A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Increasing Mortality.

OBJECTIVE: Reducing mortality is a key target in critical care and perioperative medicine. The authors aimed to identify all nonsurgical interventions (drugs, techniques, strategies) shown by randomized trials to increase mortality in these clinical settings. DESIGN: A systematic review of the literature followed by a consensus-based voting process. SETTING: A web-based international consensus conference. PARTICIPANTS: Two hundred fifty-one physicians from 46 countries. INTERVENTIONS: The authors performed a systematic literature search and identified all randomized controlled trials (RCTs) showing a significant increase in unadjusted landmark mortality among surgical or critically ill patients. The authors reviewed such studies during a meeting by a core group of experts. Studies selected after such review advanced to web-based voting by clinicians in relation to agreement, clinical practice, and willingness to include each intervention in international guidelines. MEASUREMENTS AND MAIN RESULTS: The authors selected 12 RCTs dealing with 12 interventions increasing mortality: diaspirin-crosslinked hemoglobin (92% of agreement among web voters), overfeeding, nitric oxide synthase inhibitor in septic shock, human growth hormone, thyroxin in acute kidney injury, intravenous salbutamol in acute respiratory distress syndrome, plasma-derived protein C concentrate, aprotinin in high-risk cardiac surgery, cysteine prodrug, hypothermia in meningitis, methylprednisolone in traumatic brain injury, and albumin in traumatic brain injury (72% of agreement). Overall, a high consistency (ranging from 80% to 90%) between agreement and clinical practice was observed. CONCLUSION: The authors identified 12 clinical interventions showing increased mortality supported by randomized controlled trials with nonconflicting evidence, and wide agreement upon clinicians on a global scale.

A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Reducing Mortality.

The authors aimed to identify interventions documented by randomized controlled trials (RCTs) that reduce mortality in adult critically ill and perioperative patients, followed by a survey of clinicians' opinions and routine practices to understand the clinicians' response to such evidence. The authors performed a comprehensive literature review to identify all topics reported to reduce mortality in perioperative and critical care settings according to at least 2 RCTs or to a multicenter RCT or to a single-center RCT plus guidelines. The authors generated position statements that were voted on online by physicians worldwide for agreement, use, and willingness to include in international guidelines. From 262 RCT manuscripts reporting mortality differences in the perioperative and critically ill settings, the authors selected 27 drugs, techniques, and strategies (66 RCTs, most frequently published by the New England Journal of Medicine [13 papers], Lancet [7], and Journal of the American Medical Association [5]) with an agreement ≥67% from over 250 physicians (46 countries). Noninvasive ventilation was the intervention supported by the largest number of RCTs (n = 13). The concordance between agreement and use (a positive answer both to "do you agree" and "do you use") showed differences between Western and other countries and between anesthesiologists and intensive care unit physicians. The authors identified 27 clinical interventions with randomized evidence of survival benefit and strong clinician support in support of their potential life-saving properties in perioperative and critically ill patients with noninvasive ventilation having the highest level of support. However, clinician views appear affected by specialty and geographical location.

Shaping the role of 'fast' and 'slow' drivers of change in forest-shrubland socio-ecological systems.

The temporal speeds and spatial scales at which ecosystem processes operate are often at odds with the scale and speed at which natural resources such as soil, water and vegetation are managed those. Scale mismatches often occur as a result of the time-lag between policy development, implementation and observable changes in natural capital in particular. In this study, we analyse some of the transformations that can occur in complex forest-shrubland socio-ecological systems undergoing biophysical and socioeconomic change. We use a Multiway Factor Analysis (MFA) applied to a representative set of variables to assess changes in components of natural, economic and social capitals over time. Our results indicate similarities among variables and spatial units (i.e. municipalities) which allows us to rank the variables used to describe the SES according to their rapidity of change. The novelty of the proposed framework lies in the fact that the assessment of rapidity-to-change, based on the MFA, takes into account the multivariate relationships among the system's variables, identifying the net rate of change for the whole system, and the relative impact that individual variables exert on the system itself. The aim of this study was to assess the influence of fast and slow variables on the evolution of socio-economic systems based on simplified multivariate procedures applicable to vastly different socio-economic contexts and conditions. This study also contributes to quantitative analysis methods for long-established socio-ecological systems, which may help in designing more effective, and sustainable land management strategies in environmentally sensitive areas.

Effect of lactose on gut microbiota and metabolome of infants with cow's milk allergy.

Allergic infants have an unusual gastrointestinal microbiota with low numbers of Bifidobacterium/Lactobacilli and high levels of Clostridium, staphylococci and Escherichia coli. Hydrolyzed formula used to treat these infants is deprived of lactose that instead may influence the gut microbial composition. The aim of the present study is to investigate the influence of lactose on the composition of the gut microbiota and metabolome of infants with cow's milk allergy. Infants prospectively enrolled received an extensively hydrolyzed formula with no lactose for 2 months followed by an identical lactose-containing formula for an additional 2 months. Healthy, age-gender-matched infants were used as controls. The following determinations were performed before and after the introduction of lactose in the diet: enumeration of cells present in the feces using FISH, counts of viable bacterial cells and gas-chromatography mass spectrometry/solid-phase microextraction analysis. The addition of lactose to the diet significantly increases the counts of Bifidobacteria and lactic acid bacteria (p < 0.01), decreases that of Bacteroides/clostridia (p < 0.05) reaching counts found in healthy controls; lactose significantly increases the concentration of total short-chain fatty acids (p < 0.05). The addition of lactose to an extensively hydrolyzed formula is able to positively modulate the composition of gut microbiota by increasing the total fecal counts of Lactobacillus/Bifidobacteria and decreasing that of Bacteroides/Clostridia. The positive effect is completed by the increase of median concentration of short chain fatty acids, especially for acetic and butyric acids demonstrated by the metabolomic analysis.

Complex Adaptive Systems, soil degradation and land sensitivity to desertification: A multivariate assessment of Italian agro-forest landscape.

Degradation of soils and sensitivity of land to desertification are intensified in last decades in the Mediterranean region producing heterogeneous spatial patterns determined by the interplay of factors such as climate, land-use changes, and human pressure. The present study hypothesizes that rising levels of soil degradation and land sensitivity to desertification are reflected into increasingly complex (and non-linear) relationships between environmental and socioeconomic variables. To verify this hypothesis, the Complex Adaptive Systems (CAS) framework was used to explore the spatiotemporal dynamics of eleven indicators derived from a standard assessment of soil degradation and land sensitivity to desertification in Italy. Indicators were made available on a detailed spatial scale (773 agricultural districts) for various years (1960, 1990, 2000 and 2010) and analyzed through a multi-dimensional exploratory data analysis. Our results indicate that the number of significant pair-wise correlations observed between indicators increased with the level of soil and land degradation, although with marked differences between northern and southern Italy. 'Fast' and 'slow' factors underlying soil and land degradation, and 'rapidly-evolving' or 'locked' agricultural districts were identified according to the rapidity of change estimated for each of the indicators studied. In southern Italy, 'rapidly-evolving' districts show a high level of soil degradation and land sensitivity to desertification during the whole period of investigation. On the contrary, those districts in northern Italy are those experiencing a moderate soil degradation and land sensitivity to desertification with the highest increase in the level of sensitivity over time. The study framework contributes to the assessment of complex local systems' dynamics in affluent but divided countries. Results may inform thematic strategies for the mitigation of land and soil degradation in the framework of action plans to combat desertification.