IgG ASC measured by ELISPOT (memory B-cells) at Baseline and after Vaccination.

<p>Data were derived from HIV-infected youth and children who received 2 doses of pH1N1 inactivated monovalent vaccine (30 μg/dose) approximately 3 weeks apart. Data represent medians and IQR of the IgG ASC/10⁶ PBMCs at each timepoint. The number of subjects per group at each time point is listed on the graph. <b>A</b> presents the IgG responses for all subjects and also for the subjects divided by baseline pH1N1 HAI immune serostatus (HAI titer <1:40 versus ≥1:40). After the first immunization there was a significant increase in IgG ASC (p = 0.048). There were no statistical differences in IgG ASC within each HAI immune serostatus group between baseline and the two vaccinations, but subjects with baseline HAI ≥1:40 titers had significantly higher IgG ASC after vaccination than those with titers <1:40 (p = 0.03). <b>B</b> depicts the median IgG ASC by age group. There were no statistical differences in IgG ASC within each age group between baseline and the two vaccinations.</p

Characteristics of the Study Population.

<p>a. The lower limit of detection varied among subjects depending on the assay used at the specific clinical research site; RNA values below the limit of detection were replaced with the lower limit of the assay (eg, 18 cp/mL was replaced with 50 cp/mL for an assay with the limit of detection of 50 cp/mL).</p><p>b. Complete response is defined as persons achieving both seroresponse and seroprotection.</p><p>c. P values among age groups were calculated by:</p><p>* Fisher’s Exact Test</p><p>**Analysis of Variance</p><p>Characteristics of the Study Population.</p

Flow Chart after Enrollment.

<p>Abbreviations: ARVs, antiretrovirals; HAI, hemagglutinin inhibition; PBMCs, Peripheral blood mononuclear cells. *Reasons for exclusion from the final analysis included: insufficient sample to perform assay, invalid results of assay</p

Changes in Antibody Avidity after pH1N1 Vaccination by Age Group and Baseline HAI.

<p>Data were derived from HIV-infected children and youth who received 2 doses of pH1N1 monovalent vaccine (30 μg/dose) approximately 3 weeks apart. Data represent medians and Inter Quartile Range (IQR) of the avidity index (AI). The number of subjects per group at each time point is listed on the graph. <b>A</b> presents the AI responses for all subjects and also for the subjects divided by baseline pH1N1 HAI immune serostatus (HAI titer <1:40 versus ≥1:40). Overall, AI significantly increased post-dose 2 (p = 0.04) and remained slightly higher at 7 mo (p = 0.07). Only subjects seroprotected at baseline had significant AI increases after vaccination (p<0.0001, <0.0001 and 0.003 post-dose 1, post-dose 2 and 7 months post-dose 1, respectively). Baseline seropositive participants with HAI titers ≥ 1:40 had a significantly higher AI response to vaccination compared with participants with baseline HAI titers <1:40 (p = 0.02 at both post-dose 1 and post-dose 2). <b>B</b> shows AI responses in each age group. In the 4 to <9-year old group, there were no significant differences in AI between baseline and any subsequent time point. In the 9 to <18-year old group, there were significant AI increases at post-dose 2 and at 7 months (p = 0.04 and 0.048 respectively). In the 18 to <25-years old group, there were significant differences from baseline at all time points (p = 0.02, 0.04 and 0.002, respectively).</p

Monitoring Central Venous Catheter Resistance to Predict Imminent Occlusion: A Prospective Pilot Study

<div><p>Background</p><p>Long-term central venous catheters are essential for the management of chronic medical conditions, including childhood cancer. Catheter occlusion is associated with an increased risk of subsequent complications, including bloodstream infection, venous thrombosis, and catheter fracture. Therefore, predicting and pre-emptively treating occlusions should prevent complications, but no method for predicting such occlusions has been developed.</p><p>Methods</p><p>We conducted a prospective trial to determine the feasibility, acceptability, and efficacy of catheter-resistance monitoring, a novel approach to predicting central venous catheter occlusion in pediatric patients. Participants who had tunneled catheters and were receiving treatment for cancer or undergoing hematopoietic stem cell transplantation underwent weekly catheter-resistance monitoring for up to 12 weeks. Resistance was assessed by measuring the inline pressure at multiple flow-rates via a syringe pump system fitted with a pressure-sensing transducer. When turbulent flow through the device was evident, resistance was not estimated, and the result was noted as “non-laminar.”</p><p>Results</p><p>Ten patients attended 113 catheter-resistance monitoring visits. Elevated catheter resistance (>8.8% increase) was strongly associated with the subsequent development of acute catheter occlusion within 10 days (odds ratio = 6.2; 95% confidence interval, 1.8–21.5; p <0.01; sensitivity, 75%; specificity, 67%). A combined prediction model comprising either change in resistance greater than 8.8% or a non-laminar result predicted subsequent occlusion (odds ratio = 6.8; 95% confidence interval, 2.0–22.8; p = 0.002; sensitivity, 80%; specificity, 63%). Participants rated catheter-resistance monitoring as highly acceptable.</p><p>Conclusions</p><p>In this pediatric hematology and oncology population, catheter-resistance monitoring is feasible, acceptable, and predicts imminent catheter occlusion. Larger studies are required to validate these findings, assess the predictive value for other clinical outcomes, and determine the impact of pre-emptive therapy.</p><p>Trial Registration</p><p>Clinicaltrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01737554?term=NCT01737554&rank=1" target="_blank">NCT01737554</a></p></div

Patient positioning during CRM.

<p>(A) Resistance measurements were performed with the participant lying at an angle of approximately 45°. The pressure sensor was placed below the estimated height of the participant’s right atrium. The relative heights and positions of the patient and pump were not altered between or during measurements. (B) Illustration of a tunneled external CVC. (C) Diagram of the catheter cross-section showing the different luminal diameters.</p

Flow diagram of CRM results and clinical outcomes.

<p>Per the STARD (STAndards for Reporting Diagnostic accuracy studies) initiative, the design of the study and flow of the patients are diagrammed [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135904#pone.0135904.ref014" target="_blank">14</a>]. The reasons for inconclusive CRM included first visit (n = 10), previous visit <i>R</i>^<i>2</i> was less than 85% (n = 7), TPA since previous visit (n = 10), and abnormal CVC function (n = 1). “CRM normal” indicates that the change in resistance was less than 8.8%. “CRM abnormal” indicates that either the change in resistance was at least 8.8% or the <i>R</i>^<i>2</i> was less than 85%. Clinical outcomes are also noted.</p

Receiver operating characteristic analysis for maximal change from Last Visit to predict catheter occlusion within 10 days.

<p>(A) Any occlusion event and (B) an occlusion event requiring TPA therapy.</p

Feasibility and acceptability of catheter-resistance monitoring.

<p>^a The data represent the proportion of planned CRM visits that the participants attended.</p><p>^b The data represent CRM visits during which catheter resistance measures were obtained for at least 3 flow rates in each CVC lumen.</p><p><b>Abbreviations:</b> CRM, catheter-resistance monitoring; CVC, central venous catheter; SD, standard deviation</p><p>Feasibility and acceptability of catheter-resistance monitoring.</p

Metrics used to report change in resistance.

<p>Change in resistance at each visit was described as the proportional change in estimated resistance within each lumen compared to that at Baseline (i.e., enrollment or first CRM visit), Reset (i.e., first CRM visit after TPA administration), or Last Visit (i.e., immediately previous CRM visit). Figure shows data from a single study participant and catheter lumen.</p