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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.

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 =

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.

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.

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.

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.

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.

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.

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.

BACKGROUND: About 25-40% of hospital patients are malnourished. With current clinical practices, only 50% of malnourished patients are identified by the medical and nursing staff.OBJECTIVE: The objective of this study was to report the cost and effectiveness of early recognition and treatment of malnourished hospital patients with the use of the Short Nutritional Assessment Questionnaire (SNAQ).DESIGN: The intervention group consisted of 297 patients who were admitted to 2 mixed medical and surgical wards and who received both malnutrition screening at admission and standardized nutritional care. The control group consisted of a comparable group of 291 patients who received the usual hospital clinical care. Outcome measures were weight change, use of supplemental drinks, use of tube feeding, use of parenteral nutrition and in-between meals, number of consultations by the hospital dietitian, and length of hospital stay.RESULTS: The recognition of malnutrition improved from 50% to 80% with the use of the SNAQ malnutrition screening tool during admission to the hospital. The standardized nutritional care protocol added approximately 600 kcal and 12 g protein to the daily intake of malnourished patients. Early screening and treatment of malnourished patients reduced the length of hospital stay in malnourished patients with low handgrip strength (ie, frail patients). To shorten the mean length of hospital stay by 1 d for all malnourished patients, a mean investment of 76 euros (91 US dollars) in nutritional screening and treatment was needed. The incremental costs were comparably low in the whole group and in the subgroup of malnourished patients with low handgrip strength.CONCLUSIONS: Screening with the SNAQ and early standardized nutritional care improves the recognition of malnourished patients and provides the opportunity to start treatment at an early stage of hospitalization. The additional costs of early nutritional care are low, especially in frail malnourished patients.

Physicians often take shortcuts in diagnostic reasoning by being selective in the information that they gather and follow-up on. Although necessary, these shortcuts are susceptible to cognitive biases and may cause diagnostic errors. The aim of this study is to examine the occurrence of inappropriate selectivity in the information-gathering and information-processing stages of the diagnostic process and study how it relates to diagnostic errors and patient harm in clinical practice. Expert internists reviewed the patient records of 247 dyspnea patients of five acute-care hospitals in the Netherlands, to detect reasoning faults, diagnostic errors and patient harm. The cases with reasoning faults were discussed with the treating physicians. Based on the record review and the clarifications from the treating physicians, the occurrence of inappropriate selectivity in information-gathering and information-processing was established and related to the occurrence of diagnostic errors and patient harm. Inappropriate selectivity in the diagnostic reasoning process occurred in 45.7% (113 of 247) of the cases. Specifically, selective information-gathering occurred in 33.2% of the cases and selective information-processing in 12.6% of the cases. Diagnostic errors occurred in 18.3% of the cases with selective information-gathering, and in 35.5% of the cases with selective information-processing. Patient harm occurred in 11.0% of the cases with selective information-gathering and in 38.7% of the cases with selective information-processing. The results showed that inappropriate selectivity in the diagnostic process occurred in a substantial number of cases. Particularly inappropriate selective information-processing was related to diagnostic errors and patient harm. Prevention strategies should include an increase in promoting the falsification strategies in the diagnostic process.

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.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.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. computer-assisted 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.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.

BACKGROUND: Predicting resting energy expenditure (REE) in malnourished hospitalized older patients is important for establishing optimal goals for nutritional intake. Measuring REE by indirect calorimetry is hardly feasible in most clinical settings.OBJECTIVE: To study the most accurate and precise REE predictive equation for malnourished older patients at hospital admission and again three months after discharge.DESIGN: Twenty-three equations based on weight, height, gender, age, fat free mass (FFM) and/or fat mass (FM) and eleven fixed factors of kcal/kg were compared to measured REE. REE was measured by indirect calorimetry. Accuracy of REE equations was evaluated by the percentage patients predicted within 10% of REE measured, the mean percentage difference between predicted and measured values (bias) and the Root Mean Squared prediction Error (RMSE).RESULTS: REE was measured in 194 patients at hospital admission (mean 1473 kcal/d) and again three months after hospital discharge in 107 patients (mean 1448 kcal/d). The best equations predicted 40% accuracy at hospital admission (Lazzer, FAO/WHO-wh and Owen) and 63% three months after discharge (FAO/WHO-wh). Equations combined with FFM, height or illness factor predicted slightly better. Fixed factors produce large RMSE's. All predictive equations showed proportional bias, with overestimation of low REE values and underestimation of high REE values. Correction by regression analysis did not improve results.CONCLUSIONS: The REE predictive equations are not adequate to predict REE in malnourished hospitalized older patients. There is an urgent need for either a new accurate REE predictive equation, or accurate easy-to-use equipment to measure REE in clinical practice.

Background Diagnostic error is an important error type since diagnostic adverse events are regularly judged as being preventable and the consequences are considered to be severe. Existing research often focuses on either diagnostic adverse events or on the errors in diagnostic reasoning. Whether and when an incorrect diagnostic process results in adverse outcomes has not been studied extensively. The present paper describes the design of a study that aims to study the relationship between a suboptimal diagnostic process and patient outcomes. In addition, the role of personal and circumstantial factors on the quality of the diagnostic process will be examined. Methods/Design The research questions were addressed using several data sources. First, the differential diagnosis was assessed concurrently to the diagnostic process. Second, the patient records of 248 patients suffering from shortness of breath were reviewed by expert internists in order to reveal suboptimal cognitive acts and (potential) consequences for the patient. The suboptimal cognitive acts were discussed with the treating physicians and classified with the taxonomy of unsafe acts. Third, workload, fatigue and work experience were measured during the physicians work. Workload and fatigue were measured during the physicians shift using the NASA tlx questionnaire on a handheld computer. Physicians participating in the study also answered questions about their work experience. Discussion The design used in this study provides insight into the relationship between suboptimal cognitive acts in the diagnostic process and possible consequences for the patient. Suboptimal cognitive acts in the diagnostic process and its causes can be revealed. Additional measurements of workload, fatigue and experience allow examining the influence of these factors on the diagnostic process. In conclusion, the present design provides a method with which insights in weaknesses of the diagnostic process and the effect on patient outcomes can be studied and opportunities for improvement can be obtained.

Background/Aim: Haemodialysis-treated patients are at a high risk of developing cardiovascular disease. Part of this risk may be attributable to the type of the dialysis membrane used. We evaluated whether different dialysis membranes differ with respect to platelet activation. Methods: In a randomized crossover trial, the platelet activation was measured in 14 patients treated with two different dialyzers (cuprammonium rayon membrane and polysulfone membrane). We compared the platelet activation over the dialyzer and between dialyzers after several weeks of dialysis. Results: There were no differences between the two dialyzers in platelet activation over the dialyzer. After 2 weeks, however, the expression of CD62P, CD63, and PAC-1 was statistically significantly lower after cuprammonium membrane treatment than after polysulfone membrane treatment (mean fluorescence intensity in arbitrary units 8.0 vs. 11.1, 2.64 vs. 4.01, and 5.61 vs. 9.74, respectively). Conclusion: Dialysis with a polysulfone membrane seems to lead to more platelet activation than dialysis with a cuprammonium membrane.

Objective: To characterize malnutrition in a nonspecific group of newly admitted hospital patients. Design: A prospective, descriptive study aiming to identify typical symptoms of malnutrition in a heterogeneous population of newly admitted patients to the wards of internal medicine. Setting: The wards of internal medicine of the VU University Medical Center. Subjects: A total of 106 patients were included in the study, 70 patients underwent the full interview. Next to nutritional status, the sociodemographics, underlying disease, estimated care complexity, care situation before admission, journey through the care system, nutritional intervention and nutritional follow-up after discharge were described for each patient. Results: Of 70 patients 24 (34%) were malnourished. Malnourished patients suffered two chronic diseases vs one for well-nourished patients (P =0.05). They also had a higher estimated care complexity (P =0.035) and a trend towards longer length of hospital stay (P =0.09). Malnourished patients did not differ from well-nourished patients in age, sex, partner status and care received at home. In all, 54% of the malnourished patients were identified correctly by the medical staff. The reasons for admission to the hospital were diverse in only four out of 24 patients malnutrition was the primary reason for admission. Discharge letters to the general practitioner (GP) contained only fragmentary information about the patients' nutritional status. At 3 months after discharge, most of the GPs were scarcely aware of any nutritional problems of their patients. Conclusions: Malnutrition is difficult to recognize in a nonspecific hospital population. Patients do not present with unique symptoms indicating malnutrition. To be able to correctly identify all malnourished patients, screening of the nutritional status of all newly admitted patients seems to be necessary.

Hormone replacement therapy (HRT) is accompanied by many changes in the hemostatic system. Because several individual hemostatic variables have been suspected to be reasonable indicators of the hemostatic balance and because this balance is thought to play an important role in the pathogenesis of several diseases, careful examination of the changes in this system induced by HRT could be helpful, first to improve HRT and second to improve our understanding of mechanisms of cardiovascular disease. The effects of (several forms of) HRT on individual hemostatic variables are discussed in this article. The pattern that emerges is that HRT stimulates coagulation, inhibits anticoagulation, and stimulates fibrinolysis (partly by inhibition of fibrinolysis). There are, however, few data that give clear insight into the effects of HRT on hemostatic variables. Controlled randomized clinical studies are needed to evaluate further the effects of HRT on the hemostatic system, to understand the interplay between inflammation and coagulation (both pathways being affected by HRT), and to understand how HRT-associated changes are affected by differences in genetic background.

Postmenopausal women with type 2 diabetes mellitus have a high risk of cardiovascular disease. Hormone replacement therapy (HRT) with estrogens with or without progestagens relieves many climacteric symptoms. Although hormone replacement in theory could have beneficial effects on cardiovascular morbidity, to date no randomized controlled clinical trial has shown positive results in this regard. There are few data with respect to diabetic postmenopausal women. There is no basis for prescription of HRT to diabetic women if the aim is to lower cardiovascular morbidity. On the other hand, there is also no reason not to prescribe HRT to diabetic women to treat climacteric symptoms.