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Guidelines are undeniably of great value to practicing physicians, but there are also objections. Due to the multitude of guidelines, it is sometimes difficult to find the most appropriate and it is not always clear how well-founded recommendations are. In addition, guidelines can limit the freedom of action. Also, in individual patients - especially in the case of multimorbidity - recommendations from different guidelines can conflict with each other. Finally, drawing up guidelines takes a lot of time, which is at the expense of patient care, and conflicts of interest are difficult to avoid completely. It is therefore important to put the recommendations from guidelines into perspective: they are an aid to individual patient care, not a law. This perspective is also important in education, so that students are taught to use guidelines in a wise way. Finally, it is important to regularly evaluate recommendations and revise them if necessary.

Disciplinary law originally intends to promote quality in individual health care. One could argue on the basis of empirical data that the current practice of medical disciplinary law does not demonstrably contribute to 'defensive medicine', a putative adverse effect of this form of jurisdiction. However, the practice and perception of disciplinary law should demonstrate that the possible other side effects (e.g. time consuming, emotionally distressful, impeding transparency to patients and colleagues, increasing the burden of uncertainty in medicine) of this form of case law dwarfs the yield: this postulated quality improvement. The words 'discipline' and 'law' are in themselves barriers in catalyzing an open attitude towards discussing suboptimal processes in health care with both patients and colleagues. Further reflection on the scope of practice and the perception of disciplinary law is necessary in order to further shape a cultural shift towards such an attitude and an dialogue. We have to move from the disciplinary law to a learning portal.

Background Cardiovascular risk is increased in transgender persons using gender-affirming hormone therapy. To gain insight into the mechanism by which sex hormones affect cardiovascular risk in transgender persons, we investigated the effect of hormone therapy on markers of inflammation and hemostasis. Methods In this exploratory study, 48 trans women using estradiol patches plus cyproterone acetate (CPA) and 47 trans men using testosterone gel were included. They were between 18 and 50 years old and did not have a history of cardiovascular events. Measurements were performed before and after 3 and 12 months of hormone therapy. Results After 12 months, in trans women, systemic and endothelial inflammatory markers decreased (hs-CRP -66%, (95% CI -76; -53), VCAM-1–12%, (95% CI -16; -8)), while platelet activation markers increased (PF-4 +17%, (95% CI 4; 32), β-thromboglobulin +13%, (95% CI 2; 24)). The coagulation marker fibrinogen increased transiently, after 3 months (+15%, (95% CI 1; 32)). In trans men, hs-CRP increased (+71%, (95% CI 19; 145)); platelet activation and coagulation markers were not altered. In both trans women and trans men, leptin and adiponectin changed towards reference values of the experienced gender. Conclusions Platelet activation and coagulation marker concentrations increased in trans women using transdermal estradiol plus CPA, but not in trans men using testosterone. Also, concentrations of inflammatory markers decreased in trans women, while hs-CRP increased in trans men. Our results indicate that hormone therapy may affect hemostasis in transgender persons, which could be an underlying mechanism explaining the increased cardiovascular risk in this population.

Objectives The objective of this study is to investigate possible changes in aspirin resistance during and after pregnancy over time. Study design A longitudinal cohort study in obstetric high risk women with an indication for aspirin usage during pregnancy to prevent placenta mediated pregnancy complications. Main outcome measures Aspirin resistance measured in the first, second and third trimester of pregnancy and at least three months postpartum by four complementary test: PFA-200, VerifyNow®, Chronolog light transmission aggregometry (Chronolog LTA) and serum thromboxane B2 (TxB2) level measurements. Correlation between the devices was investigated. Results In total, 23 pregnant women participated in the present study. Aspirin resistance according to the PFA-200, VerifyNow®, Chronolog LTA and serum TxB2, was 30.4%, 17.4%, 26.1% and 23.8% respectively. Resistance by any device was 69.6%. Aspirin resistance measured by the VerifyNow®, Chronolog LTA, serum TxB2 and aspirin resistance by any device during pregnancy was demonstrated more frequently than aspirin resistance after pregnancy. Correlation between the different devices was weak. Conclusion Aspirin resistance was found in a considerable part of the participants. Considerable variation between participants, within participants over time and between the different devices was found. Prevalence of aspirin resistance during pregnancy differs from after pregnancy. More research on aspirin resistance and clinical obstetric outcome is needed.

Context: The impact of gender-affirming hormone therapy (HT) on cardiometabolic parameters is largely unknown. Objective: The effects of 1 year of treatment with oral or transdermal administration of estrogen (plus cyproterone) and transdermal or IM application of testosterone on serum lipid levels and blood pressure (BP) were assessed in transgender persons. Design and Methods: In this prospective, observational substudy of the European Network for the Investigation of Gender Incongruence, measurements were performed before and after 12 months of HT in 242 transwomen and 188 transmen from 2010 to 2017. Results: Mean values are reported. In transmen, HT increased diastolic BP (2.5%; 95% CI, 0.6 to 4.4) and levels of total cholesterol (TC; 4.1%; 95% CI, 1.5 to 6.6), low-density lipoprotein-cholesterol (LDL-C; 13.0%; 95% CI, 9.2 to 16.8), and triglycerides (36.9%; 95% CI, 29.8 to 44.1); high-density lipoprotein-cholesterol levels decreased (HDL-C; 10.8%; 95% CI, 214.0 to 27.6). In transwomen, HT slightly decreased BP (systolic BP, 22.6%, 95% CI, 24.2 to 21.0; diastolic BP, 22.2%, 95% CI, 24.0 to 20.4) and decreased levels of TC (29.7%; 95% CI, 211.3 to 28.1), LDL-C (26.0%; 95% CI, 28.6 to 3.6), HDL-C (29.3%; 95% CI, 211.4 to 27.3), and triglycerides (210.2%; 95% CI, 214.5 to 25.9). Conclusion: Unfavorable changes in lipid profile were observed in transmen; a favorable effect was noted in transwomen. HT effects on BP were negligible. Long-term studies are warranted to assess whether and to what extent HT in trans individuals results in a differential effect on cardiovascular disease outcomes.

Research into diagnostic reasoning often focuses on diagnostic errors, while ignoring the also important concepts of overdiagnosis and cost of the diagnostic process. A popular theoretic model guiding studies on the subject is the dual process model in which cognitive errors play an important role. This paradigm is also used in the study of Mamede and colleagues, who studied the effect of disease specific knowledge on the occurrence of diagnostic errors due to availability bias in internal medicine residents. The study, which used case vignettes, is well set up but its experimental design cannot account for the influence of clinical context which limits its clinical value. Further research into this topic should be performed in actual clinical situations to provide more insight in how to improve diagnostic reasoning in medicine.

Context Erythrocytosis is a known side effect of testosterone therapy that can increase the risk of thromboembolic events. Objectives To study the prevalence and determinants in the development of erythrocytosis in trans men using testosterone. Methods A 20-year follow-up study in adult trans men who started testosterone therapy and had monitoring of hematocrit at our center (n = 1073). Results Erythrocytosis occurred in 11% (hematocrit > 0.50 L/L), 3.7% (hematocrit > 0.52 L/L), and 0.5% (hematocrit > 0.54 L/L) of trans men. Tobacco use (odds ratio [OR] 2.2; 95% CI, 1.6-3.3), long-acting undecanoate injections (OR 2.9; 95% CI, 1.7-5.0), age at initiation of hormone therapy (OR 5.9; 95% CI, 2.8-12.3), body mass index (BMI) (OR 3.7; 95% CI, 2.2-6.2), and pulmonary conditions associated with erythrocytosis and polycythemia vera (OR 2.5; 95% CI, 1.4-4.4) were associated with hematocrit > 0.50 L/L. In the first year of testosterone therapy hematocrit increased most: 0.39 L/L at baseline to 0.45 L/L after 1 year. Although there was only a slight continuation of this increase in the following 20 years, the probability of developing erythrocytosis still increased (10% after 1 year, 38% after 10 years). Conclusion Erythrocytosis occurs in trans men using testosterone. The largest increase in hematocrit was seen in the first year, but also after the first years a substantial number of people present with hematocrit > 0.50 L/L. A reasonable first step in the care for trans men with erythrocytosis while on testosterone is to advise them to quit smoking, to switch to a transdermal administration route, and if BMI is high, to lose weight.

Cardiovascular events occur most frequently in the early morning. Similarly, the release of reticulated platelets (RP) by megakaryocytes has a peak in the late night and early morning. Which aspirin regimen most effectively inhibits platelets during these critical hours is unknown. Hence, the primary objective of this trial was to assess platelet function and RP levels at 8.00 AM, in stable cardiovascular (CVD) patients, during three different aspirin regimens. In this open-label randomized cross-over study subjects were allocated to three sequential aspirin regimens: once-daily (OD) 80 mg morning; OD-evening, and twice-daily (BID) 40 mg. Platelet function was measured at 8.00 AM & 8.00 PM by serum Thromboxane B2 (sTxB2) levels, the Platelet Function Analyzer (PFA)-200® Closure Time (CT), Aspirin Reaction Units (ARU, VerifyNow®), and RP levels. In total, 22 patients were included. At 8.00 AM, sTxB2 levels were the lowest after OD-evening in comparison with OD-morning (p =

Aspirin is traditionally taken once daily in the morning and considered to be effective throughout the 24h interval. Cardiovascular events occur most frequently in the early morning, suggesting that these hours are critical in terms of adequate platelet inhibition. This study therefore assed platelet function in the early morning—8.00 AM—in healthy volunteers, during a once-daily (OD) 80 mg morning in comparison with an OD evening regimen and a twice-daily (BID) 40 mg regimen. It was an open-label randomized cross-over study, comprising 12 healthy subjects. Subjects were allocated to three sequential dosage regimens: 80 mg OD at 8.00 AM, 80mg OD at 8.00 PM, and 40 mg BID at 8.00 AM and PM. Platelet function 12 and 24 hours after aspirin intake was measured by means of serum thromboxane B2 (sTxB2) levels, the collagen/epinephrine closure time (Platelet Function Analyzer(PFA)-200®) and the Aspirin Reaction Units (ARU, VerifyNow®). The results demonstrated that early morning sTxB2 concentrations were 5843pg in the morning regimen, 2877pg in the evening OD regimen, and 3343pg in the BID regimen (morning- vs evening regimen p =

Aim of this study was to compare cardiovascular risk in women with and without inheritable thrombophilia after hypertensive disorders of pregnancy (HDP). Blood pressure, anthropometrics and blood samples were measured 9-13 years after early-onset ( 25 kg/m2 (43.8% vs. 53.1%, OR 0.69 95% CI (0.24–2.00)) or metabolic syndrome (18.8% vs. 13.3%, OR 1.51 95% CI (0.38–6.02)) were found. These data show similar cardiovascular risk profile in women with and without inheritable thrombophilia.

Background/Aim: Low-dose aspirin therapy (1 × 75–150 mg) is used in the secondary prevention of cardiovascular diseases. Recently it has been suggested that a twice daily regimen is more effective (2 × 40–75 mg). We therefore compared the precision of four subdivision methods. Method: A total of 280 aspirin tablets (acetylsalicylic acid 80 mg) were subdivided using four different methods (PillTool, hand, knife and Pilomat). Precision was compared using a difference score and loss of mass. The accuracy (uniformity of weight) was evaluated according to an adapted version of the European Pharmacopoeia test. Loss of mass was analysed using the criteria of the US Food and Drug Administration. Results: Evaluating the difference score (mean ± SD: PillTool 22 ± 14; hand 14 ± 8; knife 36 ± 23; and Pilomat 20 ± 13), the knife method was less precise than the PillTool, the hand method and the Pilomat (for all p < 0.001). Furthermore, the hand (p < 0.001) and the PillTool (p < 0.001) had statistically significantly a smaller loss of mass (mg) than the knife and the Pilomat (median (interquartile range): PillTool 1 (2), hand 0 (2), knife 4 (6) and Pilomat 3 (5)). Only breaking by hand complied with the adapted European Pharmacopoeia test. Tablets broken by PillTool and hand fulfilled the criteria of the US Food and Drug Administration test for loss of mass. Conclusion: Based on the results of our study, we recommend hand breaking and to avoid a knife for the best weight uniform tablets. If a tablet splitting device is necessary we advise use of the PillTool.

Objective: To study pregnancy chance in adult women with classic galactosemia and primary ovarian insufficiency. Despite dietary treatment, >90% of women with classic galactosemia develop primary ovarian insufficiency, resulting in impaired fertility. For many years, chance of spontaneous conception has not been considered, leading to counseling for infertility. But an increasing number of reports on pregnancies in this group questions whether current counseling approaches are correct.Design: Multicenter retrospective observational study.Setting: Metabolic centers.Patient(s): Adult women (aged >18 y) with confirmed classic galactosemia and primary ovarian insufficiency were included.Intervention(s): Participants and medical records were consulted to obtain study data in a standardized manner with the use of a questionnaire.Main outcome measure(s): Conception opportunities, time to pregnancy, pregnancy outcome, hormone replacement therapy use, fertility counseling, and the participants' vision of fertility were evaluated. Potential predictive factors for increased pregnancy chance were explored.Result(s): Eighty-five women with classic galactosemia and primary ovarian insufficiency participated. Twenty-one women actively attempted to conceive or did not take adequate contraceptive precautions. Of these 21 women, nine became pregnant spontaneously (42.9%). This was higher than reported in primary ovarian insufficiency due to other causes (5%-10%). After a period of 12 months, a cumulative proportion of 27.8% of couples had conceived, which increased to 48.4% after 24 months and 61.3% after 27 months. Predictive factors could not be identified. A considerable miscarriage rate of 30% was observed (6 of 20 pregnancies). Although a substantial proportion of women expressed a child-wish (n = 28/53; 52.8%), the vast majority of participants (n = 43/57; 75.4%) considered conceiving to be highly unlikely, owing to negative counseling in the past.Conclusion(s): The pregnancy rate in women with classic galactosemia and primary ovarian insufficiency was higher than for women with primary ovarian insufficiency of any cause. This shifting paradigm carries significant implications for fertility counseling and potential application of fertility preservation techniques. (C) 2017 American Society for Reproductive Medicine.

BACKGROUND: Previous analyses have shown that a post-discharge individualized nutritional intervention had positive effects on body weight, lean body mass, functional limitations and fall incidents in malnourished older patients. However, the impact of this intervention on survival has not yet been studied.OBJECTIVE: The objective of this randomized controlled study was to examine the effect of a post-discharge individualized nutritional intervention on survival in malnourished older patients.METHODS: Malnourished older patients, aged ≥ 60 years, were randomized during hospitalization to a three-months post-discharge nutritional intervention group (protein and energy enriched diet, oral nutritional supplements, vitamin D3/calcium supplement and telephone counseling by a dietitian) or to a usual care regimen (control group). Survival data were collected 4 years after enrollment. Survival analyses were performed using intention-to-treat analysis by Log-rank tests and Cox regression adjusted for confounders.RESULTS: The study population consisted of 94 men (45%) and 116 women with a mean age of 74.5 (SD 9.5) years. There were no statistically significant differences in baseline characteristics. Survival data was available in 208 out of 210 patients. After 1 and 4 years of follow-up, survival rates were respectively 66% and 29% in the intervention group (n=104) and 73% and 30% in the control group (n=104). There were no statistically significant differences in survival between the two groups 1 year (HR= 0.933, 95% CI=0.675-1.289) and 4 years after enrollment (HR=0.928, 95% CI=0.671-1.283).CONCLUSION: The current study failed to show an effect of a three-months post-discharge multi-component nutritional intervention in malnourished older patients on long-term survival, despite the positive effects on short-term outcome such as functional limitations and falls.

Introduction: The interplay between platelets and pro-thrombotic factors may have been under-investigated in the identification of aspirin users at high risk for cardiovascular event reoccurrences. There is growing evidence that a Prothrombin G20210A (FII) or a Factor V Leiden (FVL) mutation might increase platelet activity. Subsequently, this study assessed on-aspirin platelet (re-)activity in non-pregnant participants with a FII - or a FVL mutation in comparison with non-pregnant data derived from controls. Methods: This study was conducted with data derived from the follow-up FRUIT-RCT. This is a unique cohort namely, participants without a history of cardiovascular disease or thrombotic events, but who are a carrier of a pro-thrombotic mutation. All participants were instructed to ingest aspirin once daily for 10 days. Platelet (re-)activity was measured by the PFA Closure Time (PFA-CT), the VerifyNow (VN-ARU), and serum Thromboxane B2 (sTxB2) levels. Results: In total, eight participants with a FII-, 15 with a FVL mutation, and 21 controls were included. The FII mutation carriers demonstrated significantly higher on-aspirin platelet (re)-activity (PFA-CT, −92 sec.; VN-ARU, +37 ARU) vs. controls. The FVL carriers demonstrated similar on-aspirin platelet (re-)activity vs. controls. The sTxB 2 levels were similar in either of the carrier groups vs. controls. Conclusion: We feel these data are suggestive of increased on-aspirin platelet (re-)activity, as measured by the PFA-200 and the VerifyNow, in non-pregnant carriers of a FII-mutation, but not in carriers of FVL-mutation. Interestingly, this increased on-aspirin platelet (re-)activity is present in spite of low sTxB2 levels.

Background: Erythrocytosis is a known side effect of testosterone therapy in hypogonadal men and can increase the risk of thromboembolic events. Erythrocytosis is also seen in trans men (birth-assigned female, male gender identity) receiving testosterone therapy. Currently there are no clinical guidelines for the management of this problem in trans men. Specific aims: 1. To study the prevalence and determinants in the development of erythrocytosis in trans men using testosterone. 2. To study the association between duration of testosterone treatment and hematocrit levels. Methods: A 20 year follow-up study in adult trans men who started testosterone, and had monitoring of hematocrit levels at our center (n=1073). Results: Erythrocytosis (defined as hematocrit levels of >0.50 l/l twice) occurred in 11% of trans men. Multilevel analyses showed former or current smoking (OR 2.2, 95%CI 1.6-3.3), testosterone administration as long-acting intramuscular injection (OR 2.9, 95% CI 1.7-5.0), a higher age at initiation of hormone therapy (up to OR 5.9, 95% CI 2.8-12.3) for people above 40 compared to 30 g/m2 compared to 18.5-25 kg/m2) (OR 3.7, 95% CI 2.2-6.2) and a medical history for chronic pulmonary diseases, sleep apnea or polycythemia vera (OR 2.5, 95% CI 1.4-4.4) as determinants that increased the risk of high hematocrit levels. In the first year of testosterone therapy hematocrit levels increased most: from 0.39 l/l at baseline to 0.45 l/l after 1 year. Although there was only a slight continuation of this increase in the following 20 years (0.45 at 1 year and 0.46 at 20 years), the probability of developing erythrocytosis still increased (10% after 1 year, 38% after 20 years). Conclusion: Erythrocytosis frequently occurs in trans men using testosterone. The biggest increase in hematocrit was seen in the first year, but also after the first years there is a substantial number of people that present with hematocrit >0.50. Because smoking, obesity and use of injection as dosage form are associated with a higher risk for erythrocytosis, a reasonable first step in the care for transmen with erythrocytosis while on testosterone is to advise them to quit smoking and to switch to a transdermal administration type and if BMI is high, to lose weight.

Objective Aspirin reduces the risk of recurrent hypertensive disorders of pregnancy (HD) and fetal growth restriction (FGR). This study examined the non-adherence rates of aspirin in women with high-risk pregnancies. Study design All consecutive women between 24 and 36 weeks gestation with an indication for aspirin use during pregnancy were invited for this study. A survey was used which included two validated questionnaires, the simplified medication adherence questionnaire (SMAQ) and the Beliefs and Behaviour Questionnaire (BBQ). Main outcome measures To determine the non-adherence rates of aspirin, and to identify the beliefs and behavior concerning aspirin. Results Indications for aspirin use during pregnancy were previous HD, FGR, intrauterine fetal death or current maternal disease. Non-adherence rates according to the SMAQ and BBQ were 46.3% and 21.4% respectively. No differences in demographic background or obstetrical characteristics between adherent and non-adherent women could be demonstrated. Conclusions Adherence for aspirin in this high-risk population cannot be taken for granted. The non-adherence rates in pregnant women are comparable with the non-adherence rates for aspirin in the non-pregnant population.

Background Epidemiological studies have suggested an increased risk of cardiovascular events (CVE) during acute stressful and/or frightful moments. A possible explanation for this could be an effect of acute stress on hemostasis. A recent study demonstrated an increase in factor VIII after watching a horror movie. Primary hemostasis, however, is thought to play a more prominent role in the etiology of CVE. The objective of this study was therefore to assess the influence of viewing a ‘bloodcurdling’ horror movie on platelet reactivity in healthy volunteers. Methods We performed a randomized cross-over study in healthy adults. Subjects were allocated to two movies in random sequence: a horror and a control movie. Blood was drawn at baseline and after 24 min of viewing time. The primary endpoint was the change in Platelet Function Analyzer® Closure Time (Δ PFA-CT) after watching the movie. Results In total, 20 participants, aged 18–30 years, completed the study protocol. The delta PFA-CT was statistically significantly shorter with a mean in the delta difference of −9.7 s (SEM 4.0, 95% C.I. −18.0 to −1.3) during the horror movie versus the control movie. The Light Transmission Aggregometry endpoints were in line with the PFA-CT, albeit only the highest level of Arachidonic Acid agonist demonstrated a statistically significant mean difference in the delta of aggregation of 13.15% (SEM 7.0, 95% C.I. 1.6–27.9). Conclusion A ‘blood curdling’ horror movie increases platelet reactivity. These data are supportive of a role of platelet reactivity in acute stress induced cardiovascular event risk.

Background: Dutch cardiovascular risk management guidelines state almost every older adult (≥70 years) is eligible for a lipid lowering drug (LLD). However, life expectancy, frailty or comorbidities may influence this treatment decision. Objective: investigate how many older adults, according to age, frailty (Drubbel-frailty index) and comorbidities were prescribed LLDs. Methods: data of 244,328 adults ≥70 years from electronic health records of 415 Dutch general practices from 2011-15 were used. Number of LLD prescriptions in patients with (n = 55,309) and without (n = 189,019) cardiovascular disease (CVD) was evaluated according to age, frailty and comorbidities. Results: about 69% of adults ≥70 years with CVD and 36% without CVD were prescribed a LLD. LLD prescriptions decreased with age; with CVD: 78% aged 70-74 years and 29% aged ≥90 years were prescribed a LLD, without CVD: 37% aged 70-74 years and 12% aged ≥90 years. In patients with CVD and within each age group, percentage of LLD prescriptions was 20% point(pp) higher in frail compared with non-frail. In patients without CVD, percentage of LLD prescriptions in frail patients was 11pp higher in adults aged 70-74 years and 40pp higher in adults aged ≥90 years compared to non-frail. Similar trends were seen in the analyses with number of comorbidities. Conclusion: in an older population, LLD prescriptions decreased with age but - contrary to our expectations - LLD prescriptions increased with higher frailty levels.

Aspirin is traditionally taken once daily in the morning and considered to be effective throughout the 24h interval. Cardiovascular events occur most frequently in the early morning, suggesting that these hours are critical in terms of adequate platelet inhibition. This study therefore assed platelet function in the early morning-8.00 AM-in healthy volunteers, during a once-daily (OD) 80 mg morning in comparison with an OD evening regimen and a twice-daily (BID) 40 mg regimen. It was an open-label randomized cross-over study, comprising 12 healthy subjects. Subjects were allocated to three sequential dosage regimens: 80 mg OD at 8.00 AM, 80mg OD at 8.00 PM, and 40 mg BID at 8.00 AM and PM. Platelet function 12 and 24 hours after aspirin intake was measured by means of serum thromboxane B

Item does not contain fulltext BACKGROUND: Undernutrition is a common complication of disease and a major determinant of hospital stay outcome. Dutch hospitals are required to screen for undernutrition on the first day of admission. OBJECTIVE: We sought to determine the prevalence of the screening score "undernourished" with use of the Short Nutritional Assessment Questionnaire (SNAQ) or Malnutrition Universal Screening Tool (MUST) and its relation to length of hospital stay (LOS) in the general hospital population and per medical specialty. DESIGN: We conducted an observational cross-sectional study at 2 university, 3 teaching, and 8 general hospitals. All adult inpatients aged >/=18 y with an LOS of at least 1 d were included. Between 2007 and 2014, the SNAQ/MUST score, admitting medical specialty, LOS, age, and sex of each patient were extracted from the digital hospital chart system. Linear regression analysis with ln(LOS) as an outcome measure and SNAQ >/=3 points/MUST >/=2 points, sex, and age as determinant variables was used to test the relation between SNAQ/MUST score and LOS. RESULTS: In total, 564,063 patients were included (48% males and 52% females aged 62 +/- 18 y). Of those, 74% (419,086) were screened with SNAQ and 26% (144,977) with MUST, and 13.7% (SNAQ) and 14.9% (MUST) of the patients were defined as being undernourished. Medical specialties with the highest percentage of the screening score of undernourished were geriatrics (38%), oncology (33%), gastroenterology (27%), and internal medicine (27%).Patients who had an undernourished screening score had a higher LOS than did patients who did not (median 6.8 compared with 4.0 d; P < 0.001). Regression analysis showed that a positive SNAQ/MUST score was significantly associated with LOS [SNAQ: +1.43 d (95% CI: 1.42, 1.44 d), P < 0.001; MUST: +1.47 d (95% CI: 1.45, 1.49 d), P < 0.001]. CONCLUSIONS: This study provides benchmark data on the prevalence of undernutrition, including more than half a million patients. One out of 7 patients was scored as undernourished. For geriatrics, oncology, gastroenterology, and internal medicine, this ratio was even greater (1 out of 3-4). Hospital stay was 1.4 d longer among undernourished patients than among those who were well nourished.

Daily generation of novel platelets may compromise aspirin's platelet inhibitory action, especially near the end of the regular 24-h dosing interval. A contributor to this attenuation could be the endogenous circadian rhythm. The primary objective of this study was to assess platelet activity 12 and 24 h after different times of aspirin intake (c.q. 8.00 AM and 8.00 PM). A randomized open-label crossover study was conducted, comprising outpatients with stable cardiovascular disease taking aspirin once daily. We measured platelet aggregation with the platelet function analyzer (PFA)-200(®) and light transmission aggregometry (LTA). The attenuation of aspirin's inhibitory action was most apparent in the 8.00 AM regimen. The platelet function analyzer-closure time was 78 s faster at 24 h than at 12 h after intake in the 8.00 AM regimen (IQR: 166.8-301 vs. 132.8-301; p = 0.006) and 0 s faster at 24 h than at 12 h after intake in the 8.00 PM regimen (IQR: 198.8-837.0 vs. 169.8-301; p = 0.653). The adenosine diphosphate 1.0 µmol/L maximum amplitude was 5.40% higher at 24 h than at 12 h after intake in the 8.00 AM regimen (95% confidence interval (CI): -0.03--10.8; p = 0.040) and was 0.75% higher 24 h than at 12 h after intake in the 8.00 PM regimen (95% CI: -4.83-3.33; p = 0.705). The platelet inhibitory effect of aspirin decreases after 24 h, particularly after intake in the morning. These results suggest that patients might benefit from evening intake or twice daily intake regimens.

ᅟ Medical students should be better prepared for their future role as prescribers. A new educational concept to achieve this is learning by doing. This encompasses legitimate, context-based training and gives students responsibility as early as possible in their medical education. Student-run clinics (SRCs) are an example of this concept. Aim Describe the development of a new SRC for insured patients, primarily focused on medical (pharmacotherapy) education, the learner-centered student-run clinic (LC-SRC), and its feasibility. Methods Teams each comprising of three students (first, third, and fifth year) performed consultations including proposing management plans, all under the supervision of an internist. Patients were voluntary selected from the internal medicine outpatient clinic for follow-up in the LC-SRC. Feasibility was evaluated using a set of questionnaires for patients, supervisors, and students. Results In total, 31 consultations were conducted; 31 students and 4 clinical specialists participated. A pharmacotherapeutic treatment plan was drawn up in 33 % of the consultations. Patients were content with the care provided and rated the consultation with a 7.9 (SD 1.21) (1(min)-10(max)). Supervisors regarded LC-SRC safe for patients with guaranteed quality of care. They found the LC-SRC a valuable tool in medical education although it was time-consuming. Students appreciated their (new) responsibility for patient care and considered the LC-SRC a very valuable extracurricular activity. Discussion The LC-SRC is feasible, and all participants considered it to be a valuable educational activity. It offers students the opportunity to learn in a real interprofessional and longitudinal setting for their future role as prescriber in clinical practice. The benefits and learner effects need to be investigated in a larger study with a longer follow-up. Electronic supplementary material The online version of this article (doi:10.1007/s00228-015-1916-x) contains supplementary material, which is available to authorized users.

Background The Learner-Centered Student-run Clinic (LC-SRC) was designed to teach and train prescribing skills grounded in a real-life context, to provide students with early clinical experience and responsibility. The current studies’ theoretical framework was based on the Self-determination Theory. According to the Self-determination Theory, early involvement in clinical practice combined with a high level of responsibility makes the LC-SRC an environment that can stimulate intrinsic motivation. We investigated the different types of motivation and the proficiency in CanMEDS competencies of the participating students. Method Type of motivation was measured using the Academic Motivation Scale and Intrinsic Motivation Inventory. CanMEDS competencies were evaluated by faculty using a mini-clinical examination and by the students themselves using a post-participation questionnaire. Results The 29 participating students were highly intrinsic motivated for this project on all subscales of the Intrinsic Motivation Inventory. Motivation for medical school on the Academic Motivation Scale was high before and was not significantly changed after participation. Students considered that their CanMEDS competencies “Collaborator”, “Communicator”, “Academic”, and “Medical expert” had improved. Their actual clinical team competence was judged by faculty to be at a junior doctor level. Conclusion Students showed a high level of intrinsic motivation to participate in the LC-SRC and perceived an improvement in competence. Furthermore their actual clinical competence was at junior doctor level in all CanMEDS competencies. The stimulating characteristics of the LC-SRC, the high levels of intrinsic motivation and the qualitative comments of the students in this study makes the LC-SRC an attractive place for learning. Electronic supplementary material The online version of this article (doi:10.1186/s12909-017-0856-9) contains supplementary material, which is available to authorized users.

OBJECTIVE: The FRUIT-RCT concluded that low-molecular-weight heparin added to aspirin compared to treatment with aspirin alone is beneficial in the prevention of early-onset hypertensive disorders of pregnancy (HD) in women with inheritable thrombophilia and prior HD and/or a small-for-gestational age (SGA) infant leading to delivery before 34 weeks gestation. The aim of this study is to answer the question whether aspirin resistance is associated with recurrent HD.STUDY DESIGN: Women with and without recurrent HD matched for age, study arm, and chronic hypertension were invited for this follow-up study 6-16 years after they participated in the FRUIT-RCT. Aspirin resistance was tested after 10days of aspirin intake using three complementary tests: PFA-200, VerifyNow(®) and serum thromboxane B2 (TXB2). An independent t-test, Mann-Whitney U test, Fisher's Exact test and Chi(2) test were used for the statistical analyses.RESULTS: Thirteen of 24 women with recurrent HD and 16 of 24 women without recurrent HD participated. The prevalence of laboratory aspirin resistance was 34.5% according to the PFA-200, 3.4% according to the VerifyNow(®) and 24.1% according to TXB2. The prevalence of aspirin resistance by any test was 51.7%. Aspirin resistance per individual test did not differ between women with and without recurrent HD. Aspirin resistance measured by any test occurred more frequently in women without recurrent HD (pCONCLUSIONS: No relation could be demonstrated between recurrent HD and aspirin resistance per test, measured up to 16 years after pregnancy. On the contrary, complementary aspirin resistance measurements were encountered more frequently in women without recurrent HD.

Objective: To described cardiovascular risk factors in women with inheritable thrombophilia 8–19 years after early-onset hypertensive disorders of pregnancy (HD) with or without recurrent HD. Methods: Women with recurrent HD were compared with women with single HD, for physical examination and cardiovascular parameters in serum. Results: Systolic blood pressure, diastolic blood pressure, and albumin: creatinine ratio were higher in women with recurrent HD compared with women with single HD (p = 0.046, p = 0.029, and p = 0.008, respectively). In both groups 72.7% had an increased cardiovascular risk. Conclusion: Women with inheritable thrombophilia after single or recurrent HD have a high cardiovascular risk.

Ruling out disease often requires expensive or potentially harmful confirmation testing. For such testing, a less invasive triage test is often used. Intuitively, few negative confirmatory tests suggest success of this approach. However, if negative confirmation tests become too rare, too many disease cases could have been missed. It is therefore important to know how many negative tests are needed to safely exclude a diagnosis. We quantified this relationship using Bayes' theorem, and applied this to the example of pulmonary embolism (PE), for which triage is done with a Clinical Decision Rule (CDR) and D-dimer testing, and CT-angiography (CTA) is the confirmation test. For a maximum proportion of missed PEs of 1% in triage-negative patients, we calculate a 67% 'mandatory minimum' proportion of negative CTA scans. To achieve this, the proportion of patients with PE undergoing triage testing should be appropriately low, in this case no higher than 24%. Pre-test probability, triage test characteristics, the proportion of negative confirmation tests, and the number of missed diagnoses are mathematically entangled. The proportion of negative confirmation tests--not too high, but definitely not too low either--could be a quality benchmark for diagnostic processes.

Rationale: To support doctors in diagnosing patients who are suspected to have pulmonary embolism, the Christopher evidence-based decision rule was implemented in hospitals in the Netherlands. This study examines whether the Christopher evidence-based decision rule is applied in clinical practice. In addition, doctors’ considerations for not applying the decision rule are explored. Method: Dyspnoea patients were included in the study prospectively. The diagnostic process of the patients with suspected pulmonary embolism, as judged by the treating doctor, was compared with the Christopher evidence-based decision rule using patient record reviews. In addition, 14 interviews were conducted with doctors who did not follow the Christopher evidence-based decision rule to obtain insights into their considerations. Results: In 80 of 247 dyspnoea cases, the treating doctors suspected pulmonary embolism. The Christopher evidence-based decision rule was applied in 17 out of 80 cases. In 22 cases, more tests were performed than was suggested by the decision rule [i.e. computerassisted tomographic angiography (CTa) or d-dimer], while in 41 cases fewer tests were performed than suggested by the decision rule. Considerations for not following the decision rule included judging another diagnosis to be more likely and not wanting to expose the patient to CTa radiation. Conclusions: The Christopher evidence-based decision rule for diagnosing pulmonary embolism was not always followed in everyday clinical practice. Doctors seem to base their diagnostic strategy on their own estimate of the likelihood of pulmonary embolism, rather than the whole decision rule. Better adherence to the decision rule could be beneficial by making doctors aware that pulmonary embolism is more likely than they initially thought. However, in a substantial number of cases, it seemed justifiable that doctors deviated from the decision rule. Therefore, further research is needed to determine the value of the Christopher evidence-based decision rule in clinical practice. (aut. ref.)

OBJECTIVES: To evaluate the effects of a short-term nutritional intervention with protein and vitamin D on falls in malnourished older adults.DESIGN: Randomized controlled trial.SETTING: From hospital admission until 3 months after discharge.PARTICIPANTS: Malnourished older adults (≥ 60) newly admitted to an acute hospital (n = 210).INTERVENTION: Participants were randomized to receive nutritional intervention (energy- and protein-enriched diet, oral nutritional supplements, calcium-vitamin D supplement, telephone counseling by a dietitian) for 3 months after discharge or usual care.MEASUREMENTS: Number of participants who fell, fall incidents, serum 25-hydroxyvitamin D, and dietary intake. Measurements were performed on admission to hospital and 3 months after discharge.RESULTS: Three months after discharge, 10 participants (10%) in the intervention group had fallen at least once, compared with 24 (23%) in the control group (hazard ratio = 0.41, 95% confidence interval (CI) = 0.19-0.86). There were 57 fall incidents (16 in the intervention group; 41 in the control group). A significantly higher intake of energy (280 kcal, 95% CI = 37-524 kcal) and protein (11 g, 95% CI = 1-25 g) and significantly higher serum 25-hydroxyvitamin D levels (10.9 nmol/L, 95% CI = 2.9-18.9 nmol/L) were found in participants in the intervention group than in controls.CONCLUSION: A short-term nutritional intervention consisting of oral nutritional supplements and calcium and vitamin D supplementation and supported by dietetic counseling in malnourished older adults decreases the number of patients who fall and fall incidents.

Purpose The relationship between faults in diagnostic reasoning, diagnostic errors, and patient harm has hardly been studied. This study examined suboptimal cognitive acts (SCAs; i.e., faults in diagnostic reasoning), related them to the occurrence of diagnostic errors and patient harm, and studied the causes. Method

Background The burden of health care expenditure on national budgets has increased dramatically over the past decade. A pilot study in our hospital demonstrated that many unnecessary diagnostic tests were performed routinely. The aim of this study was to reduce the costs of unnecessary diagnostic tests. Methods All diagnostic costs between 2006 and 2008 of the internal medicine department of the VU University Centre were evaluated. A target was set to reduce diagnostic expenditure by 7.5% in 2009 compared to 2008. A few interventions were introduced including introducing posters and pocket cards detailing the costs of diagnostic tests, six weekly feedback on diagnostics costs, mentorship of junior doctors, unbundling panel tests and increasing protocol adherence. Main outcome measures were the reduction in the total diagnostic costs and the total number of laboratory tests performed in the internal medicine department in 2009. Results In 2009, we achieved a 13% reduction in the total diagnostic costs compared to 2008. The department of internal medicine spent 2.80 million euro and 2.45 million euro on the diagnostic tests in 2008 and 2009 respectively and thereby saved 350.000 euro in 2009. The largest reduction was achieved by reducing the number of laboratory tests performed. Conclusion Introduction of a few simple measures to improve awareness among the physicians led to a significant reduction in the diagnostic costs in the department of internal medicine. Extending these measures to the entire hospital and even entire country will in our opinion lead to significant reduction in the health care costs.

BACKGROUND & AIMS: Older people are vulnerable to malnutrition which leads to increased health care costs. The aim of this study was to evaluate the cost-effectiveness of nutritional supplementation from a societal perspective.DESIGN: This randomized controlled trial included hospital admitted malnourished elderly (≥ 60 y) patients. Patients in the intervention group received nutritional supplementation (energy and protein enriched diet, oral nutritional support, calcium-vitamin D supplement, telephone counselling by a dietician) until three months after discharge from hospital. Patients in the control group received usual care (control). Primary outcomes were Quality Adjusted Life Years (QALYs), physical activities and functional limitations. Measurements were performed at hospital admission and three months after discharge. Data were analyzed according to the intention-to-treat principle and multiple imputation was used to impute missing data. Incremental cost-effectiveness ratios were calculated and bootstrapping was applied to evaluate cost-effectiveness. Cost-effectiveness was expressed by cost-effectiveness planes and cost-effectiveness acceptability curves.RESULTS: 210 patients were included, 105 in each group. After three months, no statistically significant differences in quality of life and physical activities were observed between groups. Functional limitations decreased significantly more in the intervention group (mean difference -0.72, 95% CI-1.15; -0.28). There were no differences in costs between groups. Cost-effectiveness for QALYs and physical activities could not be demonstrated. For functional limitations we found a 0.95 probability that the intervention is cost-effective in comparison with usual care for ceiling ratios > €6500.CONCLUSIONS: A multi-component nutritional intervention to malnourished elderly patients for three months after hospital discharge leads to significant improvement in functional limitations and is neutral in costs. A follow-up of three months is probably too short to detect changes in QALYs or physical activities.

BACKGROUND: Older people are vulnerable to malnutrition, which leads to negative outcomes. This study evaluates the effectiveness of nutritional supplementation in malnourished elderly patients after hospital discharge.METHODS: Hospital-admitted malnourished elderly patients (≥ 60 years) were randomized to receive either nutritional supplementation (energy and protein enriched diet, oral nutritional support, calcium-vitamin D supplement, telephone counseling by a dietitian) for 3 months postdischarge or usual care. Outcomes were functional limitations, physical performance, physical activities, body weight, fat-free mass, and handgrip strength. Measurements were performed at hospital admission (baseline) and at 3 months after discharge. Data were analyzed according to the intention-to-treat principle.FINDINGS: A total of 210 patients were included, 105 in each group. Body weight increased more in the intervention group than in the control group; this was significant for the highest body weight category (mean difference 3.4 kg, 95% CI 0.2-6.6). Functional limitations decreased more (mean difference -0.5 (95% CI -1.0-0.1) in the intervention group than in the control group. When excluding patients who had already received nutritional support before the start of the study, this reached significance. No significant differences could be demonstrated for physical performance, physical activities, fat-free mass, or handgrip strength.INTERPRETATION: Three months of oral nutritional support to malnourished elderly decreased functional limitations and increased body weight. It can be questioned if a follow-up of only 3 months was not too short to detect differences on physical performance and physical activities as well.

Introduction Women who develop hypertensive disorders of pregnancy (HD) are at increased risk for cardiovascular disease later in life. Presence of inheritable thrombophilia is associated with poor placentation in HD. It is unknown whether the combination of inheritable thrombophilia and early-onset HD (HD Objective To compare cardiovascular risk factors 12.5 years in women after early-onset HD with and without inheritable thrombophilia. Methods We compared two prospective cohorts of women with a history of early-onset of HD. Women with inheritable thrombophilia (protein C deficiency, protein S deficiency, heterozygous factor V Leiden mutation and heterozygous prothrombin gene G20210A mutation) were compared to women without thrombophilia. Women with pre-existing hypertension were excluded. Physical examination was performed and cardiovascular parameters in serum were measured. Results Sixteen women with inheritable thrombophilia and 98 without thrombophilia were included. Seventy-five percent of all women developed one or more cardiovascular risk factor(s). Hypertension was present in 31.3% of women with thrombophilia and 33.7% without (p = 1.000), increased body mass index >25 kg/m[b] in 43.8% with thrombophilia and 53.1% without (p = 0.593) and hypercholesterolemia in 31.3% with thrombophilia and 43.9% without (p = 0.420). Differences were not significant. Discussion Our preliminary findings demonstrated similar cardiovascular risk factors in women after early-onset HD with and without inheritable thrombophilia. It raises the question whether there is a difference between the pathophysiological origin of HD between women with and without thrombophilia. In general, the role of thrombophilia in the development of cardiovascular risk factors is unclear. However, in this subgroup of women with a history of early-onset HD, thrombophilia does not modify the development of cardiovascular risk factors.

Can we improve our understanding of cardiovascular disease (CVD) causality and prediction? Intuitively, we can. Recent publications, however, could be misinterpreted as suggesting the opposite. First, the Interheart study, which concluded that nine conventional risk factors explain >90% of premature myocardial infarction, is at risk for being interpreted as saying that other, 'new' cardiovascular risk factors can only cause a small remaining fraction of disease of at most 10%. Secondly, papers addressing the predictive value of new risk factors or markers of early CVD risk have concluded that risk prediction does not improve by adding these variables to risk models. In this paper, we will explain that searching for 'new causes' of CVD is still highly relevant, and that improvement of risk prediction is often assessed using inappropriate statistical methodology. © The Author 2008.

Summary Background & aims Malnutrition continues to be an important problem in health care which is still under recognized and underrated in developed countries. This study aims to describe current practice in diagnosing and treating malnutrition by medical doctors, medical students and nurses prior, during and after hospitalisation. Methods Prospective analysis of current practice in assessing nutritional status and prescribing treatment by medical and nursing staff in a cohort of hospitalised patients from the general medical wards of the VU University Medical Center, Amsterdam. Comparison of objective identification of malnutrition by an independent observer with subjective identification by the medical and nursing staff. Quantification of diagnosing, treating and communicating malnutrition before, during and following hospital stay by medical doctors, medical students and nurses by evaluating the written information in medical and nursing charts, and referral and discharge letters. Results Three hundred and ninety-five women and men, aged 19–96 years, were included from June to September 2005. The prevalence of malnutrition was 31.9%. Nutritional information was not mentioned in written referrals. Medical doctors performed nutritional assessment in 15.3%, medical students in 52.8%, and nurses in 29.9% of their patients. Medical doctors were the most capable of differentiating between malnourished and well-nourished patients as a basis for undertaking nutritional assessment, although this was still inadequate. Little nutritional intervention was applied during hospital stay. Information on nutritional status was lacking in most discharge letters. Nutritional follow-up was appointed in 1.2%. Conclusions Nutritional assessment and intervention were not sufficiently applied by any professional at any stage of the pre-, actual and post-hospitalisation period.