Assessment of three frequently used blood glucose monitoring devices in clinical routine

Self-monitoring of blood glucose plays an important role in the management of diabetes and has been shown to improve metabolic control. The use of blood glucose meters in clinical practice requires sufficient reliability to allow adequate treatment. Direct comparison of different blood glucose meters in clinical practice, independent of the manufactures is scarce. We, therefore, aimed to evaluate three frequently used blood glucose meters in daily clinical practice.

Enamel matrix protein adsorption to root surfaces in the presence or absence of human blood

Background: The clinical use of an enamel matrix derivative (EMD) has been shown to promote formation of new cementum, periodontal ligament (PDL), and bone and to significantly enhance the clinical outcomes after regenerative periodontal surgery. It is currently unknown to what extent the bleeding during periodontal surgery may compete with EMD adsorption to root surfaces. The aim of this study is to evaluate the effect of blood interactions on EMD adsorption to root surfaces mimicking various clinical settings and to test their ability to influence human PDL cell attachment and proliferation. Methods: Teeth extracted for orthodontic reasons were subjected to ex vivo scaling and root planing and treated with 24% EDTA, EMD, and/or human blood in six clinically related settings to determine the ability of EMD to adsorb to root surfaces. Surfaces were analyzed for protein adsorption via scanning electron microscopy and immunohistochemical staining with an anti-EMD antibody. Primary human PDL cells were seeded on root surfaces and quantified for cell attachment and cell proliferation. Results: Plasma proteins from blood samples altered the ability of EMD to adsorb to root surfaces on human teeth. Samples coated with EMD lacking blood demonstrated a consistent even layer of EMD adsorption to the root surface. In vitro experiments with PDL cells demonstrated improved cell attachment and proliferation in all samples coated with EMD (irrespective of EDTA) when compared to samples containing human blood. Conclusion: Based on these findings, it is advised to minimize blood interactions during periodontal surgeries to allow better adsorption of EMD to root surfaces.

Effects of epinephrine, norepinephrine, and phenylephrine on microcirculatory blood flow in the gastrointestinal tract in sepsis

OBJECTIVE: The use of vasopressors for treatment of hypotension in sepsis may have adverse effects on microcirculatory blood flow in the gastrointestinal tract. The aim of this study was to measure the effects of three vasopressors, commonly used in clinical practice, on microcirculatory blood flow in multiple abdominal organs in sepsis. DESIGN: Random order, cross-over design. SETTING: University laboratory. SUBJECTS: Eight sedated and mechanically ventilated pigs. INTERVENTIONS: Pigs were exposed to fecal peritonitis-induced septic shock. Mesenteric artery flow was measured using ultrasound transit time flowmetry. Microcirculatory flow was measured in gastric, jejunal, and colon mucosa; jejunal muscularis; and pancreas, liver, and kidney using multiple-channel laser Doppler flowmetry. Each animal received a continuous intravenous infusion of epinephrine, norepinephrine, and phenylephrine in a dose increasing mean arterial pressure by 20%. The animals were allowed to recover for 60 mins after each drug before the next was started. MEASUREMENTS AND MAIN RESULTS: During infusion of epinephrine (0.8 +/- 0.2 mug/kg/hr), mean arterial pressure increased from 66 +/- 5 to 83 +/- 5 mm Hg and cardiac index increased by 43 +/- 9%. Norepinephrine (0.7 +/- 0.3 mug/kg/hr) increased mean arterial pressure from 70 +/- 4 to 87 +/- 5 mm Hg and cardiac index by 41 +/- 8%. Both agents caused a significant reduction in superior mesenteric artery flow (11 +/- 4%, p < .05, and 26 +/- 6%, p < .01, respectively) and in microcirculatory blood flow in the jejunal mucosa (21 +/- 5%, p < .01, and 23 +/- 3%, p < .01, respectively) and in the pancreas (16 +/- 3%, p < .05, and 8 +/- 3%, not significant, respectively). Infusion of phenylephrine (3.1 +/- 1.0 mug/kg/min) increased mean arterial pressure from 69 +/- 5 to 85 +/- 6 mm Hg but had no effects on systemic, regional, or microcirculatory flow except for a 30% increase in jejunal muscularis flow (p < .01). CONCLUSIONS: Administration of the vasopressors phenylephrine, epinephrine, and norepinephrine failed to increase microcirculatory blood flow in most abdominal organs despite increased perfusion pressure and-in the case of epinephrine and norepinephrine-increased systemic blood flow. In fact, norepinephrine and epinephrine appeared to divert blood flow away from the mesenteric circulation and decrease microcirculatory blood flow in the jejunal mucosa and pancreas. Phenylephrine, on the other hand, appeared to increase blood pressure without affecting quantitative blood flow or distribution of blood flow.

Prediction of hypertensive crisis based on average, variability and approximate entropy of 24-h ambulatory blood pressure monitoring

Approximate entropy (ApEn) of blood pressure (BP) can be easily measured based on software analysing 24-h ambulatory BP monitoring (ABPM), but the clinical value of this measure is unknown. In a prospective study we investigated whether ApEn of BP predicts, in addition to average and variability of BP, the risk of hypertensive crisis. In 57 patients with known hypertension we measured ApEn, average and variability of systolic and diastolic BP based on 24-h ABPM. Eight of these fifty-seven patients developed hypertensive crisis during follow-up (mean follow-up duration 726 days). In bivariate regression analysis, ApEn of systolic BP (P<0.01), average of systolic BP (P=0.02) and average of diastolic BP (P=0.03) were significant predictors of hypertensive crisis. The incidence rate ratio of hypertensive crisis was 14.0 (95% confidence interval (CI) 1.8, 631.5; P<0.01) for high ApEn of systolic BP as compared to low values. In multivariable regression analysis, ApEn of systolic (P=0.01) and average of diastolic BP (P<0.01) were independent predictors of hypertensive crisis. A combination of these two measures had a positive predictive value of 75%, and a negative predictive value of 91%, respectively. ApEn, combined with other measures of 24-h ABPM, is a potentially powerful predictor of hypertensive crisis. If confirmed in independent samples, these findings have major clinical implications since measures predicting the risk of hypertensive crisis define patients requiring intensive follow-up and intensified therapy.

Blood donor screening: how to decrease the risk of transfusion-transmitted hepatitis B virus?

QUESTIONS UNDER STUDY: The risk of transfusion-transmitted HBV remains significant in Switzerland, where routine screening for hepatitis B virus (HBV) in blood donations relies solely on serological hepatitis B surface antigen (HBsAg) testing. This study was designed to determine the prevalence of anti-hepatitis B core (anti-HBc) and HBV nucleic acid testing (NAT) positive donations in two different Swiss donor populations, to help in deciding whether supplemental testing may bring additional safety to blood products. METHODS: In a first population of donors, 18143 consecutive donations were screened initially for HBsAg, anti-HBc (with one EIA assay) and with HBV NAT in minipools of 24 donations. The screening repeatedly reactive anti-HBc donations were then "confirmed" with two supplemental anti-HBc assays, an anti-hepatitis B surface assay (anti-HBs) and with single donation HBV NAT. In a second population of donors, 4186 consecutive donations were screened initially with two different anti-HBc assays in addition to the mandatory HBsAg screening test. The screening repeatedly reactive donations with at least one anti-HBc assay were tested for anti-HBs. RESULTS: In the first subset of 18143 donations, 17593 (97.0%) were negative for HBsAg, anti-HBc and HBV NAT in minipools. 549 (3.0%) were HBsAg and HBV NAT negative, but repeatedly reactive for anti-HBc. Of these 549 donations, 287 could not be "confirmed" with two additional anti-HBc assays and were negative with an anti-HBs assay, as well as with single donation HBV NAT. Only 211 (1.2% of the total screened donations) were "confirmed" positive with at least one of two supplemental anti-HBc assays. One repeatedly reactive HBsAg donation, from a first-time donor, was confirmed positive for HBsAg and anti-HBc, as well as with single donation HBV NAT. In the second subset of 4186 donations, 4014 (95.9%) were screened negative for HBsAg and for anti-HBc, tested with two independent anti-HBc assays. 172 donations (4.1%) were HBsAg negative but repeatedly reactive with at least one of the two anti-HBc assays. Of these 172 samples, 86 were reactive with the first anti-HBc assay only, 13 were reactive with the second anti-HBc assay only and 73 (1.7% of the total screened donations) were "confirmed" positive with both anti-HBc assays. CONCLUSION: The prevalence of anti-HBc "confirmed" positive donations in the two Swiss blood donor populations studied was low (<2%) and we found only one HBV NAT positive (HBsAg positive) donation among more than 18000. Concerning blood product safety, an increase in the deferral rate of less than 2% of anti-HBc positive, potentially infectious donors, would in our opinion make routine anti-HBc testing of blood donations cost-effective. There is however still a need for more specific assays to avoid an unacceptably high deferral rate of "false" positive donors. In contrast, the introduction of HBV NAT in minipools gives minimal benefit due to the inadequate sensitivity of the assay. It remains to evaluate more extensively the value of individual donation NAT, alone or in addition to anti-HBc, as supplemental testing in the context of several Swiss blood donor populations.

Addition of dextran sulfate to blood cardioplegia attenuates reperfusion injury in a porcine model of cardiopulmonary bypass

OBJECTIVE: Contact of blood with artificial surfaces and air as well as ischemia/reperfusion injury to the heart and lungs mediate systemic and local inflammation during cardiopulmonary bypass (CPB). Activation of complement and coagulation cascades leads to and accompanies endothelial cell damage. Therefore, endothelial-targeted cytoprotection with the complement inhibitor and endothelial protectant dextran sulfate (DXS, MW 5000) may attenuate CBP-associated myocardial and pulmonary injury. METHODS: Eighteen pigs (DXS, n=10; phosphate buffered saline [PBS], n=8) underwent standard cardiopulmonary bypass. After aortic cross-clamping, cardiac arrest was initiated with modified Buckberg blood cardioplegia (BCP), repeated after 30 and 60 min with BCP containing either DXS (300 mg/10 ml, equivalent to 5mg/kg) or 10 ml of PBS. Following 30 min reperfusion, pigs were weaned from CPB. During 2h of observation, cardiac function was monitored by echocardiography and invasive pressure measurements. Inflammatory and coagulation markers were assessed regularly. Animals were then sacrificed and heart and lungs analyzed. RESULTS: DXS significantly reduced CK-MB levels (43.4+/-14.8 ng/ml PBS, 35.9+/-11.1 ng/ml DXS, p=0.042) and significantly diminished cytokine release: TNFalpha (1507.6+/-269.2 pg/ml PBS, 222.1+/-125.6 pg/ml DXS, p=0.0071), IL1beta (1081.8+/-203.0 pg/ml PBS, 110.7+/-79.4 pg/ml DXS, p=0.0071), IL-6 (173.0+/-91.5 pg/ml PBS, 40.8+/-19.4 pg/ml DXS, p=0.002) and IL-8 (304.6+/-81.3 pg/ml PBS, 25.4+/-14.2 pg/ml DXS, p=0.0071). Tissue endothelin-1 levels were significantly reduced (6.29+/-1.90 pg/100mg PBS, 3.55+/-1.15 pg/100mg DXS p=0.030) as well as thrombin-anti-thrombin formation (20.7+/-1.0 microg/ml PBS, 12.8+/-4.1 microg/ml DXS, p=0.043). Also DXS reduced cardiac and pulmonary complement deposition, neutrophil infiltration, hemorrhage and pulmonary edema (measured as lung water content, 81+/-3% vs 78+/-3%, p=0.047), indicative of attenuated myocardial and pulmonary CPB-injury. Diastolic left ventricular function (measured as dp/dt(min)), pulmonary artery pressure (21+/-3 mmHg PBS, 19+/-3 mmHg DXS, p=0.002) and right ventricular pressure (21+/-1 mmHg PBS, 19+/-3 mmHg DXS p=0.021) were significantly improved with the use of DXS. CONCLUSIONS: Addition of DXS to the BCP solution ameliorates post-CPB injury and to a certain extent improves cardiopulmonary function. Endothelial protection in addition to myocyte protection may improve post-CPB outcome and recovery.

Monitoring thrombin generation by electrochemistry: development of an amperometric biosensor screening test for plasma and whole blood

BACKGROUND: Complete investigation of thrombophilic or hemorrhagic clinical presentations is a time-, apparatus-, and cost-intensive process. Sensitive screening tests for characterizing the overall function of the hemostatic system, or defined parts of it, would be very useful. For this purpose, we are developing an electrochemical biosensor system that allows measurement of thrombin generation in whole blood as well as in plasma. METHODS: The measuring system consists of a single-use electrochemical sensor in the shape of a strip and a measuring unit connected to a personal computer, recording the electrical signal. Blood is added to a specific reagent mixture immobilized in dry form on the strip, including a coagulation activator (e.g., tissue factor or silica) and an electrogenic substrate specific to thrombin. RESULTS: Increasing thrombin concentrations gave standard curves with progressively increasing maximal current and decreasing time to reach the peak. Because the measurement was unaffected by color or turbidity, any type of blood sample could be analyzed: platelet-poor plasma, platelet-rich plasma, and whole blood. The test strips with the predried reagents were stable when stored for several months before testing. Analysis of the combined results obtained with different activators allowed discrimination between defects of the extrinsic, intrinsic, and common coagulation pathways. Activated protein C (APC) predried on the strips allowed identification of APC-resistance in plasma and whole blood samples. CONCLUSIONS: The biosensor system provides a new method for assessing thrombin generation in plasma or whole blood samples as small as 10 microL. The assay is easy to use, thus allowing it to be performed in a point-of-care setting.

Assessment of splanchnic blood flow using magnetic resonance imaging

BACKGROUND AND AIMS: The splanchnic circulation has an important function in the body under both physiological and pathophysiological conditions. Despite its importance, no reliable noninvasive procedures for estimating splanchnic circulation have been established. The aim of this study was to evaluate MRI as a tool for assessing intra-abdominal blood flows of the aorta, portal vein (VPO) and the major intestinal and hepatic vessels. METHODS: In nine healthy volunteers, the proximal aorta (AOP) and distal abdominal aorta (AOD), superior mesenteric artery (SAM), celiac trunk (CTR), hepatic arteries (common and proper hepatic arteries, AHC and AHP, respectively), and VPO were localized on contrast-enhanced magnetic resonance angiography images. Volumetric flow was measured using a two-dimensional cine echocardiogram-gated phase contrast technique. Measurements were taken before and 30 min after continuous intravenous infusion of somatostatin (250 microg/h) and were independently evaluated by two investigators. RESULTS: Blood flow measured by MRI in the VPO, SAM, AOP, AHP, and CTR significantly decreased after drug infusion. Flows in the AOD and AHC showed a tendency to decrease (P>0.05). Interrater agreement on flows in MRI was very good for large vessels (VPO, AOP, and AOD), with a concordance correlation coefficient of 0.94, as well as for smaller vessels such as the CTR, AHC, AHP, and SAM (concordance correlation coefficient =0.78). CONCLUSION: Somatostatin-induced blood flow changes in the splanchnic region were reliably detected by MRI. MRI may be useful for the noninvasive assessment of blood flow changes in the splanchnic region.

Comparison of arterial blood pressure measurements and hypertension scores obtained by use of three indirect measurement devices in hospitalized dogs

OBJECTIVE: To evaluate the agreement of blood pressure measurements and hypertension scores obtained by use of 3 indirect arterial blood pressure measurement devices in hospitalized dogs. Design-Diagnostic test evaluation. ANIMALS: 29 client-owned dogs. PROCEDURES: 5 to 7 consecutive blood pressure readings were obtained from each dog on each of 3 occasions with a Doppler ultrasonic flow detector, a standard oscillometric device (STO), and a high-definition oscillometric device (HDO). RESULTS: When the individual sets of 5 to 7 readings were evaluated, the coefficient of variation for systolic arterial blood pressure (SAP) exceeded 20% for 0% (Doppler), 11 % (STO), and 28% (HDO) of the sets of readings. After readings that exceeded a 20% coefficient of variation were discarded, repeatability was within 25 (Doppler), 37 (STO), and 39 (HDO) mm Hg for SAP. Correlation of mean values among the devices was between 0.47 and 0.63. Compared with Doppler readings, STO underestimated and HDO overestimated SAP. Limits of agreement between mean readings of any 2 devices were wide. With the hypertension scale used to score SAP, the intraclass correlation of scores was 0.48. Linear-weighted inter-rater reliability between scores was 0.40 (Doppler vs STO), 0.38 (Doppler vs HDO), and 0.29 (STO vs HDO). CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggested that no meaningful clinical comparison can be made between blood pressure readings obtained from the same dog with different indirect blood pressure measurement devices.

Depolymerization of malarial hemozoin: a novel reaction initiated by blood schizontocidal antimalarials

Malaria parasite digests hemoglobin and utilizes the globin part for its nutritional requirements. Heme released as a byproduct of hemoglobin degradation is detoxified by polymerization into a crystalline, insoluble pigment, known as hemozoin. We have identified a novel reaction of depolymerization of hemozoin to heme. This reaction is initiated by the interaction of blood schizonticidal antimalarial drugs with the malarial hemozoin. The reaction has been confirmed, with the purified hemozoin as well as the lysate of the malaria parasite. Pigment breakdown was studied by infrared spectroscopy, thin-layer chromatography and spectrophotometric analysis. It was complete within 2 h of drug exposure, which explains the selective sensitivity of late stages (trophozoites and schizonts) of malarial parasites loaded with the hemozoin pigment to the toxic action of these drugs. It is suggested that the failure of the parasite heme detoxification system due to this reaction results in the accumulation of toxic heme, which alone, or complexed with the antimalarial leads to the death of malaria parasite.

Circadian blood pressure during the early course of type 1 diabetes. Analysis of 1,011 ambulatory blood pressure recordings in 354 adolescents and young adults

OBJECTIVE Little information is available on the early course of hypertension in type 1 diabetes. The aim of our study, therefore, was to document circadian blood pressure profiles in patients with a diabetes duration of up to 20 years and relate daytime and nighttime blood pressure to duration of diabetes, BMI, insulin therapy, and HbA1c. RESEARCH DESIGN AND METHODS Ambulatory profiles of 24-h blood pressure were recorded in 354 pediatric patients with type 1 diabetes (age 14.6 +/- 4.2 years, duration of diabetes 5.6 +/- 5.0 years, follow-up for up to 9 years). A total of 1,011 profiles were available for analysis from patients not receiving antihypertensive medication. RESULTS Although daytime mean systolic pressure was significantly elevated in diabetic subjects (+3.1 mmHg; P < 0.0001), daytime diastolic pressure was not different from from the height- and sex-adjusted normal range (+0.1 mmHg, NS). In contrast, both systolic and diastolic nighttime values were clearly elevated (+7.2 and +4.2 mmHg; P < 0.0001), and nocturnal dipping was reduced (P < 0.0001). Systolic blood pressure was related to overweight in all patients, while diastolic blood pressure was related to metabolic control in young adults. Blood pressure variability was significantly lower in girls compared with boys (P < 0.01). During follow-up, no increase of blood pressure was noted; however, diastolic nocturnal dipping decreased significantly (P < 0.03). Mean daytime blood pressure was significantly related to office blood pressure (r = +0.54 for systolic and r = +0.40 for diastolic pressure); however, hypertension was confirmed by ambulatory blood pressure measurement in only 32% of patients with elevated office blood pressure. CONCLUSIONS During the early course of type 1 diabetes, daytime blood pressure is higher compared with that of healthy control subjects. The elevation of nocturnal values is even more pronounced and nocturnal dipping is reduced. The frequency of white-coat hypertension is high among adolescents with diabetes, and ambulatory blood pressure monitoring avoids unnecessary antihypertensive treatment.

Intraoperative Continuous Norepinephrine Infusion Combined with Restrictive Deferred Hydration Significantly Reduces the Need for Blood Transfusion in Patients Undergoing Open Radical Cystectomy: Results of a Prospective Randomised Trial

BACKGROUND Open radical cystectomy (ORC) is associated with substantial blood loss and a high incidence of perioperative blood transfusions. Strategies to reduce blood loss and blood transfusion are warranted. OBJECTIVE To determine whether continuous norepinephrine administration combined with intraoperative restrictive hydration with Ringer's maleate solution can reduce blood loss and the need for blood transfusion. DESIGN, SETTING, AND PARTICIPANTS This was a double-blind, randomised, parallel-group, single-centre trial including 166 consecutive patients undergoing ORC with urinary diversion (UD). Exclusion criteria were severe hepatic or renal dysfunction, congestive heart failure, and contraindications to epidural analgesia. INTERVENTION Patients were randomly allocated to continuous norepinephrine administration starting with 2 μg/kg per hour combined with 1 ml/kg per hour until the bladder was removed, then to 3 ml/kg per hour of Ringer's maleate solution (norepinephrine/low-volume group) or 6 ml/kg per hour of Ringer's maleate solution throughout surgery (control group). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Intraoperative blood loss and the percentage of patients requiring blood transfusions perioperatively were assessed. Data were analysed using nonparametric statistical models. RESULTS AND LIMITATIONS Total median blood loss was 800 ml (range: 300-1700) in the norepinephrine/low-volume group versus 1200 ml (range: 400-2800) in the control group (p<0.0001). In the norepinephrine/low-volume group, 27 of 83 patients (33%) required an average of 1.8 U (±0.8) of packed red blood cells (PRBCs). In the control group, 50 of 83 patients (60%) required an average of 2.9 U (±2.1) of PRBCs during hospitalisation (relative risk: 0.54; 95% confidence interval [CI], 0.38-0.77; p=0.0006). The absolute reduction in transfusion rate throughout hospitalisation was 28% (95% CI, 12-45). In this study, surgery was performed by three high-volume surgeons using a standardised technique, so whether these significant results are reproducible in other centres needs to be shown. CONCLUSIONS Continuous norepinephrine administration combined with restrictive hydration significantly reduces intraoperative blood loss, the rate of blood transfusions, and the number of PRBC units required per patient undergoing ORC with UD.

A patient-specific study of type-B aortic dissection: evaluation of true-false lumen blood exchange

BACKGROUND Aortic dissection is a severe pathological condition in which blood penetrates between layers of the aortic wall and creates a duplicate channel - the false lumen. This considerable change on the aortic morphology alters hemodynamic features dramatically and, in the case of rupture, induces markedly high rates of morbidity and mortality. METHODS In this study, we establish a patient-specific computational model and simulate the pulsatile blood flow within the dissected aorta. The k-ω SST turbulence model is employed to represent the flow and finite volume method is applied for numerical solutions. Our emphasis is on flow exchange between true and false lumen during the cardiac cycle and on quantifying the flow across specific passages. Loading distributions including pressure and wall shear stress have also been investigated and results of direct simulations are compared with solutions employing appropriate turbulence models. RESULTS Our results indicate that (i) high velocities occur at the periphery of the entries; (ii) for the case studied, approximately 40% of the blood flow passes the false lumen during a heartbeat cycle; (iii) higher pressures are found at the outer wall of the dissection, which may induce further dilation of the pseudo-lumen; (iv) highest wall shear stresses occur around the entries, perhaps indicating the vulnerability of this region to further splitting; and (v) laminar simulations with adequately fine mesh resolutions, especially refined near the walls, can capture similar flow patterns to the (coarser mesh) turbulent results, although the absolute magnitudes computed are in general smaller. CONCLUSIONS The patient-specific model of aortic dissection provides detailed flow information of blood transport within the true and false lumen and quantifies the loading distributions over the aorta and dissection walls. This contributes to evaluating potential thrombotic behavior in the false lumen and is pivotal in guiding endovascular intervention. Moreover, as a computational study, mesh requirements to successfully evaluate the hemodynamic parameters have been proposed.

Therapeutic drug monitoring of once daily aminoglycoside dosing: comparison of two methods and investigation of the optimal blood sampling strategy.

PURPOSE Therapeutic drug monitoring of patients receiving once daily aminoglycoside therapy can be performed using pharmacokinetic (PK) formulas or Bayesian calculations. While these methods produced comparable results, their performance has never been checked against full PK profiles. We performed a PK study in order to compare both methods and to determine the best time-points to estimate AUC0-24 and peak concentrations (C max). METHODS We obtained full PK profiles in 14 patients receiving a once daily aminoglycoside therapy. PK parameters were calculated with PKSolver using non-compartmental methods. The calculated PK parameters were then compared with parameters estimated using an algorithm based on two serum concentrations (two-point method) or the software TCIWorks (Bayesian method). RESULTS For tobramycin and gentamicin, AUC0-24 and C max could be reliably estimated using a first serum concentration obtained at 1 h and a second one between 8 and 10 h after start of the infusion. The two-point and the Bayesian method produced similar results. For amikacin, AUC0-24 could reliably be estimated by both methods. C max was underestimated by 10-20% by the two-point method and by up to 30% with a large variation by the Bayesian method. CONCLUSIONS The ideal time-points for therapeutic drug monitoring of once daily administered aminoglycosides are 1 h after start of a 30-min infusion for the first time-point and 8-10 h after start of the infusion for the second time-point. Duration of the infusion and accurate registration of the time-points of blood drawing are essential for obtaining precise predictions.

Associations of ambulatory blood pressure with urinary caffeine and caffeine metabolite excretions.

Intake of caffeinated beverages might be associated with reduced cardiovascular mortality possibly via the lowering of blood pressure. We estimated the association of ambulatory blood pressure with urinary caffeine and caffeine metabolites in a population-based sample. Families were randomly selected from the general population of Swiss cities. Ambulatory blood pressure monitoring was conducted using validated devices. Urinary caffeine, paraxanthine, theophylline, and theobromine excretions were measured in 24 hours urine using ultrahigh performance liquid chromatography tandem mass spectrometry. We used mixed models to explore the associations of urinary excretions with blood pressure although adjusting for major confounders. The 836 participants (48.9% men) included in this analysis had mean age of 47.8 and mean 24-hour systolic and diastolic blood pressure of 120.1 and 78.0 mm Hg. For each doubling of caffeine excretion, 24-hour and night-time systolic blood pressure decreased by 0.642 and 1.107 mm Hg (both P values <0.040). Similar inverse associations were observed for paraxanthine and theophylline. Adjusted night-time systolic blood pressure in the first (lowest), second, third, and fourth (highest) quartile of paraxanthine urinary excretions were 110.3, 107.3, 107.3, and 105.1 mm Hg, respectively (P trend <0.05). No associations of urinary excretions with diastolic blood pressure were generally found, and theobromine excretion was not associated with blood pressure. Anti-hypertensive therapy, diabetes mellitus, and alcohol consumption modify the association of caffeine urinary excretion with systolic blood pressure. Ambulatory systolic blood pressure was inversely associated with urinary excretions of caffeine and other caffeine metabolites. Our results are compatible with a potential protective effect of caffeine on blood pressure.