Hôpital Sainte-Marguerite

BACKGROUND: In patients undergoing mechanical ventilation for the acute respiratory distress syndrome (ARDS), neuromuscular blocking agents may improve oxygenation and decrease ventilator-induced lung injury but may also cause muscle weakness. We evaluated clinical outcomes after 2 days of therapy with neuromuscular blocking agents in patients with early, severe ARDS. METHODS: In this multicenter, double-blind trial, 340 patients presenting to the intensive care unit (ICU) with an onset of severe ARDS within the previous 48 hours were randomly assigned to receive, for 48 hours, either cisatracurium besylate (178 patients) or placebo (162 patients). Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FIO2) of less than 150, with a positive end-expiratory pressure of 5 cm or more of water and a tidal volume of 6 to 8 ml per kilogram of predicted body weight. The primary outcome was the proportion of patients who died either before hospital discharge or within 90 days after study enrollment (i.e., the 90-day in-hospital mortality rate), adjusted for predefined covariates and baseline differences between groups with the use of a Cox model. RESULTS: The hazard ratio for death at 90 days in the cisatracurium group, as compared with the placebo group, was 0.68 (95% confidence interval [CI], 0.48 to 0.98; P=0.04), after adjustment for both the baseline PaO2:FIO2 and plateau pressure and the Simplified Acute Physiology II score. The crude 90-day mortality was 31.6% (95% CI, 25.2 to 38.8) in the cisatracurium group and 40.7% (95% CI, 33.5 to 48.4) in the placebo group (P=0.08). Mortality at 28 days was 23.7% (95% CI, 18.1 to 30.5) with cisatracurium and 33.3% (95% CI, 26.5 to 40.9) with placebo (P=0.05). The rate of ICU-acquired paresis did not differ significantly between the two groups. CONCLUSIONS: In patients with severe ARDS, early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time off the ventilator without increasing muscle weakness. (Funded by Assistance Publique-Hôpitaux de Marseille and the Programme Hospitalier de Recherche Clinique Régional 2004-26 of the French Ministry of Health; ClinicalTrials.gov number, NCT00299650.)

BACKGROUND: Carotid stenting is less invasive than endarterectomy, but it is unclear whether it is as safe in patients with symptomatic carotid-artery stenosis. METHODS: We conducted a multicenter, randomized, noninferiority trial to compare stenting with endarterectomy in patients with a symptomatic carotid stenosis of at least 60%. The primary end point was the incidence of any stroke or death within 30 days after treatment. RESULTS: The trial was stopped prematurely after the inclusion of 527 patients for reasons of both safety and futility. The 30-day incidence of any stroke or death was 3.9% after endarterectomy (95% confidence interval [CI], 2.0 to 7.2) and 9.6% after stenting (95% CI, 6.4 to 14.0); the relative risk of any stroke or death after stenting as compared with endarterectomy was 2.5 (95% CI, 1.2 to 5.1). The 30-day incidence of disabling stroke or death was 1.5% after endarterectomy (95% CI, 0.5 to 4.2) and 3.4% after stenting (95% CI, 1.7 to 6.7); the relative risk was 2.2 (95% CI, 0.7 to 7.2). At 6 months, the incidence of any stroke or death was 6.1% after endarterectomy and 11.7% after stenting (P=0.02). There were more major local complications after stenting and more systemic complications (mainly pulmonary) after endarterectomy, but the differences were not significant. Cranial-nerve injury was more common after endarterectomy than after stenting. CONCLUSIONS: In this study of patients with symptomatic carotid stenosis of 60% or more, the rates of death and stroke at 1 and 6 months were lower with endarterectomy than with stenting. (ClinicalTrials.gov number, NCT00190398 [ClinicalTrials.gov].).

Hypertension is a major public health problem of largely unknown cause. Here, we identify two genes causing pseudohypoaldosteronism type II, a Mendelian trait featuring hypertension, increased renal salt reabsorption, and impaired K+ and H+ excretion. Both genes encode members of the WNK family of serine-threonine kinases. Disease-causing mutations in WNK1 are large intronic deletions that increase WNK1 expression. The mutations in WNK4 are missense, which cluster in a short, highly conserved segment of the encoded protein. Both proteins localize to the distal nephron, a kidney segment involved in salt, K+, and pH homeostasis. WNK1 is cytoplasmic, whereas WNK4 localizes to tight junctions. The WNK kinases and their associated signaling pathway(s) may offer new targets for the development of antihypertensive drugs.

In Brief Introduction: Perioperative complications influence long- and short-term outcomes after esophagectomy. The absence of a standardized system for defining and recording complications and quality measures after esophageal resection has meant that there is wide variation in evaluating their impact on these outcomes. Methods: The Esophageal Complications Consensus Group comprised 21 high-volume esophageal surgeons from 14 countries, supported by all the major thoracic and upper gastrointestinal professional societies. Delphi surveys and group meetings were used to achieve a consensus on standardized methods for defining complications and quality measures that could be collected in institutional databases and national audits. Results: A standardized list of complications was created to provide a template for recording individual complications associated with esophagectomy. Where possible, these were linked to preexisting international definitions. A Delphi survey facilitated production of specific definitions for anastomotic leak, conduit necrosis, chyle leak, and recurrent nerve palsy. An additional Delphi survey documented consensus regarding critical quality parameters recommended for routine inclusion in databases. These quality parameters were documentation on mortality, comorbidities, completeness of data collection, blood transfusion, grading of complication severity, changes in level of care, discharge location, and readmission rates. Conclusions: The proposed system for defining and recording perioperative complications associated with esophagectomy provides an infrastructure to standardize international data collection and facilitate future comparative studies and quality improvement projects. Complications affect every major outcome parameter after major cancer surgery. No internationally accepted system for documenting complications after esophagectomy currently exists. Using the Delphi process, high-volume esophageal surgeons from 14 countries have reached a consensus on a standardized list of complications, quality measures, and definitions for specific complications.

Background— DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders. Methods and Results— To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15 907 blood-derived DNA samples from participants in 16 cohorts (including 2433 current, 6518 former, and 6956 never smokers). Comparing current versus never smokers, 2623 cytosine–phosphate–guanine sites (CpGs), annotated to 1405 genes, were statistically significantly differentially methylated at Bonferroni threshold of P <1×10 −7 (18 760 CpGs at false discovery rate <0.05). Genes annotated to these CpGs were enriched for associations with several smoking-related traits in genome-wide studies including pulmonary function, cancers, inflammatory diseases, and heart disease. Comparing former versus never smokers, 185 of the CpGs that differed between current and never smokers were significant P <1×10 −7 (2623 CpGs at false discovery rate <0.05), indicating a pattern of persistent altered methylation, with attenuation, after smoking cessation. Transcriptomic integration identified effects on gene expression at many differentially methylated CpGs. Conclusions— Cigarette smoking has a broad impact on genome-wide methylation that, at many loci, persists many years after smoking cessation. Many of the differentially methylated genes were novel genes with respect to biological effects of smoking and might represent therapeutic targets for prevention or treatment of tobacco-related diseases. Methylation at these sites could also serve as sensitive and stable biomarkers of lifetime exposure to tobacco smoke.

BACKGROUND: Studies of the bacterial communities of the gut microbiota have revealed a shift in the ratio of Firmicutes and Bacteroidetes in obese patients. Determining the variations of microbial communities in feces may be beneficial for the identification of specific profiles in patients with abnormal weights. The roles of the archaeon Methanobrevibacter smithii and Lactobacillus species have not been described in these studies. METHODS AND FINDINGS: We developed an efficient and robust real-time PCR tool that includes a plasmid-based internal control and allows for quantification of the bacterial divisions Bacteroidetes, Firmicutes, and Lactobacillus as well as the methanogen M. smithii. We applied this technique to the feces of 20 obese subjects, 9 patients with anorexia nervosa, and 20 normal-weight healthy controls. Our results confirmed a reduction in the Bacteroidetes community in obese patients (p<0.01). We found a significantly higher Lactobacillus species concentration in obese patients than in lean controls (p=0.0197) or anorexic patients (p=0.0332). The M. smithii concentration was much higher in anorexic patients than in the lean population (p=0.0171). CONCLUSIONS: Lactobacillus species are widely used as growth promoters in the farm industry and are now linked to obesity in humans. The study of the bacterial flora in anorexic patients revealed an increase in M. smithii. This increase might represent an adaptive use of nutrients in this population.

RATIONALE: Burnout syndrome (BOS) associated with stress has been documented in health care professionals in many specialties. The intensive care unit (ICU) is a highly stressful environment. Little is known about BOS in critical care nursing staff. OBJECTIVES: To identify determinants of BOS in critical care nurses. METHODS: We conducted a questionnaire survey in France. Among 278 ICUs contacted for the study, 165 (59.4%) included 2,525 nursing staff members, of whom 2,392 returned questionnaires with complete Maslach Burnout Inventory data. MEASUREMENTS AND MAIN RESULTS: Of the 2,392 respondents (82% female), 80% were nurses, 15% nursing assistants, and 5% head nurses. Severe BOS-related symptoms were identified in 790 (33%) respondents. By multivariate analysis, four domains were associated with severe BOS: (1) personal characteristics, such as age (odds ratio [OR], 0.97/yr; confidence interval [CI], 0.96-0.99; p=0.0008); (2) organizational factors, such as ability to choose days off (OR, 0.69; CI, 0.52-0.91; p=0.009) or participation in an ICU research group (OR, 0.74; CI, 0.56-0.97; p=0.03); (3) quality of working relations (1-10 scale), such as conflicts with patients (OR, 1.96; CI, 1.16-1.30; p=0.01), relationship with head nurse (OR, 0.92/point; CI, 0.86-0.98; p=0.02) or physicians (OR, 0.81; CI, 0.74-0.87; p=0.0001); and (4) end-of-life related factors, such as caring for a dying patient (OR, 1.39; CI, 1.04-1.85; p=0.02), and number of decisions to forego life-sustaining treatments in the last week (OR, 1.14; CI, 1.01-1.29; p=0.04). CONCLUSION: One-third of ICU nursing staff had severe BOS. Areas for improvement identified in our study include conflict prevention, participation in ICU research groups, and better management of end-of-life care. Interventional studies are needed to investigate these potentially preventive strategies.

RATIONALE: Professional burnout is a psychological syndrome arising in response to chronic interpersonal stressors on the job. There is the perception that intensivists are particularly exposed to stress because lives are literally in their hands. OBJECTIVE: To evaluate the prevalence and associated factors (patients or organization) of burnout among physicians working in intensive care units (ICUs) (including interns, residents, fellows, and attending physicians). METHODS: A 1-day national survey was conducted in adult ICUs in French public hospitals. MEASUREMENTS: The level of burnout was evaluated on the basis of the Maslach Burnout Inventory (MBI). MAIN RESULTS: A total of 189 ICUs participated and 978 surveys were returned (82.3% response rate). A high level of burnout was identified in 46.5% of the respondents. Ordinal logistic regression showed that female sex (odds ratio, 1.58; 95% confidence interval, 1.09 to 2.30) was independently associated with a higher MBI score. Whereas no factor related to the severity of illness of patients was retained by the model, organizational factors were strongly associated with a higher MBI score. Workload (the number of night shifts per month, a long period of time from the last nonworking week, night shift the day before the survey) and impaired relationships (such as conflict with another colleague intensivist, and/or with a nurse) were the variables independently associated with a higher MBI score. In contrast, the quality of the relationships with chief nurses and nurses was associated with a lower MBI score. CONCLUSIONS: Approximately one-half of the intensivists presented a high level of burnout. Organizational factors, but not factors related to the patients, appeared to be associated with burnout.

BACKGROUND: Obesity is associated with increased health risk and has been associated with alterations in bacterial gut microbiota, with mainly a reduction in Bacteroidetes, but few data exist at the genus and species level. It has been reported that the Lactobacillus and Bifidobacterium genus representatives may have a critical role in weight regulation as an anti-obesity effect in experimental models and humans, or as a growth-promoter effect in agriculture depending on the strains. OBJECTIVES AND METHODS: To confirm reported gut alterations and test whether Lactobacillus or Bifidobacterium species found in the human gut are associated with obesity or lean status, we analyzed the stools of 68 obese and 47 controls targeting Firmicutes, Bacteroidetes, Methanobrevibacter smithii, Lactococcus lactis, Bifidobacterium animalis and seven species of Lactobacillus by quantitative PCR (qPCR) and culture on a Lactobacillus-selective medium. FINDINGS: In qPCR, B. animalis (odds ratio (OR)=0.63; 95% confidence interval (CI) 0.39-1.01; P=0.056) and M. smithii (OR=0.76; 95% CI 0.59-0.97; P=0.03) were associated with normal weight whereas Lactobacillus reuteri (OR=1.79; 95% CI 1.03-3.10; P=0.04) was associated with obesity. CONCLUSION: The gut microbiota associated with human obesity is depleted in M. smithii. Some Bifidobacterium or Lactobacillus species were associated with normal weight (B. animalis) while others (L. reuteri) were associated with obesity. Therefore, gut microbiota composition at the species level is related to body weight and obesity, which might be of relevance for further studies and the management of obesity. These results must be considered cautiously because it is the first study to date that links specific species of Lactobacillus with obesity in humans.

Review Panel of the ERS LAM Task Force L ymphangioleiomyomatosis (LAM) is a rare lung disease, which occurs sporadically or in association with the genetic disease tuberous sclerosis complex (TSC) Sporadic LAM affects ,1 in 400,000 adult females; in TSC, LAM occurs in 30-40% of adult females

OBJECTIVE: To assess risk factors for erysipelas of the leg (cellulitis). DESIGN: Case-control study. SETTING: 7 hospital centres in France. SUBJECTS: 167 patients admitted to hospital for erysipelas of the leg and 294 controls. RESULTS: In multivariate analysis, a disruption of the cutaneous barrier (leg ulcer, wound, fissurated toe-web intertrigo, pressure ulcer, or leg dermatosis) (odds ratio 23.8, 95% confidence interval 10.7 to 52.5), lymphoedema (71.2, 5.6 to 908), venous insufficiency (2.9, 1.0 to 8.7), leg oedema (2.5, 1.2 to 5.1) and being overweight (2.0, 1.1 to 3.7) were independently associated with erysipelas of the leg. No association was observed with diabetes, alcohol, or smoking. Population attributable risk for toe-web intertrigo was 61%. CONCLUSION: This first case-control study highlights the major role of local risk factors (mainly lymphoedema and site of entry) in erysipelas of the leg. From a public health perspective, detecting and treating toe-web intertrigo should be evaluated in the secondary prevention of erysipelas of the leg.

PURPOSE OF REVIEW: Burnout syndrome is a psychological state resulting from prolonged exposure to job stressors. Because ICUs are characterized by a high level of work-related stress, a factor known to increase the risk of burnout syndrome, we sought to review the available literature on burnout syndrome in ICU healthcare workers. RECENT FINDINGS: Based on most recent studies, severe burnout syndrome (as measured using the Maslach Burnout Inventory) is present in about 50% of critical care physicians and in one third of critical care nurses. Strikingly, determinants of burnout syndrome are different in the two groups of caregivers. Namely, intensivists who have severe burnout syndrome are those with a high number of working hours (number of night shifts and time from last vacation) but determinants of severe burnout syndrome in ICU-nurses are related to ICU organization and end-of-life-related characteristics. ICU conflicts, however, were independent predictors of severe burnout syndrome in both groups. SUMMARY: Recent studies reported high levels of severe burnout syndrome in ICU healthcare workers and identified potential targets for preventive strategies such as ICU working groups, communication strategies during end-of-life care and prevention and management of ICU conflicts.

Unexplained weight loss is common in chronic obstructive pulmonary disease (COPD). Blood levels of tumor necrosis factor-alpha (TNF-alpha), a cytokine causing cachexia in laboratory animals, are elevated in various human diseases associated with weight loss. We therefore prospectively measured TNF-alpha serum levels (immunoradiometric assay) in patients with clinically stable COPD (n = 30; all male; mean age, 65 yr) whose weight was less (Group I; n = 16) or more (Group II; n = 14) than the lower limit of normal taken from Metropolitan Life Insurance Company tables. The patients had no cause known to elevate TNF-alpha serum levels; notably, they were not infected. Group I patients had unintentionally lost weight during the previous year, whereas the weight of Group II patients had not changed during the same period. The two groups had similar chronic airflow obstruction and arterial blood gas impairment; hyperinflation and reduction in diffusing capacity were more pronounced in Group I, but differences were not significant. TNF-alpha serum levels (pg/ml; mean [SD]) were significantly higher in Group I than in Group II (70.2 [100.0] versus 6.7 [6.4]; p < 0.001). Group II TNF-alpha serum levels did not differ significantly from those of healthy subjects (7.8 [3.9]), whereas those of Group I were significantly higher (p < 0.001). Because renal function was in the normal range, we conclude that increased TNF-alpha production--and not decreased TNF-alpha clearance--is a likely cause of weight loss in patients with COPD.

Based on the knowledge of the living conditions and habitat of social Aculeatae a series of recommendations have been formulated which can potentially greatly minimize the risk of field re-sting. After a systemic sting reaction, patients should be referred to an allergy specialist for evaluation of their allergy, and if necessary venom immunotherapy (VIT). An emergency medical kit should be supplied, its use clearly demonstrated and repeatedly practised until perfected. This should be done under the supervision of a doctor or a trained nurse. Epinephrine by intramuscular injection is regarded as the treatment of choice for acute anaphylaxis. H1-antihistamines alone or in combination with corticosteroids may be effective in mild to moderate reactions confined to the skin and may support the value of treatment with epinephrine in full-blown anaphylaxis. Up to 75% of the patients with a history of systemic anaphylactic sting reaction develop systemic symptoms once again when re-stung. Venom immunotherapy is a highly effective treatment for individuals with a history of systemic reaction and who have specific IgE to venom allergens. The efficacy of VIT in yellow jacket venom allergic patients has been demonstrated also by assessing health-related quality of life. If both skin tests and serum venom specific IgE turn negative, VIT may be stopped after 3 years. After VIT lasting 3-5 years, most patients with mild to moderate anaphylactic symptoms remain protected following discontinuation of VIT even with positive skin tests. Longer term or lifelong treatment should be considered in high-risk patients. Because of the small but relevant risk of re-sting reactions, in these patients, emergency kits, including epinephrine auto-injectors, should be discussed with every patient when stopping VIT.

EDITORIAL SYNOPSIS Two hundred and five confirmed cases of pancreatitis have been classified. Primary calcifying pancreatitis is associated with alcoholism. Pancreatic changes are patchy and related to plugging of minute ducts. Cysts are frequent. Obstruction to the main pancreatic duct may also result in chronic pancreatitis. Acute pancreatitis and acute recurrent pancreatitis are often associated with gall stones. Acute pancreatitis rarely progresses towards the chronic form.

BACKGROUND: A genomewide association study has shown an association between variants at chromosome 17q21 and an increased risk of asthma. To elucidate the relationship between this locus and disease, we examined a large, family-based data set that included extensive phenotypic and environmental data from the Epidemiological Study on the Genetics and Environment of Asthma. METHODS: We tested 36 single-nucleotide polymorphisms (SNPs) in the 17q21 region in 1511 subjects from 372 families for an association with asthma. We also tested for genetic heterogeneity according to the age at the onset of asthma and exposure to environmental tobacco smoke in early life. RESULTS: Eleven SNPs were significantly associated with asthma (P<0.01), of which three (rs8069176, rs2305480, and rs4795400) were strongly associated (P<0.001). Ordered-subset regression analysis led us to select an onset at 4 years of age or younger to classify patients as having early-onset asthma. Association with early-onset asthma was highly significant (P<10(-5) for four SNPs), whereas no association was found with late-onset asthma. With respect to exposure to environmental tobacco smoke in early life, we observed a significant association with early-onset asthma only in exposed subjects (P<5x10(-5) for six SNPs). Under the best-fitting recessive model, homozygous status (GG) at the most strongly associated SNP (rs8069176) conferred an increase in risk by a factor of 2.9, as compared with other genotypes (AG and AA) in the group exposed to environmental tobacco smoke (P=2.8x10(-6); P=0.006 for the test for heterogeneity of the SNP effect on early-onset asthma between groups with tobacco exposure and those without such exposure). CONCLUSIONS: This study shows that the increased risk of asthma conferred by 17q21 genetic variants is restricted to early-onset asthma and that the risk is further increased by early-life exposure to environmental tobacco smoke. These findings provide a greater understanding of the functional role of the 17q21 variants in the pathophysiology of asthma.

BACKGROUND: Esophagectomy induces a systemic inflammatory response whose extent has been recognized as a predictive factor of postoperative respiratory morbidity. The aim of this study was to determine the effectiveness of a protective ventilatory strategy to reduce systemic inflammation in patients undergoing esophagectomy. METHODS: The authors prospectively investigated 52 patients undergoing planned esophagectomy for cancer. Patients were randomly assigned to a conventional ventilation strategy (n = 26; tidal volume of 9 ml/kg during two-lung and one-lung ventilation; no positive end-expiratory pressure) or a protective ventilation strategy (n = 26; tidal volume of 9 ml/kg during two-lung ventilation, reduced to 5 ml/kg during one-lung ventilation; positive end-expiratory pressure 5 cm H2O throughout the operative time). RESULTS: Plasmatic levels of interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor alpha were measured perioperatively and postoperatively. Pulmonary function and postoperative evolution were also evaluated. Patients who received protective strategy had lower blood levels of IL-1beta, IL-6, and IL-8 at the end of one-lung ventilation (0.24 [0.15-0.40] vs. 0.56 [0.38-0.89] pg/ml, P < 0.001; 91 [61-117] vs. 189 [127-294] pg/ml, P < 0.001; and 30 [22-45] vs. 49 [29-69] pg/ml, P < 0.05, respectively) and 18 h postoperatively (0.18 [0.13-0.30] vs. 0.43 [0.34-0.54] pg/ml, P < 0.001; 54 [36-89] vs. 116 [78-208] pg/ml, P < 0.001; 16 [11-24] vs. 35 [28-53] pg/ml, P < 0.001, respectively). Protective strategy resulted in higher oxygen partial pressure to inspired oxygen fraction ratio during one-lung ventilation and 1 h postoperatively and in a reduction of postoperative mechanical ventilation duration (115 +/- 38 vs. 171 +/- 57 min, P < 0.001). CONCLUSION: A protective ventilatory strategy decreases the proinflammatory systemic response after esophagectomy, improves lung function, and results in earlier extubation.

OBJECTIVE: To evaluate the effects of neuromuscular blocking agents (NMBAs) on pulmonary and systemic inflammation in patients with acute respiratory distress syndrome ventilated with a lung-protective strategy. DESIGN: Multiple-center, prospective, controlled, and randomized trial. SETTING: One medical and two medical-surgical intensive care units. PATIENTS: A total of 36 patients with acute respiratory distress syndrome (Pao2/Fio2 ratio of < or =200 at a positive end-expiratory pressure of > or =5 cm H2O) were included within 48 hrs of acute respiratory distress syndrome onset. INTERVENTIONS: Patients were randomized to receive conventional therapy plus placebo (n = 18) or conventional therapy plus NMBAs (n = 18) for 48 hrs. Both groups were ventilated with a lung-protective strategy (tidal volume between 4 and 8 mL/kg ideal body weight, plateau pressure of < or =30 cm H2O). MEASUREMENTS AND MAIN RESULTS: Bronchoalveolar lavages and blood samples were performed, before randomization and at 48 hrs, to determine the concentrations of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and IL-8. Pao2/Fio2 ratio was evaluated before randomization and at 24, 48, 72, 96, and 120 hrs. A decrease over time in IL-8 concentrations (p = .034) was observed in the pulmonary compartment of the NMBA group. At 48 hrs after randomization, pulmonary concentrations of IL-1beta (p = .005), IL-6 (p = .038), and IL-8 (p = .017) were lower in the NMBA group as compared with the control group. A decrease over time in IL-6 (p = .05) and IL-8 (p = .003) serum concentrations was observed in the NMBA group. At 48 hrs after randomization, serum concentrations of IL-1beta (p = .037) and IL-6 (p = .041) were lower in the NMBA group as compared with the control group. A sustained improvement in Pao2/Fio2 ratio was observed and was reinforced in the NMBA group (p < .001). CONCLUSION: Early use of NMBAs decrease the proinflammatory response associated with acute respiratory distress syndrome and mechanical ventilation.

BACKGROUND: Little is known about international variations in employment rates among people with schizophrenia or about the factors associated with employment in this disorder. AIMS: To describe employment patterns and the variables associated with working in an international sample of people with schizophrenia. METHOD: An analysis was made of baseline data from the European Schizophrenia Cohort study, a 2-year investigation of people with schizophrenia in contact with secondary services and living in France, Germany and the UK (n=1208). RESULTS: Participants were working in all sections of the job market. People who had a degree, were living with their families or had experienced only a single episode of illness were more likely to be working. A continuous illness course, more severe non-psychotic symptoms and drug misuse reduced the odds of employment. There were large variations between centres in employment rates, which were highest in the three German study sites. These differences persisted after adjustment for individual characteristics. CONCLUSIONS: Local social contexts may be as important as individual or illness-related factors in explaining employment status.

BACKGROUND: Fat distribution abnormalities have been reported in patients treated with various antiretroviral drug regimens. The LIPOCO study is an ongoing observational study of unselected HIV-infected patients which aims to better characterize such disorders and their metabolic correlations. METHODS: Cross-sectional analysis of data collected at baseline in the first 154 male patients included. Investigators divided patients into four predetermined clinical categories of fat distribution: lipoatrophy, obesity, mixed condition and normal. Body composition (tetrapolar bioelectrical impedance analysis and skinfold thickness), fat distribution [computed tomography (CT) scan], plasma glucose and insulin concentrations both fasting and during an oral glucose tolerance test and endocrine and lipid profile were measured and compared between the four groups. RESULTS: Patients in the lipoatrophy group had significantly decreased abdominal and mid-thigh subcutaneous fat area values and elevated levels of plasma triglycerides. Patients in the obese and mixed groups had significantly increased intra-abdominal fat area values and elevated levels of plasma insulin and C-peptide. The CT scans identified some patients with isolated subcutaneous fat accumulation but no other alterations in fat distribution and no insulin resistance. Visceral adipose tissue measured by CT scan was positively correlated with fasting insulin and the sum of insulin levels (P < 0.0001). Fasting insulin as well as the sum of insulin levels were negatively correlated with the delta HIV-RNA (log(10)). In a multivariate logistic regression model, the use of stavudine significantly correlated with fat wasting in both nucleoside reverse transcriptase inhibitor and protease inhibitor groups: odds ratio (OR), 413 [95% confidence interval (CI), 5.2-999; P = 0.0068] and OR, 2.08 (95% CI, 0.92-7.0; P = 0.058) respectively, when compared with the use of zidovudine. Neither lamivudine or didanosine use, nor the use of protease inhibitors were significantly associated with fat distribution abnormalities or fat wasting. CONCLUSIONS: These preliminary results suggest that three major types of fat distribution abnormalities may occur in isolation or in association in HIV-infected patients undergoing active antiretroviral therapy: a fat depletion or 'lipoatrophy' syndrome which might be related to the use of stavudine; a mixed or fat redistribution syndrome related to an unusual side-product of effective virus control; and a subcutaneous adiposity syndrome reflecting increase in caloric intake.