Randomized controlled trials define shape of dose response for Pollinex Quattro Birch allergoid immunotherapy

Background

The Birch Allergoid, Tyrosine Adsorbate, Monophosphoryl Lipid A (POLLINEX^® Quattro Plus 1.0 ml Birch 100%) is an effective, well‐tolerated short course subcutaneous immunotherapy. We performed 2 phase II studies to determine its optimal cumulative dose.

Methods

The studies were conducted in Germany, Austria and Poland (EudraCT numbers: 2012‐004336‐28 PQBirch203 and 2015‐000984‐15 PQBirch204) using a wide range of cumulative doses. In both studies, subjects were administered 6 therapy injections weekly outside the pollen season. Conjunctival Provocation Tests were performed at screening, baseline and 3‐4 weeks after completing treatment, to quantify the reduction in Total Symptom Scores (as the primary endpoint) with each cumulative dose. Multiple Comparison Procedure and Modeling analysis was used to test for the dose response, shape of the curve and estimation of the median effective dose (ED₅₀), a measure of potency.

Results

Statistically significant dose responses (P < .01 & .001) were seen, respectively. The highest cumulative dose in PQBirch204 (27 300 standardized units [SU]) approached a plateau. Potency of the PQBirch was demonstrated by an ED₅₀ 2723 SU, just over half the current dose. Prevalence of treatment‐emergent adverse events was similar for active doses, most being short‐lived and mild. Compliance was over 85% in all groups.

Conclusion

Increasing the cumulative dose of PQBirch 5.5‐fold from 5100 to 27 300 SU achieved an absolute point difference from placebo of 1.91, a relative difference 32.3% and an increase in efficacy of 50%, without compromising safety. The cumulative dose response was confirmed to be curvilinear in shape.     

Caring connection: developing an Internet resource for family caregivers of children with cancer

This article describes the development of a family-focused Internet resource, the Caring Connection Web site, designed to provide individualized clinical information, patient-centered information, and access to online communication for caregivers of children with cancer. Data from surveys with family caregivers described the scope and characteristics of their current Internet use. Web site prototype development and user testing provided additional insights that inform the ongoing design of the Caring Connection Web site. The family caregivers and oncology healthcare providers who participated are active users of Internet health information. The preliminary data they provided support the feasibility and usability of the Caring Connection prototype. Ongoing development of the Caring Connection Web site will provide an innovative approach to assist these family caregivers in meeting currently unmet information and communication needs, and will provide evidence regarding "best practice" in design and development of Internet resources to support communication and information sharing.     

Human infection with Wuchereria bancrofti in Matara,Sri Lanka: the use,in parallel,of an ELISA to detect filaria-specific IgG4 in urine and of ICT card tests to detect filarial antigen in whole blood

The ICT card test to detect circulating filarial antigen and an ELISA that detects filaria-specific urinary IgG(4) were each used to screen 473 subjects from a community in Sri Lanka where Wuchereria bancrofti is endemic. When the ICT test was used as the gold standard, the ELISA was found to have a sensitivity of 91.2%. However, far more of the subjects were found ELISA-positive than ICT-positive (76.5% v. 31.1%). The youngest children studied (aged 1-10 years) were similar to the adult subjects in terms of the prevalence of antigenaemia (33.8%) and the prevalence (72.1%) and concentration of filaria-specific IgG(4) in their urine. Therefore, especially as urine samples are easier, less painful and safer to collect than blood samples, the ELISA may be particularly useful to screen very young and school-age children, to estimate current levels of transmission in a particular area.     

Primitive neuroectodermal tumour of the tongue

Peripheral primitive neuroectodermal tumours, which belong to the Ewing sarcoma tumour family, are extremely rare. These tumours are highly aggressive and are known to have a poor prognosis. Immunostaining with at least two neural markers and evidence of an abnormal t(11;22)(q24;q12) translocation are hallmark features in this diagnosis. We present the first reported case of peripheral primitive neuroectodermal tumour to occur in the tongue.     

Prevalence and characteristics of left ventricular noncompaction in a community hospital cohort of patients with systolic dysfunction

BACKGROUND: Left ventricular noncompaction (LVNC) is felt to be a rare form of cardiomyopathy, although its prevalence in a nonreferred population is unknown. We examined the prevalence and clinical characteristics of LVNC in a community hospital cohort of adult patients with echocardiographic evidence of left ventricular (LV) systolic dysfunction. METHODS: All adult echocardiograms with global LV dysfunction and an LVEF < or = 45% over a 1-year period were reviewed for signs of LV noncompaction. Its presence was confirmed by the consensus of at least 2/3 readers specifically searching for this using standard criteria for noncompaction. RESULTS: A 3.7% prevalence of definite or probable LVNC was found in those with LVEF < or = 45% and a 0.26% prevalence for all patients referred for echocardiography during this period. This is appreciably higher than prior reports from tertiary centers. CONCLUSION: Noncompaction may not be a rare phenomenon and is comparable to other more widely recognized but less common causes of heart failure such as peripartum myopathy, connective tissue diseases, chronic substance abuse and HIV disease.     

Challenges in implementing best practice DVI guidelines in low resource settings: lessons learnt from the Meethotamulla garbage dump mass disaster

Forensic Science, Medicine and Pathology - The management of mass fatalities following disasters is a complex process which requires the involvement of multiple stakeholders and resources. A...     

Diagnostic Applications of Ultrasmall Superparamagnetic Particles of Iron Oxide for Imaging Myocardial and Vascular Inflammation

Cardiac magnetic resonance (CMR) is at the forefront of noninvasive methods for the assessment of myocardial anatomy, function, and most importantly tissue characterization. The role of CMR is becoming even more significant with an increasing recognition that inflammation plays a major role for various myocardial diseases such as myocardial infarction, myocarditis, and takotsubo cardiomyopathy. Ultrasmall superparamagnetic particles of iron oxide (USPIO) are nanoparticles that are taken up by monocytes and macrophages accumulating at sites of inflammation. In this context, USPIO-enhanced CMR can provide valuable additional information regarding the cellular inflammatory component of myocardial and vascular diseases. Here, we will review the recent diagnostic applications of USPIO in terms of imaging myocardial and vascular inflammation, and highlight some of their future potential.