Frank Dusemund

Effectiveness and Safety of Procalcitonin-Guided Antibiotic Therapy in Lower Respiratory Tract Infections in “Real Life”: An International, Multicenter Poststudy Survey (ProREAL)

BACKGROUND In controlled studies, procalcitonin (PCT) has safely and effectively reduced antibiotic drug use for lower respiratory tract infections (LRTIs). However, controlled trial data may not reflect real life. METHODS We performed an observational quality surveillance in 14 centers in Switzerland, France, and the United States. Consecutive adults with LRTI presenting to emergency departments or outpatient offices were enrolled and registered on a website, which provided a previously published PCT algorithm for antibiotic guidance. The primary end point was duration of antibiotic therapy within 30 days. RESULTS Of 1759 patients, 86.4% had a final diagnosis of LRTI (community-acquired pneumonia, 53.7%; acute exacerbation of chronic obstructive pulmonary disease, 17.1%; and bronchitis, 14.4%). Algorithm compliance overall was 68.2%, with differences between diagnoses (bronchitis, 81.0%; AECOPD, 70.1%; and community-acquired pneumonia, 63.7%; P < .001), outpatients (86.1%) and inpatients (65.9%) (P < .001), algorithm-experienced (82.5%) and algorithm-naive (60.1%) centers (P < .001), and countries (Switzerland, 75.8%; France, 73.5%; and the United States, 33.5%; P < .001). After multivariate adjustment, antibiotic therapy duration was significantly shorter if the PCT algorithm was followed compared with when it was overruled (5.9 vs 7.4 days; difference, -1.51 days; 95% CI, -2.04 to -0.98; P < .001). No increase was noted in the risk of the combined adverse outcome end point within 30 days of follow-up when the PCT algorithm was followed regarding withholding antibiotics on hospital admission (adjusted odds ratio, 0.83; 95% CI, 0.44 to 1.55; P = .56) and regarding early cessation of antibiotics (adjusted odds ratio, 0.61; 95% CI, 0.36 to 1.04; P = .07). CONCLUSIONS This study validates previous results from controlled trials in real-life conditions and demonstrates that following a PCT algorithm effectively reduces antibiotic use without increasing the risk of complications. Preexisting differences in antibiotic prescribing affect compliance with antibiotic stewardship efforts. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN40854211.

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

BackgroundProadrenomedullin (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.MethodsWe 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.ResultsCURB65 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.ConclusionsThe 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 RegistrationProcalcitonin-guided antibiotic therapy and hospitalisation in patients with lower respiratory tract infections: the prohosp study; isrctn.org Identifier: ISRCTN: ISRCTN95122877

Biomarker-enhanced triage in respiratory infections: a proof-of-concept feasibility trial

Concerns about inadequate performance and complexity limit routine use of clinical risk scores in lower respiratory tract infections. Our aim was to study feasibility and effects of adding the biomarker proadrenomedullin (proADM) to the confusion, urea >7 mmol·L−1, respiratory rate ≥30 breaths·min−1, blood pressure <90 mmHg (systolic) or ≤60 mmHg (diastolic), age ≥65 years (CURB-65) score on triage decisions and length of stay. In a randomised controlled proof-of-concept intervention trial, triage and discharge decisions were made for adults with lower respiratory tract infection according to interprofessional assessment using medical and nursing risk scores either without (control group) or with (proADM group) knowledge of proADM values, measured on admission, and on days 3 and 6. An adjusted generalised linear model was calculated to investigate the effect of our intervention. On initial presentation the algorithms were overruled in 123 (39.3%) of the cases. Mean length of stay tended to be shorter in the proADM (n=154, 6.3 days) compared with the control group (n=159, 6.8 days; adjusted regression coefficient -0.19, 95% CI -0.41–0.04; p=0.1). This trend was robust in subgroup analyses and for overall length of stay within 90 days (7.2 versus 7.9 days; adjusted regression coefficient -0.18, 95% CI -0.40–0.05; p=0.13). There were no differences in adverse outcomes or readmission. Logistic obstacles and overruling are major challenges to implement biomarker-enhanced algorithms in clinical settings and need to be addressed to shorten length of stay. Proof-of-concept trial: how to shorten LOS in patients with LRTIs by reducing medically unnecessary days in the hospital http://ow.ly/nI7z4

Optimised patient transfer using an innovative multidisciplinary assessment in Kanton Aargau (OPTIMA I): an observational survey in lower respiratory tract infections.

BACKGROUND Current medical scores have limited efficiency and safety profiles to enable assignment to the most appropriate treatment site in patients with lower respiratory tract infections (LRTIs). We describe our current triage practice and assess the potential of a combination of CURB65 with proadrenomedullin (ProADM) levels for triage decisions. METHODS Consecutive patients with LRTIs presenting to our emergency department were prospectively followed and retrospectively classified according to CURB65 and ProADM levels (CURB65-A). Low medical risk patients were further subgrouped according to biopsychosocial and functional risks. We compared the proportion of patients virtually allocated to triage sites with actual triage decisions and assessed the added impact of ProADM in a subgroup. RESULTS Overall, 93% of 146 patients were hospitalised. Among the 138 patients with available CURB65-A, 17.4% had a low medical risk indicating possible treatment in an outpatient or non-acute medical setting; 34.1% had an intermediate medical risk (short-hospitalisation); and 48.6% had a high medical risk (hospitalisation). Fewer patients were in a low CURB65-A class (I) than a low CURB65 class (0,1) (17.4% vs. 46.3%, p <0.001). Mean length of hospitalisation was 9.8 days including 3.6 days after reaching medical stability. In 60.3% of patients, hospitalisation was prolonged after medical stability mainly for medical reasons. CONCLUSIONS Current rates of hospitalisation are high in patients with LRTI and length of stay frequently extended beyond time of medical stabilization. The lower proportion of patients reclassified as low risk by adding ProADM to the CURB65 score might improve confidence in the triage algorithm.

Multidisciplinary Assessment to Personalize Length of Stay in Acute Decompensated Heart Failure (OPTIMA II ADHF)

Background Acute decompensated heart failure (ADHF) causes a substantial burden for health care systems. Data to rationally define the need for hospitalization or the appropriate length of stay (LOS) is limited. Our aim was to personalize length of stay in patients admitted to hospital for acute decompensated heart failure. Methods Consecutive patients with ADHF presenting to our emergency department were prospectively followed. We daily conducted a multidisciplinary risk assessment and compared proposed with actually observed triage decisions. Results At presentation, all patients required hospitalization. Median LOS was 11 days including 1 day after reaching medical stability. In 42.7% of patients, hospitalization was prolonged after medical stability mainly for nursing and organizational reasons. Within 30 days of enrollment, 7 (9.3%) patients were rehospitalized, 3 of them for persisting or relapsing heart failure. Conclusions There appears to be potential to shorten inhospital stay in patients with ADHF mainly by providing post discharge ambulatory nursing care in order to improve resource utilization and to diminish “hospitalization-associated disability”.

Efficacy and Safety of Procalcitonin-Guided Antibiotic Therapy in Lower Respiratory Tract Infections

Background: In 14 randomized controlled studies to date, a procalcitonin (PCT)-based algorithm has been proven to markedly reduce the use of antibiotics along with an unimpaired high safety and low complication rates in patients with lower respiratory tract infections (LRTIs). However, compliance with the algorithm and safety out of controlled study conditions has not yet been sufficiently investigated. Methods: We performed a prospective international multicenter observational post-study surveillance of consecutive adults with community-acquired LRTI in 14 centers (Switzerland (n = 10), France (n = 3) and the United States (n = 1)). Results: Between September 2009 and November 2010, 1,759 patients were enrolled (median age 71; female sex 44.4%). 1,520 (86.4%) patients had a final diagnosis of LRTI (community-acquired pneumonia (CAP), 53.7%; acute exacerbation of chronic obstructive pulmonary disease (AECOPD), 17.1%; and acute bronchitis, 14.4%). Compliance with the PCT-guided therapy (overall 68.2%) was highest in patients with bronchitis (81.0% vs. AECOPD, 70.1%; CAP, 63.7%; p < 0.001), outpatients (86.1% vs. inpatients, 65.9%; p < 0.001) and algorithm-experienced centers (82.5% vs. algorithm-naive, 60.1%; p < 0.001) and showed significant geographical differences. The initial decision about the antibiotic therapy was based on PCT value in 72.4%. In another 8.6% of patients, antibiotics were administered despite low PCT values but according to predefined criteria. Thus, the algorithm was followed in 81.0% of patients. In a multivariable Cox hazard ratio model, longer antibiotic therapy duration was associated with algorithm-non-compliance, country, hospitalization, CAP vs. bronchitis, renal failure and algorithm-naïvety of the study center. In a multivariable logistic regression complications (death, empyema, ICU treatment, mechanical ventilation, relapse, and antibiotic-associated side effects) were significantly associated with increasing CURB65-Score, CAP vs. bronchitis, multilobar pneumonia, but not with algorithm-compliance. Discussion: Cultural and geographic differences in antibiotic prescribing affected the compliance with our PCT-guided algorithm. Efforts to reinforce compliance are needed. Antibiotic stewardship with PCT is possible, effective and safe without increasing the risk of complications in real-life conditions.

The outcome of community-acquired pneumonia in patients with chronic lung disease A case control study

BACKGROUND The impact of chronic lung diseases on outcome in community-acquired pneumonia (CAP) is not well established. We aimed to investigate the outcome of adult CAP-patients with underlying chronic obstructive pulmonary disease (COPD), asthma or interstitial lung disease (ILD) in a case-control study. METHODS We used a nationwide database including all hospitalisations in Switzerland from 2002 to 2010. Endpoints were the incidence of lung abscess, parapneumonic pleural effusion, empyema, acute respiratory distress syndrome, in-hospital mortality and length of stay. RESULTS We found less disease-related complications of CAP in COPD (n = 17,075) and asthma (n = 2700) patients compared with their controls. This difference was mainly related to a lower incidence of pleural effusion (COPD: 4.3% vs 4.9%, p = 0.011; asthma: 3.4% vs 5.2%, p <0.001). In-hospital mortality was lower in the COPD and - much more pronounced - asthma cohorts (COPD: 5.8% vs 6.7%, p <0.001; asthma: 1.4% vs 4.8%, p <0.001). For ILD (n = 916), the complication rate was similar as compared to the control group, whereas in-hospital mortality was markedly higher (16.3% vs 6.8%, p <0.001). CONCLUSIONS These rather unexpected results should be viewed as hypothesis generating, with various possible explanations for our findings. These include the possible influence of inhaled corticosteroid therapy, a possibly higher awareness of general practitioners and hospital physicians while treating patients with chronic lung diseases, a different infective agent spectrum or a different immune response.

Optimized Patient Transfer through Innovative Multidisciplinary Assessment: Project Description of Phase I

Introduction: OPTIMA is a multi-professional quality management and research project, conducted at the Cantonal Hospital of Aarau (KSA), Switzerland in cooperation with post-acute care institutions from November 2009 until December 2012. Objective: The goal of this study was to optimize patient care pathways and to provide patient-centered, costeffective care that is conform with the introduction of the Diagnosis Related Groups (DRG) in 2012. Methods: The “Post-Acute Care Discharge Scores” (PACD) was applied to assess the risk for transfer to postacute care facilities in 240 patients suffering from lower respiratory tract infections during the first phase of the study (OPTIMA I) from October 2009 until April 2010. In order to assess the patients’ self-care ability, the “Self-Care Index” (SPI) tool was applied on admission and during the course of inpatient treatment. Results: The PACD predicted that 55% of patients (N=202) were at medium to high risk of requiring post-acute care. According to the SPI, 38% of patients (N=217) showed reduced ability to care for themselves. The discharge of 69% of medically stable patients (N=43) was postponed due to shortage of beds in post-acute care facilities. Correspondingly, 62% of the medically stable patients (N=141) could imagine receiving post-acute care in a “Nurseled Unit” (NLU). Despite being medically stable, one third of the patients (N=124) was not ready to return to their homes because they felt too weak or insecure to cope with everyday life. Conclusion: Using standardized tools to predict patients at risk for transfer to post-acute care facilities and reduced self-care abilities and the continuous evaluation of medical stability are all methods that could be applied to enhance interdisciplinary care and optimize discharge management. Furthermore, setting up NLU is expected to unburden the occupancy of acute care beds by a considerable amount of patients who are in need of post-acute care.

Krank oder krank gemacht? Rezidivierende Episoden kutaner Ulzera, Aphten, Kolitis, Arthralgien, Haarausfall... eine systemische Erkrankung oder iatrogen?

Recurrent episodes of cutaneous and subcutaneous ulcers, especially in the oral cavity, represent a high psychological and painful burden for the patient. If there in addition are symptoms of arthralgia and/or colitis, an autoimmune disease with vasculitis, particularly a Morbus Behçet has to be considered as a possible differential diagnosis. The therapy therefore would be an immunosuppressive one. Also a wide immunologic diagnostic process has to be started. Furthermore, a chronic inflammatory bowel disease has to be excluded by colonoscopic biopsy. An infectious etiology of the symptoms (viral/bacterial/parasitic) should be investigated by microbiological and laboratory tests. A thrush or a herpes-infection caused by immunosuppression (toxic or due to illness) has to be considered as a further differential diagnosis. Also a precise medical and drug history is very important because of possible toxic adverse effects. Until confirmation of a final diagnosis, only a symptomatic analgetic or antifungal or antiviral therapy in case of a positive thrush or herpes culture respectively should be initiated with respect to the very different kinds of treatment of the diseases included in the differential diagnosis.