Globally, hypertension is poorly controlled and its treatment consists mainly of preventive behavior, adherence to treatment and risk-factor management. The aim of this study was to explore patients' experiences of an interactive mobile phone-based system designed to support the self-management of hypertension. Forty-nine patients were interviewed about their experiences of using the self-management system for 8 weeks regarding: (i) daily answers on self-report questions concerning lifestyle, well-being, symptoms, medication intake and side effects; (ii) results of home blood-pressure measurements; (iii) reminders and motivational messages; and (iv) access to a web-based platform for visualization of the self-reports. The audio-recorded interviews were analyzed using qualitative thematic analysis. The patients considered the self-management system relevant for the follow-up of hypertension and found it easy to use, but some provided insight into issues for improvement. They felt that using the system offered benefits, for example, increasing their participation during follow-up consultations; they further perceived that it helped them gain understanding of the interplay between blood pressure and daily life, which resulted in increased motivation to follow treatment. Increased awareness of the importance of adhering to prescribed treatment may be a way to minimize the cardiovascular risks of hypertension. However, the prevalence of headache and dizziness may be as high as about 57%, and correlates with blood pressure in both untreated and treated patients.4 Poor understanding of the relation between blood pressure, symptoms and lifestyle may contribute to poor outcomes of antihypertensive treatment.5Extensive research has shown that hypertension is poorly controlled, and that treatment is a question of preventive behavior and risk-factor management.6 offers new opportunities, and can be a way to support self-management behavior.7 Actively engaging patients in their care may improve outcomes, save money by avoiding unnecessary treatment, and reduce the number of office visits.6 mHealth may also enhance communication between health-care professionals and the patient, and thereby support self-management.8 A number of studies have reported improved blood-pressure control using mHealth solutions. For example, a mobile phone-based automated medication reminder application was shown to significantly improve adherence and blood-pressure levels among high-risk patients with hypertension.9 Moreover, Logan et al.11 reported improved blood-pressure control with a mobile phone-based blood-pressure monitoring system. On the other hand, recent Cochrane reviews13 conclude that there is limited evidence that self-monitoring and mobile phone messaging interventions provide benefit in supporting long-term illnesses. The best effect on blood-pressure control was found for treatment regimens in which self-monitoring was combined with education and/or counselling.13 The reviews conclude that, although research results to date are promising, there is a need for further research into these issues.Mobile health  technology14 The overall aim of this paper was to explore patients' experiences of using this self-management system.This study is part of a research program aiming to develop and evaluate an interactive mobile phone-based system aimed at supporting self-management in hypertension.What were the patients' experiences of the technology used in the self-management system?Did the patients feel that the system helped them self-manage their hypertension; and if so, how?Specific research questions were:15 The patient is seen as a dignified and capable person, and it is of value to find a common ground and shared responsibilities between the patient and professionals.16 Three of the core concepts of person-centered care have been used: (i) partnership and participation, taking into account patient views; (ii) experiences of high blood pressure through patient reports; and (iii) documentation of patient reports in the mobile phone.15 The interdisciplinary group of researchers has also been guided by the US Food and Drug Administration's framework for the development of patient-reported outcome measures,17 by taking into account professionals' and patients' views about what is important to be aware of in daily life with hypertension.18An important perspective in the research program is person-centeredness; that is, emphasizing the value of the patient's own experiences of his/her situation and personal resources.19 with respect to age and gender.Interviews were conducted with 49 of the 51 patients who had actively used the system for an 8-week period. The inclusion criteria for the patients were: >30 years, currently taking medication for hypertension, and having a mobile phone with an Internet connection. The patients were referred to the study by their treating health-care professional from four different primary health-care centers in southern Sweden. In total, 51 patients were included in the study. The study sample was comparable with a general hypertensive population in Sweden20 The self-management system has three main components: (i) a mobile phone platform for self-reporting blood pressure, symptoms, medication use, medication side effects, lifestyle behaviors and well-being, and for receiving tailored reminders and motivational messages; (ii) a device for measuring blood pressure; and (iii) a web-based feedback system showing graphs of selected self-reported data. The patients' self-reports were made once a day for 8 weeks. The study procedures and the intervention are briefly summarized in 21Detailed descriptions of the development of the self-management system can be found elsewhere.http://www.cqmobil.se), supports platforms including Java J2ME, iPhone and Androids, and from 2013, also newer editions of Windows Mobile. In this study, the patient's own mobile phone was used. The technology is based on data traffic, which is more cost-effective than SMS and also a secure way to handle data.A communication system for mobile phones, Circadian Questions, was used. The system, developed by 21st Century Mobile, Stockholm, Sweden , validated according to the international protocol of the European Society of Hypertension, was used.23Considerable emphasis was placed on the standardization of procedures outlined in the study protocol.n=25) or telephone interviews (n=24) with the patients were conducted after completion of the intervention. The interviews lasted an average of 29 min (range 13–63 min). Examples of interview questions are: ‘What are your experiences from participating in the mobile phone project?', ‘How did it work to measure your blood pressure and report in your mobile phone?' ‘How did it work to look at the graphs?' and ‘Were the motivational messages helpful?' Interviewers posed probing questions to deepen, clarify and develop the responses. Data were collected from April to June 2012.Semi-structured and audio-recorded face-to-face interviews , a qualitative research software program designed to help users organize and analyze nonnumerical data. Qualitative thematic analysis was used to analyze data.24 The analysis was iterative, and was performed by the first author in collaboration with the co-authors and discussed to reach agreement in our understanding of the data.We developed a coding framework to organize the data systematically based on analyses of the transcripts. When searching for themes, we considered how they could be combined into sub-themes from which overarching themes could be derived. We reviewed the suggested themes to determine whether they worked in relation to our codes and whether they were valid in relation to the entire data set, by reading all assembled quotes for each theme. Codes were organized into sub-themes, from which overarching themes were derived. To present and visualize the results, quotes were identified.25 All patients were informed about the study both in writing and orally before giving their written informed consent. Transcripts were anonymized, and the patients were ensured confidentiality. The study was registered in the Clinical Trial Protocol Registration System , under the acronym MIHM (Mobile phone In Hypertension Management), and was further monitored by an independent monitoring board.The project, approved by the Regional Ethics Board in Gothenburg, Sweden (study codes 551-09 and T-100-12), was planned and conducted in accordance with the Declaration of Helsinki.Forty-nine of the 51 included patients completed the study with an interview after 8 weeks. One patient dropped out 4 weeks into the study, and one was not available for interview after the study. Patient characteristics are presented in Utility of the self-management system and Insights and benefits from using the self-management system. The sub-themes within each theme are displayed in The analysis resulted in two themes: This theme focuses on the patients' experiences of the technology used.Almost all the patients felt it was easy to self-report in the mobile phone, and that the questions were relevant. They also pointed out that it was much easier to use a mobile phone than log into a computer to answer questions:‘It's been great, easy, outstanding. Easier than logging on to my computer.'  number 32)However, patients who did not perceive any symptoms or who had stable blood pressure found some questions to be less relevant. Technical difficulties in the startup of their participation were reported. A few others mentioned a weakness in the form of connection problems when using their mobile phone. Problems with self-reporting were mentioned, such as how to go back and change an answer that had been registered. More outright suggestions for improvement included offering a better manual. Other patients wanted the option to add comments to their answers  and more reminders of how to answer in case they had forgotten how to do this.For many of the patients, using the blood-pressure monitor was also easy in conjunction with reporting using their mobile phones. Nevertheless, a few perceived a somewhat unpredictable weakness in the form of problems using the monitor, which sometimes by accident measured their blood pressure more than three times if they mistakenly touched the start button:‘Sometimes the monitor measured more than three times, but I might not be sitting still, but otherwise there were no problems.' Many different views were expressed about the graphs; for example, some felt it was easy to read, interpret and understand them, whereas others found it difficult. Another weakness was that, for some, simply logging into the computer to look at the graphs was a problem in itself because they had forgotten how to do this. Therefore, some patients did not in fact look at the graphs themselves in their own homes but instead did so during their visit to the clinic:‘Haven't looked at the graphs beforehand because I'm not good with computers, but I've kept it in mind and thought about what I've done on the days when my blood pressure has been high…when I looked [at the graphs] with the nurse it wasn't hard to see.' However, some said they did not consider it necessary to look at the graphs, as their answers and values were quite similar without significant variation. Others suggested improvement in how the graphs were displayed; for example, using different colors for the variables. They also needed some help interpreting the results. A suggestion was made for improvement in the form of a question about whether one wants to look at the graphs in the mobile phone directly after answering the questions.Patients expressed different views about receiving motivational messages in their mobile phones. Many described them as stimulating and creating a feeling of getting ‘pepped up', whereas others ignored them or had chosen not to receive them at the beginning of their participation in the research project:‘It was good…for example ‘Made food today?' Even if I didn't need them there was a thought…that made you think about it and stuff…I think it's pretty good to have those kinds of questions, kind of encouraging.' Suggestions for improvement included having the option to formulate one's own motivational messages instead of choosing from a repertoire provided in the mobile phone platform. Another idea involved tailoring messages to particular answers, such as when a patient reported less exercise than advisable, he/she would receive motivational messages about increasing it; or, alternatively, when one had exercised sufficiently, receiving a message when this had in fact influenced one's blood pressure positively.This theme describes how the patients perceived that the system had helped them self-manage their hypertension.Patients reported greater insight and motivation to manage their health through lifestyle changes and adherence to treatment when using the self-management system. Almost all the patients had experienced having an ‘eye-opener' regarding the importance of good lifestyle with regard to their hypertension. Others said they had made lifestyle changes, such as losing weight or quitting smoking. Follow-up was perceived as important for feeling motivated to follow the treatment. One of the patients expressed this as follows:‘Follow-up is incredibly important for feeling motivated to follow the treatment. Sometimes it can be pretty annoying to take medicine and you can think ‘Nah, I felt pretty good before' and just not do it.' Many of the patients also received confirmation that they needed to take their medicine to keep their blood pressure at a normal level. This became evident to those who missed their antihypertensive medication at some point and then personally detected that their blood pressure had gone up the same day:‘Yeah, I saw an effect [in the graphs] when I forgot my medication one day; that taught me a lesson, I never thought it could be seen only by forgetting one day. I was surprised; it's almost a little frightening. The consequence will be that I'll be less sloppy in the future.' Patients were motivated to follow their treatment when they became aware of the various factors affecting blood pressure, either via the graphs or through answering questions and measuring their blood pressure. In addition, some patients used their own notebook to make notes of their measured blood-pressure values and how they felt.Many patients felt they had received confirmation of the interplay between blood pressure, symptoms and perceived health, and of how changes in blood pressure depended on one's state of health and what happened in everyday life:‘I've gained more insight into things that affect my well-being. That's very valuable indeed. It's not easy to pinpoint how one feels or the reasons why - so the graphs really helped to show how things were related to one another [...] They helped me understand why things turn out the way they do, what affects me, and so now I feel I have better control, which I haven't felt before.' The interplay between physical activity, stress and blood pressure was the most obvious insight for the patients. Although they knew in a general sense that physical activity is good for decreasing high blood pressure, this became more obvious and they gained new knowledge that it really is true:‘The most important thing I've learned is that you should be more physically active; I've never really thought about or known that…If you're more physically active then…yeah, maybe I've read about it in health magazines…but haven't reflected that much on it like this…now you can actually see it on the curve…you get motivated to do something beyond the norm.' Other patients did not experience the self-management system as very useful, mainly because they had had stable blood pressure or had not perceived any symptoms. Still others believed it could be very useful and valuable when new antihypertensive medicine was prescribed, when their dose was adjusted, during periods of perceived symptoms, or as an aid in getting motivated for treatment.The patients mentioned feeling more involved in the follow-up consultation after using the self-management system. They described their participation during the visit as playing a more active role in the conversation and taking more responsibility for discussing their health, compared with previous health-care visits. Moreover, they perceived it as a better and more meaningful consultation as the graphs functioned as a common ground for discussion. Also, patients said they could now take more responsibility for their own care:‘I mean I've lived with this high blood pressure a long time and sometimes I can have quite bad headaches, and I don't think much about it, I'm so used to it; but here I really think and consider how I feel, and realize I actually have to try to do something about it.' The self-reporting was generally perceived as a source of support and as valuable for discussing how one's well-being, symptoms and lifestyle had varied over the study period, even if the patient not had looked at the graphs at home. Overall, the patients perceived it as positive to self-report and assess how their blood pressure, symptoms and lifestyle varied from day to day:‘Normally you go for a visit […] and they check your blood pressure and just say it's good, but I don't know what would be good or bad, really. Now I know more; that gives me an awareness of how my body works. Yes, now the visit's different for both me and the nurse. Now I had information collected over a longer period of time; before it's only been about when you're there [at the visit]…' et al.,26 who report that hypertensive patients' ability to perform self-management is affected by their daily life experiences. From a general practitioner's perspective, Howes et al.27 recently identified barriers to lifestyle management in hypertension. Patient reluctance and ambivalence to follow treatment advice were identified as major barriers affecting patients' ability to initiate and maintain lifestyle changes. They conclude that many interventions to decrease blood pressure in the past may have failed owing to a lack of understanding of the underlying barriers, for example, motivation to make lifestyle changes. The challenge now is therefore how to best address these barriers.Using the self-management system gave insights and perceived benefits that led to an increased awareness of the factors that influence blood pressure. The interplay between blood pressure, stress and physical activity was the most obvious insight. The possibility to see how one's blood pressure is affected by one's daily life situation, lifestyle and medication may motivate adherence. This is in concordance with a study by Bokhour 28 According to the patients' experiences, the self-management system we have developed offered possibilities for a more active and responsible role in the follow-up consultation. Further, the patients perceived that the self-management system contributed to a better and a more meaningful discussion at the consultation thanks to the graphs, which visualized factors affecting their blood pressure. We argue that the use of mHealth via a mobile phone platform would further strengthen patient involvement in care. mHealth offers new opportunities to manage healthcare, but little is known about the impact of interventions on outcomes.13 The possibilities for better management using new technology and the importance of increased patient participation have been pointed out in several new guidelines for the treatment of hypertension.30The importance of effective communication has previously been emphasized as a prerequisite for a successful encounter between patient and health-care professional.31 our results show a technical solution and a situation in which this seems to have been the case. The results also provide insight into potential issues for improvement. Worth noting is that for some patients, reporting in the mobile phone and connecting to it as well as to the computer to look at the graphs can still be somewhat difficult. For example, the self-management system could be more useful if the graphs were adjusted for viewing on the mobile phone. Other ideas for improvement involved, for example, bettering the manual as well as offering the opportunity to tailor questions and graphs according to personal preferences to increase the usefulness for the individual patient. In line with this, reminders and motivating messages should be tuned according to answers. This is especially important, we argue, to ensure that all groups of patients will use the system to reach positive health effects. This potential improvement is therefore important, but would demand a somewhat more advanced technological solution with the capacity to continuously react to patient reports of data.In general, the patients perceived the self-management system as easy and relevant to use. This kind of platform for mobile phone-based self-management must function as a whole in a practical situation with all its parts. The participating patients' attitude toward using new technology for self-monitoring a treatment regimen is important. The design shall reflect the needs of the users,use of some or all of the components of the self-management system.In sum, patients' experiences and insights gained from using the self-management system are thus multifaceted and entail various aspects . It is i32 The importance of engaging patients as active and responsible partners in their own care and in the decision-making about it have been shown to be of high value. The results of our project show a concrete way to situate person-centered care by taking into account patients' views and experiences. An even more important way is the layout of the self-management system, which puts patient reports and documentation15 in the hands of both professionals and patients. In this manner, our results provide an example of how this person-centered approach can be applied in practice, and give some indication of the effects of care. More specifically, McManus et al.33 recently showed that allowing hypertensive patients at high risk of cardiovascular disease to be more active in their care through self-monitoring and medication self-titration resulted in lower systolic blood pressure.Person-centered care is an increasingly important perspective in today's healthcare.et al.34 reported that the telemonitoring-based management of uncontrolled hypertension was both significantly more expensive and more effective than usual care, and recommended a long-term modeling of costs to examine the cost-effectiveness implications. The use of the patient's own mobile phone and data traffic for self-reports probably makes our system cost-effective. However, economic evaluation is important in future research.Socioeconomic issues should be addressed further. Stoddart 35 The telephone interviews allowed the patients to be interviewed at home, in the same environment where they had used the self-management system. Further, interviewing by telephone made it possible to validate the results from the face-to-face interviews. Thus, we saw the different modalities as complementary and useful in this context.The experience from the different interview methods is that interviewing face-to-face allowed more in-depth insights through visual cues, for instance, how to proceed with the dialogue or whether to ask follow-up questions.24 Furthermore, the method is well suited to large data sets. Credibility was addressed through critical judgment, with all authors taking an active part in the data analysis. The analyses were discussed at several meetings, until consensus was reached. Transferability was addressed through describing the context and characteristics of the patients. The use of quotations to illustrate the findings may help the reader judge the relevance of the interpretation.36The strength of this study is its use of a qualitative method to generate rich insight into patients' experiences from using the self-management system daily for 8 weeks. Thematic analysis was considered appropriate for analyzing the data, owing to the method's flexibility regarding inductive and deductive approaches.The study's limitations include the selection bias of the patients. Like in many other studies, it is often the responsive patients who are already adhering to treatment who are included. Non-adherent patients, for whom the intervention is potentially most beneficial, are often not willing to participate; had they participated, they would have most likely reported other experiences. The findings from this qualitative study cannot be generalized to all patients with hypertension, but may generate hypotheses for further research.In conclusion, the study shows that the mobile phone-based system is useful for patients in self-managing their hypertension. It gave them insights, motivation and an understanding to help them adhere to their treatment. Thus, our study has important implications for further research and clinical practice regarding the renewal of hypertension treatment as well as technological development. Furthermore, the study gives an example of how important it is to strengthen the patient's possibility to play an active and responsible role in his/her own care to minimize the cardiovascular risks of hypertension.


Metabolic syndrome (MS) is related with progressive decrease of renal function. Although hypertension has a major role on this relationship, it is not clear how its behavior is related to decreased renal function.To study how blood pressure (BP) measured by 24-hour ambulatory BP is related to renal function in patients with and without MS.We designed a cross-sectional study of consecutive individuals  from the Diabetes Clinic of a university hospital. MS was defined by the International Diabetes Federation criteria. BP was measured at office and its circadian variation was determined by 24-h ambulatory BP monitoring, after withdrawal from anti-hypertensive medications. Patients were classified according to their BP behavior: normotension , white-coat hypertension  and ambulatory hypertension . Fasting and 2h-plasma glucose levels, lipid profile, creatinine and 24-h urinary albumin excretion (UAER) were measured. Glomerular filtration rate (GFR) was estimated by the CKD-EPI equation. A two-sided P value <0.05 was considered significant.Estimated GFR (EGFR) was lower in subjects with MS than in those without MS . EGFR was related to age , fasting glucose , and 24-h systolic BP , but not to diastolic BP. EGFR was inversely related to sleep-time BP , morning systolic BP  and pulse pressure . Subjects with WCH and AHT compared to those with NT had lower EGFR  and higher UAER .A higher sleep-time BP, morning systolic BP, and pulse pressure were the components of BP homeostasis mostly related to decreased renal function and may be taken into account in the assessment of subjects with MS. The findings should prompt further research in order to evaluate whether or not interventions impacting on BP during sleep-time and early morning period may prevent renal damage.


Fluid therapy is the first important step in patients with signs of shock but assessment of the volume status is difficult and invasive measurements are not readily available in the emergency department. We have investigated whether the respiratory variation in diameter of the inferior vena cava is a reliable parameter to predict fluid responsiveness in spontaneous breathing emergency department patients with signs of shock.All patients admitted to the emergency department during a 15 week period were screened for signs of shock. If the attending physician planned to give a fluid challenge, the caval index was determined by transabdominal ultrasonography in supine position. Immediately afterwards 500 ml NaCl 0.9% was administered in 15 minutes and the clinical response was observed. An adequate response was defined as an increase in systolic blood pressure of at least 10 mm Hg. Based on this definition patients were divided into responders and non-responders.After selection a total number of 45 patients was included. A low caval index (< 36.5%) in patients with signs of shock reliably predicted the absence of an adequate response to fluid therapy . The positive predictive value of a high caval index was much lower (48%) despite the fact that responders had a significantly higher pre-infusion caval index than non-responders .In spontaneously breathing patients with signs of shock in the emergency department, a high caval index (>36.5%) does not reliably predict fluid responsiveness in our study, while a low caval index (<36.5%) makes fluid responsiveness unlikely. An explanation for the absence of a blood pressure response in the group of patients with a low high caval index might be that these patients represent a group requiring more volume therapy than 500 ml. Fluid therapy is considered to be the first step in the resuscitation of hemodynamically unstable patients with signs of shock in the emergency department (ED) . AlthougThe diameter of the inferior vena cava (IVC) increases when the total blood volume increases and decreases when the total blood volume decreases. The diameter also varies during the respiratory cycle due to the changes in intrathoracic pressure during inspiration and expiration . This vaSeveral studies have investigated the use of IVC measurements as a marker of volume status.A caval index greater than or equal to 50% is strongly associated with a low central venous pressure of 8 mmHg or less in intubated and non-intubated patients in the emergency department . There iStudies in intensive care unit patients showed that measurements of the respiratory variation in IVC diameter can be used to predict fluid responsiveness in mechanically ventilated patients –15. ReseThe aim of this study is to investigate the caval index as a non-invasive parameter to predict fluid responsiveness in non-intubated patients with signs of shock in the ED. To our knowledge this is the first study to address this question in the ED.The study is a prospective, cross-sectional observational study.During 15 weeks all patients admitted for the internist or the emergency physician to the ED of the University Medical Center Groningen between 09.00 am and 05.00 pm were screened for signs of shock. Signs of shock were defined as: systolic blood pressure < 90 mm Hg or a decrease ≥ 40 mm Hg in patients with known hypertension, heart rate > 100 beats/minute, capillary refill time > 2 seconds, or lactate concentration > 2 mmol/l. The blood pressure was measured by non-invasive cuff. Patients with one or more signs of shock were included in the study when the attending physician decided to start with intravenous fluid resuscitation of at least 500 ml NaCl 0.9%.Exclusion criteria were documented ascites, peritoneal dialysis, history of liver transplantation, pregnancy, Kussmaul breathing, the inability of the patient to maintain the supine position for several minutes, the inability to obtain adequate ultrasonographic measurements, and hemodynamic or respiratory instability requiring intubation.Patient characteristics and vital parameters ) were registered at baseline. Before any fluid therapy was given IVC diameters were measured in supine position; the maximal diameter was measured during expiration and the minimal diameter during inspiration. Subsequently a fluid challenge (500 ml NaCl 0.9%) was given in 15 minutes. Vital parameters were registered 15 minutes later after the initial fluid challenge, and after 60 minutes.In the absence of invasive hemodynamic measurements an increase in systolic blood pressure is a reasonable parameter in the determination of fluid responsiveness. An adequate response to fluid therapy was defined as an increase in systolic blood pressure of at least 10 mm Hg after a fluid challenge of 500 ml NaCl 0,9% in 15 minutes. This cut-off point is based on the change in vital parameters found in several studies investigating fluid responsiveness in different settings using a fluid challenge , 16–19. Patients were assessed for the presence of sepsis. Sepsis was defined as the presence of two or more systemic inflammatory response syndrome(SIRS)-criteria, most likely caused by an infection .Informed consent was obtained from every patient. The study was approved by the Medical Ethical committee of the University Medical Center Groningen.The IVC was examined from a subcostal view in a longitudinal section. The maximal and minimal diameter were measured during a normal respiratory cycle, no breathing instructions were given. The IVC was examined where its vessel walls were visualized best, preferably no further than 3 cm caudal to the junction of the right atrium , 21–24. To avoid the limitation of differing skills in IVC measurement, all measurements were performed by one investigator (S.d.V.). In accordance with the ‘Emergency Ultrasound Guidelines’ from ‘the American College of Emergency Physicians (ACEP)’ this investigator completed a training of 50 supervised IVC evaluations and measurements , 26. AllThe statistical analysis was performed with SPSS PASW-18. Baseline characteristics in responders and non-responders were compared using the Mann Whitney U test, and for nominal variables using the Fisher exact test. The Wilcoxon signed rank test was used to compare paired values before and after fluid therapy. Linear correlation between the change in systolic blood pressure and the caval index was tested using the Spearman Rank method. A receiver operating characteristic (ROC) curve was plotted to determine the threshold value of the caval index which provided the prediction of the response to fluid therapy with the best sensitivity and specificity. A P-value less than 0.05 was considered statistically significant.933 patients were screened for signs of shock in a 15-week period. In case of shock the investigator tried to obtain adequate ultrasonographic IVC diameter measurements. Patients with inadequate measurements (IVC not visible or measurements assessed as inadequate by the independent reviewer) were excluded. 52 patients met the inclusion criteria, 7 had inadequate measurements, so the study population contained 45 patients.Most patients in the study population were admitted with the diagnosis sepsis  or dehydration (n = 14).Based on the increase in systolic blood pressure in response to a fluid challenge of 500 ml NaCl 0.9% patients were classified as responders and non-responders. Response was defined as an increase in systolic blood pressure of at least 10 mm Hg. Table 15 minutes after the fluid challenge the change in vital parameters (apart from the blood pressure on which the division in responders and non-responders is based) is not significantly different in responders compared to non-responders.The fluid volume administered in the first 15 minutes was standardized as 500 ml NaCl 0.9%, after 15 minutes the amount of fluid administered depended on the attending physician. The mean amount of fluid administered in 60 minutes for responders was 1209.1 (±321.6) ml and for non-responders 958.6 (±401.8) ml, with a wide individual range from 500 ml to 2300 ml. After 60 minutes the change in vital parameters was not significantly different in responders compared to non-responders.Figure In the non-responders with a high caval index there is a trend to more diagnosis of sepsis  and a trend towards a higher heart rate after 15 minutes (p = 0.051) compared to the responders with a high caval index. Differences are not statistically significant, probably due to low number of patients in both groups.Although a caval index < 36.5% in ED patients with signs of shock was associated with fluid unresponsiveness in our study, we could not reproduce a strong correlation between the respiratory variation in IVC diameter and the response to fluid therapy as was previously found in mechanically ventilated intensive care patients.The pre-infusion caval index in our study population is significantly higher in responders compared to non-responders, but we found only a weak correlation between the caval index and the increase in systolic blood pressure. This is caused by a relatively large group of non-responders with a high caval index but no increase in systolic blood pressure in response to a 500 ml fluid challenge. These patients are more frequently diagnosed with ‘sepsis’ and had a higher heart rate after 15 minutes compared to the group of responders with a high caval index. These findings might indicate that this group was more hypovolemic than the group responders with a high caval index. Considering the large variation in fluid therapy after 60 minutes it is not possible to make any conclusions about the change in vital parameters after 60 minutes (data not shown).In this study adequate response to a fluid challenge was defined as an increase in systolic blood pressure of at least 10 mm Hg, but this definition of fluid responsiveness might not be suitable. Patients with severe hypovolemic shock  probably need more fluid therapy to achieve an increase in systolic blood pressure of 10 mm Hg and may therefore be mistaken for non-responders. A remarkable finding was a decrease in systolic blood pressure after the fluid challenge in a considerable part of the patients in our study population in both groups that can be explained by an initial higher blood pressure due to raised stress response during the first minutes in the emergency department.Our results are in contrast with the findings of Muller and colleagues. They concluded that a high caval index (>40%) in an intensive care unit patient with spontaneous breathing activity is associated with fluid responsiveness whereas a low caval index (<40%) was inconclusive . We founA limitation of this study is the small study population. Furthermore, we could not obtain adequate ultrasonographic measurements in 13% of the patients who met the inclusion criteria, which was comparable with 10-15% found in previous studies , 29. TheThe caval index is not only influenced by the total blood volume, but also by the abdominal pressure and the compliance of the IVC. In our study the abdominal pressure was not measured. No corrections were made for medications such as analgetics or anxiolytics administered to patients. However none of the patients received vasopressor or inotropic agents during the study period. In patients with known right heart failure, severe pulmonary hypertension, severe tricuspid regurgitation the caval index has to be interpreted with caution as any right atrial overload will tend to result in distention of the IVC.This study is the first study in the ED investigating the respiratory variation in IVC diameter  as a parameter for fluid responsiveness using clinical definitions. We found that a caval index of < 36.5% in a patient with signs of shock predicts the absence of an adequate response to a fluid challenge of 500 ml NaCl 0.9% with a reliability of 92%. Aggressive fluid therapy might not be indicated or even harm these patients. However it is not possible to predict the response to a fluid challenge for a patient with a caval index of > 36.5%. This is reflected by the low positive predictive value (48%) and weak correlation between caval index and fluid responsiveness. An explanation for the absence of a blood pressure response might be that these patients represent a group requiring more volume therapy than 500 ml. In future studies we will investigate this issue.This is the first study investigating the use of the caval index for the assessment of fluid responsiveness in the emergency departmentIn line with physiological expectations and previous studies, a caval index of < 36.5% in a patient with signs of shock predicts the absence of an adequate response to a fluid challenge of 500 ml NaCl 0.9% with a reliability of 92%.A high caval index of > 36.5% has a low positive predictive value for fluid responsiveness after a 500 ml fluid challenge, which might reflect the need for more aggressive fluid resuscitation.


The contrast between a high prevalence of chronic kidney disease (CKD) and the low incidence of end-stage renal disease highlights the need for new biomarkers of progression beyond albuminuria testing. Urinary proteomics is a promising method, but more studies focusing on progression rate and patients with hypertensive nephropathy are needed.p = 0.02). Results for hypertensive nephropathy were similar to other CKD diagnoses. Adding the proteomic score to an albuminuria model improved detection of rapid kidney function decline (>4 ml/min/1.73 m2 per year) substantially: area under ROC curve increased from 0.762 to 0.909 (p = 0.042), and 38% of rapid progressors were correctly reclassified to a higher risk and 55% of slow progressors were correctly reclassified to a lower risk category. Reduced excretion of collagen types I–III, uromodulin, and other indicators of interstitial inflammation, fibrosis and tubular dysfunction were associated with CKD diagnosis and rapid progression. Patients with hypertensive nephropathy displayed the same findings as other types of CKD.We analyzed urine samples with capillary electrophoresis coupled to a mass-spectrometer from 18 well characterized patients with CKD stage 4–5 (of whom six with hypertensive nephropathy) and 17 healthy controls. Classification scores based on a previously developed panel of 273 urinary peptides were calculated and compared to urine albumin dipstick results. Urinary proteomics classified CKD with a sensitivity of 0.95 and specificity of 1.00. Overall diagnostic accuracy (area under ROC curve) was 0.98, which was better than for albuminuria (0.85, Urinary proteomic analyses had a high diagnostic accuracy for CKD, including hypertensive nephropathy, and strongly improved identification of patients with rapid kidney function decline beyond albuminuria testing. Chronic kidney disease (CKD) has a high prevalence and represents a large burden of morbidity and health care cost , 2. DiagEmerging gene-based tests typically report relative risks of 1.2–1.4 for polygenetic diseases like hypertension and CKD, which renders them largely useless as diagnostic tools . Other rOur study describes phenotype characteristics, progression rates, and outcomes in unselected Norwegian CKD outpatients, and relate them to their urine proteomic findings, with special attention to clinically diagnosed hypertensive nephropathy.2 in the CKD cases, and their mean decline in kidney function over the past 1–11 years prior to inclusion was very similar to the decline over the two and a half years following inclusion . We therefore used data from the total observation period to indicate their rate of progression. Controls did not show any significant decline in kidney function over the 2 years, and we display baseline characteristics for rapid progressors (eGFR decline >4 ml/min/1.73 m2 per year) versus slow progressor (eGFR decline ≤4 ml/min/1.73 m2 per year). Patients with hypertensive nephropathy typically had higher age, less albuminuria, and slightly slower decline in kidney function compared to patients with glomerulonephritis and diabetes nephropathy. By 2012, three CKD patients were on dialysis, four had been transplanted, and six had died.Eighteen CKD stage 4–5 patients with a wide range of kidney diagnoses were included: eight with glomerulonephritis/diabetic nephropathy, six with hypertensive nephropathy and four cases with miscellaneous causes of CKD . Seventeen healthy controls were also included. Baseline demographics and kidney status are described in Table p < 0.001), indicating excellent overall discrimination. The box-and-whisker plots in Fig. p = 0.02).The urine proteomic analyses detected 4,276 different proteins, and information from 273 of these were converted into a classification score for each subject with values above the predefined 0.343 cutoff indicating high probability for CKD . The mea2 per year. The corresponding relationship for albuminuria is shown in Fig. 2 per year). Corresponding results for the urine proteomics score was 0.864. Adding proteomic score to an albuminuria model, which is a clinically relevant evaluation, significantly increased the diagnostic accuracy to AUC 0.909 . Furthermore, reclassification analysis showed that two out of five rapid progressors with intermediate predicted risk were (correctly) reclassified into the high risk group, while one out of five was (incorrectly) reclassified to the low risk group. For the slow progressors, three out of four with intermediate risk were (correctly) reclassified into the low risk group  . They foA central question is whether urinary proteomics can improve clinical handling of patients beyond what is possible with current diagnostic tests. CE-MS based urinary proteomics was recently found to have better ability to predict which patients with diabetes mellitus would progress to diabetes nephropathy over the next 5 years compared to microalbuminuria testing  . Using tExcessive accumulation of extracellular matrix and subsequent fibrosis is a general pathophysiological mechanism involved in many if not all types of progressive kidney disease. If the triggering event is not cleared, epithelial tubular cells will transition to a more mesenchymal like cell type starting a chronic interstitial process with increased production of collagen type 1 and type III . Both ex2 they seem to be suffering from the common pathophysiological pathway found in most types of progressing CKD.Several other urinary protein findings in our study also support on-going interstitial inflammation, fibrosis and tubular damage with similar results across CKD diagnosis, including hypertensive nephropathy. Uromodulin is exclusively produced in tubular cells in the thick ascending limb of Henle’s loop and increasingly found to be associated with kidney disease . Low uriThe current study has some limitations. First, the number of participants was rather low, which could lead to loss of precision and risk of type 2 errors. Second, we compared patients with rather advanced CKD stages with healthy subjects, so the differences between the groups were presumably large. Also, we measured albuminuria by dipstick, which is less precise than urinary albumin/creatinine ratio. However, the association of the dipstick test with both mortality, cardiovascular morbidity and CKD progression has been well validated in large international studies . Also, mIn conclusion, a panel of urinary proteins was able to accurately diagnose CKD, and in combination with albuminuria was significantly better to detect patients with rapid kidney function decline than albuminuria alone. Reduced urine levels of collagen types I and III, uromodulin, CD99 antigen and osteopontin, all implicated in fibrosis-promoting processes such as extracellular matrix deposition, inflammation and reduced collagen breakdown, were found in our CKD patients. Urine proteomics performed equally well in patients with hypertensive nephropathy as in patients with other CKD causes. Further studies with prospective designs using this new potentially useful tool are highly required.2 not yet on renal replacement therapy (RRT), from the outpatient clinic at St Olav’s Hospital, Trondheim, Norway, in December 2009–February 2010. A convenient sample of healthy persons working in our department not taking any medication and with no history of CKD, cardiovascular disease or diabetes, was included as controls. Age, sex, CKD diagnosis, and blood pressure were recorded in all participants. Blood was drawn for standard evaluation of kidney function. A second morning urine sample was tested with a dipstick, and then immediately frozen to −20 and thereafter to −80°C within 24 h. Creatinine measurements available prior to inclusion and over a 2.5 years follow-up period were recorded in order to calculate eGFR decline per year using the CKD-EPI equation [We included consecutive CKD patients with eGFR below 30 ml/min/1.73 mequation . IndividUrine samples were prepared as previously discussed . BrieflyFor data processing, mass spectral ion peaks representing identical molecules at different charge states were deconvoluted into single masses using Mosaiques Visu software . For norPrevious CE-MS measurements of urine samples have resulted in a maximum of 5,010 distinct peptides, which describes the human urinary low molecular-weight proteome . The CKDStatistical analysis were done using Stata 13.1 software . Decline in kidney function over time was compared with linear regression analysis. Mean proteomic score in different groups were compared with two-sample t test. Stata function “roccomp” was used to test for ROC area equality of logistic regression based models . We also used the Stata function “incrisk” from Longton and Pepe, which is a collection of performance improvement measures comparing a base model versus an enhanced model. Significance testing is difficult in risk reclassification, but these are useful for demonstrating how different risk prediction models changes the risk estimates in subjects with and without the outcome . PredictThe study was approved by the Regional Committee for Medical and Research Ethics. It was carried out in accordance with the Declaration of Helsinki. All participants gave written consent.


Corticosteroids are preferred to treat patients with active IgA nephropathy (IgAN), and beneficial effects from the short-term use of corticosteroids have been confirmed. However, a large number of patients will progress to end-stage renal disease after a long time follow-up. This study aimed to evaluate kidney disease progression and risk factors on kidney survival in IgAN patients receiving steroids treatment.Two hundred biopsy-proven IgAN patients who received corticosteroid therapy were enrolled and followed for a median period of 63.33 months. Risk factors on kidney survival were retrospectively investigated by the Cox proportional hazards model.2 were less likely to recover from kidney progression. Patients were more likely to show kidney function deterioration, when they had non-remission or relapse after corticosteroids treatment.Of the two hundred patients, twenty patients showed progression of renal impairment at the end of follow-up. The median and interquartile range values for initial serum creatinine were 89.2 and 68.08–121.35 µmol/L, respectively. Multivariate Cox regression analyses revealed that relapse, non-remission, time-averaged eGFR (TA-eGFR), and time-averaged serum albumin (TA-ALB) were independently associated with the kidney progression. Those with TA-ALB levels <35 g/L and TA-eGFR levels <60 mL/min/1.73 mThis study demonstrated that relapse, non-remission, TA-eGFR, and TA-ALB could serve as independent predictors of long term prognosis of IgAN patients receiving corticosteroid therapy. IgA nephropathy (IgAN) is the most commonly occurring glomerulopathy and very likely progresses to end-stage renal disease (ESRD) worldwide –4. The p2, receive a 6-month course of corticosteroid therapy . Two hundred patients with primary IgAN, who had been biopsied between January 2005 and December 2010 and received steroids treatment at the Department of Nephrology, Ren Ji Hospital, Shanghai, China, were included in this study. The study was approved by the Ethics Committee of Ren Ji Hospital, and all the participants gave written informed consent. All the kidney biopsy slides were reviewed by an experienced kidney pathologist.The influence of clinical parameters, histological grade and treatment on kidney survival was retrospectively examined. Clinical parameters and laboratory data used for analyses were obtained at the time of diagnosis of IgAN and during the follow-up, including age, gender, baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP), medical history, medications, follow-up duration, time to remission, time to endpoint, and responsiveness to treatment, hemoglobin (Hb) (measured by cyanide methemoglobin method), UPE , hematuria (uRBC/HP), serum creatinine (SCr) (measured by ammonia iminohydrolase-PAP), serum uric acid (UA) (measured by a biosensor based on urate oxidase- peroxidase coupled enzyme system), blood urea nitrogen (BUN) (measured by urease coupling rate method), and ALB (measured by dye bromcresol green method).2) = 180 × [SCr (mg/dL)]−1.154 × (age)−0.203 ×  [As for the treatment, the effect of steroids therapy was examined. Any antihypertensive agent was permitted to control blood pressure during the follow-up. Using the modification of diet in kidney disease (MDRD) study equation calculated the estimated glomerular filtration rate (eGFR): eGFR  –21. The  female) .After 6 months’ steroids therapy, the treatment response was evaluated. Complete remission (CR) was defined as a UPE <0.3 g/day, along with normalization of all biochemical findings and a lack of worsening of kidney function at the sixth month; partial remission (PR) was defined as at least a 50% reduction in UPE at the sixth month compared with baseline; no response (NR) was defined as a <50% reduction in UPE or an increase in UPE with or without kidney deterioration after receiving 6 months of therapy . RelapseMost of the patients were treated according to the accepted standards at our center . Long-teAnalyses of the data were carried out using SPSS software . The normally distributed variables were expressed as the mean ± SD and the non-parametric variables were expressed as the median and range. Cox’s proportional hazards models for estimating the hazard ratios and the 95% confidence intervals (CI) were used to identify the predictive factors for the development of IgAN progression. The multivariate models used a stepwise forward selection procedure based on a likelihood-ratio test with P > 0.10 for the removal and P < 0.05 for the entry of the variables. Kidney survival was estimated with the Kaplan–Meier method, and comparisons were performed using the log-rank test. Values of P less than 0.05 were considered statistically significant.From 2005 to 2010, the data of a total of 200 patients with IgAN who had received steroids treatment were utilized in the analyses  values for initial SCr were 89.2 and 68.08–121.35 µmol/L, respectively. Sixty-seven patients were classified in CKD stage I, 60 in stage II, 68 in stage III and 5 in stage IV–V. The median and IQR values for the initial ALB were 38.20 and 34.10–40.80 g/L, respectively. The median and IQR values for the initial proteinuria were 2.27 and 1.35–3.41 g/day, respectively. One hundred and eighty-three patients were classified in histological Lee’s grade III–IV.2, respectively. The median and IQR values for TA-UPE were 0.89 and 0.51–1.75 g/day, respectively.The characteristics of the patients during the follow-up were shown in Table Finally, a total of 160 patients with IgAN achieved remission within 6 months of initiation of steroids therapy. The remaining 40 patients (20.0%) exhibited a minimal response or NR. Additionally, 17.3% of the remission patients experienced relapse during the follow-up. During the median follow-up period of 63.33 months, 10.0% of the 200 included patients met the criteria of progression in this study.Both univariate and multivariate Cox analyses were performed to evaluate the impact of the potential predictors on kidney progression in IgAN patients receiving steroids treatment. As shown in Table Those factors that were significantly correlated with progression on the basis of univariate analyses were further evaluated by the multivariate analyses. Three multivariate Cox regression models were created, as shown in Table 2  patients of the combination therapy group and in 33/49 (67.3%) patients of the monotherapy group at 6 months of follow-up . In thisRelapse of proteinuria was commonly seen in IgAN patients. In this study, 28/160 (17.3%) patients appeared relapse after achieving remission, and individuals who experienced relapse had a significantly increased risk of kidney progression after adjusting for the effects of age, gender, eGFR, ALB, and UPE. This result verified previous viewpoint as well .Serum albumin was a biomarker of nutritional status and inflammation . In our Damaged baseline eGFR was a traditional risk factor for kidney progression. Similar to prior reports , 33–35, This is a study to use a cohort of IgAN patients having received steroids treatment after diagnose to assess kidney outcomes and the related risk factors for kidney progression. Our study may help explain the reason of a large number of patients receiving prednisone still progressed to ESRD. This study is unique in that it identified predictors for clinical outcomes among a pool of IgAN patients receiving steroids therapy. The strengths of this study also included a relative large number of IgAN patients, a uniform therapy strategy, and the robust database. Using this robust database, we examined the impact that clinical patterns have on progression to ESRD. Several shortcomings of this study existed. This study was a retrospective study and most of the patients recruited came from the southern regions of China. Therefore, the analyses had an inherent selection bias and limited representation. Thus, more studies are required to evaluate the progression of IgAN in patients under steroids treatment regimen in the future.In summary, our data clearly showed that relapse, non-remission, TA-eGFR, and TA-ALB were associated with renal outcomes. Furthermore, these characteristics could serve as independent predictors of long term prognosis of IgAN patients receiving corticosteroid therapy.


Accurate blood pressure measurements are needed in clinical practice, intervention studies and health examination surveys. Blood pressure measurements are sensitive: their accuracy can be affected by measurement environment, behaviour of the subject, measurement procedures, devices used for the measurement and the observer. To minimize errors in blood pressure measurement, a standardized measurement protocol is needed.The European Health Examination Survey (EHES) Pilot project was conducted in 2009–2012. A pilot health examination survey was conducted in 12 countries using a standardized protocol. The measurement protocols used in each survey, training provided for the measurers, measurement data, and observations during site visits were collected and evaluated to assess the level of standardization.The EHES measurement protocol for blood pressure was followed accurately in all 12 pilot surveys. Most of the surveys succeeded in organizing a quiet and comfortable measurement environment, and staff instructed survey participants appropriately before examination visits. In all surveys, blood pressure was measured three times, from the right arm in a sitting posture. The biggest variation was in the device used for the blood pressure measurement.It is possible to reach a high level of standardization for blood pressure measurements across countries and over time. A detailed, standardized measurement protocol, and adequate training and monitoring during the fieldwork and centrally organized quality assessment of the data are needed. The recent EU regulation banning the sale of mercury sphygmomanometer in European Union Member States has set new challenges for the standardization of measurement devices since the validity of oscillometric measurements is device-specific and performance of aneroid devices depends very much on calibration. High blood pressure is a major risk factor for vascular disease, such as ischaemic heart disease and stroke. High blood pressure can be lowered by lifestyle changes and medical treatment. Small changes in the average blood pressure values of the population may be of considerable importance to public health . AccuracEnvironmental factors such as the temperature of the room in which the blood pressure is measured and possible disturbance  during the measurement may affect the outcome . ActivitThe simple mercury sphygmomanometer has long been considered as a ‘gold standard’ for blood pressure measurement. Commonly used alternatives for the mercury sphygmomanometer are oscillometric devices, which should prevent the observer error present when the mercury sphygmomanometer is used. Validation protocols have been defined to ensure that oscillometric devices measure accurately in comparison with the mercury sphygmomanometer. It is important to ensure that devices used have passed the validation against at least one of the following: the British Hypertension Society protocol , InternaCommon observer errors in the auscultation method are systematic error, terminal digit preference and observer prejudice or bias . SystemaTable To minimize errors in blood pressure measurement, standardized measurement protocols have been proposed, for example by the European Society of Hypertension  and the The aim of this paper is to evaluate the level of standardization of blood pressure measurement in the EHES Pilot Project.EHES is a collaboration for standardizing national health examination surveys in Europe. The EHES Pilot Project was conducted in 2009–2012. The EHES Reference Centre (EHES RC) was established to coordinate the activities. The EHES RC prepared the European level standardized health examination survey (HES) protocol; provided support to the countries in planning and preparing their national HESs; organized European level training and provided training materials; organized external quality assessment; and evaluated the survey outcomes.Twelve countries  planned and prepared for their national HES and conducted a pilot survey to test the feasibility of their survey protocol . In fourThese pilot surveys, consisting in total of 4127 participants aged 25–64 years, were conducted in geographically defined populations. The pilot surveys were not nationally representative. Each survey was conducted by a local survey team after approval from the national/regional ethics committee . WrittenThe EHES Manual provides standardized protocols for conducting HESs, including planning, running the fieldwork and reporting ,32. The The EHES Manual has a template for a recording form for the blood pressure measurements. This form includes activities and behaviours of the participant before measurement, reasons for deviations from the standardized protocol, information about the measurement environment and measurement results .The national trainers participated in the three day European level training seminar organized by the EHES RC. The key points of the measurements were discussed and practical training on real subjects was conducted. During the training, both mercury sphygmomanometer and oscillometric devices were used. The training included details about the posture of the subject during the measurement, how the arm circumference should be measured and the correct cuff size selected, instruction to be given to the participant , and how actual measurements should be taken. For the mercury sphygmomanometer, measurement training also included determination of the peak inflation level, the deflation rate to be used and determination of Korotkoff sounds (Phase I and Phase V). Training materials (presentations and videos) are available at the EHES web site .The joint training session was followed by national training of the fieldwork personnel in each country. The duration and contents of the training varied both by country and the previous experience of the fieldwork staff.The success of the standardization was assessed during site visits by members of the EHES RC to observe the fieldwork in each country. The measurement environment , interaction between the subject and the measurer, the measurement procedure and equipment used for the blood pressure measurement  were recorded. Observations were documented in site visit reports and feedback to local survey organizers and fieldwork teams was provided.A retrospective quality assessment of the measurements was conducted, based on national survey protocols and collected data. This assessment included comparison of the national survey protocols with the EHES protocol, evaluation of the proportion of missing data for each data item, proportion of identical sequential readings and the proportion of terminal digits. High proportions of identical sequential readings or terminal digit preference is an indicator of problems with the measurements, usually reflecting the lack of proper training.Most of the EHES pilot surveys were conducted in a clinical setting, either in the facilities of the local health care system or in temporary clinics set up specifically for the survey. In one survey, the measurements were conducted in the participants’ home and another survey used a mobile examination unit. From the measurement environment, the room temperature was measured and recorded routinely in nine surveys. The average room temperature varied from 19.4°C to 25.0°C, with relatively small variation within survey  before the examination recorded.In all surveys, three blood pressure measurements were taken in a sitting posture from the right arm. In most surveys, occasional deviations for medical reasons were recorded. Table  During tThe simple mercury sphygmomanometer was used in three surveys and oscillometric devices in nine. For oscillometric devices, six different models from three manufacturers were used. Each model of the oscillometric devices had passed validation following the British Hypertension Society protocol , InternaIn nine out of 12 surveys, more than one cuff size was available Table . When coThe proportion of identical sequential measurements was lower between the first and the second measurement than between the second and the third measurement for both systolic and diastolic blood pressure in three surveys using simple mercury sphygmomanometers. In each survey, the proportion of identical readings was higher for diastolic than for systolic blood pressure. Overall, the proportion of identical sequential measurements was high only in two surveys (28% or over) using simple mercury sphygmomanometer Table .Terminal digit preference was not a problem when oscillometric devices were used. In one of the three surveys which used mercury sphygmomanometers, a clear terminal digit preference for zero was seen for both systolic and diastolic blood pressure Tables  and 5.TaReliable population level information on blood pressure levels and prevalence of hypertension are needed for developing evidence based policy and planning prevention activities as well as for research. Obtaining such information is challenging, since the measurement environment, behaviour of the subject, measurement protocol, device used for the measurements and the observers can each affect the accuracy of the blood pressure measurements.To overcome the challenges, the EHES Pilot Project prepared a European level standardized protocol for blood pressure measurement, a training programme and quality control to support the collection of high quality and comparable blood pressure data across populations. The protocol was tested in 12 pilot surveys with encouraging results.In general, the room temperature could be standardized to a comfortable level and it was possible to eliminate outside disturbance. This is easiest when examinations are carried out in existing health care facilities designed for medical examinations or in a mobile unit especially designed for this purpose. When temporary examination clinics are set up for the survey, it may be difficult to find suitable locations which are available for a relatively short period of time. It is more difficult to standardize the measurement environment when the measurements are conducted at the participants’ home. In this case, the survey organizers cannot control the room temperature or possible disturbances during the measurement. Therefore it is particularly important to record the room temperature and possible disturbances during the measurement.Controlling the behaviour of the participant before the examination requires clear instructions for the survey invitees. The person welcoming the participant to the examination centre or staff taking the blood pressure measurements should check that the participant does not have an uncomfortably full bladder before the blood pressure measurement begins. Information on activities before measurement should be recorded.The importance of standardized measurement procedures in multicentre and international studies has been reported ,34. The To evaluate the use of a standardized protocol in the field, monitoring is required during the fieldwork. These monitoring visits should be done on a regular basis to observe how fieldwork teams conduct measurements, how they interact with survey invitees and also how they interact with each other. The interval between monitoring visits depends on the duration of the fieldwork. When the fieldwork is conducted within a few months, at least one monitoring visit should be done at the beginning of the fieldwork and one during the remaining fieldwork period. In surveys with a longer fieldwork period, the interval of the monitoring visits should be conducted so that they take into account changes of examination sites and also possible changes in the fieldwork personnel. Depending on the survey, these visits can be every 2–4 months. Also, re-training or refresher sessions, during which standardized measurement protocols are gone through and measurements are conducted under supervision, are needed to maintain the level of standardization, especially if the fieldwork last several months or years.Traditionally, the mercury sphygmomanometer has been considered as the ‘gold standard’ for blood pressure measurement. In Europe, the use of mercury sphygmomanometers in HESs has declined during the past decades. In future, all European HESs will have to use devices other than mercury sphygmomanometers, as the EU regulation 847/2012 banned the sale of mercury sphygmomanometers from 10 April 2014 onwards . It has http://www.bhsoc.org/bp-monitors/bp-monitors and the dabl® Educational Trust web site at http://www.dableducational.org/sphygmomanometers.html. Comparison of the different oscillometric devices is difficult, since their algorithms used for determination of the systolic and diastolic blood pressure are not openly accessible and these are likely to change over time as the measurement devices are improved. This also makes it difficult to replicate the validation studies for the older models. Therefore, the auscultation method with calibrated devices will remain superior and should be considered as ‘gold standard’ also in future. For the auscultation method, there are validated alternatives to the mercury sphygmomanometer [A variety of oscillometric devices for blood pressure measurement is on the market. Many of them have passed at least one of the validation tests based on the British Hypertension Society protocol , Internaanometer ,41.The importance of correct cuff size for the accuracy of the blood pressure measurement has been emphasized. Use of too large a cuff can result up to 10–30 mmHg lower systolic and diastolic blood pressure readings and on the other hand, use of too small a cuff to 3–12 mmHg higher systolic and 2–8 mmHg higher diastolic blood pressure readings . RegardiMiss-cuffing was not a major problem in the EHES pilot. Some countries encountered problems in obtaining more than one cuff size  for their oscillometric device through their national supplier.Observer error can be minimized when oscillometric devices are used. For mercury sphygmomanometers, minimizing the observer error requires thorough practical training ,44.The final decision on the blood pressure measurement protocol to be used in national HES in Europe is made by each country. The actual deviations between protocols used were small and could be easily corrected; in most cases, differences were only in the devices used. These and other possible deviations were usually caused by the need to follow trends from past surveys within the country. Nevertheless, there is a shared desire for comparability of the blood pressure measurement results between countries. This can be obtained through a joint protocol. The EHES blood pressure measurement protocol was followed well in all 12 EHES pilot surveys, and the external quality control helped to minimize observer errors. In the countries which had an on-going full-size national HES, the EHES protocol was also followed well. These surveys had based their blood pressure measurement protocols for previous European level standards of the European Health Risk Monitoring (EHRM) Project, which was the base for the EHES protocol .Our experience from the EHES Pilot Project is in line with the results of previous studies showing that blood pressure measurements can be standardized across countries and over time. This requires a detailed, standardized measurement protocol; adequate training; and monitoring during the fieldwork as well as retrospective quality assessment. However, the recent EU regulation banning the sale of the mercury sphygmomanometers in European Union Member States  and the


The delta neutrophil index (DNI) is the fraction of circulating immature granulocytes, which reflect infectious and/or septic condition. Acute graft pyelonephritis (AGPN) versus acute graft rejection is a frequently encountered diagnostic and therapeutic dilemma in kidney transplant recipients, but little is known about the clinical usefulness of DNI value in the differentiation of the two conditions.A total of 90 episodes of AGPN or acute graft rejection were evaluated at the Kangdong Sacred Heart Hospital between 2008 and 2014. We performed retrospective analysis of demographic, clinical, and laboratory parameters data. Receiver operating curves (ROC) and multivariate logistic regression were conducted to ascertain the utility of DNI in discriminating between AGPN and acute graft rejection.AGPN group had significantly higher DNI values than acute graft rejection group . The area under the ROC curve for DNI value to discriminate between AGPN and acute graft rejection was 0.85 . A DNI value of 2.7% was selected as the cut-off value for AGPN, and kidney transplant recipients with a DNI value ≥ 2.7% were found to be at a higher risk of infection than those with a DNI < 2.7% . In a multivariate logistic regression analysis, DNI was a significant independent factor for predicting AGPN after adjusting age, sex, log WBC count, log neutorphil count, log lymphocyte count, CRP concentration, and procalcitonin concentration .This study showed that DNI was an effective marker to differentiate between AGPN and acute graft rejection. Thus, these finding suggest that DNI may be a useful marker in the management of these patients. Acute graft pyelonephritis (AGPN) is a common form of bacterial infection in kidney transplant recipients and acute graft rejection frequently encounter in those people –3. HowevThe presence of immature granulocytes (IGs), including metamyelocytes, myelocytes and promyelocytes, as well as the granulocytic shift to the left in peripheral blood, usually reflect the enhanced production of granulocytes in bone marrow, as a result of bacterial infection ,11. AlthThe delta neutrophil index (DNI) is a novel value designed to determine the fraction of IGs more readily and reliably. It is calculated by an automatic hematologic analyzer ADVIA2120  using myeloperoxidase (MPO) and nuclear lobularity channels in the test system. The difference between the leukocyte differentials measured in the two channels is designated as the DNI, which correlates with the IGs fraction in peripheral blood calculated by manual counting . ResultsWe conducted a retrospective cohort study at Kangdong Sacred Heart Hospital, which is a 600-bed teaching hospital where 472 kidney transplants have been performed in the last 30 years. Between January 2008 and February 2014, kidney transplant recipients who had acute graft rejection or AGPN, those whose DNI values were checked, and those who were older than 18 years were considered eligible in this study. There were 45 kidney transplant recipients who had 51 acute graft rejection episodes and 49 kidney transplant recipients who had 54 AGPN episodes, respectively. Of these episodes, 15 episodes were excluded because those episodes occurred in recipients who had neutropenia resulting from drug-induced bone marrow suppression (n = 4), those episodes occurred in recipients who had other infections such as pneumonia and enteritis (n = 5), and those episodes occurred in recipients whose procalcitonin levels were not checked (n = 6). After these exclusions, 75 kidney transplant recipients with 90 episodes were enrolled in this study. At the time the episodes occurred, there were no occurrence of other diseases such as polyoma virus infection, CMV infection, and recurrent native kidney disease.This study was carried out in accordance with the Declaration of Helsinki and approved by the Institutional Review Board (IRB) of the Kangdong Sacred Heart Hospital (Ref. 14-2-46). None of the transplant donors belonged to a vulnerable population or were subject to coercion. All patients participating in the current study were aware of this investigation. However, because this was a retrospective medical record-based study and the subjects were de-identified, the IRB waived the need for written consent from the patients.4 colony-forming units (CFU)/mL. Symptoms of cystitis were as follows: a strong and persistent urge to urinate, a burning sensation when urinating, passing frequent and small amounts of urine, discomfort in the pelvic area, and a feeling of pressure in lower abdomen. Kidney allograft dysfunction was defined as increase in serum creatinine concentration of 25% over baseline levels. The kidney allograft outcomes were evaluated at one month after starting antibiotic therapy in AGPN patients with kidney allograft dysfunction. The outcome was defined as follows: good, > 25% reduction in serum creatinine; moderate, ≤ 25% reduction in serum creatinine; poor, no reduction in serum creatinine. Acute graft rejection was suspected in recipients with established kidney allograft function who experienced within 1–2 days a rapid increase in their plasma creatinine concentration of 10–25% over baseline levels with or without decreased urine output, graft tenderness, or fever in the absence of other obvious causes of acute renal allograft dysfunction , neutrophil counts , lymphocyte counts , CRP concentration  were significantly higher in AGPN group than in acute graft rejection group. However, no differences were observed in the duration of the episodes from the time of kidney transplant, immunosuppressive regimen, hemoglobin concentration, platelet counts, blood urea nitrogen concentration, and creatinine concentration between the two groups.Demographic, clinical, and biochemical data of patients presenting with AGPN or acute graft rejection are shown in Microbiological isolates were confirmed in the all 52 episodes of AGPN. The most frequently isolated pathogen were Escherichia coli (n = 26), Pseudomonas aeruginosa (n = 11), and Klebsiella pneumonia (n = 4) . In contThere were significant positive correlations between DNI values and procalcitonin concentration  while there were no correlation DNI values and WBC counts, neutrophil counts, platelet counts and CRP concentration.To evaluate the influence of the degree of bacterial infection on DNI values, we divided AGPN group into two subgroups; with bacteremia (7 episodes), without bacteremia (45 episodes). Compared to the AGPN group without bacteremia, DNI values were significantly increased in the AGPN group with bacteremia . Additionally, DNI values were also significantly higher in AGPN group without bacteremia than in acute graft rejection group  . On noteTo compare of the ability of the WBC count, DNI value, CRP concentration, and procalcitonin concentration to predict AGPN, we used ROC curve analysis with AUC. The AUC of procalcitonin concentration and DNI values were comparable . Additionally, the AUC of DNI values was also larger than that of WBC counts  and CRP concentration , suggesting that DNI value was a better predictor of AGPN than WBC count and CRP concentration . Even afTo obtain the optimal DNI cutoff value to predict AGPN, we also used ROC curve analysis with AUC. The best cutoff value for DNI to predict AGPN was 2.7% with a sensitivity and specificity of 69.23%  and 97.37% , respectively . In patiP < 0.001). Additionally, due to skewed distribution, WBC counts, neutrophil counts and lymphocyte counts were log-transformed in regression analyses. Log-transformed neutrophil counts , DNI values , CRP concentration  and procalcitonin concentration  were found to be associated with a higher risk of AGPN. Lastly, the impact of DNI value on AGPN remained significant even after adjustment for age, sex, log WBC count, log neutrophil count, log lymphocyte count, DNI value, CRP concentration, and procalcitonin concentration   . Additio< 0.001) .To examine the impact of DNI on kidney allograft function in AGPN, the episodes with kidney allograft dysfunction and their outcomes were divided according to tertile of DNI values as follow: tertile 1, DNI < 2.8%; tertile 2, 2.8%–3.8%; tertile 3, > 3.8%. Among 52 episodes with AGPN, 21 (40.4%) episodes had kidney allograft dysfunction. The proportion of episodes with kidney allograft dysfunction was significantly higher in the highest tertile of DNI (P for trend = 0.004). Additionally, as DNI values increased, kidney allograft outcome was significantly poor at one month after antibiotics therapy among them (P for trend = 0.016) .This study showed that DNI, which reflects the number of circulating granulocyte precursors in the blood, was an effective marker to differentiate between AGPN and acute graft rejection in renal transplant recipients. Our finding suggests that kidney transplant recipients with elevated DNI value are found to be at a higher risk for infection than those with decreased DNI value.5 CFU per mL or higher in midstream urine cultures were predictive of bladder bacteriuria in women who are asymptomatic or have pyelonephritis, whereas lower counts were more likely to be associated with contamination [5 CFU per mL as the threshold for the diagnosis of AGPN.The value of quantitative urine culture in the diagnosis of pyelonephritis has been demonstrated in early studies in which this method was able to discriminate between true urinary tract infections and contaminated urine specimens. In other words, bacterial counts of 10mination , 28. Howmination , 29. TheIn kidney transplant recipients, urinary tract infection (UTI) is the most common form of bacterial infection , 3. As iIn previous studies, the proportion of IGs was better correlated with positive blood culture results and infection than the WBC count , whereasIn line with recent finding, the results from the present study clearly showed that DNI values were higher in patients with AGPN compared to those with acute graft rejection. In addition, we observed that DNI values significantly correlated with procalcitonin concentration in AGPN group. Moreover, ROC analysis showed that the diagnostic value of DNI for AGPN was comparable to procalcitonin concentration and it was superior to WBC count and CRP concentration. Furthermore, we proposed a novel cutoff value of DNI at 2.7% to predict infection, with a sensitivity of 69.2% and a specificity of 97.4% which is comparable to the 2.8% value reported by Pyo et al . Lastly,Our study had several limitations. First, it was an uncontrolled retrospective study based on a small population who underwent kidney transplant at a single center. Second, protocol renal allograft biopsy was not performed. Thus, the episodes of AGPN with asymptomatic or atypical clinical presentation might not be included in this study. For this reason, our results should be regarded as preliminary, and further prospective studies including protocol renal allograft biopsy are needed. Third, although we excluded episodes occurring in recipients who had neutropenia resulting from drugs inducing bone marrow suppression, DNI value can be influenced by immunosuppressive drugs. Because they may reduce the hematopoietic function of bone marrow, resulting in relatively decreased changes in the number of IGs. In this regard, the sensitivity of DNI to predict AGPN was not high in this study. Lastly, as DNI was measured at the time that patients presented with AGPN or acute graft rejection, DNI alterations along a longer course of each disease are still unclear.In conclusion, the present study demonstrated that a DNI value above 2.7% was an independent predictive marker for AGPN in patients in whom a differential diagnosis between AGPN and acute graft rejection is needed. Therefore, these finding suggest that DNI may be a useful marker in the management of these patients.S1 FigBar and error bar show the median and range, respectively. There were 59 kidney transplant recipients with 62 episodes of low urinary tract infection during study follow-up period. *P < 0.001 vs. low urinary tract infection group.(TIF)Click here for additional data file.S1 Table(DOC)Click here for additional data file.S2 Table(DOC)Click here for additional data file.