creasing bacterial resistance and increases medical costs and the risks of drug-related adverse events. 1-3 The most frequent indication for antibiotic prescriptions in the northwestern hemisphere is lower respiratory tract infections (LRTIs),which range in severity from self-limited acute bronchitis to severe acute exacerbation of chronic obstructive pulmonary disease (COPD), and to life-threatening bacterial community-acquired pneumonia (CAP). 4 Clinical signs and symptoms, as well as commonly used laboratory markers, are unreliable in distinguishing viral from bacterial LRTI. 5-7 As many as 75% of patients with LRTI are treated with antibiotics, despite the predominantly viral origin of their infection. 8 An approach to estimate the probability of bacterial origin in LRTI is the measurement of serum procalcitonin (PCT). For editorial comment see p 1115.
IntroductionMeasurement of prohormones representing different pathophysiological pathways could enhance risk stratification in patients with community-acquired pneumonia (CAP) and other lower respiratory tract infections (LRTI).MethodsWe assessed clinical parameters and five biomarkers, the precursor levels of adrenomedullin (ADM), endothelin-1 (ET1), atrial-natriuretic peptide (ANP), anti-diuretic hormone (copeptin), and procalcitonin in patients with LRTI and CAP enrolled in the multicenter ProHOSP study. We compared the prognostic accuracy of these biomarkers with the pneumonia severity index (PSI) and CURB65 (Confusion, Urea, Respiratory rate, Blood pressure, Age 65) score to predict serious complications defined as death, ICU admission and disease-specific complications using receiver operating curves (ROC) and reclassification methods.ResultsDuring the 30 days of follow-up, 134 serious complications occurred in 925 (14.5%) patients with CAP. Both PSI and CURB65 overestimated the observed mortality (X2 goodness of fit test: P = 0.003 and 0.01). ProADM or proET1 alone had stronger discriminatory powers than the PSI or CURB65 score or any of either score components to predict serious complications. Adding proADM alone (or all five biomarkers jointly) to the PSI and CURB65 scores, significantly increased the area under the curve (AUC) for PSI from 0.69 to 0.75, and for CURB65 from 0.66 to 0.73 (P < 0.001, for both scores). Reclassification methods also established highly significant improvement (P < 0.001) for models with biomarkers if clinical covariates were more flexibly adjusted for. The developed prediction models with biomarkers extrapolated well if evaluated in 434 patients with non-CAP LRTIs.ConclusionsFive biomarkers from distinct biologic pathways were strong and specific predictors for short-term adverse outcome and improved clinical risk scores in CAP and non-pneumonic LRTI. Intervention studies are warranted to show whether an improved risk prognostication with biomarkers translates into a better clinical management and superior allocation of health care resources.Trial RegistrationNCT00350987.
Background:Lower respiratory tract infections like acute bronchitis, exacerbated chronic obstructive pulmonary disease and community-acquired pneumonia are often unnecessarily treated with antibiotics, mainly because of physicians' difficulties to distinguish viral from bacterial cause and to estimate disease-severity. The goal of this trial is to compare medical outcomes, use of antibiotics and hospital resources in a strategy based on enforced evidence-based guidelines versus procalcitonin guided antibiotic therapy in patients with lower respiratory tract infections.Methods and design:We describe a prospective randomized controlled non-inferiority trial with an open intervention. We aim to randomize over a fixed recruitment period of 18 months a minimal number of 1002 patients from 6 hospitals in Switzerland. Patients must be >18 years of age with a lower respiratory tract infections <28 days of duration. Patients with no informed consent, not fluent in German, a previous hospital stay within 14 days, severe immunosuppression or chronic infection, intravenous drug use or a terminal condition are excluded. Randomization to either guidelines-enforced management or procalcitonin-guided antibiotic therapy is stratified by centre and type of lower respiratory tract infections. During hospitalization, all patients are reassessed at days 3, 5, 7 and at the day of discharge. After 30 and 180 days, structured phone interviews by blinded medical students are conducted. Depending on the randomization allocation, initiation and discontinuation of antibiotics is encouraged or discouraged based on evidence-based guidelines or procalcitonin cut off ranges, respectively. The primary endpoint is the risk of combined disease-specific failure after 30 days. Secondary outcomes are antibiotic exposure, side effects from antibiotics, rate and duration of hospitalization, time to clinical stability, disease activity scores and cost effectiveness. The study hypothesis is that procalcitonin-guidance is non-inferior (i.e., at worst a 7.5% higher combined failure rate) to the management with enforced guidelines, but is associated with a reduced total antibiotic use and length of hospital stay.Discussion:Use of and prolonged exposure to antibiotics in lower respiratory tract infections is high. The proposed trial investigates whether procalcitonin-guidance may safely reduce antibiotic consumption along with reductions in hospitalization costs and antibiotic resistance. It will additionally generate insights for improved prognostic assessment of patients with lower respiratory tract infections.Trial registration:ISRCTN95122877
. Neidert S, Katan M, Schuetz P, Fluri F, Ernst A, Bingisser R, Kappos L, Engelter ST, Steck A, Müller B, Christ‐Crain M (University Hospital Basel, Basel, Switzerland; SphingoTec GmbH, Borgsorf, Germany; Kantonsspital Aarau, Aarau, Switzerland) Anterior pituitary axis hormones and outcome in acute ischaemic stroke. J Intern Med 2011; 269: 420–432. Background. Early and accurate prediction of outcome in acute stroke is important and influences risk‐optimized therapeutic strategies. Endocrine alterations of the hypothalamic–pituitary axis are amongst the first measurable alterations after cerebral ischaemia. We therefore evaluated the prognostic value of cortisol, triiodothyronine (T3), free thyroxine (fT4), thyroid‐stimulating hormone (TSH) and growth hormone (GH) in patients with an acute ischaemic stroke. Methods. In an observational study including 281 patients with ischaemic stroke, anterior pituitary axis hormones (i.e. cortisol, T3, fT4, TSH and GH) were simultaneously assessed to determine their value to predict functional outcome and mortality within 90 days and 1 year. Results. In receiver operating characteristic curve analysis, the prognostic accuracy of cortisol was higher compared to all measured hormones and was in the range of the National Institutes of Health Stroke Scale (NIHSS). Cortisol was an independent prognostic marker of functional outcome and death [odds ratio (OR) 1.0 (1.0–1.01) and 1.62 (1.37–1.92), respectively, P < 0.0002 for both, adjusted for age and the NIHSS] in patients with ischaemic stroke, but added no significant additional predictive value to the clinical NIHSS score. Conclusion. Cortisol is an independent prognostic marker for death and functional outcome within 90 days and 1 year in patients with ischaemic stroke. By contrast, other anterior pituitary axis hormones such as peripheral thyroid hormones and GH are only of minor value to predict outcome in stroke.
Although limited by small sample size, this study found that plasma copeptin level appears to add very little information to the work up of sodium imbalance in this cohort of medical inpatients. It is likely that the non-osmotic "stress"-stimulus in acute hospitalised patients is a major confounder and overrules the osmotic stimulus.
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