Extracting relevant biological information from large data sets is a major challenge in functional genomics research. Different aspects of the data hamper their biological interpretation. For ...instance, 5000-fold differences in concentration for different metabolites are present in a metabolomics data set, while these differences are not proportional to the biological relevance of these metabolites. However, data analysis methods are not able to make this distinction. Data pretreatment methods can correct for aspects that hinder the biological interpretation of metabolomics data sets by emphasizing the biological information in the data set and thus improving their biological interpretability.
Different data pretreatment methods, i.e. centering, autoscaling, pareto scaling, range scaling, vast scaling, log transformation, and power transformation, were tested on a real-life metabolomics data set. They were found to greatly affect the outcome of the data analysis and thus the rank of the, from a biological point of view, most important metabolites. Furthermore, the stability of the rank, the influence of technical errors on data analysis, and the preference of data analysis methods for selecting highly abundant metabolites were affected by the data pretreatment method used prior to data analysis.
Different pretreatment methods emphasize different aspects of the data and each pretreatment method has its own merits and drawbacks. The choice for a pretreatment method depends on the biological question to be answered, the properties of the data set and the data analysis method selected. For the explorative analysis of the validation data set used in this study, autoscaling and range scaling performed better than the other pretreatment methods. That is, range scaling and autoscaling were able to remove the dependence of the rank of the metabolites on the average concentration and the magnitude of the fold changes and showed biologically sensible results after PCA (principal component analysis).In conclusion, selecting a proper data pretreatment method is an essential step in the analysis of metabolomics data and greatly affects the metabolites that are identified to be the most important.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IMPORTANCE: Therapeutic hypothermia is used for patients following both out-of-hospital and in-hospital cardiac arrest. However, randomized trials on its efficacy for the in-hospital setting do not ...exist, and comparative effectiveness data are limited. OBJECTIVE: To evaluate the association between therapeutic hypothermia and survival after in-hospital cardiac arrest. DESIGN, SETTING, AND PATIENTS: In this cohort study, within the national Get With the Guidelines–Resuscitation registry, 26 183 patients successfully resuscitated from an in-hospital cardiac arrest between March 1, 2002, and December 31, 2014, and either treated or not treated with hypothermia at 355 US hospitals were identified. Follow-up ended February 4, 2015. EXPOSURE: Induction of therapeutic hypothermia. MAIN OUTCOMES AND MEASURES: The primary outcome was survival to hospital discharge. The secondary outcome was favorable neurological survival, defined as a Cerebral Performance Category score of 1 or 2 (ie, without severe neurological disability). Comparisons were performed using a matched propensity score analysis and examined for all cardiac arrests and separately for nonshockable (asystole and pulseless electrical activity) and shockable (ventricular fibrillation and pulseless ventricular tachycardia) cardiac arrests. RESULTS: Overall, 1568 of 26 183 patients with in-hospital cardiac arrest (6.0%) were treated with therapeutic hypothermia; 1524 of these patients (mean SD age, 61.6 16.2 years; 58.5% male) were matched by propensity score to 3714 non–hypothermia-treated patients (mean SD age, 62.2 17.5 years; 57.1% male). After adjustment, therapeutic hypothermia was associated with lower in-hospital survival (27.4% vs 29.2%; relative risk RR, 0.88 95% CI, 0.80 to 0.97; risk difference, −3.6% 95% CI, −6.3% to −0.9%; P = .01), and this association was similar (interaction P = .74) for nonshockable cardiac arrest rhythms (22.2% vs 24.5%; RR, 0.87 95% CI, 0.76 to 0.99; risk difference, −3.2% 95% CI, −6.2% to −0.3%) and shockable cardiac arrest rhythms (41.3% vs 44.1%; RR, 0.90 95% CI, 0.77 to 1.05; risk difference, −4.6% 95% CI, −10.9% to 1.7%). Therapeutic hypothermia was also associated with lower rates of favorable neurological survival for the overall cohort (hypothermia-treated group, 17.0% 246 of 1443 patients; non–hypothermia-treated group, 20.5% 725 of 3529 patients; RR, 0.79 95% CI, 0.69 to 0.90; risk difference, −4.4% 95% CI, −6.8% to −2.0%; P < .001) and for both rhythm types (interaction P = .88). CONCLUSIONS AND RELEVANCE: Among patients with in-hospital cardiac arrest, use of therapeutic hypothermia compared with usual care was associated with a lower likelihood of survival to hospital discharge and a lower likelihood of favorable neurological survival. These observational findings warrant a randomized clinical trial to assess efficacy of therapeutic hypothermia for in-hospital cardiac arrest.
Summary Background During in-hospital cardiac arrests, how long resuscitation attempts should be continued before termination of efforts is unknown. We investigated whether duration of resuscitation ...attempts varies between hospitals and whether patients at hospitals that attempt resuscitation for longer have higher survival rates than do those at hospitals with shorter durations of resuscitation efforts. Methods Between 2000 and 2008, we identified 64 339 patients with cardiac arrests at 435 US hospitals within the Get With The Guidelines—Resuscitation registry. For each hospital, we calculated the median duration of resuscitation before termination of efforts in non-survivors as a measure of the hospital's overall tendency for longer attempts. We used multilevel regression models to assess the association between the length of resuscitation attempts and risk-adjusted survival. Our primary endpoints were immediate survival with return of spontaneous circulation during cardiac arrest and survival to hospital discharge. Findings 31 198 of 64 339 (48·5%) patients achieved return of spontaneous circulation and 9912 (15·4%) survived to discharge. For patients achieving return of spontaneous circulation, the median duration of resuscitation was 12 min (IQR 6–21) compared with 20 min (14–30) for non-survivors. Compared with patients at hospitals in the quartile with the shortest median resuscitation attempts in non-survivors (16 min IQR 15–17), those at hospitals in the quartile with the longest attempts (25 min 25–28) had a higher likelihood of return of spontaneous circulation (adjusted risk ratio 1·12, 95% CI 1·06–1·18; p<0·0001) and survival to discharge (1·12, 1·02–1·23; 0·021). Interpretation Duration of resuscitation attempts varies between hospitals. Although we cannot define an optimum duration for resuscitation attempts on the basis of these observational data, our findings suggest that efforts to systematically increase the duration of resuscitation could improve survival in this high-risk population. Funding American Heart Association, Robert Wood Johnson Foundation Clinical Scholars Program, and the National Institutes of Health.
The goal of therapy for bradycardia or tachycardia is to rapidly identify and treat patients who are hemodynamically unstable or symptomatic due to the arrhythmia. Drugs or, when appropriate, pacing ...may be used to control unstable or symptomatic bradycardia. Cardioversion or drugs or both may be used to control unstable or symptomatic tachycardia. ACLS providers should closely monitor stable patients pending expert consultation and should be prepared to aggressively treat those with evidence of decompensation.
Summary Background The American Heart Association recommends cardiopulmonary resuscitation (CPR) by bystanders with chest compression only for adults who have cardiac arrests, but not for children. ...We assessed the effect of CPR (conventional with rescue breathing or chest compression only) by bystanders on outcomes after out-of-hospital cardiac arrests in children. Methods In a nationwide, prospective, population-based, observational study, we enrolled 5170 children aged 17 years and younger who had an out-of-hospital cardiac arrest from Jan 1, 2005, to Dec 31, 2007. Data collected included age, cause, and presence and type of CPR by bystander. The primary endpoint was favourable neurological outcome 1 month after an out-of-hospital cardiac arrest, defined as Glasgow-Pittsburgh cerebral performance category 1 or 2. Findings 3675 (71%) children had arrests of non-cardiac causes and 1495 (29%) cardiac causes. 1551 (30%) received conventional CPR and 888 (17%) compression-only CPR. Data for type of CPR by bystander were not available for 12 children. Children who were given CPR by a bystander had a significantly higher rate of favourable neurological outcome than did those not given CPR (4·5% 110/2439 vs 1·9% 53/2719; adjusted odds ratio OR 2·59, 95% CI 1·81–3·71). In children aged 1–17 years who had arrests of non-cardiac causes, favourable neurological outcome was more common after bystander CPR than no CPR (5·1% 51/1004 vs 1·5% 20/1293; OR 4·17, 2·37–7·32). However, conventional CPR produced more favourable neurological outcome than did compression-only CPR (7·2% 45/624 vs 1·6% six of 380; OR 5·54, 2·52–16·99). In children aged 1–17 years who had arrests of cardiac causes, favourable neurological outcome was more common after bystander CPR than no CPR (9·5% 42/440 vs 4·1% 14/339; OR 2·21, 1·08–4·54), and did not differ between conventional and compression-only CPR (9·9% 28/282 vs 8·9% 14/158; OR 1·20, 0·55–2·66). In infants (aged <1 year), outcomes were uniformly poor (1·7% 36/2082 with favourable neurological outcome). Interpretation For children who have out-of-hospital cardiac arrests from non-cardiac causes, conventional CPR (with rescue breathing) by bystander is the preferable approach to resuscitation. For arrests of cardiac causes, either conventional or compression-only CPR is similarly effective. Funding Fire and Disaster Management Agency and the Ministry of Education, Culture, Sports, Science and Technology (Japan).
Abstract Aim The aim of this investigation was to estimate and contrast the global incidence and outcome of out-of-hospital cardiac arrest (OHCA) to provide a better understanding of the variability ...in risk and survival of OHCA. Methods We conducted a review of published English-language articles about incidence of OHCA, available through MEDLINE and EmBase. For studies including adult patients and both adult and paediatric patients, we used Utstein data reporting guidelines to calculate, summarize and compare incidences per 100,000 person-years of attended OHCAs, treated OHCAs, treated OHCAs with a cardiac cause, treated OHCA with ventricular fibrillation (VF), and survival-to-hospital discharge rates following OHCA. Results Sixty-seven studies from Europe, North America, Asia or Australia met inclusion criteria. The weighted incidence estimate was significantly higher in studies including adults than in those including adults and paediatrics for treated OHCAs (62.3 vs 34.7; P < 0.001); and for treated OHCAs with a cardiac cause (54.6 vs 40.8; P = 0.004). Neither survival to discharge rates nor VF survival to discharge rates differed statistically significant among studies. The incidence of treated OHCAs was higher in North America (54.6) than in Europe (35.0), Asia (28.3), and Australia (44.0) ( P < 0.001). In Asia, the percentage of VF and survival to discharge rates were lower (11% and 2%, respectively) than those in Europe (35% and 9%, respectively), North America (28% and 6%, respectively), or Australia (40% and 11%, respectively) ( P < 0.001, P < 0.001). Conclusions OHCA incidence and outcome varies greatly around the globe. A better understanding of the variability is fundamental to improving OHCA prevention and resuscitation.
Summary Background Everolimus (RAD001) is an orally administered inhibitor of the mammalian target of rapamycin (mTOR), a therapeutic target for metastatic renal cell carcinoma. We did a phase III, ...randomised, double-blind, placebo-controlled trial of everolimus in patients with metastatic renal cell carcinoma whose disease had progressed on vascular endothelial growth factor-targeted therapy. Methods Patients with metastatic renal cell carcinoma which had progressed on sunitinib, sorafenib, or both, were randomly assigned in a two to one ratio to receive everolimus 10 mg once daily (n=272) or placebo (n=138), in conjunction with best supportive care. Randomisation was done centrally via an interactive voice response system using a validated computer system, and was stratified by Memorial Sloan-Kettering Cancer Center prognostic score and previous anticancer therapy, with a permuted block size of six. The primary endpoint was progression-free survival, assessed via a blinded, independent central review. The study was designed to be terminated after 290 events of progression. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00410124. Findings All randomised patients were included in efficacy analyses. The results of the second interim analysis indicated a significant difference in efficacy between arms and the trial was thus halted early after 191 progression events had been observed (101 37% events in the everolimus group, 90 65% in the placebo group; hazard ratio 0·30, 95% CI 0·22–0·40, p<0·0001; median progression-free survival 4·0 95% CI 3·7–5·5 vs 1·9 1·8–1·9 months). Stomatitis (107 40% patients in the everolimus group vs 11 8% in the placebo group), rash (66 25% vs six 4%), and fatigue (53 20% vs 22 16%) were the most commonly reported adverse events, but were mostly mild or moderate in severity. Pneumonitis (any grade) was detected in 22 (8%) patients in the everolimus group, of whom eight had pneumonitis of grade 3 severity. Interpretation Treatment with everolimus prolongs progression-free survival relative to placebo in patients with metastatic renal cell carcinoma that had progressed on other targeted therapies. Funding Novartis Oncology.
The critical lifesaving steps of BLS are ● Immediate Recognition and Activation of the emergency response system ● Early CPR and ● Rapid Defibrillation for VF. When an adult suddenly collapses, ...whoever is nearby should activate the emergency system and begin chest compressions (regardless of training). Trained lay rescuers who are able and healthcare providers should provide compressions and ventilations. Contrary to the belief of too many in this situation, CPR is not harmful. Inaction is harmful and CPR can be lifesaving. However, the quality of CPR is critical. Chest compressions should be delivered by pushing hard and fast in the center of the chest (ie, chest compressions should be of adequate rate and depth). Rescuers should allow complete chest recoil after each compression and minimize interruptions in chest compressions. They should also avoid excessive ventilation. If and when available, an AED should be applied and used without delaying chest compressions. With prompt and effective provision of these actions, lives are saved every day.
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