Predictors for hospitalization and outpatient visits in patients with inflammatory bowel disease: results from the Swiss Inflammatory Bowel Disease Cohort Study.

OBJECTIVES: Patients with inflammatory bowel disease (IBD) have a high resource consumption, with considerable costs for the healthcare system. In a system with sparse resources, treatment is influenced not only by clinical judgement but also by resource consumption. We aimed to determine the resource consumption of IBD patients and to identify its significant predictors. MATERIALS AND METHODS: Data from the prospective Swiss Inflammatory Bowel Disease Cohort Study were analysed for the resource consumption endpoints hospitalization and outpatient consultations at enrolment [1187 patients; 41.1% ulcerative colitis (UC), 58.9% Crohn's disease (CD)] and at 1-year follow-up (794 patients). Predictors of interest were chosen through an expert panel and a review of the relevant literature. Logistic regressions were used for binary endpoints, and negative binomial regressions and zero-inflated Poisson regressions were used for count data. RESULTS: For CD, fistula, use of biologics and disease activity were significant predictors for hospitalization days (all P-values <0.001); age, sex, steroid therapy and biologics were significant predictors for the number of outpatient visits (P=0.0368, 0.023, 0.0002, 0.0003, respectively). For UC, biologics, C-reactive protein, smoke quitters, age and sex were significantly predictive for hospitalization days (P=0.0167, 0.0003, 0.0003, 0.0076 and 0.0175 respectively); disease activity and immunosuppressive therapy predicted the number of outpatient visits (P=0.0009 and 0.0017, respectively). The results of multivariate regressions are shown in detail. CONCLUSION: Several highly significant clinical predictors for resource consumption in IBD were identified that might be considered in medical decision-making. In terms of resource consumption and its predictors, CD and UC show a different behaviour.

Ketoacidosis and adrenocortical insufficiency.

We herein report an autopsy case involving a 27-year-old Caucasian woman suffering from chronic adrenocortical insufficiency with a background of a polyendocrine disorder. Postmortem biochemistry revealed pathologically decreased aldosterone, cortisol, and dehydroepiandrosterone levels in postmortem serum from femoral blood as well as decreased cortisol and 17-hydroxycorticosteroid in urine. Decreased vitreous sodium and increased 3-beta-hydroxybutyrate and C-reactive protein concentrations were observed. The cause of death was determined to be acute adrenocortical insufficiency. Fasting ketoacidosis was postulated to have precipitated the Addisonian crisis. Traumatic causes of death and third-party involvement were excluded. The case highlights the importance of systematically performing exhaustive postmortem biochemical investigations to formulate appropriate hypothesis regarding the pathophysiological mechanisms involved in the death process.

Commentary : beyond vague causal effect estimation of obesity on health outcomes

In the current issue of epidemiology, Danaei and colleagues elegantly estimated both the direct effect and the indirect effect-that is, the effect mediated by blood pressure, cholesterol, glucose, fibrinogen, and high-sensitivity C-reactive protein-of body mass index (BMI) on the risk of coronary heart disease (CHD). they analyzed data from 9 cohort studies including 58,322 patients and 9459 CHD events, with baseline measurements between 1954 and 2001. Using sophisticated and cutting-edge methods for direct and indirect effect estimations, the authors estimated that half of the risk of overweight and obesity would be mediated by blood pressure, cholesterol, and glucose. Few additional percentage points of the risk would be mediated by fibrinogen and hs-CRP. How should we understand these estimates? Can we say that if obese persons reduce their body weight and reach a normal body weight, their excess risk of CHD would be reduced by half through an improvement in these mediators and by half through the reduction in BmI itself? Is that also true if these individuals are prevented from becoming obese in the first place? Can we also conclude that if these mediators are well controlled in obese individuals through other means than a body weight reduction, their excess risk of CHD would be reduced by half? Let us confront these estimates with observations from studies evaluating 2 interventions to reduce body weight, that is, bariatric surgery in patients with severe obesity and intensive lifestyle intervention in overweight patients with diabetes

Cytokines and hs-CRP levels in individuals treated with aspirin for cardiovascular prevention: a population-based study (CoLaus Study)

Backgrounds: Pro-inflammatory cytokines and high-sensitive C-reactive protein (hs-CRP) are associated with increased risk for cardiovascular disease. Low-dose aspirin for cardiovascular (CV) prevention is reported to have anti-inflammatory effects. The aim of this study was to determine the association between cytokines and hs-CRP levels and low-dose aspirin use for CV prevention in a population-based cohort (CoLaus Study). Methods and Results: Blood samples were assessed in 6,085 participants (3,201 women) aged 35-75 years. Medications' use and indications were recorded. Among aspirin users (n=1'034; 17%), overall low-dose (351; 5.8%) and low-dose for CV prevention (324; 5.3%) users were specifically selected for analysis. IL-1beta, IL-6 and TNF-alpha were assessed by a multiplex particle-based flow cytometric assay and hs-CRP by an immunometric assay. Cytokines and hs-CRP were presented in quartiles. Multivariate analysis adjusting for sex, age, smoking status, body mass index, concomitant use of various immunomodulatory drugs, diabetes mellitus showed no association between cytokines and hs-CRP levels and low-dose aspirin use for CV prevention either comparing the topmost vs. the three other quartiles (OR 95% CI, 0.84 (0.59 - 1.18), 1.03 (0.78 - 1.32), 1.10 (0.83 - 1.46), 1.00 (0.67 - 1.69) for IL-1beta, IL-6, TNF-alpha and hs-CRP, respectively), or comparing the topmost quartile vs. the first one (OR 95% CI, 0.87 (0.60 - 1.26), 1.19 (0.79 - 1.79), 1.26 (0.86 - 1.84), 1.06 (0.67 - 1.69)). Conclusions: Low-dose aspirin use for cardiovascular prevention does not seem to impact plasma cytokine and hs-CRP levels in a population-based cohort.

Usefulness of pericardial and pleural fluids for the postmortem diagnosis of sepsis.

The purpose of this study was to evaluate the postmortem distributions of procalcitonin (PCT), C-reactive protein (CRP), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and soluble interleukin-2 receptor (sIL-2R) levels in postmortem serum from femoral blood, pericardial fluid and pleural fluid in a series of sepsis-related fatalities (12 subjects) and control cases (20 subjects) that underwent medico-legal investigations. Our aim was to assess the diagnostic potential of the results obtained from pericardial and pleural fluid analysis in identifying sepsis-related deaths. All sepsis-related cases had a documented, clinical diagnosis that was established in vivo during hospitalization. Pneumonia was the main infectious focus identified during autopsy and histology. Pseudomonas aeruginosa, Klebsiella pnemoniae and Escherichia coli were the most commonly identified bacteria in blood and lung tissue cultures. The preliminary results corroborate the usefulness of PCT, CRP, sTREM-1 and sIL-2R determination in postmortem serum for the identification of sepsis-related deaths. Moreover, the data suggest that, as far as PCT, CRP, sTREM-1 and sIL-2R measurements are concerned, pericardial and pleural fluids can be considered suitable alternatives to postmortem serum should femoral blood prove unavailable at autopsy.

Angiotensin converting enzyme inhibitor induced angio-oedema: a review of the pathophysiology and risk factors.

Angio-oedema (AE) is a known adverse effect of angiotensin converting enzyme inhibitor (ACE-I) therapy. Over the past several decades, evidence of failure to diagnose this important and potentially fatal reaction is commonly found in the literature. Because this reaction is often seen first in the primary care setting, a review was undertaken to analyse and document the keys to both diagnostic criteria as well as to investigate potential risk factors for ACE-I AE occurrence. A general review of published literature was conducted through Medline, EMBASE, and the Cochrane Database, targeting ACE-I-related AE pathomechanism, diagnosis, epidemiology, risk factors, and clinical decision making and treatment. The incidence and severity of AE appears to be on the rise and there is evidence of considerable delay in diagnosis contributing to significant morbidity and mortality for patients. The mechanism of AE due to ACE-I drugs is not fully understood, but some genomic and metabolomic information has been correlated. Additional epidemiologic data and clinical treatment outcome predictors have been evaluated, creating a basis for future work on the development of clinical prediction tools to aid in risk identification and diagnostic differentiation. Accurate recognition of AE by the primary care provider is essential to limit the rising morbidity associated with ACE-I treatment-related AE. Research findings on the phenotypic indicators relevant to this group of patients as well as basic research into the pathomechanism of AE are available, and should be used in the construction of better risk analysis and clinical diagnostic tools for ACE-I AE.

Lu pour vous: Prévention cardiovasculaire: efficacité des statines chez les plus de 70 ans

Résumé de: Glynn RJ et al. Rosuvastatin for primary prevention in older persons with elevated C-reactive protein and low to average low-density lipoprotein cholesterol levels: exploratory analysis of a randomized trial. Ann Intern Med. 2010 Apr 20;152(8):488-96, PMID: 20404379.

Effect of n-3 fatty acids on markers of brain injury and incidence of sepsis-associated delirium in septic patients.

BACKGROUND: Data regarding immunomodulatory effects of parenteral n-3 fatty acids in sepsis are conflicting. In this study, the effect of administration of parenteral n-3 fatty acids on markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients was investigated. METHODS: Fifty patients with sepsis were randomized to receive either 2 ml/kg/day of a lipid emulsion containing highly refined fish oil (equivalent to n-3 fatty acids 0.12 mg/kg/day) during 7 days after admission to the intensive care unit or standard treatment. Markers of brain injury and inflammatory mediators were measured on days 1, 2, 3 and 7. Assessment for sepsis-associated delirium was performed daily. The primary outcome was the difference in S-100β from baseline to peak level between both the intervention and the control group, compared by t-test. Changes of all markers over time were explored in both groups, fitting a generalized estimating equations model. RESULTS: Mean difference in change of S-100β from baseline to peak level was 0.34 (95% CI: -0.18-0.85) between the intervention and control group, respectively (P = 0.19). We found no difference in plasma levels of S-100β, neuron-specific enolase, interleukin (IL)-6, IL-8, IL-10, and C-reactive protein between groups over time. Incidence of sepsis-associated delirium was 75% in the intervention and 71% in the control groups (risk difference 4%, 95% CI -24-31%, P = 0.796). CONCLUSION: Administration of n-3 fatty acids did not affect markers of brain injury, incidence of sepsis-associated delirium, and inflammatory mediators in septic patients.

Compliance with preoperative oral nutritional supplements in patients at nutritional risk─only a question of will?

BACKGROUND/OBJECTIVES: Preoperative nutrition has been shown to reduce morbidity after major gastrointestinal (GI) surgery in selected patients at risk. In a randomized trial performed recently (NCT00512213), almost half of the patients, however, did not consume the recommended dose of nutritional intervention. The present study aimed to identify the risk factors for noncompliance. SUBJECTS/METHODS: Demographic (n=5) and nutritional (n=21) parameters for this retrospective analysis were obtained from a prospectively maintained database. The outcome of interest was compliance with the allocated intervention (ingestion of ⩾11/15 preoperative oral nutritional supplement units). Uni- and multivariate analyses of potential risk factors for noncompliance were performed. RESULTS: The final analysis included 141 patients with complete data sets for the purpose of the study. Fifty-nine patients (42%) were considered noncompliant. Univariate analysis identified low C-reactive protein levels (P=0.015), decreased recent food intake (P=0.032) and, as a trend, low hemoglobin (P=0.065) and low pre-albumin (P=0.056) levels as risk factors for decreased compliance. However, none of them was retained as an independent risk factor after multivariate analysis. Interestingly, 17 potential explanatory parameters, such as upper GI cancer, weight loss, reduced appetite or co-morbidities, did not show any significant correlation with reduced intake of nutritional supplements. CONCLUSIONS: Reduced compliance with preoperative nutritional interventions remains a major issue because the expected benefit depends on the actual intake. Seemingly, obvious reasons could not be retained as valid explanations. Compliance seems thus to be primarily a question of will and information; the importance of nutritional supplementation needs to be emphasized by specific patients' education.

Evidence for chronic low-grade systemic inflammation in individuals with agoraphobia from a population-based prospective study.

BACKGROUND: Anxiety disorders have been linked to an increased risk of incident coronary heart disease in which inflammation plays a key pathogenic role. To date, no studies have looked at the association between proinflammatory markers and agoraphobia. METHODS: In a random Swiss population sample of 2890 persons (35-67 years, 53% women), we diagnosed a total of 124 individuals (4.3%) with agoraphobia using a validated semi-structured psychiatric interview. We also assessed socioeconomic status, traditional cardiovascular risk factors (i.e., body mass index, hypertension, blood glucose levels, total cholesterol/high-density lipoprotein-cholesterol ratio), and health behaviors (i.e., smoking, alcohol consumption, and physical activity), and other major psychiatric diseases (other anxiety disorders, major depressive disorder, drug dependence) which were treated as covariates in linear regression models. Circulating levels of inflammatory markers, statistically controlled for the baseline demographic and health-related measures, were determined at a mean follow-up of 5.5 ± 0.4 years (range 4.7 - 8.5). RESULTS: Individuals with agoraphobia had significantly higher follow-up levels of C-reactive protein (p = 0.007) and tumor-necrosis-factor-α (p = 0.042) as well as lower levels of the cardioprotective marker adiponectin (p = 0.032) than their non-agoraphobic counterparts. Follow-up levels of interleukin (IL)-1β and IL-6 did not significantly differ between the two groups. CONCLUSIONS: Our results suggest an increase in chronic low-grade inflammation in agoraphobia over time. Such a mechanism might link agoraphobia with an increased risk of atherosclerosis and coronary heart disease, and needs to be tested in longitudinal studies.

Common Variants of TLR1 Associate with Organ Dysfunction and Sustained Pro- Inflammatory Responses during Sepsis

Background: Toll-like receptors (TLRs) are critical components for host pathogen recognition and variants in genes participating in this response influence susceptibility to infections. Recently, TLR1 gene polymorphisms have been found correlated with whole blood hyper-inflammatory responses to pathogen-associated molecules and associated with sepsis-associated multiorgan dysfunction and acute lung injury (ALI). We examined the association of common variants of TLR1 gene with sepsis-derived complications in an independent study and with serum levels for four inflammatory biomarker among septic patients. Methodology/Principal Findings: Seven tagging single nucleotide polymorphisms of the TLR1 gene were genotyped in samples from a prospective multicenter case-only study of patients with severe sepsis admitted into a network of intensive care units followed for disease severity. Interleukin (IL)-1 b, IL-6, IL-10, and C-reactive protein (CRP) serum levels were measured at study entry, at 48 h and at 7th day. Alleles -7202G and 248Ser, and the 248Ser-602Ile haplotype were associated with circulatory dysfunction among severe septic patients (0.001<=p <= 0.022), and with reduced IL-10 (0.012<= p <=0.047) and elevated CRP (0.011<= p <=0.036) serum levels during the first week of sepsis development. Additionally, the -7202GG genotype was found to be associated with hospital mortality (p =0.017) and ALI (p =0.050) in a combined analysis with European Americans, suggesting common risk effects among studies Conclusions/Significance: These results partially replicate and extend previous findings, supporting that variants of TLR1 gene are determinants of severe complications during sepsis.

Inflammatory and coagulation biomarkers and mortality in patients with HIV infection.

Background In the Strategies for Management of Anti-Retroviral Therapy trial, all-cause mortality was higher for participants randomized to intermittent, CD4-guided antiretroviral treatment (ART) (drug conservation [DC]) than continuous ART (viral suppression [VS]). We hypothesized that increased HIV-RNA levels following ART interruption induced activation of tissue factor pathways, thrombosis, and fibrinolysis. Methods and Findings Stored samples were used to measure six biomarkers: high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), amyloid A, amyloid P, D-dimer, and prothrombin fragment 1þ2. Two studies were conducted: (1) a nested case-control study for studying biomarker associations with mortality, and (2) a study to compare DC and VS participants for biomarker changes. For (1), markers were determined at study entry and before death (latest level) for 85 deaths and for two controls (n¼170) matched on country, age, sex, and date of randomization. Odds ratios (ORs) were estimated with logistic regression. For each biomarker, each of the three upper quartiles was compared to the lowest quartile. For (2), the biomarkers were assessed for 249 DC and 250 VS participants at study entry and 1 mo following randomization. Higher levels of hsCRP, IL-6, and D-dimer at study entry were significantly associated with an increased risk of all-cause mortality. Unadjusted ORs (highest versus lowest quartile) were 2.0 (95% confidence interval [CI], 1.0-4.1; p¼0.05), 8.3 (95% CI, 3.3-20.8; p , 0.0001), and 12.4 (95% CI, 4.2-37.0; p , 0.0001), respectively. Associations were significant after adjustment, when the DC and VS groups were analyzed separately, and when latest levels were assessed. IL-6 and D-dimer increased at 1 mo by 30% and 16% in the DC group and by 0% and 5% in the VS group (p , 0.0001 for treatment difference for both biomarkers); increases in the DC group were related to HIV-RNA levels at 1 mo (p , 0.0001). In an expanded case-control analysis (four controls per case), the OR (DC/VS) for mortality was reduced from 1.8 (95% CI, 1.1-3.1; p¼0.02) to 1.5 (95% CI, 0.8-2.8) and 1.4 (95% CI, 0.8-2.5) after adjustment for latest levels of IL-6 and D-dimer, respectively. Conclusions IL-6 and D-dimer were strongly related to all-cause mortality. Interrupting ART may further increase the risk of death by raising IL-6 and D-dimer levels. Therapies that reduce the inflammatory response to HIV and decrease IL-6 and D-dimer levels may warrant investigation.

PTX3 Polymorphisms and Invasive Mold Infections After Solid Organ Transplant.

Donor PTX3 polymorphisms were shown to influence the risk of invasive aspergillosis among hematopoietic stem cell transplant recipients. Here, we show that PTX3 polymorphisms are independent risk factors for invasive mold infections among 1101 solid organ transplant recipients, thereby strengthening their role in mold infection pathogenesis and patients' risk stratification.

Effect of corticosteroids on the clinical course of community-acquired pneumonia: a randomized controlled trial

Introduction The benefit of corticosteroids as adjunctive treatment in patients with severe community-acquired pneumonia (CAP) requiring hospital admission remains unclear. This study aimed to evaluate the impact of corticosteroid treatment on outcomes in patients with CAP. Methods This was a prospective, double-blind and randomized study. All patients received treatment with ceftriaxone plus levofloxacin and methyl-prednisolone (MPDN) administered randomly and blindly as an initial bolus, followed by a tapering regimen, or placebo. Results Of the 56 patients included in the study, 28 (50%) were treated with concomitant corticosteroids. Patients included in the MPDN group show a more favourable evolution of the pO2/FiO2 ratio and faster decrease of fever, as well as greater radiological improvement at seven days. The time to resolution of morbidity was also significantly shorter in this group. Six patients met the criteria for mechanical ventilation (MV): five in the placebo group (22.7%) and one in the MPDN group (4.3%). The duration of MV was 13 days (interquartile range 7 to 26 days) for the placebo group and three days for the only case in the MPDN group. The differences did not reach statistical significance. Interleukin (IL)-6 and C-reactive protein (CRP) showed a significantly quicker decrease after 24 h of treatment among patients treated with MPDN. No differences in mortality were found among groups. Conclusions MPDN treatment, in combination with antibiotics, improves respiratory failure and accelerates the timing of clinical resolution of severe CAP needing hospital admission.