Evaluation of the impact of oximeter averaging times on automated FiO2 control in routine NICU care: a randomized cross-over study.

Objective: Changes in oximeter averaging times have been noted to affect alarm settings. Automated algorithms (A-FiO2) assess FiO2 faster than oximeter averaging, potentially impacting their effectiveness. Methods: In a single NICU routinely using 15 fabian-PRICO A-FiO2 systems, neonates were randomly exposed to SpO2 averaging time settings switched every 12 h among short (2-4 s), medium (10 s), and long (16 s) oximeter averaging times for the entire duration of their A-FiO2 exposure. Primary endpoints were the percent time in the set SpO2 target range (dependent on PMA), SpO2 < 80%, and SpO2 > 98%, excluding FiO2 = 0.21. Results: Ten VLBW neonates were enrolled over 11 months. At entry, they were 17 days old (IQR: 14-19), with an adjusted gestational age of 29 weeks (IQR: 27-30). The study included data from 272 days of A-FiO2 control (34% short, 32% medium, and 34% long). Respiratory support was predominantly non-invasive (53% NCPAP, 40% HFNC, and 6% NIPPV). The aggregate SpO2 exposure levels were 67% (IQR: 55-82) in the target range, 5.4% (IQR: 2.0-10) with SpO2 < 80%, and 1.2% (IQR: 0.4-3.1) with SpO2 > 98%. There were no differences in the target range time between the SpO2 averaging time settings. There were differences at the SpO2 extremes (p ≤ 0.001). The medium and long averaging were both lower than the short, with the difference larger than predicted. Multivariate analysis revealed that these findings were independent of subject, ventilation mode, target range, and overall stability. Conclusions: This A-FiO2 algorithm is effective regardless of the SpO2 averaging time setting. There is an advantage to the longer settings, which suggest an interaction with the controller.

Routine use of automated FiO2 control in Poland: prospective registry and survey.

Objective: The performance of automated control of inspired oxygen (A-FiO2) has been confirmed in dozens of studies but reports of routine use are limited. Broadly adopted in Poland, our aim is to share that experience. Methods: We used a prospectively planned observational study of the performance, general use patterns, unit practices, and problems with A-FiO2, based on a web registry of case reports, complemented by surveys of subjective impressions. Results: In 2019, a total of 92 A-FiO2 systems were in routine use in 38 centers. Of the 38 centers, 20 had agreed in 2013 to participate in the project. In these centers, A-FiO2 was applied in infants of all weights, but some centers restricted its use to weaning from oxygen and unstable infants. A cohort had reported their experience with each use (5/20 centers, 593 cases). A quarter of those infants were managed with a lower target range and three-quarters with alarms looser than European guidelines for manual SpO2 control. The perceived primary advantages of A-FiO2 were as follows: keeping the readings in the target range, reducing exposure to SpO2 extremes, reducing risk from nurse distraction, reducing workload, and reducing alarm fatigue. Practices did evolve with experience, including implementing changes in the alarm strategy, indications for use, and target range. The potential for over-reliance on automation was cited as a risk. There were a few reports of limited effectiveness (moderate 12/593 and poor 2/593). Conclusions: Automated oxygen control is broadly perceived by users as an improvement in controlling SpO2 with infrequent problems.

The effect of implementing an automated oxygen control on oxygen saturation in preterm infants.

OBJECTIVE: To evaluate the effect of implementing automated oxygen control as routine care in maintaining oxygen saturation (SpO2) within target range in preterm infants. METHODS: Infants <30 weeks gestation in Leiden University Medical Centre before and after the implementation of automated oxygen control were compared. The percentage of time spent with SpO2 within and outside the target range (90-95%) was calculated. SpO2 values were collected every minute and included for analysis when infants received extra oxygen. RESULTS: In a period of 9 months, 42 preterm infants (21 manual, 21 automated) were studied. In the automated period, the median (IQR) time spent with SpO2 within target range increased (manual vs automated: 48.4 (41.5-56.4)% vs 61.9 (48.5-72.3)%; p<0.01) and time SpO2 >95% decreased (41.9 (30.6-49.4)% vs 19.3 (11.5-24.5)%; p<0.001). The time SpO2<90% increased (8.6 (7.2-11.7)% vs 15.1 (14.0-21.1)%; p<0.0001), while SpO2<80% was similar (1.1 (0.4-1.7)% vs 0.9 (0.5-2.1)%; ns). CONCLUSIONS: During oxygen therapy, preterm infants spent more time within the SpO2 target range after implementation of automated oxygen control, with a significant reduction in hyperoxaemia, but not hypoxaemia.

Impact of the shift to neonatal noninvasive ventilation in Poland: a population study.

OBJECTIVE: This study was undertaken to document the real impact of a directed shift in the standard of neonatal practice to a pervasive use of noninvasive respiratory support. DESIGN: Before-after observational study. SETTING: All 18 neonatal ICUs in the capital region of Poland. PATIENTS: Every infant admitted to a neonatal ICU who received respiratory pressure support over a 7-year period of interest (12-month transition to the new noninvasive standard and 36 months before and after). INTERVENTION: Education as to the benefits of noninvasive respiratory support and widespread availability of Infant Flow noninvasive ventilation systems. MEASUREMENTS AND MAIN RESULTS: Five thousand five hundred fifty-one infants required respiratory support in this period. Of these, 14% were less than 28 weeks estimated gestational age, 33% between 28 and 32 weeks, 31% between 33 and 36 weeks, and 22% more than 36 weeks. The use of noninvasive support, as the first form of respiratory support, increased by 19% (p < 0.001). The use of noninvasive support, for weaning following extubation, increased by 32% (p = 0.06). The increased use in weaning was the most pronounced in infants younger than or equal to 32 weeks estimated gestational age (p < 0.001). There were two prospective primary endpoints, mortality and bad outcome among survivors younger than or equal to 32 weeks estimated gestational age. Mortality decreased from 11% to 7%, and the difference remained statistically significant after controlling for baseline factors (p < 0.001). The reduced mortality was more apparent in infants younger than or equal to 32 weeks estimated gestational age. In infants younger than or equal to 32 weeks estimated gestational age, bad outcome in survivors (grade III bronchopulmonary dyplasia and retinopathy of prematurity requiring laser treatment) did not increase (p = 0.669) after controlling for significant baseline variables. CONCLUSIONS: We believe that the adoption of an approach emphasizing noninvasive ventilation in Poland resulted in decreased mortality without an increase in significant pulmonary or retinal morbidity.

A Novel Acquisition Technique to Utilize Swan-Ganz Catheter data as a Surrogate for High-fidelity Micromanometry within the Right Ventricle and Pulmonary Circuit.

We explored the possibility of using conventional right-heart catheterization data, gathered both prospectively and retrospectively, as a surrogate for high-fidelity micro-manometery when analyzing systolic and diastolic RV function and calculating various ventricular and pulmonary hemodynamic parameters in the time domain. Right heart catheterizations were performed on 13 patients (7 female), who were suspected of having pulmonary hypertension. The procedure included use of both fluid-filled catheter and high-fidelity micromanometry to measure right ventricular and pulmonary arterial pressures. A digital data acquisition system was used to record micromanometer readings and data from the fluid-filled catheter system during prospective portion of the study. Retrospective data was obtained by direct digitization of screen captures taken by the conventional clinical system (fluid-filled catheter). From the 13 patients, 12-13 RV waveforms and 12 PA waveforms were acquired from each method. Basic measurements of heart rate, systolic pressure, diastolic pressure, dP/dtmax, and dP/dtmin were compared between micromanometry, direct acquisition from the PA catheter (voltage acquisition), and re-digitization of the hemodynamic waveforms (tracing). Correlation between Swan and tracing was stronger than that of Millar and Swan. SBP, followed by HR, has the strongest correlation of any parameter for all three methods, while DBP appears to be the weakest. Bland-Altman analysis shows all parameters to have minimal biases that are within clinical limits. Interoperator and intraoperator variability was minimal. Digital right-heart catheterization (RHC) data can be used as a surrogate for micromanometric data under ideal conditions for hemodynamic measures in the time domain. Pre-existing RHC data can be re-digitized for more rigorous hemodynamic analysis.

Factors affecting outcomes in very low birth weight infants treated electively with nasal continuous positive airway pressure.

OBJECTIVE: Although interest in nasal continuous positive airway pressure (nCPAP) to avoid intubation is increasing, there is limited data regarding patient selection and outcome. We sought to determine the baseline parameters associated with failure. STUDY DESIGN: In all, 938 cases of elective nCPAP use were extracted from our registry. Two primary end points, Treatment Failure (need for intubation) and Bad Outcome (death, need for respiratory support at 40 weeks post conceptual age, grade 4 intraventricular hemorrhage or periventricular leucomalacia), and 12 potentially predictive baseline parameters were prospectively defined and evaluated using logistic regression. RESULT: Intubation occurred in 31%, and Bad Outcome occurred in 11%. Besides estimated gestational age (EGA), only a few variables were significant predictors in the multivariate models: Intubation (PaO(2)/FiO(2)<150 or pH< 7.25) and Bad Outcome (FiO(2), low weight for EGA). The relative risk doubled between infants of 34 and 26 weeks EGA and increased by about 50% for those meeting the other criteria. CONCLUSION: We hope these findings will help those using elective nCPAP to refine their practice and those considering its use in establishing reasonable guidelines, as well as be useful for designing clinical research.

[Electrochemical reduction of cytochrome P450s based on electrodes with immobilized substrates].

A new approach for the electrochemical reduction of cytochromes P450 (P450s, CYPs) with electrodes chemically modified with appropriate substrates of P450s ("reverse" electrodes) has been proposed. The method is based on the analysis of cyclic voltammograms, square wave voltammograms, amperograms and determination of such electrochemical characteristics as catalytic current and redox potential. The sensitivity of the proposed method is 0.2-1 nmol P450/electrode. The differences of maximal current and potentials in square wave voltammograms and catalytic current in amperometric measurements are more sensitive and reliable. Planar regime of screen-printed electrodes permits to use 20-60 microl of electrolyte volume. We investigated P450 2B4--benzphetamine or P450scc--cholesterol enzyme - substrate pairs. Electrochemical parameters of electrodes with nonspecific P450 substrate were differed from electrodes with appropriate substrates.

Thermophilic anaerobic digester with ultrafilter for solids stabilization.

A thermophilic anaerobic digester with ultrafilter (TADU) for solids separation offers potential advantages of higher VS destruction, biomass retention, and pathogen removal. However, potential disadvantages include ultrafilter fouling, decreasing flux, and high VFA concentrations. In this study, a thermophilic anaerobic digester coupled to a sintered titanium, cross-flow ultrafilter was operated for over five months. Dairy manure was digested (HRT of 23 days). The filtrate VFA concentration was low (220 mg/L as HAc), average VS destruction was 49%, and a low average effluent fecal coliform concentration of 10(2) MPN/100 mL was observed. The low coliform value may be beneficial if dewatered biosolids are used for livestock bedding since low pathogen counts help prevent mastitis. Ultrafilter fluxes of 40-80 L/m2-hr were maintained by cleaning using caustic (3.5% NaOH) followed by water and acid (3% phosphoric acid). Sand from livestock bedding was found to damage the pump and ultrafilter. If TADU were implemented at full scale, then replacing sand bedding with dewatered biosolids should be considered.

Acetylcholinesterase assay for rapid expression screening in liquid and solid media.

The synaptic enzyme acetylcholinesterase (AChE), which is the target of many insecticides and potential warfare agents, is implied in Alzheimer's disease and is a good potential candidate to be used in biosensors. This promotes a strong demand for production of recombinant AChE to be used in various studies. A promising expression system is the yeast Pichia pastoris, but the expression efficiency needs to be improved. Optimization studies require a rapid and efficient screening test to detect positive yeast colonies after transformation. Using indoxylacetate as a substrate, we designed a chromogenic test that is not interfered with by the culture media background color and, thus, is suitable for microplate screening. Moreover, it was possible to adapt the test for direct on-plate detection of AChE-expressing colonies.

Inducible nitric oxide synthase and blood pressure.

In the present studies, the influence of inducible nitric oxide synthase (NOS) inhibition with aminoguanidine on renal function and blood pressure was examined in rats. Intravenous aminoguanidine infusion (60 mg x kg-1 x hr-1) for 40 minutes to anesthetized Sprague-Dawley rats (n=7) resulted in no significant changes in mean arterial pressure or renal cortical blood flow, while medullary blood flow was slightly increased. Despite minimal effects on renal blood flow, urine flow was significantly decreased from 14.2+/-2.7 to 10.4+/-2.3 microL x min-1 x g kidney wt-1 during aminoguanidine infusion. To examine the possible effects of inducible NOS on blood pressure, aminoguanidine (10 mg x kg-1 x h-1 IV) was infused chronically into uninephrectomized rats maintained on a high salt (4.0% NaCl) diet. Mean arterial pressure significantly increased from 104+/-2 to 118+/-3 mm Hg after 6 days of aminoguanidine infusion (n=7) and returned to levels not different from those in the control group after 2 days of postcontrol infusion. Calcium-independent NOS activity in the renal medulla, a tissue that expresses inducible NOS in normal rats, was significantly decreased by 49% in the aminoguanidine-infused group (n=6) compared with that activity in the vehicle-infused control animals (n=6). In contrast, calcium-dependent NOS activity in the renal medulla was not significantly altered by aminoguanidine infusion, indicating specificity of aminoguanidine for inducible NOS in these experiments. In a final group of rats (n=5), oral L-arginine administration in drinking water (2% wt/vol) increased plasma arginine levels from 118+/-5 to 232+/-16 micromol/L and blocked the increase in arterial pressure after 6 days of aminoguanidine infusion. The present experiments provide evidence supporting a role for inducible NOS in the control of arterial pressure, possibly by renal tubular effects.

Intraventricular hemorrhage and high-frequency ventilation: a meta-analysis of prospective clinical trials.

OBJECTIVE: The association between high-frequency ventilation (HFV) and intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) has been debated. PURPOSE: To determine if premature neonates treated with HFV are at greater risk for developing IVH and/or PVL than neonates treated with conventional ventilation, we completed a meta-analysis of all prospective randomized control trials comparing HFV and conventional ventilation in the management of respiratory distress syndrome. METHODS: The meta-analysis included nine studies comparing HFV and conventional ventilation in the management of preterm neonates. To summarize the data, we calculated the difference in absolute risk for IVH and PVL between neonates treated with HFV and those treated with standard ventilation. These differences were combined to determine an overall difference in the absolute risk and its confidence interval. We examined the effect of estimated gestational age, birth weight, surfactant, and age at study entry on the results. Because one trial (HIFI study) was much larger than the other studies, it dominated the analysis, so we evaluated the data with and without including data from the HIFI trial. RESULTS: The occurrences of IVH and PVL ranged from 14% to 47% and 5% to 16%, respectively. This variation may be explained by the difference in the populations of neonates treated. The meta-analysis showed that use of HFV was associated with an increased risk of PVL (odds ratio = 1.7 with a confidence interval of 1.06 to 2.74), but not IVH or severe (> or = grade 3) IVH. When the results of the HIFI study were excluded, there were no differences between HFV and conventional ventilation in the occurrence of IVH or PVL. CONCLUSIONS: The association between HFV and adverse neurologic outcomes is primarily influenced by the results of the HIFI trial. Meta-analysis of more recent studies does not confirm the findings of the HIFI trial and suggests that HFV is not associated with increased occurrence of IVH or PVL.

Methotrexate-associated lymphoma in patients with rheumatoid arthritis: report of two cases.

This report describes 2 patients with longstanding seropositive rheumatoid arthritis (RA) treated with oral methotrexate (MTX) who developed large cell lymphoma of B cell phenotype. In situ hybridization studies showed nuclear staining for Epstein-Barr virus (EBV) within the malignant lymphoid cells. In both cases, the lymphoma was undetectable several weeks after diagnostic biopsy followed by discontinuation of MTX. These observations suggest that, in patients with RA who develop an EBV-associated lymphoproliferative disorder, a trial of discontinuation of immunosuppressive agents may be warranted before chemotherapy is considered. In addition, there is a need for a heightened awareness of the development of lymphoma in this patient population.

Characterization of cellular responses involved in reparative dentinogenesis in rat molars.

During primary dentin formation, differentiating primary odontoblasts secrete an organic matrix, consisting principally of type I collagen and non-collagenous proteins, that is capable of mineralizing at its distal front. In contrast to ameloblasts that form enamel and undergo programmed cell death, primary odontoblasts remain metabolically active in a functional tooth. When dentin is exposed to caries or by operative procedures, and when exposed dentinal tubules are treated with therapeutic dental materials, the original population of odontoblasts is often injured and destroyed. The characteristics of the replacement pool of cells that form reparative dentin and the biologic mechanisms that modulate the formation of this matrix are poorly understood. Based on the hypothesis that events governing primary dentinogenesis are reiterated during dentin repair, the present study was designed to test whether cells that form reparative dentin are odontoblast-like. Cervical cavities were prepared in rat first molars to generate reparative dentin, and animals were killed at various time intervals. In situ hybridization with gene-specific riboprobes for collagen types I and III was used to study de novo synthesis by cells at the injured dentin-pulp interface. Polyclonal antibodies raised against dentin sialoprotein (DSP), a dentin-specific protein that marks the odontoblast phenotype, were used in immunohistochemical experiments. Data from our temporal and spatial analyses indicated that cells forming reparative dentin synthesize type I but not type III collagen and are immunopositive for DSP. Our results suggest that cells that form reparative dentin are odontoblast-like.

The reliability of patient positioning for evaluating static radiologic parameters of the human pelvis.

OBJECTIVE: To determine the reproducibility of patient positioning on radiographically evaluated static configurations of the human pelvis. DESIGN: Repeat anteroposterior radiography of the human pelvis was performed in vivo. Comparative examinations were performed after 1 hr in one subject pool. A second sample underwent repeat examination after a mean of 18 days. SETTING: Outpatient private practice chiropractic clinic. SUBJECTS: Thirty-seven relatively asymptomatic subjects participated in the experiment. MAIN OUTCOME MEASURES: Millimetric evaluations were made for leg length inequality, right/left sacral discrepancies and right/left innominate differences. The null hypothesis was that the difference of the measurements from the two radiographs would be equal to zero. A paired t-test was used to analyze if there were any significant differences. The mean measured difference in millimeters and correlation coefficients were also determined for each variable. RESULTS: Individual variations for several roentgenometric parameters, including leg length inequality and pelvic torsion, did not reach statistical significance (p > .05) although minor millimetric discrepancies were recorded. Correlation coefficients, in most cases, were relatively high. CONCLUSION: A subject can be reliably positioned for repeat anteroposterior pelvic radiography for both 1 hr and 18-day intervals. The methodology described has applicability to full spine radiography when roentgenometric parameters of the pelvis are scrutinized.

Chiropractic management of a hypertensive patient.

OBJECTIVE: Although many chiropractors may treat patients who have concomitant hypertensive disease, there is a paucity of literature on the nuances of case management for these patients. We report a patient who underwent a course of chiropractic care with a previous diagnosis of chronic essential hypertension. CLINICAL FEATURES: A 38-yr-old male presented for chiropractic care with complaints of hypertension, drug-related side effects and lower back pain. He was also receiving concurrent medical care for his hypertension. INTERVENTION AND OUTCOME: The patient received specific contact, short lever arm spinal adjustments as the primary mode of chiropractic care. During the course of chiropractic treatment, the patient's need for hypertensive medication was reduced. The patient's medical physician gradually withdrew the medication over 2 months. CONCLUSION: Specific contact short lever arm spinal adjustments may cause a hypotensive effect in a medicated hypertensive patient that may lead to complications (e.g., hypotension). Since a medicated hypertensive patient's blood pressure may fall below normal while he or she is undergoing chiropractic care, it is advised that the blood pressure be closely monitored and medications adjusted, if necessary, by the patient's medical physician.

Temperature rise due to finishing of direct restorative materials.

An in vitro study was performed to evaluate the effect of four variables on the temperature rise produced by the finishing of restorations. The four variables were: restorative material, finishing agent, finishing time, and depth of dentin under the restoration. Class V preparations were cut on extracted premolars and restored with amalgam, composite, or glass ionomer cement. Finishing was done with wet pumice and cup, wet pumice and a brush, a grit rubber polishing point, and an aluminum oxide- coated disc. Finishing time was continuous or intermittent for up to 1 minute. Dentin thickness under the restoration was 0.5 mm to 3.0 mm. Amalgam produced the highest temperature rises at the pulp, while composite and glass ionomer were no different than the untreated (virgin) tooth. Aluminum oxide discs produced the largest temperature rise, wet pumice with a brush the least. Temperature rise increased almost linearly with continuous finishing, while intermittent finishing significantly reduced temperature rise in all cases. Thickness of remaining dentin was only significant for the amalgam restoration, and then only at 1.0 and 0.5 mm.