Quality of interhospital transport of the critically ill: impact of a Mobile Intensive Care Unit with a specialized retrieval team

Introduction: In order to minimize the additional risk of interhospital transport of critically ill patients, we started a mobile intensive care unit (MICU) with a specialized retrieval team, reaching out from our university hospital-based intensive care unit to our adherence region in March 2009. To evaluate the effects of this implementation, we performed a prospective audit comparing adverse events and patient stability during MICU transfers with our previous data on transfers performed by standard ambulance. Methods: All transfers performed by MICU from March 2009 until December 2009 were included. Data on 14 vital variables were collected at the moment of departure, arrival and 24 hours after admission. Variables before and after transfer were compared using the paired-sample T-test. Major deterioration was expressed as a variable beyond a predefined critical threshold and was analyzed using the McNemar test and the Wilcoxon Signed Ranks test. Results were compared to the data of our previous prospective study on interhospital transfer performed by ambulance. Results: A total of 74 interhospital transfers of ICU patients over a 10-month period were evaluated. An increase of total number of variables beyond critical threshold at arrival, indicating a worsening of condition, was found in 38 percent of patients. Thirty-two percent exhibited a decrease of one or more variables beyond critical threshold and 30% showed no difference. There was no correlation between patient status at arrival and the duration of transfer or severity of disease. ICU mortality was 28%. Systolic blood pressure, glucose and haemoglobin were significantly different at arrival compared to departure, although significant values for major deterioration were never reached. Compared to standard ambulance transfers of ICU patients, there were less adverse events: 12.5% vs. 34%, which in the current study were merely caused by technical (and not medical) problems. Although mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score was significantly higher, patients transferred by MICU showed less deterioration in pulmonary parameters during transfer than patients transferred by standard ambulance. Conclusions: Transfer by MICU imposes less risk to critically ill patients compared to transfer performed by standard ambulance and has, therefore, resulted in an improved quality of interhospital transport of ICU patients in the north-eastern part of the Netherlands

Folate reference interval estimation in the Dutch general population

Background: Folate functions as an enzyme co-factor within the one-carbon metabolic pathway, providing key metabolites required for DNA synthesis and methylation. Hence, insufficient intake of folate can negatively affect health. As correct interpretation of folate status is dependent on a well-established reference interval, we set out to perform a new estimation following the restandardization of the Roche folate assay against the international folate standard. Materials and methods: The folate reference interval was estimated using samples obtained from the Dutch population-based Lifelines cohort. The reference interval was estimated using two methods: a nonparametric estimation combined with bootstrap resampling and by fitting the data to a gamma distribution. The lower reference limit was verified in a patient cohort by combined measurement of folate and homocysteine. Results: Dependent on the method used for estimation and in- or exclusion of individuals younger than 21 years of age, the lower reference limit ranged from 6.8 to 7.3 nmol/L and the upper reference limit ranged from 26 to 38.5 nmol/L. Applying a lower reference limit of 7.3 nmol/L resulted in the following percentage of folate deficiencies over a period of 12 months: general practitioner 15.5% (IQR 4.0%), general hospital 12.8% (IQR 5.3%), academic hospital 9.6% (IQR 4.3%). Conclusions: We estimated the folate reference interval in the Dutch general population which is not affected by a folic acid fortification program and verified the obtained lower reference limit by homocysteine measurements. Based on our results, we propose a folate reference interval independent of age of 7.3-38.5 nmol/

Maternal and fetal brain contents of docosahexaenoic acid (DHA) and arachidonic acid (AA) at various essential fatty acid (EFA), DHA and AA dietary intakes during pregnancy in mice

We investigated essential fatty acids (EFA) and long-chain polyunsaturated fatty acids (LCP) in maternal and fetal brain as a function of EFA/LCP availability to the feto-maternal unit in mice. Diets varying in parent EFA, arachidonic acid (AA), and docosahexaenoic acid (DHA) were administered from day 3 prior to conception till day 15 of pregnancy. We concentrated on DHA, AA, Mead acid, and EFA-index [(omega-3+omega-6)/(omega-7+omega-9)] in maternal erythrocytes, maternal brain, and fetal brain. It was found that erythrocyte EFA/LCP sensitively reflects declining EFA/LCP status in pregnancy, although this decline was not apparent in maternal brain. Differences in erythrocyte EFA/LCP coincided with larger differences in fetal brain EFA/LCP as compared to EFA/LCP in maternal brain. Both maternal and fetal brains were affected by short-term EFA/LCP intake, but the developing fetal brain proved most sensitive. The inverse relationship between fetal brain AA and DHA suggests the need of a maternal dietary DHA/AA balance, at least in mice

Folate reference interval estimation in the Dutch general population

Background: Folate functions as an enzyme co-factor within the one-carbon metabolic pathway, providing key metabolites required for DNA synthesis and methylation. Hence, insufficient intake of folate can negatively affect health. As correct interpretation of folate status is dependent on a well-established reference interval, we set out to perform a new estimation following the restandardization of the Roche folate assay against the international folate standard. Materials and methods: The folate reference interval was estimated using samples obtained from the Dutch population-based Lifelines cohort. The reference interval was estimated using two methods: a nonparametric estimation combined with bootstrap resampling and by fitting the data to a gamma distribution. The lower reference limit was verified in a patient cohort by combined measurement of folate and homocysteine. Results: Dependent on the method used for estimation and in- or exclusion of individuals younger than 21 years of age, the lower reference limit ranged from 6.8 to 7.3 nmol/L and the upper reference limit ranged from 26 to 38.5 nmol/L. Applying a lower reference limit of 7.3 nmol/L resulted in the following percentage of folate deficiencies over a period of 12 months: general practitioner 15.5% (IQR 4.0%), general hospital 12.8% (IQR 5.3%), academic hospital 9.6% (IQR 4.3%). Conclusions: We estimated the folate reference interval in the Dutch general population which is not affected by a folic acid fortification program and verified the obtained lower reference limit by homocysteine measurements. Based on our results, we propose a folate reference interval independent of age of 7.3-38.5 nmol/

Future of Dutch NGS-Based Newborn Screening:Exploring the Technical Possibilities and Assessment of a Variant Classification Strategy

In this study, we compare next-generation sequencing (NGS) approaches (targeted panel (tNGS), whole exome sequencing (WES), and whole genome sequencing (WGS)) for application in newborn screening (NBS). DNA was extracted from dried blood spots (DBS) from 50 patients with genetically confirmed inherited metabolic disorders (IMDs) and 50 control samples. One hundred IMD-related genes were analyzed. Two data-filtering strategies were applied: one to detect only (likely) pathogenic ((L)P) variants, and one to detect (L)P variants in combination with variants of unknown significance (VUS). The variants were filtered and interpreted, defining true/false positives (TP/FP) and true/false negatives (TN/FN). The variant filtering strategies were assessed in a background cohort (BC) of 4833 individuals. Reliable results were obtained within 5 days. TP results (47 patient samples) for tNGS, WES, and WGS results were 33, 31, and 30, respectively, using the (L)P filtering, and 40, 40, and 38, respectively, when including VUS. FN results were 11, 13, and 14, respectively, excluding VUS, and 4, 4, and 6, when including VUS. The remaining FN were mainly samples with a homozygous VUS. All controls were TN. Three BC individuals showed a homozygous (L)P variant, all related to a variable, mild phenotype. The use of NGS-based workflows in NBS seems promising, although more knowledge of data handling, automated variant interpretation, and costs is needed before implementation.</p

Optimization of folic acid, vitamin B-12, and vitamin B-6 supplements in pediatric patients with sickle cell disease

Using homocysteine as a functional marker, we determined optimal folic acid, vitamin B-12, and vitamin B-6 dosages in 21 pediatric sickle cell disease (SCD) patients (11 HbSS, 10 HbSC; 7-16 years). Daily supplements of folic acid (400, 700, or 1,000 mug), vitamin B-12 (1, 3, or 5 U.S. 1989 RDA), and vitamin B-6 (1 or 3 U.S. 1989 RDA) were gradually increased in an 82-week dose-escalation study. Blood was taken at 9 occasions for measurements of erythrocyte (RBC) and serum folate, plasma vitamin B-12, whole-blood vitamin B-6, and plasma homocysteine. Augmentation of folic acid from 700 to 1,000 mug and vitamin B-12 from 3 to 5 RDA did not further decrease homocysteine. Percentages of patients exhibiting significant individual homocysteine decreases amounted to 43% (folic acid from 0 to 400 mug, vitamins B-12 and B-6 from 0 to 1 RDA), 14% (folic acid from 400 to 700 mug), 24% (vitamin B-12 from 1 to 3 RDA), and 18% (vitamin B-6 from 1 to 3 RDA). The lowest plasma homocysteine at 82 weeks was 5.9 +/- 2.2 mumol/L. Patients with HbSS had higher RBC folate than HbSC. The entire group exhibited an inverse relation between RBC folate and hemoglobin. We conclude that RBC folate is less valuable for folate status assessment in SCD patients. Optimal dosages are as follows: 700 mug folic acid (3.5-7 U.S. 1989 RDA), 3 U.S. 1989 RDA vitamin B-12 (4.2-6.0 mug), and 3 U.S. 1989 RDA vitamin B-6 (4.2-6.0 mg). A practical daily combination is 1 mg folic acid (4.3-8.5 U.S. 1998 RDA when taken with meals), 6 mug vitamin B-12 (2.5-5 U.S. 1998 RDA), and 6 mg vitamin B-6 (4.6-10 U.S. 1998 RDA). This combination may by simple and relatively inexpensive means reduce these patients' inherently high risk of endothelial damage

Радиационная стойкость нитевидных кристаллов SiGe, используемых для сенсоров физических величин

Приведены результаты исследования влияния облучения γ-квантами дозами до 1·10¹⁸ см⁻² и магнитного поля с индукцией до 14 Тл на электропроводность нитевидных кристаллов Si1-xGex в интервале температуры 4,2-300 К.Вивчено вплив опромінення γ-квантами (випромінювання Co⁶⁰) з дозами до 1·10¹⁸ см⁻² та магнітного поля з індукцією до 14 Тл на електропровідність ниткоподібних кристалів Si1-xGex (х = 0,03) з питомим опором 0,08,0,025 Ом·см в інтервалі температур 4,2 .300 К. Встановлено, що опір кристалів слабо змінюється в процесі опромінення дозами до 2·10¹⁷ см⁻², в той же час спостерігаються істотні зміни магнітоопору. На основі проведених досліджень запропоновано умови створення радіаційно стійких сенсорів деформації, дієздатних в умовах сильних магнітних полів.An influence of γ-irradiation (Co⁶⁰) with doze up to 1·10¹⁸ cm⁻² and magnetic field with induction up to 14 T on conduction of Si1-xGex (x = 0,03) whisker crystals with resistivity of 0,08-0,025 Ohm·cm in temperature range 4,2-300 K have been studied. It is shown that whisker crystals resistance faintly varies under irradiation with doze 2·10¹⁷ cm⁻², while their magnetoresistance substantially changes. The strain sensors stable to irradiation action operating in high magnetic fields on the base of the whiskers have been designed