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Background Studies from several countries show that self-management of vitamin K antagonist (e.g., warfarin) therapy reduce the risk of complications compared with conventional management. Objectives The aim of this study was to investigate the quality of warfarin management when patients were transferred from conventional management to self-management in Norway. In addition, quality of life (QoL) before and after 2 years of warfarin self-management was investigated. Materials and Methods The study was longitudinal with a retrospective and prospective design where 126 patients on conventional management of long-term warfarin therapy underwent a 21-week training program of warfarin self-management followed by 2 years of self-management. The outcomes of the study were time in therapeutic range (TTR), the variance of international normalized ratio (INR) values, extreme INR values (INR ≤ 1.5 and ≥ 5), complications, and QoL, comparing the 2-year period of the conventional management with the 2-year period with the self-management. Results The median TTR was higher during self-management compared with conventional management (78.1% vs. 65.9%, respectively, p Conclusion We used five different measures and found improved quality of warfarin self-management 2 years after patients were transferred from the conventional management.

The National Diabetes Plan 2017-21 has implemented measures to improve diagnosis and follow-up of persons with type 2 diabetes by the primary health services. The objective of this study was to explore the experiences and thoughts of Norwegian general practitioners (GPs) with regard to diagnosis and follow-up of this patient group.In this qualitative study, three focus-group interviews were conducted with a total of 17 GPs. The interviews were recorded, transcribed and analysed using systematic text condensation.The GPs reported having a busy daily schedule that rarely allowed for targeted identification of patients in the risk zone to be prioritised. They described a patient-centred diabetes care, in which motivating for lifestyle change was considered a necessary but demanding task. The doctors identified the need to find a balance between following the general clinical guidelines on the one hand and individually adapting the follow-up to each patient on the other. Furthermore, the participants reported being less updated on current medical knowledge than they wanted, due to time constraints.The GPs in the study described a patient-centred diabetes care that was driven by clinical experience. The guidelines have an advisory, but not mandatory function. This approach enables personalised and adapted treatment, but could also be a contributory cause of the failure to provide sufficient follow-up as required by the national guidelines.

BACKGROUND The National Diabetes Plan 2017-21 has implemented measures to improve diagnosis and follow-up of persons with type 2 diabetes by the primary health services. The objective of this study was to explore the experiences and thoughts of Norwegian general practitioners (GPs) with regard to diagnosis and follow-up of this patient group. MATERIAL AND METHOD In this qualitative study, three focus-group interviews were conducted with a total of 17 GPs. The interviews were recorded, transcribed and analysed using systematic text condensation. RESULTS The GPs reported having a busy daily schedule that rarely allowed for targeted identification of patients in the risk zone to be prioritised. They described a patient-centred diabetes care, in which motivating for lifestyle change was considered a necessary but demanding task. The doctors identified the need to find a balance between following the general clinical guidelines on the one hand and individually adapting the follow-up to each patient on the other. Furthermore, the participants reported being less updated on current medical knowledge than they wanted, due to time constraints. INTERPRETATION The GPs in the study described a patient-centred diabetes care that was driven by clinical experience. The guidelines have an advisory, but not mandatory function. This approach enables personalised and adapted treatment, but could also be a contributory cause of the failure to provide sufficient follow-up as required by the national guidelines.

Sensitivity and specificity of rapid antigen detection tests (RADTs) for detection of group A hemolytic streptococcus (GAS) vary. The purpose is to present the first SKUP (Scandinavian evaluation of laboratory equipment for point of care testing) evaluations concerning the assessment of the diagnostic performance and user-friendliness of two RADTs for detection of GAS when used under real-life conditions in primary health care. Throat samples were collected in duplicates at primary health care centers (PHCCs) from patients with symptoms of pharyngitis. The performance of QuickVue Dipstick Strep A test (307 samples) and DIAQUICK Strep A Blue Dipstick (348 samples) was evaluated using culture results at a clinical microbiology laboratory as comparison. The user-friendliness was evaluated using a questionnaire. The diagnostic sensitivity was 92% (90% confidence interval (CI) 87–96%) and 72% (90% CI 65–79%), while the diagnostic specificity was 86% (90% CI 81–90%) and 98% (90% CI 96–99%) for QuickVue Dipstick Strep A test and DIAQUICK Strep A Blue Dipstick, respectively. Both RADTs obtained acceptable assessments for user-friendliness and fulfilled SKUP’s quality goal for user-friendliness. The diagnostic sensitivity for QuickVue Dipstick Strep A test and the diagnostic specificity for DIAQUICK Strep A Blue Dipstick in this objective and supplier-independent evaluation were higher compared with previous meta-analyses of RADTs. However, the diagnostic specificity for QuickVue Dipstick Strep A test and the diagnostic sensitivity for DIAQUICK Strep A Blue Dipstick were lower compared with previous meta-analyses of RADTs.

Background:Many pharmacy services involve laboratory testing using point-of-care (POC) instruments. Our aim was to describe the implementation of quality control of the HbA1c POC instruments and investigate the performance in internal quality control (IQC) and external quality control (EQA) for HbA1c POC instruments in Norwegian community pharmacies.Methods:Two project pharmacists from each of 11 pharmacies participated in a training program covering capillary blood sampling, how to use the POC HbA1c instrument (DCA Vantage) and IQC and EQA. The pharmacies were enrolled in an EQA program for HbA1c, and their performance was compared with that of general practitioners’ (GP) offices.Results:Two of 89 (2.2%) IQC measurements were outside the acceptance interval. Seven out of 11 pharmacies sent in results in EQA in all the three surveys during six months. Two pharmacies did not analyze the control material in any of the surveys, one pharmacy analyzed the control material in one of the surveys, and one pharmacy analyzed two of the surveys. Of these pharmacies, 56-100% obtained “very good” evaluation for trueness and 71-100% obtained “very good” evaluation for precision. The corresponding numbers for GP offices were 75-87% for trueness and 84-94% for precision. No pharmacies obtained a “poor” evaluation.Conclusions:Norwegian community pharmacies can perform IQC and EQA on a HbA1c POC instrument, and the performance is comparable with that of GP offices. The compliance in the EQA surveys was modest, but the duration of the study and participation in the EQA program was probably too short to implement all the new procedures for all pharmacies.

BACKGROUND The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) European Biological Variation Study (EuBIVAS) has been established to deliver rigorously determined biological variation (BV) indices. EuBIVAS determined BV for serum creatinine using the enzymatic and alkaline picrate measurement methods. METHOD In total, 91 healthy individuals (38 males, 53 females; age range, 21–69 years) were bled for 10 consecutive weeks at 6 European laboratories. An equivalent protocol was followed at each center. Sera were stored at −80 °C before analysis. Analyses for each patient were performed in duplicate within a single run on an ADVIA 2400 system (San Raffaele Hospital, Milan). The data were subjected to outlier and homogeneity analysis before performing CV-ANOVA to determine BV and analytical variation (CVA) estimates with confidence intervals (CI). RESULTS The within-subject BV estimates [CVI (95% CI)] were similar for enzymatic [4.4% (4.2–4.7)] and alkaline picrate [4.7% (4.4–4.9)] methods and lower than the estimate presently available online (CVI = 5.9%). No significant male/female BV differences were found. Significant differences were observed in mean creatinine values between men and women and between Turkish individuals and those of other nationalities. Between-subject BV (CVG) estimates, stratified accordingly, produced CVG values similar to historical BV data. CVA was 1.1% for the enzymatic and 4.4% for alkaline picrate methods, indicating that alkaline picrate methods fail to fulfill analytical performance specifications for imprecision (CVAPS). CONCLUSIONS The serum creatinine CVI obtained by EuBIVAS specifies a more stringent CVAPS than previously identified. The alkaline picrate method failed to meet this CVAPS, raising questions regarding its future use.

Background Healthcare services such as diabetes risk-assessment are increasingly common in community pharmacies. Knowledge of community pharmacists’ experiences of such services could ease the implementation of a larger-scale service. Objectives To explore Norwegian pharmacists’ experience of a diabetes risk-assessment service, including analytical quality control, in a community-pharmacy setting. Methods Three focus-group interviews were conducted in Norway between August and September 2017. Systematic text condensation was used, an analytic approach well suited for thematic content analysis across interview data. Fourteen pharmacists took part, recruited from a project offering a diabetes risk-assessment service, including measurements of Glycated hemoglobin A1c (HbA1c), in Norwegian community pharmacies. Results The pharmacists emphasized the importance of using their knowledge and skills to promote good health. They considered offering this service as being compatible with their role as pharmacists. As communication is an essential part of their work, the pharmacists evaluated their communication skills as being good. Nevertheless, how to communicate the offering of this service was seen as a challenge, for instance recruiting participants and communicating in an understandable and professional way. Inclusion of the whole pharmacy staff as a team was experienced as an important success factor for implementation of a risk-assessment service. Analytical quality control was perceived as being a natural part of their job and a manageable task. Conclusions Offering a diabetes risk-assessment service is in line with the way a selected group of Norwegian community pharmacists perceived their professional role. However, they were uncomfortable recruiting participants, and expressed the wish for more support from the pharmacy chain. Our results add performance of analytical quality control as part of the ongoing development involving expansion of pharmacists' professional role. Future implementation studies may also benefit from giving both the pharmacy staff and customers sufficient time to familiarize themselves with the new service before measuring effects. Keywords Community pharmacy, healthcare services, diabetes risk assessment, focus groups, pharmacists' experiences, analytical quality control publishedVersion

BACKGROUNDThe optimal situation in external quality assessment (EQA) is to use commutable materials. No previous study has examined the commutability of a whole-blood material for point-of-care (POC) testing. The aim of this study was to determine the commutability of the Norwegian Quality Improvement of Laboratory Examinations (Noklus) organization's “in-house” whole-blood EQA material for C-reactive protein (CRP), glucose, and hemoglobin for frequently used POC instruments in Norway and to determine the possibility of using a common target value for each analyte.METHODSThe study was performed according to the Clinical and Laboratory Standards Institute guidelines. The EQA material was pooled stabilized EDTA venous whole-blood containing different concentrations of the analytes. The EQA material and native routine patient samples were analyzed using 17 POC and 3 hospital instruments. The commutability was assessed using Deming regression analysis with 95% prediction intervals for each instrument comparison.RESULTSThe EQA material was commutable for all CRP and hemoglobin POC instruments, whereas for glucose the material was commutable for all POC instruments at the lowest concentration analyzed [126.0 mg/dL (7.0 mmol/L)] and for 3 POC instruments at all of the concentrations analyzed.CONCLUSIONSNoklus EQA participants using CRP and hemoglobin POC instruments now receive results that are compared with a reference target value, whereas the results for participants using glucose POC instruments are still compared with method-specific target values. Systematic deviations from a reference target value for the commutable glucose POC instruments can be calculated, and this additional information can now be offered to these participants and to the manufacturers.

BACKGROUNDThe European Federation of Clinical Chemistry and Laboratory Medicine European Biological Variation Study (EuBIVAS) has been established to deliver rigorously determined data describing biological variation (BV) of clinically important measurands. Here, EuBIVAS-based BV estimates of serum electrolytes, lipids, urea, uric acid, total protein, total bilirubin, direct bilirubin, and glucose, as well as their associated analytical performance specifications (APSs), are presented.METHODSamples were drawn from 91 healthy individuals (38 male, 53 female; age range, 21–69 years) for 10 consecutive weeks at 6 European laboratories. Samples were stored at −80 °C before duplicate analysis of all samples on an ADVIA 2400 (Siemens Healthineers). Outlier and homogeneity analyses were performed, followed by CV-ANOVA on trend-corrected data, when relevant, to determine BV estimates with CIs.RESULTSThe within-subject BV (CVI) estimates of all measurands, except for urea and LDL cholesterol, were lower than estimates available in an online BV database, with differences being most pronounced for HDL cholesterol, glucose, and direct bilirubin. Significant differences in CVI for men and women/women CONCLUSIONSThe EuBIVAS, which is fully compliant with the recently published Biological Variation Data Critical Appraisal Checklist, has produced well-characterized, high-quality BV estimates utilizing a stringent experimental protocol. These new reference data deliver revised and more exacting APS and reference change values for commonly used clinically important measurands, thus having direct relevance to diagnostics manufacturers, service providers, clinical users, and ultimately patients.

BACKGROUND Clinical studies from other countries show that self-management of warfarin therapy may reduce the risk of mortality, thromboembolism and complications when compared to conventional therapy. The purpose of this study was to train patients in self-management and compare the results with conventional therapy in Norway. METHOD A total of 23 patients who had previously been given conventional therapy by their GPs were instructed in how to measure INR (using the CoaguChek XS device) and administer warfarin dosage through a structured training programme over the course of 27 weeks. The participants continued with self-management for a further 28 weeks after the end of the training period. The time in the therapeutic range (TTR, measured as a percentage) was calculated and the TTR for conventional therapy and self-management were compared. RESULTS No significant difference in average TTR was found when comparing conventional therapy (70 % (95 % confidence interval (CI) 62 – 78)) with the self-management period (75 % (95 % CI 69 – 81, p = 0.24)). The percentage of extreme INR values ( 5.0) was higher during conventional therapy than during self-management (6.8 % vs. 1.0 %, p < 0.001). INTERPRETATION No significant difference in TTR was found when comparing self-management and conventional warfarin therapy in our study, but for self-management there was a lower percentage of extreme INR values compared to conventional warfarin therapy.

Background. Biological variation is usually estimated in healthy individuals during steady-state conditions. The aim of this study was to estimate the in-treatment biological variation of the International normalised ratio (INR) and to investigate to what extent the different levels of coagulation factors could explain this variation. Methods. Blood samples were collected from randomly included patients on warfarin treatment. INR was determined on a laboratory instrument (STA Compact ® ) and on three point-of-care instruments (Simple Simon ® PT, CoaguChek ® XS and INRatio ™ ). The level of fiand the activity of coagulation factors II, V, VII and X were determined. Results. The in-treatment within- and between-subject coeffi cients of variation of INR were dependent on the method and varied between 18 and 24% and 13 and 19%, respectively, and were reduced to 3.9 – 5.1% and 2.3 – 5.8%, after correction for coagulation factors which could explain 91 – 95% of the variance of INR. Conclusions. The in-treatment biological variation of INR was higher than reported for healthy individuals as well as patients in a steady-state condition, but by correcting for appropriate coagulation factors it was reduced. The association between INR and coagulation factors was different for the different PT methods mainly due to different sensitivity towards FII and FVII.

To the Editor: Accurate and reproducible blood glucose results are important for adequate therapeutic decision for people with diabetes. Few studies assessing the accuracy of systems for self-monitoring of blood glucose (SMBG)1 systems against the requirements from the International Organization for Standardization (ISO) standard 15197:2013 (1) have been published, and none of them has addressed analytical quality in the hands of the users. To our knowledge, no studies have evaluated SMBG systems against the requirements for accuracy in the new US Food and Drug Administration (FDA) draft guidance for SMBG systems for over-the-counter use (2). The aim of this study was to assess the accuracy of 10 SMBG systems under optimal conditions achieved by biomedical laboratory scientists (BLSs) and by people with diabetes against the minimum accuracy requirements specified in ISO 15197:2013, ISO 15197:2003, and FDA draft guidance. We used data from 10 SMBG system evaluations performed from 2005 to 2013 by the Scandinavian evaluation of laboratory equipment for primary healthcare (SKUP). The evaluations were carried out in line with common guidelines and standardized protocols according to international recommendations. All measurements on …

BACKGROUND Hemoglobin A1c (Hb A1c) measurement by hospital laboratory instruments, but not by point-of-care (POC) instruments, has been recommended for use to diagnose diabetes mellitus. We evaluated results from 13 Hb A1c external quality assurance (EQA) surveys over a 6-year period in Norway, from both POC instruments used in general practice (GP) offices and instruments in hospital laboratories, against the analytical quality specifications recommended for use of Hb A1c to diagnose diabetes mellitus. METHODS All GP offices (n = 1288) and hospital laboratories (n = 52) measuring Hb A1c in Norway participated in the EQA survey. The percentage of participants that performed measurements within the quality specifications was calculated. Pooled within-laboratory CVs were estimated for the Afinion, DCA 2000, DCA 2000+, DCA VantageTM, and Nycocard Hb A1c Reader instruments and for hospital laboratory instruments. RESULTS Between 60% to 90% of Afinion and DCA users and hospital laboratories performed Hb A1c measurements within the quality specifications for both trueness (6.0%) and imprecision (CV ≤2.0%) at 2 levels in each EQA survey. The pooled within-laboratory CVs for the Afinion and DCA instruments and hospital laboratories were below the recommended limit of 2.0% for most of the surveys. CONCLUSIONS A large proportion of GP offices using Afinion and DCA POC instruments to measure Hb A1c fulfill the analytical quality specifications for diagnosing diabetes mellitus, and these instruments demonstrate analytical quality comparable to that of hospital laboratory instruments. When GP offices participate in a stringent quality assurance program and generate Hb A1c measurements that meet analytical quality specifications, these measurements can be recommended for use to diagnose diabetes mellitus.

BACKGROUND An important objective in external quality assessment (EQA) is to evaluate systematic deviations between methods. However, this is not possible when noncommutable control materials are used. The aim of this study was to develop an EQA model that incorporates a method bias evaluation using native patient samples into EQA schemes in which noncommutable materials are used. METHODS The model was applied twice in a point-of-care (POC) international normalized ratio survey among 1341 and 1578 participants. To estimate bias, about 100 native patient samples for each POC method were analyzed by a selected group of “expert” primary healthcare centers and on a designated comparison method. In addition, the expert centers as well as all the other EQA participants analyzed 2 noncommutable control materials, and method-specific target values were established. Both method bias and the deviation of a single-participant result from the method target value were evaluated against analytical quality specifications, making combined assessment possible. The best-case scenario occurred when both results were within the quality specifications. RESULTS Two POC methods fulfilled the quality specification for bias, whereas one did not. The best-case scenario was achieved by more than 90% of the participants using the methods with no bias, whereas none of the participants using the method with unacceptable bias achieved this result. CONCLUSIONS We propose an EQA model for which the bias of POC methods can be evaluated in situations in which commutable control materials are not available.

Background:Errors in the preanalytical phase in clinical laboratories affect patient safety. The aim of this study was to evaluate the effect of intensive educational efforts together with external quality assessment (EQA) of the preanalytical phase from 2013 to 2015 to improve patient identification in primary health care in Norway. In addition, routines for venous and capillary blood sampling were investigated.Methods:A preanalytical EQA was circulated in 2013 by the Norwegian Quality Improvement of Laboratory Examinations (Noklus) to general practitioner offices and nursing homes (n=2000) to obtain information about important issues to focus on before launching an intensive educational program with courses, posters and visits in 2013–2015. Preanalytical EQA surveys were further circulated in 2014 and 2015.Results:The response rate varied between 42% and 55%. The percentages of participants asking for the patients’ name and the Norwegian identification number increased from about 8% in 2013 to about 35% in 2015. The increase was similar for those participating in only one EQA survey and for those who participated in EQA surveys both in 2013 and 2015. Guidelines for venous and capillary blood sampling were not always followed.Conclusions:Educational efforts more than the preanalytical EQA influenced the actions and resulted in an increase in the percentages of participants that followed the guidelines for patient identification. Some aspects of blood sampling routines need improvement.

Background Type 2 diabetes is a common diagnosis in care home residents that is associated with potentially inappropriate prescribing and thus risk of additional suffering. Previous studies found that diabetes medicines can be safely withdrawn in care home residents, encouraging further investigation of the potential for deprescribing amongst these patients. Objectives Describe comorbidities and medicine use in care home residents with Type 2 diabetes; identify number of potentially inappropriate medicines prescribed for these residents using a medicines optimisation tool; assess clinical applicability of the tool. Setting Thirty care homes for older people, East Anglia, UK. Method Data on diagnoses and medicines were extracted from medical records of 826 residents. Potentially inappropriate medicines were identified using the tool ‘Optimising Safe and Appropriate Medicines Use’. Twenty percent of results were validated by a care home physician. Main outcome measure Number of potentially inappropriate medicines. Results The 106 residents with Type 2 diabetes had more comorbidities and prescriptions than those without. Over 90 % of residents with Type 2 diabetes had at least one potentially inappropriate medication. The most common was absence of valid indication. The physician unreservedly endorsed 39 % of the suggested deprescribing, and would consider discontinuing all but one of the remaining medicines following access to additional information. Conclusion UK care home residents with Type 2 diabetes had an increased burden of comorbidities and prescriptions. The majority of these patients were prescribed potentially inappropriate medicines. Validation by a care home physician supported the clinical applicability of the medicines optimisation tool. Electronic supplementary material The online version of this article (doi:10.1007/s11096-016-0323-4) contains supplementary material, which is available to authorized users.

Background: Biological variation (BV) data have many fundamental applications in laboratory medicine. At the 1st Strategic Conference of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) the reliability and limitations of current BV data were discussed. The EFLM Working Group on Biological Variation is working to increase the quality of BV data by developing a European project to establish a biobank of samples from healthy subjects to be used to produce high quality BV data. Methods: The project involved six European laboratories (Milan, Italy; Bergen, Norway; Madrid, Spain; Padua, Italy; Istanbul, Turkey; Assen, The Netherlands). Blood samples were collected from 97 volunteers (44 men, aged 20–60 years; 43 women, aged 20–50 years; 10 women, aged 55–69 years). Initial subject inclusion required that participants completed an enrolment questionnaire to verify their health status. The volunteers provided blood specimens once per week for 10 weeks. A short questionnaire was completed and some laboratory tests were performed at each sampling consisting of blood collected under controlled conditions to provide serum, K2EDTA-plasma and citrated-plasma samples. Results: Samples from six out of the 97 enroled subjects were discarded as a consequence of abnormal laboratory measurements. A biobank of 18,000 aliquots was established consisting of 120 aliquots of serum, 40 of EDTA-plasma, and 40 of citrated-plasma from each subject. The samples were stored at –80 °C. Conclusions: A biobank of well-characterised samples collected under controlled conditions has been established delivering a European resource to enable production of contemporary BV data.

Clinical studies from other countries show that self-management of warfarin therapy may reduce the risk of mortality, thromboembolism and complications when compared to conventional therapy. The purpose of this study was to train patients in self-management and compare the results with conventional therapy in Norway.A total of 23 patients who had previously been given conventional therapy by their GPs were instructed in how to measure INR (using the CoaguChek XS device) and administer warfarin dosage through a structured training programme over the course of 27 weeks. The participants continued with self-management for a further 28 weeks after the end of the training period. The time in the therapeutic range (TTR, measured as a percentage) was calculated and the TTR for conventional therapy and self-management were compared.No significant difference in average TTR was found when comparing conventional therapy (70% (95% confidence interval (CI) 62-78)) with the self-management period (75% (95% CI 69-81, p = 0.24)). The percentage of extreme INR values (1.5 or5.0) was higher during conventional therapy than during self-management (6.8% vs. 1.0%, p0.001).No significant difference in TTR was found when comparing self-management and conventional warfarin therapy in our study, but for self-management there was a lower percentage of extreme INR values compared to conventional warfarin therapy.

CoaguChek S is a point-of-care, whole-blood, prothrombin time monitor. The purpose of this study was to compare two different methods for external quality assessments of CoaguChek S.In the traditional external quality assessment scheme, commercial control material was sent to office laboratories and the results were compared with a method-specific target value. In the alternative external quality assessment (the split-sample survey) patient samples were analyzed on CoaguChek S at office laboratories, and venous blood samples from the same patients were analyzed at a hospital laboratory using an assigned comparison method. To obtain comparable performance criteria for the two methods, the limits for "good", "acceptable" and "poor" performance evaluation in the split-sample survey had to be expanded because of uncertainties in preanalytical factors and the comparison method.In the traditional external quality assessment the total imprecision (between-office and within-office) was 8.0% at the low level (1.6 INR (International Normalized Ratio)) and 10.5% at the therapeutic level (3.4 INR). In the split-sample survey the total imprecision was 12.3% at the low level (2.1 INR) and 10.7 % at the high level (3.0 INR). Seventy-five percent of the participating office laboratories were characterized as "good" with the traditional external quality assessments, whereas the corresponding number was 73% using the split-sample model.Available commercial control material for CoaguChek S is different from patient samples. This study demonstrates that split-sample survey is achievable, and is an acceptable alternative to traditional external quality assessment for point-of-care prothrombin time monitors where appropriate control material is difficult to obtain.

Background Whereas complement is a key mediator of hyperacute xenograft rejection, its role in acute vascular rejection (AVR) is a matter of controversy. AVR is associated with de novo synthesis of endothelial cell-derived inflammatory mediators, including the leukocyte-recruiting adhesion molecule E-selectin. Here we investigate the role and mechanism of complement in human serum-induced porcine endothelial cell activation. Methods An in vitro xenotransplantation method was designed using porcine aortic endothelial cells stimulated with human serum in microculture wells. E-selectin expression was measured by cell-enzyme immunoassay. Complement inhibitors acting at different levels in the cascade were investigated for their effect on E-selectin expression. Results E-selectin was strongly induced by normal human serum but not by heat-inactivated serum. Compstatin, a synthetic C3 inhibitor, markedly reduced human serum-induced E-selectin expression. Purified C1-inhibitor suppressed E-selectin induction completely, indicating activation through the classical or lectin pathway. Furthermore, a monoclonal antibody (mAb) that inhibits cleavage of C5 or another mAb that blocks the function of C7, completely inhibited the expression of serum-induced E-selectin, consistent with the terminal C5b-9 complement complex being the mediator of the endothelial cell activation. Inhibition of the alternative pathway using a novel antifactor D mAb did not reduce E-selectin expression. Conclusion Human serum-induced expression of porcine E-selectin is totally complement dependent, induced by a C1-inhibitor regulated pathway and mediated through the terminal complement complex. The data may have implications for therapeutic strategies, particularly of C1-inhibitor and anti-C5 mAb, to protect against endothelial cell activation and subsequent AVR of porcine xenografts.

Aims: Determine prevalence of diabetes, and describe use of blood glucose lowering (BGL) drugs and glycemic control in Norwegian nursing homes. Methods: In this cross-sectional study we collected details of BGL drugs, capillary blood glucose measurements (CBGM) in the last four weeks and HbA1c measurements in the last 12 months from the medical records of patients with diabetes, within a population of 742 long-term care patients from 19 randomly selected nursing homes in Western Norway. Descriptive statistics were applied, and Pearson’s chi-squared (P 0.05) or non-overlapping 95% confidence intervals were interpreted as significant effects. Results: 116 patients (16%) had diabetes, 100 of these gave informed consent and medical data were available. BGL treatment was as follows: (1) insulin only (32%), (2) insulin and oral antidiabetics (OADs) (15%), (3) OADs only (27%) and (4) no drugs (26%). Patients with cognitive impairment were less likely to receive medical treatment (P = 0.04). CBGM and HbA1c measurements were performed for 73% and 77% of patients, respectively. Mean HbA1c was 7.3% (57 mmol/mol), 46% of patients had an HbA1c

BACKGROUND The reasons for discrepancies between International Normalized Ratio (INR) results determined by point-of-care-instruments and laboratory measurements are not fully understood. In this study we investigated whether different levels of coagulation factors in the plasma of patients can explain some of the systematic and/or random parts of the difference in INR between the instruments. METHODS Blood samples were collected at four different patient visits from each of 34 outpatients on warfarin treatment. INR was determined on a laboratory instrument (STA Compact(®)) and on three point-of-care instruments (Simple Simon(®)PT, CoaguChek(®)XS and INRatio™). In addition, the level of fibrinogen, coagulation factors II, V, VII and X was determined. INR instruments were compared in pairs. Simple linear regressions as well as multiple linear regressions and nested ANOVA analyses were used to examine the data. RESULTS The coagulation factors, especially fibrinogen, factors II and VII, could explain between 16% and 45% of the total variance of the differences in INR between instruments dependent on instruments compared. After correction for factors no systematic difference was seen for four of the six comparisons and the between- and within-subject variation of the differences were reduced by up to 69% and 52%, respectively. CONCLUSIONS By correcting for the appropriate coagulation factors, especially the systematic differences, but also the between- and within-subject variation of the differences between instruments, were reduced. This indicates that different levels of coagulation factors in the plasma of the patients play an important role in explaining discrepancies between INR instruments.

BACKGROUND Observed differences between results obtained from comparison of instruments used to measure international normalized ratio (INR) have been higher than expected from the imprecision of the instruments. In this study the variation of these differences was divided into subcomponents, and each of the subcomponents was estimated. METHODS Blood samples were collected at 4 different patient visits from each of 36 outpatients who were receiving warfarin treatment and were included in the study. INR was determined on 1 laboratory instrument (STA Compact®) and 3 point-of-care instruments (Simple Simon®PT, CoaguChek®XS, and INRatio™). All 4 INR instruments were compared in pairs. Linear regression was used to correct for systematic deviations. The remaining variation of the differences was subdivided into between-subject, within-subject, and analytical variation in an ANOVA nested design. RESULTS The mean difference between instruments varied between 1.0% and 14.3%. Between-subject variation of the differences (expressed as CV) varied between 3.3% and 7.4%, whereas within-subject variation of the differences was approximately 5% for all 6 comparisons. The analytical imprecision of the differences varied between 3.8% and 8.6%. CONCLUSIONS The differences in INR between instruments were subdivided into calibration differences, between- and within-subject variation, and analytical imprecision. The magnitude of each subcomponent was estimated. Within results for individual patients the difference in INR between 2 instruments varied over time. The reasons for the between- and within-subject variations of the differences can probably be ascribed to different patient-specific effects in the patient plasma. To minimize this variation in a monitoring situation, each site and patient should use results from only 1 type of instrument.

SummaryMany primary care laboratories use point-of-care (POC) instruments to monitor patients on anticoagulant treatment. The internal analytical quality control of these instruments is often assessed by analysing lyophilised control materials and/or by sending patient samples to a local hospital laboratory for comparison (split sample).The aim of this study was to evaluate the utility of these two models of prothrombin time quality control. The models were evaluated by power functions created by computer simulations based on empirical data from 18 primary care laboratories using the POC instruments Thrombotrack, CoaguChek S, or Hemochron Jr. Signature. The control rules 12S, 13S, exponential weighted moving average, and the deviation limits of ± 10% and ± 20% were evaluated by their probability of error detection and false rejections. The total within-lab coefficient of variation was 3.8% and 6.9% for Thrombotrack, 8.9% and 10.5% for CoaguChek S, and 9.4% and 14.8% for Hemochron Jr. Signature for the control sample measurements and the split sample measurements, respectively. The probability of error detection was higher using a lyophilised control material than a patient split sample for all three instruments, whereas the probability of false rejection was similar. A higher probability of error detection occurred when lyophilised control material was used compared with the patient split samples; therefore, lyophilised control material should be used for internal analytical quality control of prothrombin time in primary health care.

To gather further information about the effects on blood platelet activation of in vivo exposure to nitric oxide (NO), platelet reactivity was studied in blood from healthy, non-smoking male volunteers before and after 30 min inhalation of 40 ppm NO. Whole blood was stimulated in vitro with adenosine diphosphate or thrombin receptor activation peptide (TRAP-6). In an ex vivo perfusion model, non-anticoagulated blood was exposed to immobilised collagen at arterial blood flow conditions (2600 s(-1)). Blood samples from both the in vitro and ex vivo experiments were stained with fluorochrome-labelled Annexin-V and antibodies against CD42a, CD45, CD49b, CD61, CD62P and fibrinogen, and analysed with a three-colour flow cytometry technique. NO inhalation reduced the platelet activation response to adenosine diphosphate (ADP) stimulation by decreasing platelet-platelet aggregation, alpha-granule release and platelet-leukocyte conjugate formation. TRAP-stimulated platelet activation, collagen-induced platelet activation and thrombus growth was unaffected by NO inhalation. We therefore suggest an ADP receptor inhibitor mode of action of inhaled NO, selective on the newly suggested G protein- and phospholipase C-coupled P2Y1 receptor. Our results demonstrate that blood platelet activation in healthy subjects is modulated by inhalation of NO in therapeutically relevant doses, although the clinical impact of our findings remains unclear.

Background Capillary blood glucose measurements are regularly used for nursing home residents with diabetes. The usefulness of these measurements relies on clear indications for use, correct measurement techniques, proper documentation and clinical use of the resulting blood glucose values. The use of a regular, invasive procedure may also entail additional challenges in a population of older, multimorbid patients who often suffer from cognitive impairment or dementia. The aim of this study was to explore the perspectives of physicians, registered nurses and auxiliary nurses on the use, usefulness and potential challenges of using capillary blood glucose measurements in nursing homes, and the procedures for doing so. Methods This was a qualitative study that used three profession-specific focus group interviews. Interviews were transcribed in modified verbatim form and analysed in accordance with Malterud’s principles of systematic text condensation. Five physicians, four registered nurses and three auxiliary nurses participated in the focus groups. Results All professional groups regarded capillary blood glucose measurements as a necessity in the management of diabetes, the physicians to ensure that the treatment is appropriate, and the nurses to be certain and assured about their caring decisions. Strict glycaemic control and excessive measurements were avoided in order to promote the well-being and safety of the residents. Sufficient knowledge of diabetes symptoms, equivalent practices for glucose measurement, and unambiguous documentation and communication of results were determined to be most helpful. However, all professional groups seldom involved the residents in managing their own measurements and stated that guidelines and training had been inconsistent or lacking. Conclusion Inadequate procedures and training in diabetes care may compromise the rationale for capillary blood glucose measurements in nursing homes, and hence the residents’ safety. These concerns should be addressed together with the possibility of involving and empowering residents by exploring their ability and wish to manage their own disease. publishedVersion