The impact of non-blinding in critical care medicine trials.

PURPOSE: It is uncertain whether, in critical care medicine, non-blinded trials are associated with a bias toward a different effect size. The aim of our study was to assess if conducting non-blinded/open label studies leads to greater effect size than blinded studies, and to provide an estimate of the weight of this difference. MATERIALS AND METHODS: We systematically searched all papers published in peer-reviewed journals between January 2000 and December 2015, dealing with non surgical interventions in critically ill adults and reporting a statistically significant difference in mortality. We assessed the number needed to treat (NNT) of each trial to estimate the treatment effect size and we divided studies into non-blinded, single-blinded and double-blinded. We searched for correlation between the treatment effect size and blinding, and adjusted for the other trial variables. RESULTS: We identified 119 critically ill randomized controlled trials. Of these, 69 studies were non-blinded and 50 were blinded. The median NNT in non-blinded studies was 5 [IQR 4-7] while it was 7 [IQR 5-7] in the blinded studies (p < .001). CONCLUSIONS: The NNT for blinded studies is 40% higher than for unblinded studies. This should be taken into account when planning and interpreting the findings of non-blinded studies performed in critically ill settings.

The Effect of inotropes and vasopressors on mortality: a meta-analysis of randomized clinical trials.

BACKGROUND: Inotropes and vasopressors are frequently administered to critically ill patients in order to improve haemodynamic function and restore adequate organ perfusion. However, some studies have suggested a possible association between inotrope administration and increased mortality. We therefore performed a meta-analysis of randomized trials published in the last 20 yr to investigate the effect of these drugs on mortality. METHODS: BioMedCentral, PubMed, Embase and the Cochrane Central Register were searched (all updated April 8th, 2015). Inclusion criteria were: random allocation to treatment, at least one group receiving an inotropic or vasopressor drug compared with at least one group receiving a non-inotropic/vasopressor treatment, study published after 1st January 1994, and systemic drug administration. Exclusion criteria were overlapping populations, studies published as abstract only, crossover studies, paediatric studies and lack of data on mortality. RESULTS: A total of 28 280 patients from 177 trials were included. Overall, pooled estimates showed no difference in mortality between the group receiving inotropes/vasopressors and the control group [4255/14 036 (31.7%) vs. 4277/14 244 (31.8%), risk ratio=0.98 (0.96-1.01), P for effect=0.23, P for heterogeneity=0.30, I2=6%]. A reduction in mortality was associated with inotrope/vasopressor therapy use in settings of vasoplegic syndromes, sepsis and cardiac surgery. Levosimendan was the only drug associated with improvement in survival. Subgroup analysis did not identify any groups with increased mortality associated with inotrope/vasopressor therapy. CONCLUSIONS: Our systematic review found that inotrope/vasopressor therapy is not associated with differences in mortality in the overall population and in the majority of subsettings.

[The new aspect of pneumonia in an area of the Middle Adriatic]. / Il nuovo volto delle polmoniti in un'area del medio Adriatico.

The present work reports the findings of a ten-year, research, the aim of which is to outline current views of pneumonia in a zone of the Middle Adriatic (USL 17-Regione Marche). The study confirmed, in its entirety, a lesser aggressiveness and loss of the "seasonal feature" of today's pneumonias. The high incidence of Atypical Pneumonia (AP) due to viral-like microorganisms (mycoplasma, chlamydia, coxiella, legionella) and an even higher one of unknown etiology is reported. After having analysed the most likely reasons for such a change and its various implications, the authors conclude that this type of research should be extended in order to trace a map of the more common infectious agents in single geographical zones, as an indispensable premise for a more concrete etiological diagnosis and for a more rational choice of the antibiotic.