Validation of the Asthma Predictive Index and comparison with simpler clinical prediction rules

Background The loose and stringent Asthma Predictive Indices (API), developed in Tucson, are popular rules to predict asthma in preschool children. To be clinically useful, they require validation in different settings. Objective To assess the predictive performance of the API in an independent population and compare it with simpler rules based only on preschool wheeze. Methods We studied 1954 children of the population-based Leicester Respiratory Cohort, followed up from age 1 to 10 years. The API and frequency of wheeze were assessed at age 3 years, and we determined their association with asthma at ages 7 and 10 years by using logistic regression. We computed test characteristics and measures of predictive performance to validate the API and compare it with simpler rules. Results The ability of the API to predict asthma in Leicester was comparable to Tucson: for the loose API, odds ratios for asthma at age 7 years were 5.2 in Leicester (5.5 in Tucson), and positive predictive values were 26% (26%). For the stringent API, these values were 8.2 (9.8) and 40% (48%). For the simpler rule early wheeze, corresponding values were 5.4 and 21%; for early frequent wheeze, 6.7 and 36%. The discriminative ability of all prediction rules was moderate (c statistic ≤ 0.7) and overall predictive performance low (scaled Brier score < 20%). Conclusion Predictive performance of the API in Leicester, although comparable to the original study, was modest and similar to prediction based only on preschool wheeze. This highlights the need for better prediction rules.

Development and validation of decision rules to guide frequency of monitoring CD4 cell count in HIV-1 infection before starting antiretroviral therapy

Background Although CD4 cell count monitoring is used to decide when to start antiretroviral therapy in patients with HIV-1 infection, there are no evidence-based recommendations regarding its optimal frequency. It is common practice to monitor every 3 to 6 months, often coupled with viral load monitoring. We developed rules to guide frequency of CD4 cell count monitoring in HIV infection before starting antiretroviral therapy, which we validated retrospectively in patients from the Swiss HIV Cohort Study. Methodology/Principal Findings We built up two prediction rules (“Snap-shot rule” for a single sample and “Track-shot rule” for multiple determinations) based on a systematic review of published longitudinal analyses of CD4 cell count trajectories. We applied the rules in 2608 untreated patients to classify their 18 061 CD4 counts as either justifiable or superfluous, according to their prior ≥5% or <5% chance of meeting predetermined thresholds for starting treatment. The percentage of measurements that both rules falsely deemed superfluous never exceeded 5%. Superfluous CD4 determinations represented 4%, 11%, and 39% of all actual determinations for treatment thresholds of 500, 350, and 200×106/L, respectively. The Track-shot rule was only marginally superior to the Snap-shot rule. Both rules lose usefulness for CD4 counts coming near to treatment threshold. Conclusions/Significance Frequent CD4 count monitoring of patients with CD4 counts well above the threshold for initiating therapy is unlikely to identify patients who require therapy. It appears sufficient to measure CD4 cell count 1 year after a count >650 for a threshold of 200, >900 for 350, or >1150 for 500×106/L, respectively. When CD4 counts fall below these limits, increased monitoring frequency becomes advisable. These rules offer guidance for efficient CD4 monitoring, particularly in resource-limited settings.

Gradient estimation in dendritic reinforcement learning

We study synaptic plasticity in a complex neuronal cell model where NMDA-spikes can arise in certain dendritic zones. In the context of reinforcement learning, two kinds of plasticity rules are derived, zone reinforcement (ZR) and cell reinforcement (CR), which both optimize the expected reward by stochastic gradient ascent. For ZR, the synaptic plasticity response to the external reward signal is modulated exclusively by quantities which are local to the NMDA-spike initiation zone in which the synapse is situated. CR, in addition, uses nonlocal feedback from the soma of the cell, provided by mechanisms such as the backpropagating action potential. Simulation results show that, compared to ZR, the use of nonlocal feedback in CR can drastically enhance learning performance. We suggest that the availability of nonlocal feedback for learning is a key advantage of complex neurons over networks of simple point neurons, which have previously been found to be largely equivalent with regard to computational capability.

Prognostic clinical prediction rules to identify a low-risk pulmonary embolism: a systematic review and meta-analysis

Prognostic assessment is important for the management of patients with a pulmonary embolism (PE). A number of clinical prediction rules (CPRs) have been proposed for stratifying PE mortality risk. The aim of this systematic review was to assess the performance of prognostic CPRs in identifying a low-risk PE.

Endobronchial donor pre-treatment with ventavis: is a second administration during reperfusion beneficial to optimize post-ischemic function of non-heart beating donor lungs?

BACKGROUND: Lung retrieval from non-heart-beating donors (NHBD) has been introduced into clinical practice successfully. However, because of potentially deleterious effects of warm ischemia on microvascular integrity, use of NHBD lungs is limited by short tolerable time periods before preservation. Recently, improvement of NHBD graft function was demonstrated by donor pre-treatment using aerosolized Ventavis (Schering Inc., Berlin, Germany). Currently, there is no information whether additional application of this approach in reperfusion can further optimize immediate graft function. MATERIAL AND METHODS: Asystolic pigs (n = 5/group) were ventilated for 180-min of warm ischemia (groups 1-3). In groups 2 and 3, 100 microg Ventavis were aerosolized over 30-min using an ultrasonic nebulizer (Optineb). Lungs were then retrogradely preserved with Perfadex and stored for 3-h. After left lung transplantation and contralateral lung exclusion, grafts were reperfused for 6-h. Only in group 3, another dose of 100 microg Ventavis was aerosolized during the first 30-min of reperfusion. Hemodynamics, pO2/FiO2 and dynamic compliance were monitored continuously and compared to controls. Intraalveolar edema was quantified stereologically, and extravascular-lung-water-index (EVLWI) was measured. Statistics comprised ANOVA analysis with repeated measurements. RESULTS: Dynamic compliance was significantly lower in both Ventavis groups, but additional administration did not result in further improvement. Oxygenation, pulmonary hemodynamics, EVLWI and intraalveolar edema formation were comparable between groups. CONCLUSIONS: Alveolar deposition of Ventavis in NHBD lungs before preservation significantly improves dynamic lung compliance and represents an important strategy for improvement of preservation quality and expansion of warm ischemic intervals. However, additional application of this method in early reperfusion is of no benefit.