Enhanced hospital-based learning at a medical school through application of management principles - a case study.

BACKGROUND: A hospital with all its brimming activity constitutes a unique learning environment for medical students. However, to organise high-quality education within this context is a task of great complexity. This paper describes a teaching hospital case, where management principles were applied to enhance the learning quality of medical education. METHODS: Traditional attempts from the faculty had been unsuccessful in improving learning among medical students at a teaching hospital. We therefore applied management principles to be able to improve the learning quality. An evaluation was performed from the perspectives of management (course directors/ heads of health care departments), medical students, and physician supervisors. Presages were defined, including educational resources and management; processes were adjusted, including learning activities and staff schedules; and products were assessed. RESULTS: Charting and benchmarking the use of local educational resources identified unused funding. Structured recurrent collaboration within resource utilization was established between course directors and heads of all concerned health care departments. By formulating a joint agreement, the identified assets were used to reorganise the course, to create constructive alignment, and to increase assigned supervisor time. This resulted in a sustainable improvement of learning quality and culture. CONCLUSION: By using management principles in combination with a scholarship of teaching and learning, it was possible to locate and redistribute educational resources in an effective way. This improved student learning and the learning culture of the health care departments. We propose that such an initiative could also be transferable to other contexts. Faculty leaders facing similar problems should consider the advantages of a structured collaboration with health care department heads.

Immediate effect of passive smoking on microcirculatory flow.

OBJECTIVE: Exposure to SHS, as by passive smoking, seems to increase the incidence of cardiovascular events. It has been shown that active smoking of a single cigarette causes an immediate and significant decrease in microcirculatory blood flow velocity, whereas the acute effects of exposure to SHS on microcirculatory flow have as yet not been demonstrated. METHODS: Healthy nonsmoking volunteers of both genders were studied during acute exposure to SHS of two cigarettes burning up to 10 minutes. Microvessels were examined by in vivo vital capillaroscopy (Capiflow(®)), allowing continuous assessment of CBV. RESULTS: CBV decreased from 514 mm/sec (CI 383-646) at baseline to 306 mm/sec (CI 191-420) at end of SHS exposure with a further decrease to a nadir of 240 mm/sec (CI 155-325) four minutes after the end of this exposure (p < 0.0001; ANOVA). CONCLUSIONS: The result of this study shows that passive inhalation of secondhand cigarette smoke induces an immediate and prolonged marked reduction in CBV in nonsmoking healthy volunteers.

Students perceive healthcare as a valuable learning environment when accepted as a part of the workplace community.

BACKGROUND: The healthcare system is complex and the education of medical and nursing students is not always a priority within it. However, education offered at the point of care provides students with opportunities to apply knowledge, and to develop the necessary skills and attitudes needed to practice their future profession. The major objective of this study was to identify students' views of generic aspects of the healthcare environment that influences their progress towards professional competence. METHODS: We collected free text answers of 75 medical students and 23 nursing students who had completed an extensive questionnaire concerning their learning in clinical wards. In order to obtain richer data and a deeper understanding, we also interviewed a purposive sample of students. Qualitative content analysis was conducted. RESULTS: We identified three themes: (1) How management, planning and organising for learning enabled content and learning activities to relate to the syllabus and workplace, and how this management influenced space and resources for supervision and learning; (2) Workplace culture elucidated how hierarchies and communication affected student learning and influenced their professional development and (3) Learning a profession illustrated the importance of supervisors' approaches to students, their enthusiasm and ability to build relationships, and their feedback to students on performance. DISCUSSION: From a student perspective, a valuable learning environment is characterised as one where management, planning and organising are aligned and support learning. Students experience a professional growth when the community of practice accepts them, and competent and enthusiastic supervisors give them opportunities to interact with patients and to develop their own responsibilities.

Differences in Supervision on Peer Learning Wards: A Pilot Survey of the Supervisor's Perspective.

Introduction: Multiple students are placed on clinical wards simultaneously due to increasing student numbers. This has the potential to create stress for the supervisor and reduce quality of student learning. Peer learning as a pedagogical framework to supervise multiple students has been widely shown to have advantages for the students by developing teaching skills, team collaboration, and independence. However, whether peer learning impacts the characteristics of supervision and the experience of the supervisor is less understood. It is unknown whether wards that use peer learning as a pedagogical framework (peer learning wards) are any different compared to wards that do not (non-peer learning wards), from the supervisor's perspective. Methods: We aimed to develop and pilot test a questionnaire to compare peer-learning wards and non-peer learning wards from the supervisor's perspective. We used the AMEE 7-step guide to develop questions investigating supervision, the learning environment and satisfaction. We piloted the questionnaire with 46 nurse supervisors working on inpatient hospital wards in Stockholm, Sweden. We compared answers from peer learning with non-peer learning wards. We used Orthogonal Projections to Latent Structures (OPLS) discriminant analysis to show what differed between the wards. Results: Peer learning wards compared to non-peer learning wards had more student-centred activities, the physical space had more adaptations for students, more support available to the supervisor, and supervisors perceived greater overall satisfaction with the quality of education and with the ward as a whole. The variables that had most influence on the discrimination between the two ward types related to peer learning activities and perceptions (p=0.0034). Conclusion: This pilot study shows that peer learning wards differ compared to non-peer learning wards regarding peer learning activities and perceptions among supervisors. Our questionnaire needs to be distributed on a larger scale to validate our findings and explore further the way in which the pedagogical framework and peer learning can affect supervision and satisfaction.

Endogenous estrogens lower plasma PCSK9 and LDL cholesterol but not Lp(a) or bile acid synthesis in women.

OBJECTIVE: Cholesterol and lipoprotein metabolism display pronounced gender differences. Premenopausal women have lower LDL and higher HDL cholesterol, whereas men display higher synthetic rates of bile acids and cholesterol. The effects of the administration of exogenous hormones to humans and animals indicate that these gender differences can often be explained by estrogens. We evaluated how increased levels of endogenous estrogens modulate cholesterol and lipoprotein metabolism in women. METHODS AND RESULTS: We studied healthy women during initiation of in vitro fertilization using blood samples obtained when endogenous estrogens were low and high. Cholesterol in VLDL and LDL, but not in HDL, was reduced 20% when estrogens were high. Apolipoprotein B levels decreased 13%. Apolipoprotein A-I and triglyceride levels increased 8% and 37%, respectively, whereas lipoprotein(a) levels were unchanged. Circulating PCSK9, a suppressor of LDL receptors, was reduced 14% when estrogens were high. Serum markers of bile acid and cholesterol synthesis were unaltered. Growth hormone levels increased 3-fold when estrogens were high, whereas insulin-like growth factor-1 and fibroblast growth factor-21 concentrations were unaltered. CONCLUSION: In women, Apolipoprotein B-containing particles and circulating PCSK9 are reduced when endogenous estrogens are high, indicating that endogenous estrogens induce hepatic LDL receptors partly through a posttranscriptional mechanism. However, estrogens do not stimulate bile acid or cholesterol synthesis.

Quality of medical certificates issued in long-term sick leave or disability in relation to patient characteristics and delivery of health care.

AIM: To assess the quality of medical certificates issued during long-term sick leave or disability. METHODS: We collected a stratified randomised sample of 250 medical certificates issued for assessment of work capacity: Certificates issued in primary health care (PHC) with a locomotor, psychiatric or other main diagnosis, in psychiatric care, and in other secondary care. Four experts performed a quality assessment per section of the certificate and globally. RESULTS: The certificates varied from short notes to extensive documents. Those issued in PHC included more diagnoses per certificate (p < 0.0001) than in secondary care. PHC physicians had a longer professional relationship to their patients (p = 0.009). Information on work capacity was entirely adequate and relevant in only 10% of the certificates. Disturbed mental function was indicated in 60% of the certificates without psychiatric main diagnosis. Whether indicated medical state influenced functional state was not assessable in 46 (19 %) of the certificates due to lack of information. Similarly, if reduced function influenced working capacity was not assessable in 66 (27 %) of the certificates. The global quality differed (p < 0.0001) between certificates issued in primary care 5.7 (CI 5.5-5.9) and secondary care 6.9 (CI 6.5-7.3). CONCLUSIONS: There is a need for improvement of the quality of medical certificates issued in cases of long-term sick leave or disability. The quality of medical certificates was low and lacked necessary information requested by the Social Insurance Agency. The quality was lower in certificates issued in primary care, which might be explained by a different case-mix.

Self-report and device-based physical activity measures and adherence to physical activity recommendations: a cross-sectional survey among people with inflammatory joint disease in four European countries.

OBJECTIVES: Self-monitoring of physical activity (PA) has the potential to contribute to successful behaviour change in PA interventions in different populations, including people with inflammatory joint diseases (IJDs). The objectives of this study were to describe the use and knowledge of self-report-based and device-based PA measures in people with IJDs in four European countries, and to explore if the use of such devices, sociodemographic or disease-related variables were associated with adherence to the recommendations of at least 150 min of moderate to vigorous PA per week. SETTING: Cross-sectional survey, performed in 2015-2016. PARTICIPANTS: People with IJDs in Belgium, Denmark, Ireland and Sweden. PRIMARY AND SECONDARY OUTCOME MEASURES: Use of self-report and device-based PA measures, receipt of instructions how to use PA measures, confidence in using them, adherence to PA recommendations and associated factors for adherence to PA recommendations. RESULTS: Of the 1305 respondents answering questions on PA measures, 600 (46%) reported use of any kind of self-report or device-based measures to self-monitor PA. Between country differences of 34%-58% was observed. Six per cent and four per cent received instructions from health professionals on how to use simple and complex devices, respectively. Independent associated factors of fulfilment of recommendations of PA were living in Ireland (OR=84.89, p<0.001) and Sweden (OR=1.68, p=0.017) compared with living in Denmark, not perceiving activity limitations in moderate activities (OR=1.92, p<0.001) and using a device to measure PA (OR=1.56, p<0.001). Those living in Belgium (OR=0.21, p<0.001) were less likely to fulfil recommendations of PA. CONCLUSIONS: Almost half of the participants with IJDs used self-report-based or deviced-based PA measures, although few used wearable devices regularly. The results indicate that participants meeting public PA health guidelines were engaged in self-monitoring of PA.

Organizational and patient-level predictors for attaining key risk factor targets in cardiac rehabilitation after myocardial infarction: The Perfect-CR study.

BACKGROUND: Benefits of cardiac rehabilitation (CR) programme components on attaining risk factor targets post-myocardial infarction (MI) and their predictive strength relative to patient characteristics remain unclear. We aimed to identify organizational and patient-level predictors of risk factor target attainment at one-year post-MI. METHODS: In this observational study data on CR organization at 78 Swedish CR centres was collected and merged with patient-level registry data (n = 7549). Orthogonal partial least squares discriminant analysis identified predictors (Variables of Importance for the Projection (VIP) values >0.8) of attaining low-density lipoprotein-cholesterol (LDL-C) <1.8 mmol/L, blood pressure (BP) <140/90 mmHg and smoking abstinence. RESULTS: The strongest predictors (VIP [95% CI]) for attaining LDL-C and BP targets were offering psychosocial management (2.14 [1.78-2.50]; 2.45 [1.91-2.99]), having a psychologist in the CR team (1.62 [1.36-1.87]; 2.05 [1.67-2.44]), extended opening hours (2.13 [2.00-2.27]; 1.50 [0.91-2.10]), adequate facilities (1.54 [0.91-2.18]; 1.89 [1.38-2.40]), and having a medical director (1.70 [0.91-2.48]; 1.46 [1.04-1.88]). The strongest patient-level predictors of attaining LDL-C and/or BP targets were low baseline LDL-C (3.95 [3.39-4.51]) and having no history of hypertension (2.93 [2.60-3.26]), respectively, followed by exercise-based CR participation (1.38 [0.66-2.10]; 1.46 [1.14-1.78]). For smoking abstinence, the strongest organizational predictor was varenicline being prescribed by CR physicians (1.88 [0.95-2.80]) and patient-level predictors were participation in exercise-based CR (2.47 [2.07-2.88]) and group education (1.92 [1.43-2-42]), and no cardiovascular disease history (2.13 [1.78-2.48]). CONCLUSIONS: We identified multiple CR organizational and patient-level predictors of attaining risk factor targets post-MI. These results may influence the future design of comprehensive CR programmes.

Microvascular reactivity in response to smoking and oral antioxidants in humans.

OBJECTIVE: To investigate whether a daily intake of a moderate dose of antioxidants modifies the microcirculatory response to smoking, assuming a major influence of oxidative stress on microcirculation. METHODS: The microvascular response to smoking was assessed in individual capillaries by capillaroscopy before and after two weeks of treatment with oral antioxidants. RESULTS: Smoking prolonged time to peak (TtP) capillary blood flow velocity in all subjects. When the subjects were pre-treated with ascorbate, TtP was comparable to baseline values of untreated subjects. No significant effect of vitamin E was observed either before or after smoking. Capillary blood flow velocity increased after treatment with ascorbate as well as after vitamin E. However, significant reductions in velocity were still observed in response to smoking even after subjects consumed ascorbate and vitamin E (p<0.0004 and p<0.000008 respectively). CONCLUSIONS: This study focused on individual capillaries, and confirms that smoking has a very pronounced, direct and reproducible microvascular effect possible to demonstrate in vivo in human capillaries. Moderate intake of the antioxidant ascorbate clearly mitigated the effects induced by smoking. TtP after smoking in subjects treated with ascorbate was similar to that observed in untreated subjects before smoking a cigarette. Thus, oxidative stress could be assumed to play a role in the effects of smoking on microcirculation.

Integrating virtual patients into courses: follow-up seminars and perceived benefit.

CONTEXT: The use of virtual patients (VPs) suggests promising effects on student learning. However, currently empirical data on how best to use VPs in practice are scarce. More knowledge is needed regarding aspects of integrating VPs into a course, of which student acceptance is one key issue. Several authors call for looking beyond technology to see VPs in relation to the course context. The follow-up seminar is proposed as an important aspect of integration that warrants investigation. METHODS: A cross-sectional explanatory study was performed in a clinical clerkship introduction course at four teaching hospitals affiliated to the same medical faculty. The VP-related activities were planned collaboratively by teachers from all four settings. However, each setting employed a different strategy to follow up the activity in the course. Sixteen questionnaire items were grouped into three scales pertaining to: perceived benefit of VPs; wish for more guidance on using VPs, and wish for assessment and feedback on VPs. Scale scores were compared across the four settings, which were ranked according to the level of intensity of students' processing of cases during VP follow-up activities. RESULTS: The perceived benefit of VPs and their usage were higher in the two intense-use settings compared with the moderate- and low-intensity settings. The wish for more guidance was high in the low- and one of the high-intensity settings. Students in all settings displayed little interest in more assessment and feedback regarding VPs. CONCLUSIONS: High case processing intensity was related to positive perceptions of the benefit of VPs. However, the low interest in more assessment and feedback on the use of VPs indicates the need to clearly communicate the added value of the follow-up seminar. The findings suggest that a more intense follow-up pays off in terms of the benefit perceived by students. This study illustrates the need to consider VPs from the perspective of a holistic course design and not as isolated add-ons.

Case-based training of evidence-based clinical practice in primary care and decreased mortality in patients with coronary heart disease.

PURPOSE: We investigated the 10-year mortality rates in a trial that tested a case-based intervention in primary care aimed at reducing the gap between evidence-based goals and clinical practice in patients with coronary heart disease (CHD). METHODS: A prospective randomized controlled pragmatic trial was undertaken in a primary care setting. New evidence-based guidelines, with intensified lipid-lowering recommendations in CHD, were mailed to all general practitioners in the region and presented at a lecture in 1995. General practitioners (n = 54) and patients with CHD (n = 88) were assigned according to their primary health care center to 2 balanced groups and randomly allocated to usual care as a control or to an active intervention. General practitioners in the intervention group participated in repeated case-based training during a 2-year period. Patients whose CHD was treated by specialists (n = 167) served as an internal specialist comparison group. Altogether, 255 consecutive patients were included. Cox regression analysis was used to detect any survival benefit of the intervention. RESULTS: At 10 years, 22% of the patients in the intervention group had died as compared with 44% in the control group (P = .02), with a hazard ratio of 0.45 (95% confidence interval, 0.20-0.95). This difference was mainly due to reduced cardiovascular mortality in the intervention group (P = .01). In addition, the mortality rate of 22% in the intervention group was comparable to the rate of 23% seen in patients treated by a specialist. CONCLUSIONS: Use of case-based training to implement evidence-based practice in primary care was associated with decreased mortality at 10 years in patients with CHD.

Pre-implant right ventricular function might be an important predictor of the response to cardiac resynchronization therapy.

OBJECTIVE: Cardiac resynchronization therapy is proven efficacious in patients with heart failure (HF). Presence of biventricular HF is associated with a worse prognosis than having only left ventricular (LV) HF and pacing might deteriorate heart function. The aim of the study was to assess a possible significance of right ventricular (RV) pre-implant systolic function to predict response to CRT. DESIGN: We studied 22 HF-patients aged 72 ± 11 years, QRS-duration 155 ± 20 ms and with an LV ejection fraction (EF) of 26 ± 6% before and four weeks after receiving a CRT-device. RESULTS: There were no changes in LV diameters or end systolic volume (ESV) during the study. However, end diastolic volume (EDV) decreased from 226 ± 71 to 211 ± 64 ml (p = 0.02) and systolic maximal velocities (SMV) increased from 2.2 ± 0.4 to 2.6 ± 0.9 cm/s (p = 0.04). Pre-implant RV-SMV (6.2 ± 2.6 cm/s) predicted postoperative increase in LV contractility, p = 0.032. CONCLUSIONS: Pre-implant decreased RV systolic function might be an important way to predict a poor response to CRT implicating that other treatments should be considered. Furthermore we found that 3D- echocardiography and Tissue Doppler Imaging were feasible to detect short-term changes in LV function.

Significance of pretreatment cardiovascular morbidity as a risk factor during treatment with parenteral oestrogen or combined androgen deprivation of 915 patients with metastasized prostate cancer: evaluation of cardiovascular events in a randomized trial.

OBJECTIVE: This study aimed to evaluate prognostic risk factors for cardiovascular events during treatment of metastatic prostate cancer patients with high-dose parenteral polyoestradiol phosphate (PEP, Estradurin®) or combined androgen deprivation (CAD) with special emphasis on pretreatment cardiovascular disease. MATERIAL AND METHODS: Nine-hundred and fifteen patients with T0-4, Nx, M1, G1-3, hormone- naïve prostate cancer were randomized to treatment with PEP 240 mg i.m. twice a month for 2 months and thereafter monthly, or to flutamide (Eulexin®) 250 mg per os three times daily in combination with either triptorelin (Decapeptyl®) 3.75 mg i.m. per month or on an optional basis with bilateral orchidectomy. Pretreatment cardiovascular morbidity was recorded and cardiovascular events during treatment were assessed by an experienced cardiologist. A multivariate analysis was done using logistic regression. RESULTS: There was a significant increase in cardiovascular events during treatment with PEP in patients with previous ischaemic heart disease (p = 0.008), ischaemic cerebral disease (p = 0.002), intermittent claudication (p = 0.031) and especially when the whole group of patients with pretreatment cardiovascular diseases was analysed together (p < 0.001). In this group 33% of the patients had a cardiovascular event during PEP treatment. In the multivariate analysis PEP stood out as the most important risk factor for cardiac complications (p = 0.029). Even in the CAD group there was a significant increase in cardiovascular events in the group with all previous cardiovascular diseases taken together (p = 0.036). CONCLUSIONS: Patients with previous cardiovascular disease are at considerable risk of cardiovascular events during treatment with high-dose PEP and even during CAD therapy. Patients without pretreatment cardiovascular morbidity have a moderate cardiovascular risk during PEP treatment and could be considered for this treatment if the advantages of this therapy, e.g. avoidance of osteopenia and hot flushes and the low price, are given priority.

Long-term effects of an expanded cardiac rehabilitation programme after myocardial infarction or coronary artery bypass surgery: a five-year follow-up of a randomized controlled study.

OBJECTIVE: To investigate the long-term effect of expanded cardiac rehabilitation on a composite end-point, consisting of cardiovascular death, myocardial infarction or readmission for cardiovascular disease, in patients with coronary artery disease. DESIGN: Single-centre prospective randomized controlled trial. SETTING: University hospital. SUBJECTS: Two hundred and twenty-four patients with acute myocardial infarction or undergoing coronary artery by-pass grafting. INTERVENTION: Patients were randomized to expanded cardiac rehabilitation (a one-year stress management programme, increased physical training, staying at a 'patient hotel' for five days after the event, and cooking sessions), or to standard cardiac rehabilitation. MAIN MEASURES: Data on cardiovascular death, myocardial infarction, readmission for cardiovascular disease and days at hospital for cardiovascular reasons were obtained from national registries of the Swedish National Board of Health and Welfare. RESULTS: The primary end-point occurred in 121 patients altogether (54%). The number of cardiovascular events were reduced in the expanded rehabilitation group compared with the standard cardiac rehabilitation (53 patients (47.7%) versus 68 patients (60.2%); hazard ratio 0.69; P =0.049). This was mainly because of a reduction of myocardial infarctions in the expanded rehabilitation group. During the five years 12 patients (10.8%) versus 23 patients (20.3%); hazard ratio 0.47; P =0.047 had a myocardial infarction. Days at hospital for cardiovascular reasons were significantly reduced in patients who received expanded cardiac rehabilitation (median 6 days) compared with standard cardiac rehabilitation (median 10 days; P =0.02). CONCLUSION: Expanded cardiac rehabilitation after acute myocardial infarction or coronary artery bypass grafting reduces cardiovascular morbidity and days at hospital for cardiovascular reasons.

Effects of interprofessional education on patient perceived quality of care.

BACKGROUND: Active patient-based learning by working together at an interprofessional clinical education ward (CEW) increases collaborative and professional competence among students. AIM: To assess the patients' perceptions of collaborative and communicative aspects of care when treated by interprofessional student teams as compared to usual care. METHOD: Patients treated by student teams (medical, nurse, physiotherapy and occupational therapy students) at a CEW comprised the intervention group. Patients treated at a regular ward were taken as controls. The patients answered a questionnaire representing collaborative and communicative aspects of care. Questionnaires from CEW (n = 84) and control (n = 62) patients were obtained (82% vs 73% response rates). RESULTS: CEW patients rated a significantly higher grade of own participation in decisions regarding treatment as compared to controls (p = 0.006). They did further rate a higher grade of satisfaction with information regarding need of help at home (p = 0.003) and perceived that the CEW staff had taken their home situation into account at a higher grade in the preparation of discharge (p = 0.0002). Finally, CEW patients felt better informed (p = 0.02). CONCLUSION: Patients perceived a higher grade of quality of care as compared to controls with no signs of disadvantages when treated and informed by supervised interprofessional student teams.

Nursing Students Learn to Handle Stress and to Prioritize in a Complex Context During Workplace Learning in Acute Internal Medicine Care - An Ethnographic Study.

INTRODUCTION: A common focus in many studies, in the short-term perspective, is to evaluate students' workplace learning and its outcome. However, the outcome can be perceived differently depending on when it was evaluated. The aim of this study was to explore student nurses' learning activities in an acute internal medicine unit and the nurses perceived learning outcome in a long-term perspective. MATERIAL AND METHODS: Repetitive ethnographic observations were performed in an internal medicine care unit at a teaching hospital in Sweden between 2011 and 2013. Four student nurses and supervisors were repetitively observed. Two years later retrospective interviews were performed with four nurses who had performed workplace learning, as students, in this unit during the observation period. An inductive comparative analysis involving all interviews and observational data was applied. RESULTS: Three themes were identified: To handle shifting situations - illustrating how student nurses learnt to adapt to shifting situations, to manage stress, to create structure and space for learning and to deal with hierarchies; To build relationships - illustrating how student nurses learnt to collaborate and to interact with patients; To act independently - illustrating how student nurses trained to act independently in the unit, took responsibility, and prioritized in this complex context. CONCLUSION: Learning activities in a complex acute medical unit setting were characterized by a high workload and frequent stressful situations, and a demand on students to interact, to take responsibility, and to prioritize. To learn in such a stressful context, have in a long-term perspective, a potential to develop students' embodied understanding of and in practice, making them more prepared to work and independently apply their nursing expertise in similar contexts as graduated nurses.

Changes in the plasma microvesicle proteome during the ovarian hyperstimulation phase of assisted reproductive technology.

The incidence of pulmonary and venous thromboembolism is increased during the first trimester of pregnancies after assisted reproductive technology (ART) compared to spontaneous conception. We previously found that haemostatic plasma variables changed but within normal limits during controlled ovarian hyperstimulation (COH) concomitant with a major increase in plasma microvesicles (MVs) and markers indicating cell activation. We now explored the proteome of these MVs. Thirty-one women undergoing ART were blood sampled at down-regulation (DR) of oestrogen and at high level stimulation (HLS) with its 10-100-fold increased oestrogen level. Samples were analysed by liquid chromatography and tandem mass spectrometry to identify and quantify the proteome. We identified 306 proteins in the MVs and 72 had changed significantly at HLS compared to DR and more than 20% of them were associated with haemostasis. Thus, proteins related to both haemostasis and complement activation altered in plasma MVs in parallel with MV activation during COH. This needs to be further explored in the clinical context.

Prognostic Value of Circulating Microvesicle Subpopulations in Ischemic Stroke and TIA.

Platelet microvesicles (PMV) have previously been found elevated in acute ischemic stroke (IS) and could be biomarkers for risk of recurrence. PMV surface antigens such as P-selectin and phosphatidylserine (PS) reflect platelet activation and procoagulance. Tissue factor-positive microvesicles (TF+MV) are considered procoagulant, in particular if co-expressing PS. We enumerated MV subpopulations with these surface antigens in a cohort of 211 patients with primarily non-cardioembolic IS or transient ischemic attack (TIA) and investigated their association with long-term outcome. MV concentrations were determined by flow cytometry in the acute and convalescent phase. Primary outcome was a composite of fatal and non-fatal recurrent IS or myocardial infarction. Secondary outcomes were recurrent IS and all-cause mortality. Outcome events were obtained from Swedish registers during a follow-up of 1100 patient years. Concentrations of PS-positive and PS-negative MV populations were elevated in patients compared with healthy controls in both the acute and convalescent phase. PS+TF+PMV displayed pronounced elevations, median fold change 77 in the acute phase (p < 0.0001) but were not associated with outcome, neither were PS+P-selectin+PMV. The only subpopulation positively associated with primary outcome was PS-TF+PMV, with adjusted hazard ratio of 1.86 (1.04-3.31, p = 0.036) by Cox regression. Unexpectedly, several MV subpopulations tended to be associated with reduced risk of poor long-term outcome. Our results suggest that PS+TF+PMV may be a promising marker for cerebral ischemia, and that the in vivo generation of PS-MV after IS/TIA warrants further study. Future MV studies should ideally enumerate PS+ and PS-MV subpopulations separately.