Paediatrics in Berlin

The aim of this report is to describe the highlights of the European Respiratory Society annual congress in Berlin, Germany. The best abstracts in asthma and allergy, cystic fibrosis, respiratory infection, paediatric and neonatal intensive care, paediatric investigative techniques (in particular respiratory physiology and bronchoscopy) and respiratory epidemiology are presented and set in the context of the current literature.

Feasibility and safety of same-day home discharge after radiofrequency catheter ablation

Interventional cardiology in a day-case setting might reduce logistic constraints on hospital resources. However, in contrast with coronary angioplasty, few data support the feasibility and safety of radiofrequency catheter ablation (RCA). The aim of this prospective, multicenter cohort study was to evaluate the feasibility and safety of RCA in 1,342 patients (814 men; mean age 57 +/- 17 years) considered eligible for ambulatory RCA, according to specific set of criteria, for common atrial flutter (n = 632), atrioventricular nodal reentrant tachycardia (n = 436), accessory pathways (n = 202), and atrial tachycardia (n = 72). Patients suitable for early discharge (4 to 6 hours after uncomplicated RCA) were scheduled for 1-month follow-up. Predictive factors for delayed complications were studied by multivariate analysis. Of the 1,342 enrolled patients, 1,270 (94.6%) were discharged the same day and followed for 1 month; no deaths occurred, and the readmission rate was 0.79% (95% confidence interval 0.30% to 1.27%). Six patients had significant puncture complications, 2 presented with symptomatic delayed pulmonary embolism, and 2 had new onset of poorly tolerated atrial flutter. None of these complications was life threatening. Multivariate analysis did not identify any significant independent predictors for delayed complications. In conclusion, these data suggest that same-day discharge after uncomplicated RCA for routine supraventricular arrhythmias is safe and may be applicable in clinical practice. This approach is known to be associated with significant patient satisfaction and cost savings and can be considered a first-line option in most patients who undergo routine ablation procedures.

Identification of pathogen and host-response markers correlated with periodontal disease

BACKGROUND: Periodontitis is the major cause of tooth loss in adults and is linked to systemic illnesses, such as cardiovascular disease and stroke. The development of rapid point-of-care (POC) chairside diagnostics has the potential for the early detection of periodontal infection and progression to identify incipient disease and reduce health care costs. However, validation of effective diagnostics requires the identification and verification of biomarkers correlated with disease progression. This clinical study sought to determine the ability of putative host- and microbially derived biomarkers to identify periodontal disease status from whole saliva and plaque biofilm. METHODS: One hundred human subjects were equally recruited into a healthy/gingivitis group or a periodontitis population. Whole saliva was collected from all subjects and analyzed using antibody arrays to measure the levels of multiple proinflammatory cytokines and bone resorptive/turnover markers. RESULTS: Salivary biomarker data were correlated to comprehensive clinical, radiographic, and microbial plaque biofilm levels measured by quantitative polymerase chain reaction (qPCR) for the generation of models for periodontal disease identification. Significantly elevated levels of matrix metalloproteinase (MMP)-8 and -9 were found in subjects with advanced periodontitis with Random Forest importance scores of 7.1 and 5.1, respectively. The generation of receiver operating characteristic curves demonstrated that permutations of salivary biomarkers and pathogen biofilm values augmented the prediction of disease category. Multiple combinations of salivary biomarkers (especially MMP-8 and -9 and osteoprotegerin) combined with red-complex anaerobic periodontal pathogens (such as Porphyromonas gingivalis or Treponema denticola) provided highly accurate predictions of periodontal disease category. Elevated salivary MMP-8 and T. denticola biofilm levels displayed robust combinatorial characteristics in predicting periodontal disease severity (area under the curve = 0.88; odds ratio = 24.6; 95% confidence interval: 5.2 to 116.5). CONCLUSIONS: Using qPCR and sensitive immunoassays, we identified host- and bacterially derived biomarkers correlated with periodontal disease. This approach offers significant potential for the discovery of biomarker signatures useful in the development of rapid POC chairside diagnostics for oral and systemic diseases. Studies are ongoing to apply this approach to the longitudinal predictions of disease activity.

Potential clinical utility of polymerase chain reaction in microbiological testing for sepsis

OBJECTIVES: To evaluate the potential improvement of antimicrobial treatment by utilizing a new multiplex polymerase chain reaction (PCR) assay that identifies sepsis-relevant microorganisms in blood. DESIGN: Prospective, observational international multicentered trial. SETTING: University hospitals in Germany (n = 2), Spain (n = 1), and the United States (n = 1), and one Italian tertiary general hospital. PATIENTS: 436 sepsis patients with 467 episodes of antimicrobial treatment. METHODS: Whole blood for PCR and blood culture (BC) analysis was sampled independently for each episode. The potential impact of reporting microorganisms by PCR on adequacy and timeliness of antimicrobial therapy was analyzed. The number of gainable days on early adequate antimicrobial treatment attributable to PCR findings was assessed. MEASUREMENTS AND MAIN RESULTS: Sepsis criteria, days on antimicrobial therapy, antimicrobial substances administered, and microorganisms identified by PCR and BC susceptibility tests. RESULTS: BC diagnosed 117 clinically relevant microorganisms; PCR identified 154. Ninety-nine episodes were BC positive (BC+); 131 episodes were PCR positive (PCR+). Overall, 127.8 days of clinically inadequate empirical antibiotic treatment in the 99 BC+ episodes were observed. Utilization of PCR-aided diagnostics calculates to a potential reduction of 106.5 clinically inadequate treatment days. The ratio of gainable early adequate treatment days to number of PCR tests done is 22.8 days/100 tests overall (confidence interval 15-31) and 36.4 days/100 tests in the intensive care and surgical ward populations (confidence interval 22-51). CONCLUSIONS: Rapid PCR identification of microorganisms may contribute to a reduction of early inadequate antibiotic treatment in sepsis.

Treatment of acute renal failure in the intensive care unit: lower costs by intermittent dialysis than continuous venovenous hemodiafiltration

Intermittent and continuous renal replacement therapies (RRTs) are available for the treatment of acute renal failure (ARF) in the intensive care unit (ICU). Although at present there are no adequately powered survival studies, available data suggest that both methods are equal with respect to patient outcome. Therefore, cost comparison between techniques is important for selecting the modality. Expenditures were prospectively assessed as a secondary end point during a controlled, randomized trial comparing intermittent hemodialysis (IHD) with continuous venovenous hemodiafiltration (CVVHDF). The outcome of the primary end points of this trial, that is, ICU and in-hospital mortality, has been previously published. One hundred twenty-five patients from a Swiss university hospital ICU were randomized either to CVVHDF or IHD. Out of these, 42 (CVVHDF) and 34 (IHD) were available for cost analysis. Patients' characteristics, delivered dialysis dose, duration of stay in the ICU or hospital, mortality rates, and recovery of renal function were not different between the two groups. Detailed 24-h time and material consumption protocols were available for 369 (CVVHDF) and 195 (IHD) treatment days. The mean daily duration of CVVHDF was 19.5 +/- 3.2 h/day, resulting in total expenditures of Euro 436 +/- 21 (21% for human resources and 79% for technical devices). For IHD (mean 3.0 +/- 0.4 h/treatment), the costs were lower (Euro 268 +/- 26), with a larger proportion for human resources (45%). Nursing time spent for CVVHDF was 113 +/- 50 min, and 198 +/- 63 min per IHD treatment. Total costs for RRT in ICU patients with ARF were lower when treated with IHD than with CVVHDF, and have to be taken into account for the selection of the method of RRT in ARF on the ICU.

Welfare Lobby Groups responding to Globalisation: A Comparison of the Australian Council of Social Service (ACOSS) and the UK Child Poverty Action Group (CPAG)

The past decade has witnessed a period of intense economic globalisation. The growing significance of international trade, investment, production and financial flows appears to be curtailing the autonomy of individual nation states. In particular, globalisation appears to be encouraging, if not demanding, a decline in social spending and standards. However, many authors believe that this thesis ignores the continued impact of national political and ideological pressures and lobby groups on policy outcomes. In particular, it has been argued that national welfare consumer and provider groups remain influential defenders of the welfare state. For example, US aged care groups are considered to be particularly effective defenders of social security pensions. According to this argument, governments engaged in welfare retrenchment may experience considerable electoral backlash (Pierson 1996; Mishra 1999). Yet, it is also noted that governments can take action to reduce the impact of such groups by reducing their funding, and their access to policy-making and consultation processes. These actions are then justified on the basis of removing potential obstacles to economic competitiveness (Pierson 1994; Melville 1999).

Impact of recommendation updates in well-controlled patients on nonrecommended antiretroviral therapies: the Swiss HIV cohort study

BACKGROUND HIV treatment recommendations are updated as clinical trials are published. Whether recommendations drive clinicians to change antiretroviral therapy in well-controlled patients is unexplored. METHODS We selected patients with undetectable viral loads (VLs) on nonrecommended regimens containing double-boosted protease inhibitors (DBPIs), triple-nucleoside reverse transcriptase inhibitors (NRTIs), or didanosine (ddI) plus stavudine (d4T) at publication of the 2006 International AIDS Society recommendations. We compared demographic and clinical characteristics with those of control patients with undetectable VL not on these regimens and examined clinical outcome and reasons for treatment modification. RESULTS At inclusion, 104 patients were in the DBPI group, 436 in the triple-NRTI group, and 19 in the ddI/d4T group. By 2010, 28 (29%), 204 (52%), and 1 (5%) patient were still on DBPIs, triple-NRTIs, and ddI plus d4T, respectively. 'Physician decision,' excluding toxicity/virological failure, drove 30% of treatment changes. Predictors of recommendation nonobservance included female sex [adjusted odds ratio (aOR) 2.69, 95% confidence interval (CI) 1 to 7.26; P = 0.01] for DPBIs, and undetectable VL (aOR 3.53, 95% CI 1.6 to 7.8; P = 0.002) and lack of cardiovascular events (aOR 2.93, 95% CI 1.23 to 6.97; P = 0.02) for triple-NRTIs. All patients on DBPIs with documented diabetes or a cardiovascular event changed treatment. Recommendation observance resulted in lower cholesterol values in the DBPI group (P = 0.06), and more patients having undetectable VL (P = 0.02) in the triple-NRTI group. CONCLUSION The physician's decision is the main factor driving change from nonrecommended to recommended regimens, whereas virological suppression is associated with not switching. Positive clinical outcomes observed postswitch underline the importance of observing recommendations, even in well-controlled patients.

Medikamentenallergie: Diagnostische Möglichkeiten mit In-vitro-Methoden

Bei Medikamentenallergien kommt es zu Immunreaktionen, die gegen das Medikament gerichtet sind und klinische Symptome verursachen. Man unterscheidet zwischen Hapten- und p-i-bedingten Reaktionen, wobei letztere nur für T-Zell-Reaktionen nachgewiesen wurden. Die häufigsten Immunmechanismen, welche Medikamentenallergien zugrunde liegen, sind Vermehrung von spezifischen IgE-produzierenden B- und/oder spezifischen T-Zellen. IgG-vermittelte Reaktionen, die z.B. eine hämolytische Anämie verursachen können, sind selten. Spezifische IgE können mittels CAP-Technologie nachgewiesen werden. Das Medikament muss an eine Trägersubstanz covalent gebunden werden, was den Nachteil mit sich bringt, dass die entsprechende Bindungsstelle im Medikament für IgE nicht erkennbar ist. Der Basophilenaktivierungstest (BAT) arbeitet meist mit freiem, ungebundenem Medikament. Wie die IgE-Vernetzung stattfindet, ist allerdings unklar. Beide Teste sind nicht genügend sensitiv um den In-vivo-Test (Prick oder i.d.) zu ersetzen. Bei T-Zell-Reaktionen wird in vitro meist die Proliferation der durch das Medikament stimulierten T-Zellen erfasst. Die Blutzellen (antikoaguliertes Blut) sollte innerhalb von 24 h im Labor zur Verarbeitung ankommen, wo die Zellseparation durchgeführt wird, um die Zellen mit dem Medikament zu stimulieren. Diese Stimulation kann durch Messung von Aktivierungsmarker (mittels Flow-Zytometrie), sezernierter Zytokine (ELISA) oder 3H-Thymidin Einbau in die sich teilende Zellen (Lymphozytentransformations- Test, LTT) erfasst werden. Am meisten Erfahrung liegt für den LTT vor. Die Sensitivität wird bei eindeutigen Fällen auf 50 – 70% geschätzt, hängt aber stark vom Krankheitsbild und Medikament ab. Schwere makulopapulöse Reaktionen und DRESS (Drug Rash with Eosinophilia and Systemic Symptoms), AGEP (acute generalized exanthematous pustulosis) sind meist positiv im LTT, aber schwere bullöse Reaktionen (SJS/TEN; Stevens-Johnson Syndrom/toxische epidermale Nekrolyse) werden besser mittels Zytotoxteste und Zytokinsekretion erfasst, da eine T-Zell-Proliferation weniger prominent ist. Trotz der limitierten Sensitivität sind diese Teste gut geeignet um Kreuzreaktionen zu erfassen, bzw. für mechanistische Studien. Da Provokationsteste bei verzögerten Medikamentenallergien nicht zur Verfügung stehen (es ist unklar, wie lange und wie hoch dosiert man das Medikament bei verzögerten Reaktionen geben muss), werden diese Teste in Zukunft eher mehr eingesetzt werden. Wichtig ist, dass sie selten falsch positiv sind, und ein positives Resultat als relevant angesehen werden kann. Für die Abklärung seltener IgG-vermittelter Reaktionen kann man einen modifizierten Coombs-Test versuchen.

Fully Automatic Segmentation of AP Pelvis X-rays via Random Forest Regression and Hierarchical Sparse Shape Composition

Knowledge of landmarks and contours in anteroposterior (AP) pelvis X-rays is invaluable for computer aided diagnosis, hip surgery planning and image-guided interventions. This paper presents a fully automatic and robust approach for landmarking and segmentation of both pelvis and femur in a conventional AP X-ray. Our approach is based on random forest regression and hierarchical sparse shape composition. Experiments conducted on 436 clinical AP pelvis x-rays show that our approach achieves an average point-to-curve error around 1.3 mm for femur and 2.2 mm for pelvis, both with success rates around 98%. Compared to existing methods, our approach exhibits better performance in both the robustness and the accuracy.