Consort flow diagram of the study.

<p>Consort flow diagram of the study.</p

KNN- prediction of asthma exacerbation based on acidity of EBC, inflammatory markers in EBC, FeNO, and asthma clinical characteristics.^*

<p>* KNN algorithm is performed as statistical technique.</p><p>KNN- prediction of asthma exacerbation based on acidity of EBC, inflammatory markers in EBC, FeNO, and asthma clinical characteristics.^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0119434#t005fn001" target="_blank">*</a>}</p

Overview of ROC-curves of 3 predictive models for asthma exacerbations.

<p>ROC1: exacerbation prediction model on the basis of the acidity of EBC and inflammatory markers in EBC alone; ROC2: model on the basis of FeNO, reversibility to a bronchodilator as increase in FEV1% of predicted value, PC₂₀, daily dosage of ICS; ROC3: model all variables of model 1 and 2.</p

Overview of study parameters.

<p>ACQ = Asthma Control Questionnaire, GINA = Global Initiative for Asthma, FeNO = Fractional exhaled Nitric Oxide, EBC = exhaled breath condensate, PC₂₀ = histamine bronchial hyperresponsiveness test.</p><p>* Symptom score based on GINA criteria was collected during 2 weeks preceding the clinical visit. This score was combined with FEV₁, to assess asthma control as defined by GINA.</p><p>^† Home monitoring consisted of daily symptom score plus FEV₁ measurements.</p><p>Overview of study parameters.</p

Performance of acidity of EBC, inflammatory markers in EBC, FeNO, and asthma clinical characteristics in prediction of asthma exacerbation.

<p>IL = interleukin, TNF = tumor necrosis factor, FeNO = Fractional exhaled Nitric Oxide, PC₂₀ = histamine bronchial hyperresponsiveness test, FEV₁ = forced expiratory volume in one second, ICS = Inhaled Corticosteroids, ACQ = Asthma Control Questionnaire.</p><p>Performance of acidity of EBC, inflammatory markers in EBC, FeNO, and asthma clinical characteristics in prediction of asthma exacerbation.</p

Patient characteristics at baseline.

<p>Site A = Maastricht, Site B = Sittard, FEV₁ = forced expiratory volume in one second, SD = Standard Deviation, ICS = Inhaled Corticosteroids, ACQ = Asthma Control Questionnaire, IQR = Inter Quartile Range, PAQLQ = Pediatric Asthma Control Quality of Life Questionnaire, FeNO = Fractional exhaled Nitric Oxide.</p><p>* Six children did not use ICS at baseline.</p><p>^† PC₂₀: concentration of histamine inducing a 20% drop in FEV₁.</p><p>^‡ Atopy is defined as a positive Phadiatop (Phadia, Uppsala, Sweden), or RAST, or a positive allergen skin test.</p><p>Patient characteristics at baseline.</p

Concentrations of inflammatory markers in EBC and FeNO.

<p>IL = interleukin, TNF = tumor necrosis factor, FeNO = Fractional exhaled Nitric Oxide.</p><p>Concentrations of inflammatory markers in EBC and FeNO.</p

Relationship between S₂₄ and T for BDQ and placebo.

<p>Relationship between S₂₄ and T for BDQ and placebo.</p

Evaluation of six months sputum culture conversion as a surrogate endpoint in a multidrug resistant-tuberculosis trial

<div><p>The emergence of multidrug resistant-tuberculosis (MDR-TB), defined as <i>Mycobacterium tuberculosis</i> strains with <i>in vitro</i> resistance to at least isoniazid and rifampicin, has necessitated evaluation and validation of appropriate surrogate endpoints for treatment response in drug trials for MDR-TB. The trial that has demonstrated efficacy of bedaquiline, a diarylquinoline that inhibits mycobacterial ATP synthase, possesses the requisite features to conduct this evaluation. Approval of bedaquiline for use in MDR-TB was based primarily on the results of the controlled C208 Stage II study (ClinicalTrials.gov number, NCT00449644) including 160 patients randomized 1:1 to receive bedaquiline or placebo for 24 weeks when added to an 18–24-month preferred five-drug background regimen. Since randomization in C208 Stage II was preserved until study end, the trial results allow for the investigation of the complex relationship between sustained durable outcome with either Week 8 or Week 24 culture conversion as putative surrogate endpoints. The relationship between Week 120 outcome with Week 8 or Week 24 culture conversion was investigated using a descriptive analysis and with a recently developed statistical methodology for surrogate endpoint evaluation using methods of causal inference.</p><p>The results demonstrate that sputum culture conversion at 24 weeks is more reliable than sputum culture conversion at 8 weeks when assessing the outcome of adding one new drug to a MDR-TB regimen.</p></div

Evaluation of six months sputum culture conversion as a surrogate endpoint in a multidrug resistant-tuberculosis trial - Fig 5

<p><b>Surrogate predictive value for A) S</b>_<b>8</b><b>and B) S</b>_<b>24</b>. The conditional probabilities of (A) ΔT given ΔS₈ or (B) ΔT given ΔS₂₄ are shown. For any individual patient, ΔT and ΔS will be -1 (Harm), 0 (Equal), and 1 (Benefit).</p