Single high-dose oral vitamin D3 (stoss) therapy — A solution to vitamin D deficiency in children with cystic fibrosis?

ObjectivesTo determine the safety and efficacy of stoss therapy on vitamin D levels over a 12 month period in children with cystic fibrosis and vitamin D deficiency (< 75 nmol/L).Study designRetrospective chart review of 142 paediatric CF patients from 2007 till 2011.ResultsThirty eight children received stoss therapy and 37 children with vitamin D deficiency were not treated and served as a control group. The stoss treated group had a significant and sustained increase in 25-hydroxyvitamin D levels measured at 1, 3, 6 and 12 months post treatment compared to controls (94.82 ± 41.0 nmol/L, p = 0.001; 81.54 ± 24.6 nmol/L, p = 0.001; 92.18 ± 36.5 nmol/L, p = 0.008 and 64.6 ± 20.0 nmol/L, p = 0.006 respectively). At 12 months post intervention, the mean difference in vitamin D levels from baseline between the stoss treated group and controls was significant at 15 nmol/L compared to 5 nmol/L (p = 0.038).ConclusionStoss therapy effectively achieves and maintains levels of 25-hydroxyvitamin D greater than 75 nmol/L over 12 months.     

Automated Quantitative Pupillometry for the Prognostication of Coma After Cardiac Arrest

Background

Sedation and therapeutic hypothermia (TH) delay neurological responses and might reduce the accuracy of clinical examination to predict outcome after cardiac arrest (CA). We examined the accuracy of quantitative pupillary light reactivity (PLR), using an automated infrared pupillometry, to predict outcome of post-CA coma in comparison to standard PLR, EEG, and somato-sensory evoked potentials (SSEP).

Methods

We prospectively studied over a 1-year period (June 2012–June 2013) 50 consecutive comatose CA patients treated with TH (33 °C, 24 h). Quantitative PLR (expressed as the % of pupillary response to a calibrated light stimulus) and standard PLR were measured at day 1 (TH and sedation; on average 16 h after CA) and day 2 (normothermia, off sedation: on average 46 h after CA). Neurological outcome was assessed at 90 days with Cerebral Performance Categories (CPC), dichotomized as good (CPC 1–2) versus poor (CPC 3–5). Predictive performance was analyzed using area under the ROC curves (AUC).

Results

Patients with good outcome [n = 23 (46 %)] had higher quantitative PLR than those with poor outcome [n = 27; 16 (range 9–23) vs. 10 (1–30) % at day 1, and 20 (13–39) vs. 11 (1–55) % at day 2, both p < 0.001]. Best cut-off for outcome prediction of quantitative PLR was <13 %. The AUC to predict poor outcome was higher for quantitative than for standard PLR at both time points (day 1, 0.79 vs. 0.56, p = 0.005; day 2, 0.81 vs. 0.64, p = 0.006). Prognostic accuracy of quantitative PLR was comparable to that of EEG and SSEP (0.81 vs. 0.80 and 0.73, respectively, both p > 0.20).

Conclusions

Quantitative PLR is more accurate than standard PLR in predicting outcome of post-anoxic coma, irrespective of temperature and sedation, and has comparable prognostic accuracy than EEG and SSEP.     

A Nonionic Polyethylene Oxide (PEO) Surfactant Model: Experimental and Molecular Dynamics Studies of Kolliphor EL

Polyethoxylated, nonionic surfactants are important constituents of many drug formulations, including lipid-based formulations. In an effort to better understand the behavior of formulation excipients at the molecular level, we have developed molecular dynamics (MD) models for the widely used surfactant Kolliphor EL (KOL), a triricinoleate ester of ethoxylated glycerol. In this work, we have developed models based on a single, representative molecular component modeled with 2 force field variations based on the GROMOS 53A6_DBW and 2016H66 force field parameters for polyethoxylate chains. To compare the computational models to experimental measurements, we investigated the phase behavior of KOL using nephelometry, dynamic light scattering, cross-polarized microscopy, small-angle X-ray scattering, and cryogenic transmission electron microscopy. The potential for digestion of KOL was also evaluated using an in vitro digestion experiment. We found that the size and spherical morphology of the KOL colloids at low concentrations was reproduced by the MD models as well as the growing interactions between the aggregates to from rod-like structures at high concentrations. We believe that this model reproduces the phase behavior of KOL relevant to drug absorption and that it can be used in whole formulation simulations to accelerate the formulation development.     

Numerical Validation of a New Method to Assess Aortic Pulse Wave Velocity from a Single Recording of a Brachial Artery Waveform with an Occluding Cuff

Recently a new method has been proposed as a tool to measure arterial pulse wave velocity (PWV), a measure of the stiffness of the large arteries and an emerging parameter used as indicator of clinical cardiovascular risk. The method is based on measurement of brachial blood pressure during supra-systolic pressure inflation of a simple brachial cuff [the device is known as the Arteriograph (Tensiomed, Budapest, Hungary)]. This occlusion yields pronounced first and secondary peaks in the pressure waveform, the latter ascribed to a reflection from the aortic bifurcation, and PWV is calculated as the ratio of twice the jugulum-symphysis distance and the time difference between the two peaks. To test the validity of this working principle, we used a numerical model of the arterial tree to simulate pressures and flows in the normal configuration, and in a configuration with an occluded brachial artery. A pronounced secondary peak was indeed found in the brachial pressure signal of the occluded model, but its timing was only related to brachial stiffness and not to aortic stiffness. We also compared PWV’s calculated with three different methods: PWV_ATG (~Arteriograph principle), PWV_car–fem (~carotid–femoral PWV, the current clinical gold standard method), and PWV_theor (~Bramwell–Hill equation). Both PWV_ATG (R ² = 0.94) and PWV_car–fem (R ² = 0.95) correlated well with PWV_theor, but their numerical values were lower (by 2.17 ± 0.42 and 1.08 ± 0.70 m/s for PWV_ATG and PWV_car–fem, respectively). In conclusion, our simulations question the working principle of the Arteriograph. Our data indicate that the method picks up wave reflection phenomena confined to the brachial artery, and derived values of PWV rather reflect the stiffness of the brachial arteries.     

Is Morbidity Influenced by Staging in the Fontan Palliation? A Single Center Review

In a retrospective study of 32 consecutive patients undergoing a total cavopulmonary connection (TCPC), we tried to determine if the trend for decreasing age at Fontan completion and reducing the intervals between the staged procedures during the past decade was associated with a change in morbidity and outcome. In 8 patients the Fontan circulation was completed in one stage and in 24 patients an intermediate step by hemi-Fontan or bidirectional cavopulmonary anastomosis was performed before Fontan completion. Mean age at TCPC and mean interval since the previous palliation have decreased significantly during the past decade. Although major complications were significantly reduced over time the occurrence and duration of postoperative pleural effusions were not. Decreasing age as well as intervals in staged Fontan palliation have beneficial influence on major complications and outcome, without significantly affecting the duration of pleural effusions at Fontan completion.     

Left ventricular outflow obstruction in rhabdomyoma of infancy: meta-analysis of the literature

Primary heart tumors are exceptional in infants and children. Most common is the rhabdomyoma, often associated with tuberous sclerosis (Bourneville's disease). This tumor is generally believed to have no hemodynamic effects in the majority of cases. Recently, severe obstruction of the left ventricular outflow tract by a solitary tumor was diagnosed during pregnancy and emergency surgery was needed soon after birth.