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      Enhancement of CURB65 score with proadrenomedullin (CURB65-A) for outcome prediction in lower respiratory tract infections: Derivation of a clinical algorithm

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          Abstract

          Background

          Proadrenomedullin (ProADM) confers additional prognostic information to established clinical risk scores in lower respiratory tract infections (LRTI). We aimed to derive a practical algorithm combining the CURB65 score with ProADM-levels in patients with community-acquired pneumonia (CAP) and non-CAP-LRTI.

          Methods

          We used data of 1359 patients with LRTI enrolled in a multicenter study. We chose two ProADM cut-off values by assessing the association between ProADM levels and the risk of adverse events and mortality. A composite score (CURB65-A) was created combining CURB65 classes with ProADM cut-offs to further risk-stratify patients.

          Results

          CURB65 and ProADM predicted both adverse events and mortality similarly well in CAP and non-CAP-LRTI. The combined CURB65-A risk score provided better prediction of death and adverse events than the CURB65 score in the entire cohort and in CAP and non-CAP-LRTI patients. Within each CURB65 class, higher ProADM-levels were associated with an increased risk of adverse events and mortality. Overall, risk of adverse events (3.9%) and mortality (0.65%) was low for patients with CURB65 score 0-1 and ProADM ≤0.75 nmol/l (CURB65-A risk class I); intermediate (8.6% and 2.6%, respectively) for patients with CURB65 score of 2 and ProADM ≤1.5 nmol/l or CURB classes 0-1 and ProADM levels between 0.75-1.5 nmol/L (CURB65-A risk class II), and high (21.6% and 9.8%, respectively) for all other patients (CURB65-A risk class III). If outpatient treatment was recommended for CURB65-A risk class I and short hospitalization for CURB65-A risk class II, 17.9% and 40.8% of 1217 hospitalized patients could have received ambulatory treatment or a short hospitalization, respectively.

          Conclusions

          The new CURB65-A risk score combining CURB65 risk classes with ProADM cut-off values accurately predicts adverse events and mortality in patients with CAP and non-CAP-LRTI. Additional prospective cohort or intervention studies need to validate this score and demonstrate its safety and efficacy for the management of patients with LRTI.

          Trial Registration

          Procalcitonin-guided antibiotic therapy and hospitalisation in patients with lower respiratory tract infections: the prohosp study; isrctn.org Identifier: ISRCTN: ISRCTN95122877

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          Most cited references34

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          Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit.

          The diagnosis of infection in critically ill patients is challenging because traditional markers of infection are often misleading. For example, serum concentrations of calcitonin precursors are increased in patients with infections. However, their predictive accuracy for the diagnosis of sepsis in unselected patients in a medical intensive care unit (ICU) is unknown. Therefore, we compared the usefulness of serum concentrations of calcitonin precursors, C-reactive protein, interleukin-6, and lactate for the diagnosis of sepsis in consecutive patients suffering from a broad range of diseases with an anticipated stay of > or =24 hrs in a medical ICU. Prospective cohort study. Medical intensive care unit in a university medical center. 101 consecutive critically ill patients. None. Blood samples were collected at various time points during the course of the disease. Systemic inflammatory response syndrome, sepsis, severe sepsis, and septic shock were diagnosed according to standardized criteria, and patients were reclassified daily without prior knowledge of the serum concentrations of calcitonin precursors or interleukin-6. At admission, 99% of the patients had systemic inflammatory response syndrome, 53% had sepsis, and 5% developed sepsis during their stay in the ICU. Calcitonin precursors, C-reactive protein, interleukin-6, and lactate levels increased with the severity of infection (p 1 ng/mL had sensitivity of 89% and specificity of 94% for the diagnosis of sepsis. High serum concentrations of calcitonin precursors were associated with poor prognosis (p = .01). In a medical ICU, serum calcitonin precursor concentrations are more sensitive and are specific markers of sepsis as compared with serum C-reactive protein, interleukin-6, and lactate levels.
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            Study of community acquired pneumonia aetiology (SCAPA) in adults admitted to hospital: implications for management guidelines.

            Since the last British study of the microbial aetiology of community acquired pneumonia (CAP) about 20 years ago, new organisms have been identified (for example, Chlamydia pneumoniae), new antibiotics introduced, and fresh advances made in microbiological techniques. Pathogens implicated in CAP in adults admitted to hospital in the UK using modern and traditional microbiological investigations are described. Adults aged 16 years and over admitted to a teaching hospital with CAP over a 12 month period from 4 October 1998 were prospectively studied. Samples of blood, sputum, and urine were collected for microbiological testing by standard culture techniques and new serological and urine antigen detection methods. Of 309 patients admitted with CAP, 267 fulfilled the study criteria; 135 (50.6%) were men and the mean (SD) age was 65.4 (19.6) years. Aetiological agents were identified from 199 (75%) patients (one pathogen in 124 (46%), two in 53 (20%), and three or more in 22 (8%)): Streptococcus pneumoniae 129 (48%), influenza A virus 50 (19%), Chlamydia pneumoniae 35 (13%), Haemophilus influenzae 20 (7%), Mycoplasma pneumoniae 9 (3%), Legionella pneumophilia 9 (3%), other Chlamydia spp 7 (2%), Moraxella catarrhalis 5 (2%), Coxiella burnetii 2 (0.7%), others 8 (3%). Atypical pathogens were less common in patients aged 75 years and over than in younger patients (16% v 27%; OR 0.5, 95% CI 0.3 to 0.9). The 30 day mortality was 14.9%. Mortality risk could be stratified by the presence of four "core" adverse features. Three of 60 patients (5%) infected with an atypical pathogen died. S pneumoniae remains the most important pathogen to cover by initial antibiotic therapy in adults of all ages admitted to hospital with CAP. Atypical pathogens are more common in younger patients. They should also be covered in all patients with severe pneumonia and younger patients with non-severe infection.
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              • Article: not found

              Clinical review 167: Procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors.

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                Author and article information

                Journal
                BMC Infect Dis
                BMC Infectious Diseases
                BioMed Central
                1471-2334
                2011
                3 May 2011
                : 11
                : 112
                Affiliations
                [1 ]Medical University Department of the University of Basel, Kantonsspital Aarau, Switzerland
                [2 ]Department of Internal Medicine, Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital Basel, Switzerland
                [3 ]Basel University Medical Clinic, Department of Internal Medicine, Kantonsspital Liestal, Switzerland
                [4 ]Department of Infectious Diseases, Kantonsspital Aarau, Switzerland
                [5 ]Department of Pulmonary Medicine, Kantonsspital Aarau, Switzerland
                [6 ]Department of Emergency Medicine, Kantonsspital Aarau, Switzerland
                [7 ]Department of Nursing, Kantonsspital Aarau, Switzerland
                [8 ]Harvard School of Public Health, Boston (MA), USA
                Article
                1471-2334-11-112
                10.1186/1471-2334-11-112
                3119069
                21539743
                9697967b-4e26-44ee-8ab2-60d78d1de251
                Copyright ©2011 Albrich et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 October 2010
                : 3 May 2011
                Categories
                Research Article

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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