Temporal evolution of new T1-weighted hypo-intense lesions and central brain atrophy in patients with a first clinical demyelinating event treated with subcutaneous interferon ß-1a.

OBJECTIVE: Evaluate the effect of subcutaneous interferon ß-1a (sc IFN ß-1a) versus placebo on the evolution of T1-weighted MRI lesions and central brain atrophy in in patients with a first clinical demyelinating event (FCDE). METHODS: Post hoc analysis of baseline-to-24 month MRI data from patients with an FCDE who received sc IFN ß-1a 44 µg once- (qw) or three-times-weekly (tiw), or placebo, in REFLEX. Patients were grouped according to treatment regimen or conversion to clinically definite MS (CDMS) status. The intensity of new lesions on unenhanced T1-weighted images was classified as T1 iso- or hypo-intense (black holes) and percentage ventricular volume change (PVVC) was assessed throughout the study. RESULTS: In patients not converting to CDMS, sc IFN ß-1a tiw or qw, versus placebo, reduced the overall number of new lesions (P < 0.001 and P = 0.005) and new T1 iso-intense lesions (P < 0.001 and P = 0.002) after 24 months; only sc IFN ß-1a tiw was associated with fewer T1 hypo-intense lesions versus placebo (P < 0.001). PVVC findings in patients treated with sc IFN ß-1a suggested pseudo-atrophy that was ~ fivefold greater versus placebo in the first year of treatment (placebo 1.11%; qw 4.28%; tiw 6.76%; P < 001); similar findings were apparent for non-converting patients. CONCLUSIONS: In patients with an FCDE, treatment with sc IFN ß-1a tiw for 24 months reduced the number of new lesions evolving into black holes.

The use of indicators to improve the quality of intensive care: theoretical aspects and experiences from the Dutch intensive care registry.

In the concept of total quality management that was originally developed in industry, the use of quality indicators is essential. The implementation of quality indicators in the intensive care unit to improve the quality of care is a complex process. This process can be described in seven subsequent steps of an indicator-based quality improvement (IBQI) cycle. With this IBQI cycle, a continuous quality improvement can be achieved with the use of indicator data in a benchmark setting. After the development of evidence-based indicators, a sense of urgency has to be created, registration should start, raw data must be analysed, feedback must be given, and interpretation and conclusions must be made, followed by a quality improvement plan. The last step is the implementation of changes that needs a sense of urgency, and this completes the IBQI cycle. Barriers and facilitators are found in each step. They should be identified and addressed in a multifaceted quality improvement strategy.

Comparing lesion segmentation methods in multiple sclerosis: Input from one manually delineated subject is sufficient for accurate lesion segmentation.

PURPOSE: Accurate lesion segmentation is important for measurements of lesion load and atrophy in subjects with multiple sclerosis (MS). International MS lesion challenges show a preference of convolutional neural networks (CNN) strategies, such as nicMSlesions. However, since the software is trained on fairly homogenous training data, we aimed to test the performance of nicMSlesions in an independent dataset with manual and other automatic lesion segmentations to determine whether this method is suitable for larger, multi-center studies. METHODS: Manual lesion segmentation was performed in fourteen subjects with MS on sagittal 3D FLAIR images from a 3T GE whole-body scanner with 8-channel head coil. We compared five different categories of automated lesion segmentation methods for their volumetric and spatial agreement with manual segmentation: (i) unsupervised, untrained (LesionTOADS); (ii) supervised, untrained (LST-LPA and nicMSlesions with default settings); (iii) supervised, untrained with threshold adjustment (LST-LPA optimized for current data); (iv) supervised, trained with leave-one-out cross-validation on fourteen subjects with MS (nicMSlesions and BIANCA); and (v) supervised, trained on a single subject with MS (nicMSlesions). Volumetric accuracy was determined by the intra-class correlation coefficient (ICC) and spatial accuracy by Dice's similarity index (SI). Volumes and SI were compared between methods using repeated measures ANOVA or Friedman tests with post-hoc pairwise comparison. RESULTS: The best volumetric and spatial agreement with manual was obtained with the supervised and trained methods nicMSlesions and BIANCA (ICC absolute agreement > 0.968 and median SI > 0.643) and the worst with the unsupervised, untrained method LesionTOADS (ICC absolute agreement = 0.140 and median SI = 0.444). Agreement with manual in the single-subject network training of nicMSlesions was poor for input with low lesion volumes (i.e. two subjects with lesion volumes ≤ 3.0 ml). For the other twelve subjects, ICC varied from 0.593 to 0.973 and median SI varied from 0.535 to 0.606. In all cases, the single-subject trained nicMSlesions segmentations outperformed LesionTOADS, and in almost all cases it also outperformed LST-LPA. CONCLUSION: Input from only one subject to re-train the deep learning CNN nicMSlesions is sufficient for adequate lesion segmentation, with on average higher volumetric and spatial agreement with manual than obtained with the untrained methods LesionTOADS and LST-LPA.

Video-Based E-Learning in Communication Skills for Physicians Provides Higher Agreement to Tissue Donation.

BACKGROUND: In hospitals, physicians are rarely confronted with tissue donation. Besides correctly identifying an eligible tissue donor, the physician also must deal with the bereaved family. When the immediate family members were asked to consent for tissue donation, objection by the next of kin appears to be the main reason for the loss of potential tissue donors, if no registration is found in the donor register. Therefore, physicians' guidance of next of kin through the consent process for tissue donation is an essential part of the recruitment process and requires adequate communication about donation skills and techniques. We analyzed if physicians educated with a video-based E-learning program on "communication about donation skills" successfully contributes to a higher consent rate for tissue donation. METHODS: This retrospective study was conducted in 2014 in a Dutch teaching hospital. Two groups of physicians were compared; physicians receiving a lecture on "tissue donation" and physicians receiving additional E-learning on "communication about donation." The results were analyzed on the outcome "obtained consent" for tissue donation from next of kin. RESULTS: Analyses show that physicians receiving a lecture about organ and tissue donation extended with video-based E-learning on communication about donation obtain a significantly (P ≤ .011) higher consent rate (55.6%) for tissue donation compared with physicians who only receive a lecture (15.5%). CONCLUSIONS: A mandatory offer for physicians to follow E-learning on communication about donation must be considered. This could help the availability of tissue donors.

Cellular pharmacology of cerulenin analogs that inhibit protein palmitoylation.

S-palmitoylation is a dynamic post-translational modification of certain proteins, which helps determine membrane association and may function to enhance the interactions of signaling molecules with their activated receptors and effector systems. Unlike enzymes that catalyze other protein lipidation reactions, e.g. farnesylation and N-myristoylation, protein palmitoyltransferase is virtually uncharacterized biochemically. We have described previously the synthesis of cerulenin analogs including cis-2,3-epoxy-4-oxononadecanamide (16C) and cis-2,3-epoxy-4-oxododecanamide (9C) that inhibit protein palmitoylation (Lawrence et al., J Med Chem 1999;42:4932-41), most likely through covalent alkylation of protein palmitoyltransferase. [3H]9C and [3H]16C were prepared by catalytic incorporation of 3H2 into unsaturated precursors for further study of their cellular pharmacology. After 4 hr, T24 bladder carcinoma cells in the absence of serum accumulated a 4-fold higher intracellular level of [3H]16C than of [3H]9C. Uptake of [3H]9C and [3H]16C was reduced by the presence of serum in the medium, suggesting their binding to serum proteins. [3H]9C and [3H]16C alkylated unique patterns of proteins in T24 cells, with proteins of approximately 80 and 31 kDa being labeled by each compound. A panel of human tumor cell lines demonstrated half-maximal proliferation inhibition at concentrations of 7-30, 4-16, and 8-36 microM, for cerulenin, 9C, and 16C, respectively, indicating that the cell lines have approximately equal sensitivity to these compounds. Different cell lines have similar patterns of protein alkylation by [3H]9C or [3H]16C, with labeling intensity related to cytotoxicity of the compounds. Since both 9C and 16C inhibit palmitoylation, the commonly labeled proteins are candidates for human protein palmitoyltransferase.