Rifampin use in acute community-acquired meningitis in intensive care units: the French retrospective cohort ACAM-ICU study

Abstract Introduction Bacterial meningitis among critically ill adult patients remains associated with both high mortality and frequent, persistent disability. Vancomycin was added to treatment with a third-generation cephalosporin as recommended by French national guidelines. Because animal model studies had suggested interest in the use of rifampin for treatment of bacterial meningitis, and after the introduction of early corticosteroid therapy (in 2002), there was a trend toward increasing rifampin use for intensive care unit (ICU) patients. The aim of this article is to report on this practice. Methods Five ICUs participated in the study. Baseline characteristics and treatment data were retrospectively collected from charts of patients admitted with a diagnosis of acute bacterial meningitis during a 5-year period (2004–2008). The ICU mortality was the main outcome measure; Glasgow Outcome Scale and 3-month mortality were also assessed. Results One hundred fifty-seven patients were included. Streptococcus pneumoniae and Neisseria meningitidis were the most prevalent causative microorganisms. The ICU mortality rate was 15 %. High doses of a cephalosporin were the most prevalent initial antimicrobial treatment. The delay between admission and administration of the first antibiotic dose was correlated with ICU mortality. Rifampin was used with a cephalosporin for 32 patients (ranging from 8 % of the cohort for 2004 to 30 % in 2008). Administration of rifampin within the first 24 h of hospitalization could be associated with a lower ICU survival. Statistical association between such an early rifampin treatment and ICU mortality reached significance only for patients with pneumococcal meningitis (p=0.031) in univariate analysis, but not in the logistic model. Conclusions We report on the role of rifampin use for patients with community-acquired meningitis, and the results of this study suggest that this practice may be associated with lower mortality in the ICU. Nevertheless, the only independent predictors of ICU mortality were organ failure and pneumococcal infection. Further studies are required to confirm these results and to explain how rifampin use would reduce mortality. </jats:sec

MRI-targeted or standard biopsy for prostate-cancer diagnosis

Background Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. Methods In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. Results A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P&lt;0.001). Conclusions The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .)

Long-term modification of cortical synapses improves sensory perception

Synapses and receptive fields of the cerebral cortex are plastic. However, changes to specific inputs must be coordinated within neural networks to ensure that excitability and feature selectivity are appropriately configured for perception of the sensory environment. Long-lasting enhancements and decrements to rat primary auditory cortical excitatory synaptic strength were induced by pairing acoustic stimuli with activation of the nucleus basalis neuromodulatory system. Here we report that these synaptic modifications were approximately balanced across individual receptive fields, conserving mean excitation while reducing overall response variability. Decreased response variability should increase detection and recognition of near-threshold or previously imperceptible stimuli, as we found in behaving animals. Thus, modification of cortical inputs leads to wide-scale synaptic changes, which are related to improved sensory perception and enhanced behavioral performance

Trees, forests and water: Cool insights for a hot world

Forest-driven water and energy cycles are poorly integrated into regional, national, continental and global decision-making on climate change adaptation, mitigation, land use and water management. This constrains humanity’s ability to protect our planet’s climate and life-sustaining functions. The substantial body of research we review reveals that forest, water and energy interactions provide the foundations for carbon storage, for cooling terrestrial surfaces and for distributing water resources. Forests and trees must be recognized as prime regulators within the water, energy and carbon cycles. If these functions are ignored, planners will be unable to assess, adapt to or mitigate the impacts of changing land cover and climate. Our call to action targets a reversal of paradigms, from a carbon-centric model to one that treats the hydrologic and climate-cooling effects of trees and forests as the first order of priority. For reasons of sustainability, carbon storage must remain a secondary, though valuable, by-product. The effects of tree cover on climate at local, regional and continental scales offer benefits that demand wider recognition. The forest- and tree-centered research insights we review and analyze provide a knowledge-base for improving plans, policies and actions. Our understanding of how trees and forests influence water, energy and carbon cycles has important implications, both for the structure of planning, management and governance institutions, as well as for how trees and forests might be used to improve sustainability, adaptation and mitigation efforts

Helicobacter pylori infection is not associated with an increased hemorrhagic risk in patients in the intensive care unit

INTRODUCTION: The potential role of Helicobacter pylori in acute stress ulcer in patients in an intensive care unit (ICU) is controversial. The aim of this study was to determine the frequency of H. pylori infection in ICU patients by antigen detection on rectal swabs, and to analyze the potential relationship between the presence of H. pylori and the risk of digestive gastrointestinal bleeding. METHODS: In this prospective, multicenter, epidemiological study, the inclusion criteria were as follows: patients admitted to the 12 participating ICU for at least two days, who were free of hemorrhagic shock and did not receive more than four units of red blood cells during the day before or the first 48 hours after admission to the ICU. Rectal swabs were obtained within the first 24 hours of admission to the ICU and were tested for H. pylori antigens with the ImmunoCard STAT! HpSA kit. The following events were analyzed according to H. pylori status: gastrointestinal bleeding, unexplained decline in hematocrit, and the number of red cell transfusions. RESULTS: The study involved 1,776 patients. Forty-nine patients (2.8%) had clinical evidence of upper digestive bleeding. Esophagogastroduodenoscopy was performed in 7.6% of patients. Five hundred patients (28.2%) required blood transfusion. H. pylori antigen was detected in 6.3% of patients (95% confidence interval 5.2 to 7.5). H. pylori antigen positivity was associated with female sex (p < 0.05) and with a higher Simplified Acute Physiology Score II (SAPS II; p < 0.05). H. pylori antigen status was not associated with the use of fiber-optic gastroscopy, the need for red cell transfusions, or the number of red cell units infused. CONCLUSION: This large study reported a small percentage of H. pylori infection detected with rectal swab sampling in ICU patients and showed that the patients infected with H. pylori had no additional risk of gastrointestinal bleeding. Thus H. pylori does not seem to have a major role in the pathogenesis of acute stress ulcer in ICU patients

A multicentre case-control study of nonsteroidal anti-inflammatory drugs as a risk factor for severe sepsis and septic shock

International audienceINTRODUCTION: We aimed to establish whether the use of nonsteroidal anti-inflammatory drugs (NSAIDs) during evolving bacterial community-acquired infection in adults is associated with severe sepsis or septic shock. METHODS: We conducted a multicentre case-control study in eight intensive care units. Cases were all adult patients admitted for severe sepsis or septic shock due to a bacterial community-acquired infection. Control individuals were patients hospitalized with a mild community-acquired infection. Each case was matched to one control for age, presence of diabetes and site of infection. RESULTS: The main outcome measures were the proportions of cases and controls exposed to NSAIDs or aspirin during the period of observation. In all, 152 matched pairs were analyzed. The use of NSAIDs or aspirin during the observation period did not differ between cases and controls (27% versus 28; odds ratio = 0.93, 95% confidence interval [CI] = 0.52 to 1.64). If aspirin was not considered or if a distinction was made between acute and chronic drug treatment, there remained no difference between groups. However, the median time to prescription of effective antibiotic therapy was longer for NSAID users (6 days, 95% CI = 3 to 7 days) than for nonusers (3 days, 95% CI = 2 to 3 days; P = 0.02). CONCLUSIONS: In this study, the use of NSAIDs or aspirin during evolving bacterial infection was frequent and occurred in one-quarter of the patients with such infection. Although the use of NSAIDs by patients with severe sepsis or septic shock did not differ from their use by those with mild infection at the same infected site, we observed a longer median time to prescription of effective antibiotic therapy in NSAID users

ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer

PURPOSE: Enzalutamide, a potent androgen-receptor inhibitor, has demonstrated significant benefits in metastatic and nonmetastatic castration-resistant prostate cancer. We evaluated the efficacy and safety of enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC). METHODS: ARCHES (ClinicalTrials.gov identifier: NCT02677896) is a multinational, double-blind, phase III trial, wherein 1,150 men with mHSPC were randomly assigned 1:1 to enzalutamide (160 mg/day) or placebo, plus androgen deprivation therapy (ADT), stratified by disease volume and prior docetaxel chemotherapy. The primary end point was radiographic progression-free survival. RESULTS: As of October 14, 2018, the risk of radiographic progression or death was significantly reduced with enzalutamide plus ADT versus placebo plus ADT (hazard ratio, 0.39; 95% CI, 0.30 to 0.50; P < .001; median not reached v 19.0 months). Similar significant improvements in radiographic progression-free survival were reported in prespecified subgroups on the basis of disease volume and prior docetaxel therapy. Enzalutamide plus ADT significantly reduced the risk of prostate-specific antigen progression, initiation of new antineoplastic therapy, first symptomatic skeletal event, castration resistance, and reduced risk of pain progression. More men achieved an undetectable prostate-specific antigen level and/or an objective response with enzalutamide plus ADT (P < .001). Patients in both treatment groups reported a high baseline level of quality of life, which was maintained over time. Grade 3 or greater adverse events were reported in 24.3% of patients who received enzalutamide plus ADT versus 25.6% of patients who received placebo plus ADT, with no unexpected adverse events. CONCLUSION: Enzalutamide with ADT significantly reduced the risk of metastatic progression or death over time versus placebo plus ADT in men with mHSPC, including those with low-volume disease and/or prior docetaxel, with a safety analysis that seems consistent with the safety profile of enzalutamide in previous clinical trials in castration-resistant prostate cancer

Contribution of the ethics committee of the French Intensive Care Society to describing a scenario for implementing organ donation after Maastricht type III cardiocirculatory death in France

Abstract French law allows organ donation after death due to cardiocirculatory arrest. In the Maastricht classification, type III non-heart-beating donors are those who experience cardiocirculatory arrest after the withdrawal of life-sustaining treatments. French authorities in charge of regulating organ donation (Agence de la Biomédecine, ABM) are considering organ collection from Maastricht type III donors. We describe a scenario for Maastricht type III organ donation that fully complies with the ethical norms governing care to dying patients. That organ donation may occur after death should have no impact on the care given to the patient and family. The dead-donor rule must be followed scrupulously: the organ retrieval procedure must neither cause nor hasten death. The decision to withdraw life-sustaining treatments, withdrawal modalities, and care provided to the patient and family must adhere strictly to the requirements set forth in patient-rights legislation (the 2005 Léonetti law in France) and should not be influenced in any way by the possibility of organ donation. A major ethical issue regarding the family is how best to transition from discussing treatment-withdrawal decisions to discussing possible organ retrieval for donation should the patient die rapidly after treatment withdrawal. Close cooperation between the healthcare team and the organ retrieval team is crucial to minimize the distress of family members during this transition. Modalities for implementing Maastricht type III organ donation are discussed here, including the best location for withdrawing life-sustaining treatments (operating room or intensive care unit).</jats:p