Delayed lymphocyte re-population following discontinuation of dimethyl fumarate and after switching to other disease modifying drug therapies.

BACKGROUND: Dimethyl fumarate (DMF) reduces absolute lymphocyte counts, CD4, and CD8 counts, without significantly affecting total white blood cell counts. However, the recovery rate of these cells after discontinuation of DMF is unknown. The effect of subsequent disease modifying therapies (DMTs) on re-population rate is also unknown. OBJECTIVES: 1. To study the re-population rate of absolute lymphocytes, CD4, and CD8 counts back to baseline after discontinuation of DMF. 2. To measure the effect of subsequent DMTs on the re-population rate of these cells after DMF therapy. 3. To study the effect of the duration of exposure to DMF on repopulation of these cells. METHODS: A retrospective chart review of subjects who had discontinued DMF and in whom, CBC with differential, CD4 and CD8 counts were available at baseline, discontinuation and at follow-up (n = 113). Linear mixed models were used to analyze and assess linear trends in lymphocyte counts after DMF had been discontinued. RESULTS: DMF causes a significant drop in absolute lymphocyte, CD4, and CD8 counts. Re-population of these cells after discontinuation of DMF is significantly delayed, irrespective of whether or not a subsequent DMT is used, although there is a difference in re-population rate among DMTs. The re-population rate is also dependent on the duration of time patients have been exposed to DMF; longer exposure was associated with more delayed recovery. CONCLUSION: During this 30 month study period, re-population rates were significantly delayed post-DMF, irrespective of what subsequent DMT the patients received. Furthermore, no recovery of lymphocyte counts occurred in patients who were started on fingolimod or alemtuzumab after DMF was discontinued; in fact there was a continued decline in all of the cell populations studied.

The effect of dimethyl fumarate (Tecfidera™) on lymphocyte counts: A potential contributor to progressive multifocal leukoencephalopathy risk.

Dimethyl fumarate (Tecfidera™) is an effective therapy for relapsing forms of multiple sclerosis (MS). Our study suggests that this drug may have immunosuppressive properties evidenced by significant sustained reduction in CD8 lymphocyte counts and, to a lesser extent, CD4 lymphocyte counts. This observation is relevant in light of the recent case of progressive multifocal leukoencephalopathy in a patient receiving this drug.

Evaluation of filtering methods for acquiring radial intra-artery blood pressure waveforms.

The methods for evaluating noninvasive blood pressure (NIBP) monitors using an intra-arterial reference are detailed in the ANSI/AAMI/ISO 81060-2:2009 standard. In a recent study, GE Healthcare obtained invasive radial arterial blood pressure waveforms. The work presented here describes the development of filtering strategies for obtaining high fidelity intra-arterial pressure waveforms for NIBP accuracy testing using the 81060-2 standard. The natural frequency and damping factor of each subject-catheter-transducer system was computed from fast-flush transients. These parameters were used to construct filters for removing or reducing resonance artifacts. Additionally, new optimal damping factors were evaluated for designing compensation filters. Theoretical measurement systems using actual damping factors (< 0.4) and natural frequencies were found capable of generating significant systolic resonance artifacts (≥ 8 mmHg). Typical filters that may be standardly available in monitoring equipment were observed to be potentially inadequate in removing resonance artifact. Filters with particular optimal damping factors (0.6-0.7) were effective in removing resonance artifact. Clinicians need to understand that resonance artifacts potentially exist in intra-arterial waveforms and that the adjustments of monitoring systems may not be adequate. Optimal filters for obtaining intra-arterial waveforms should take into account the damping factor and natural frequency of the measuring system. In research and device evaluation studies it is necessary that optimal filtering be done to minimize the effects of under-damping.

Validation of a conical cuff on the forearm for estimating radial artery blood pressure.

INTRODUCTION: There has been a growing need for and interest in measuring noninvasive blood pressure (NIBP) in obese patients. In many situations, available rectangular upper arm blood pressure cuffs do not fit properly, closing in a crisscross manner or overlapping the elbow. To address this issue, GE Healthcare has designed a conically shaped cuff for use on the forearm to estimate radial arterial blood pressure. This study evaluated using this forearm cuff with an oscillometric NIBP algorithm compared with an invasive radial arterial blood pressure reference. PATIENTS AND METHODS: Thirty-four patients were enrolled in the study with an aim to acquire a minimum of 150 paired measurements. Blood pressure was measured and recorded invasively from the radial artery of each patient, while noninvasive oscillometric measurements were acquired from the same limb using a conically shaped cuff placed on the patient's forearm. ANALYSIS: NIBP values were compared with the invasive blood pressure values acquired in the combined 30-s period preceding cuff inflation and the 30-s period following cuff deflation. The acceptance criteria for measurement accuracy were defined in accordance with the ANSI/AAMI/ISO 81060-2:2009 standard, which requires an absolute average error of 5 mmHg or less, with an SD of 8 mmHg or less. RESULTS: The systolic mean error (-0.82 mmHg) and SD (6.08 mmHg) and the diastolic mean error (1.53 mmHg) and SD (3.83 mmHg) were within the 81060-2 acceptance criteria. CONCLUSION: The statistical results show that oscillometric NIBP measurements taken with the conically shaped cuff placed on the forearm give an accurate estimation of radial arterial blood pressure.