The need to reform our assessment of evidence from clinical trials: A commentary

The ideology of evidence-based medicine (EBM) has dramatically altered the way we think, conceptualize, philosophize and practice medicine. One of its major pillars is the appraisal and classification of evidence. Although important and beneficial, this process currently lacks detail and is in need of reform. In particular, it largely focuses on three key dimensions (design, [type I] alpha error and beta [type II] error) to grade the quality of evidence and often omits other crucial aspects of evidence such as biological plausibility, reproducibility, generalizability, temporality, consistency and coherence. It also over-values the randomized trial and meta-analytical techniques, discounts the biasing effect of single centre execution and gives insufficient weight to large and detailed observational studies. Unless these aspects are progressively included into systems for grading, evaluating and classifying evidence and duly empirically assessed (according to the EBM paradigm), the EBM process and movement will remain open to criticism of being more evidence-biased than evidence-based."All scientific work is incomplete--whether it be observational or experimental. All scientific work is liable to be upset or modified by advancing knowledge. That does not confer upon us a freedom to ignore the knowledge we already have, or to postpone the action that it appears to demand at a given time". (Sir Bradford Austin Hill 1)

Effect of the medical emergency team on long-term mortality following major surgery

INTRODUCTION: Introducing an intensive care unit (ICU)-based medical emergency team (MET) into our hospital was associated with decreased postoperative in-hospital mortality after major surgery. The purpose of the present study was to assess the effect of the MET and other variables on long-term mortality in this patient population. METHODS: We conducted a prospective, controlled, before-and-after trial in a University-affiliated hospital. Participants included consecutive patients admitted for major surgery (surgery requiring hospital stay > 48 hours) during a four month control phase and a four month MET phase. The intervention involved the introduction of a hospital-wide ICU-based MET service to evaluate and treat ward patients with acutely deranged vital signs. Information on long-term mortality was obtained from the Australian death registry. The main outcome measure was patient mortality at 1500 days. Data on patient demographics, surgery undertaken and whether the surgery was scheduled or unscheduled was obtained from the hospital electronic database. Multivariable analysis was conducted to determine independent predictors of 1500-day mortality. RESULTS: There were 1,369 major operations in 1,116 patients during the control period and 1,313 operations in 1,067 patients during the MET (intervention) period. Overall survival at 1500 days was 65.8% in the control period and 71.6% during the MET period (P = 0.001). Patients in the control phase were statistically less likely to be admitted under orthopaedic surgery, urology and faciomaxillary surgery units, but more likely to be admitted under cardiac surgery or neurosurgery units. Patients in the MET period were less likely to undergo unscheduled surgery. Multivariable analysis revealed that age, unscheduled surgery and admission under thoracic surgery, neurosurgery, oncology and general medicine were independent predictors of increased 1500-day mortality. Admission during the MET period was also an independent predictor of decreased 1500-day mortality (odds ratio 0.74; P = 0.005). CONCLUSION: Introduction of a MET service in a teaching hospital was associated with increased long-term survival even after adjusting for other factors that contribute to long-term surgical mortality

Economics of dialysis dependence following renal replacement therapy for critically ill acute kidney injury patients

Background The obective of this study was to perform a cost-effectiveness analysis comparing intermittent with continuous renal replacement therapy (IRRT versus CRRT) as initial therapy for acute kidney injury (AKI) in the intensive care unit (ICU). Methods Assuming some patients would potentially be eligible for either modality, we modeled life year gained, the quality-adjusted life years (QALYs) and healthcare costs for a cohort of 1000 IRRT patients and a cohort of 1000 CRRT patients. We used a 1-year, 5-year and a lifetime horizon. A Markov model with two health states for AKI survivors was designed: dialysis dependence and dialysis independence. We applied Weibull regression from published estimates to fit survival curves for CRRT and IRRT patients and to fit the proportion of dialysis dependence among CRRT and IRRT survivors. We then applied a risk ratio reported in a large retrospective cohort study to the fitted CRRT estimates in order to determine the proportion of dialysis dependence for IRRT survivors. We conducted sensitivity analyses based on a range of differences for daily implementation cost between CRRT and IRRT (base case: CRRT day $632 more expensive than IRRT day; range from$200 to $1000) and a range of risk ratios for dialysis dependence for CRRT as compared with IRRT (from 0.65 to 0.95; base case: 0.80). Results Continuous renal replacement therapy was associated with a marginally greater gain in QALY as compared with IRRT (1.093 versus 1.078). Despite higher upfront costs for CRRT in the ICU ($4046 for CRRT versus $1423 for IRRT in average), the 5-year total cost including the cost of dialysis dependence was lower for CRRT ($37 780 for CRRT versus $39 448 for IRRT on average). The base case incremental cost-effectiveness analysis showed that CRRT dominated IRRT. This dominance was confirmed by extensive sensitivity analysis. Conclusions Initial CRRT is cost-effective compared with initial IRRT by reducing the rate of long-term dialysis dependence among critically ill AKI survivor

A pilot feasibility, safety and biological efficacy multicentre trial of therapeutic hypercapnia after cardiac arrest: study protocol for a randomized controlled trial

BACKGROUND: Cardiac arrest causes ischaemic brain injury. Arterial carbon dioxide tension (PaCO2) is a major determinant of cerebral blood flow. Thus, mild hypercapnia in the 24 h following cardiac arrest may increase cerebral blood flow and attenuate such injury. We describe the Carbon Control and Cardiac Arrest (CCC) trial. METHODS/DESIGN: The CCC trial is a pilot multicentre feasibility, safety and biological efficacy randomized controlled trial recruiting adult cardiac arrest patients admitted to the intensive care unit after return of spontaneous circulation. At admission, using concealed allocation, participants are randomized to 24 h of either normocapnia (PaCO2 35 to 45 mmHg) or mild hypercapnia (PaCO2 50 to 55 mmHg). Key feasibility outcomes are recruitment rate and protocol compliance rate. The primary biological efficacy and biological safety measures are the between-groups difference in serum neuron-specific enolase and S100b protein levels at 24 h, 48 h and 72 h. Secondary outcome measure include adverse events, in-hospital mortality, and neurological assessment at 6 months. DISCUSSION: The trial commenced in December 2012 and, when completed, will provide clinical evidence as to whether targeting mild hypercapnia for 24 h following intensive care unit admission for cardiac arrest patients is feasible and safe and whether it results in decreased concentrations of neurological injury biomarkers compared with normocapnia. Trial results will also be used to determine whether a phase IIb study powered for survival at 90 days is feasible and justified.<br /

Long term effect of a medical emergency team on cardiac arrests in a teaching hospital

INTRODUCTION: It is unknown whether the reported short-term reduction in cardiac arrests associated with the introduction of the medical emergency team (MET) system can be sustained. METHOD: We conducted a prospective, controlled before-and-after examination of the effect of a MET system on the long-term incidence of cardiac arrests. We included consecutive patients admitted during three study periods: before the introduction of the MET; during the education phase preceding the implementation of the MET; and a period of four years from the implementation of the MET system. Cardiac arrests were identified from a log book of cardiac arrest calls and cross-referenced with case report forms and the intensive care unit admissions database. We measured the number of hospital admissions and MET reviews during each period, performed multivariate logistic regression analysis to identify predictors of mortality following cardiac arrest and studied the correlation between the rate of MET calls with the rate of cardiac arrests. RESULTS: Before the introduction of the MET system there were 66 cardiac arrests and 16,246 admissions (4.06 cardiac arrests per 1,000 admissions). During the education period, the incidence of cardiac arrests decreased to 2.45 per 1,000 admissions (odds ratio (OR) for cardiac arrest 0.60; 95% confidence interval (CI) 0.43-0.86; p = 0.004). After the implementation of the MET system, the incidence of cardiac arrests further decreased to 1.90 per 1,000 admissions (OR for cardiac arrest 0.47; 95% CI 0.35-0.62; p < 0.0001). There was an inverse correlation between the number of MET calls in each calendar year and the number of cardiac arrests for the same year (r2 = 0.84; p = 0.01), with 17 MET calls being associated with one less cardiac arrest. Male gender (OR 2.88; 95% CI 1.34-6.19) and an initial rhythm of either asystole (OR 7.58; 95% CI 3.15-18.25; p < 0.0001) or pulseless electrical activity (OR 4.09; 95% CI 1.59-10.51; p = 0.003) predicted an increased risk of death. CONCLUSION: Introduction of a MET system into a teaching hospital was associated with a sustained and progressive reduction in cardiac arrests over a four year period. Our findings show sustainability and suggest that, for every 17 MET calls, one cardiac arrest might be prevented

In vitro Removal of Therapeutic Drugs with a Novel Adsorbent System

Background/Aim: Substances in the middle molecular weight range have been shown to play a significant pathogenetic role in as diverse disorders as end-stage renal disease and multiple organ failure. To overcome the limitations in the amount removed by hemofilters, new sorbents with a high biocompatibility are actively being developed. Furthermore, biocompatible sorbents by their nonspecific adsorptive behavior could have great impact on detoxification treatment in exogenous intoxications. We performed an in vitro evaluation of a newly developed highly biocompatible sorbent cartridge (Betasorb(R)), examining its adsorptive capacity concerning therapeutic drugs. Methods: Uremic blood spiked with a range of therapeutic drugs was recirculated for 2 h in an in vitro hemoperfusion circuit containing a Betasorb device for hemoperfusion. The drug concentrations before and after the passage of the cartridge were measured, and the total amount removed was calculated. Results: The sorbent showed effective removal of glycopeptide antibiotics, digoxin, theophylline, phenobarbital, phenytoin, carbamazepine, and valproic acid. Moderate removal could be demonstrated for tacrolimus and cyclosporine A; aminoglycosides were removed to a small extent only. Conclusions: Betasorb hemoperfusion shows a potent adsorptive capacity concerning therapeutic drugs (except aminoglycosides) and could be of major value in the treatment of intoxications. On the other hand, drug monitoring and possible adjustments are necessary during Betasorb hemoperfusion to maintain the therapeutic ranges of the drugs in blood. Copyright (C) 2002 S. Karger AG, Basel

Pengaruh Kompetensi Guru Terhadap Komitmen Profesional Dan Dampaknya Pada Kinerja Serta Kepuasan Kerja Guru Matematika SMP Dan Mts

Penelitian ini bertujuan untuk memperoleh model hubungan kausalitas dari variabel-variabel kompetensi, komitmen profesional, kinerja dan kepuasan kerja guru matematika. Populasi dalam penelitian ini adalah seluruh guru matematika SMP dan MTs di Kabupaten Ponorogo yang berjumlah 262 orang. Sampel sejumlah 82 orang ditentukan melalui teknik two stage cluster random sampling. Instrumen penelitian ini adalah kuesioner dan lembar penilaian/observasi. Kuesioner digunakan untuk mengumpulkan data komitmen profesional dan kepuasan kerja guru matematika, sedangkan lembar penilaian/observasi digunakan untuk mengumpulkan data kompetensi dan kinerja guru matematika. Data yang diperoleh dianalisis dengan metode Structural Equation Modeling (SEM).Hasil penelitian menunjukkan bahwa: (1) terdapat pengaruh positif kompetensi terhadap komitmen profesional sebesar 15,9%; (2) terdapat pengaruh positif kompetensi terhadap kinerja sebesar 63,6%; (3) terdapat pengaruh positif komitmen profesional terhadap kinerja sebesar 15,9%; dan (4) terdapat pengaruh positif komitmen profesional terhadap kepuasan kerja sebesar 37,8%. Hasil-hasil penelitian di atas dapat mengkonfirmasi kesimpulan penelitian-penelitian sebelumnya