response. This study compared the oral glucose tolerance test results of 3 groups of people with habitually different levels of physical activity. Methods: Thirty-one adults without diabetes (age 25.9 ± 6.6 years; body mass index 23.8 ± 3.8 kg.m-2) were recruited into 3 groups based on self-reported physical activity volume and intensity: Low Activity = < 30 min.day-1 of 'moderate' intensity activity (n = 11), Moderately Active = ≥ 30 min.day-1 of 'moderate' intensity physical activity (n = 10), and Very Active = ≥ 60 min.day-1 of 'intense' physical activity (n = 10). Participants completed an oral glucose tolerance test (50 g glucose) with capillary blood samples obtained at baseline, 15, 30, 45, 60, 90 and 120 minutes post-ingestion. Results: There were no significant differences between groups for age or percentage body fat or glycated haemoglobin (p> 0.05). The groups were significantly different in terms of baseline glucose, gender and BMI and this was accounted for in the analysis. There was a statistically significant effect of physical activity on the one hour postprandial glucose results (p=0.029), with differences between Very Active and Low Activity (p=0.008) groups but not between the Moderately Active and Low Activity groups (p=0.360), even when baseline glucose and gender differences were accounted for. For iAUC there was no significant effect of activity group once gender and bodyfat % had been accounted for. Those in the Low Activity group took an average 13.2 (95% CI: 2.8 – 23.5) minutes longer to reach peak glucose level than those in the Very Active group and this was significant (p=0.015). Conclusion: The results suggest that high levels of physical activity have a beneficial effect on postprandial blood glucose profiles when compared to low and moderate levels of activity