Nationwide claims data validated for quality assessments in acute myocardial infarction in the Netherlands.

INTRODUCTION: Since health insurance is compulsory in the Netherlands, the centrally registered medical claims data might pose a unique opportunity to evaluate quality of (cardiac) care on a national level without additional collection of data. However, validation of these claims data has not yet been assessed. DESIGN: Retrospective cohort study. METHODS: National claims data ('national registry') were compared with data collected by patient records reviews in four representative hospitals ('validation registry'). In both registries, we extracted the national diagnosis codes for ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction of 2012 and 2013. Additionally, data on medication use at one year after acute myocardial infarction (AMI) was extracted from the Dutch pharmacy information systems and also validated by local patient records reviews. The data were compared at three stages: 1) validation of diagnosis and treatment coding; 2) validation of the hospital where follow-up has taken place; 3) validation of follow-up medical treatment after 365 days. RESULTS: In total, 3,980 patients ('national registry') and 4,014 patients ('validation registry') were compared at baseline. After one-year follow-up, 2,776 and 2,701 patients, respectively, were evaluated. Baseline characteristics, diagnosis and individual medication were comparable between the two registries. Of all 52,672 AMI patients in the Netherlands in 2012 and 2013, 81% used aspirin, 76% used P2Y12 inhibitors, 85% used statins, 82% used beta-blockers and 74% angiotensin converting enzyme inhibitors/angiotensin II antagonists. Optimal medical treatment was achieved in 49% of the patients with AMI. CONCLUSION: Nationwide routinely collected claims data in patients with an acute myocardial infarction are highly accurate. This offers an opportunity for use in quality assessments of cardiac care.

Arterial stiffness is not associated with bone parameters in an elderly hyperhomocysteinemic population.

Several studies have observed positive associations between bone disease and cardiovascular disease. A potential common pathway is hyperhomocysteinemia; however, to date, there is a lack of data regarding hyperhomocysteinemic populations. Therefore, we examined both cross-sectionally and longitudinally, whether there is an association between bone parameters and arterial stiffness in a hyperhomocysteinemic population, and investigated the potential common role of homocysteine (hcy) level on these associations. Cross-sectional and longitudinal data of the B-PROOF study were used (n = 519). At both baseline and 2-year follow-up we determined bone measures-incident fractures and history of fractures, bone-mineral density (BMD) and quantitative ultrasound (QUS) measurement. We also measured arterial stiffness parameters at baseline-pulse wave velocity, augmentation index and aortic pulse pressure levels with applanation tonometry. Linear regression analysis was used to examine these associations and we tested for potential interaction of hcy level. The mean age of the study population was 72.3 years and 44.3 % were female. Both cross-sectionally and longitudinally there was no association between arterial stiffness measures and BMD or QUS measurements or with incident fractures (n = 16) within the 2-3 years of follow-up. Hcy level did not modify the associations and adjustment for hcy did not change the results. Arterial stiffness was not associated with bone parameters and fractures, and hcy neither acted as a pleiotropic factor nor as a mediator. The potential association between bone and arterial stiffness is therefore not likely to be driven by hyperhomocysteinemia.

Low vitamin D status is associated with more depressive symptoms in Dutch older adults.

PURPOSE: The existence of vitamin D receptors in the brain points to a possible role of vitamin D in brain function. We examined the association of vitamin D status and vitamin D-related genetic make-up with depressive symptoms amongst 2839 Dutch older adults aged ≥65 years. METHODS: 25-Hydroxyvitamin D (25(OH)D) was measured, and five 'vitamin D-related genes' were selected. Depressive symptoms were measured with the 15-point Geriatric Depression Scale. Results were expressed as the relative risk of the score of depressive symptoms by quartiles of 25(OH)D concentration or number of affected alleles, using the lowest quartile or minor allele group as reference. RESULTS: A clear cross-sectional and prospective association between serum 25(OH)D and depressive symptom score was observed. Fully adjusted models indicated a 22 % (RR 0.78, 95 % CI 0.68-0.89), 21 % (RR 0.79, 95 % CI 0.68-0.90), and 18 % (RR 0.82, 95 % CI 0.71-0.95) lower score of depressive symptoms in people in the second, third, and fourth 25(OH)D quartiles, when compared to people in the first quartile (P for trend <0.0001). After 2 years of daily 15 µg vitamin D supplementation, similar associations were observed. 25(OH)D concentrations did not significantly interact with the selected genes. CONCLUSION: Low serum 25(OH)D was associated with higher depressive symptom scores. No interactions between 25(OH)D concentrations and vitamin D genetic make-up were observed. In view of the probability of reverse causation, we propose that the association should be further examined in prospective studies as well as in randomized controlled trials.

Timing of intervention in high-risk non-ST-elevation acute coronary syndromes in PCI versus non-PCI centres : Sub-group analysis of the ELISA-3 trial.

AIMS: To compare the effect of timing of intervention in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) in percutaneous coronary intervention (PCI) versus non-PCI centres. METHODS AND RESULTS: A post-hoc sub-analysis was performed of the ELISA III trial, a randomised multicentre trial investigating outcome of early (< 12 h) versus late (> 48 h) angiography and revascularisation in 542 patients with high-risk NSTE-ACS. 90 patients were randomised in non-PCI centres and tended to benefit more from an early invasive strategy than patients included in the PCI centre (relative risk 0.23 vs. 0.85 [p for interaction = 0.089] for incidence of the combined primary endpoint of death, reinfarction and recurrent ischaemia after 30 days of follow-up). This was largely driven by reduction in recurrent ischaemia. In non-PCI centres, patients randomised to the late group had a 4 and 7 day longer period until PCI or coronary artery bypass grafting, respectively. This difference was less pronounced in the PCI centre. CONCLUSIONS: This post-hoc analysis from the ELISA-3 trial suggests that NSTE-ACS patients initially hospitalised in non-PCI centres show the largest benefit from early angiography and revascularisation, associated with a shorter waiting time to revascularisation. Improved patient logistics and transfer between non-PCI and PCI centres might therefore result in better clinical outcome.

The association between vitamin D status and parameters for bone density and quality is modified by body mass index.

The association of vitamin D status with bone mineral density (BMD) and Quantitative Ultrasound measurements (QUS) has been inconsistent in previous studies, probably caused by moderating effects. This study explored (1) the association of vitamin D status with QUS and BMD, and (2) whether these associations were modified by body mass index (BMI), age, gender, or physical activity. Two-independent cohorts of the Longitudinal Aging Study Amsterdam (LASA-I, 1995/1996, aged ≥65; LASA-II, 2008/2009, aged 61-71) and baseline measurement of the B-vitamins for the prevention of osteoporotic fractures (B-PROOF) study (2008-2011, aged 65+) were used. QUS measurements [broadband ultrasound attenuation (BUA) and speed of sound (SOS)] were performed at the calcaneus in all three cohorts (N = 1,235, N = 365, N = 1319); BMD was measured by Dual X-ray absorptiometry (DXA) in B-PROOF (N = 1,162 and 1,192 for specific sites) and LASA-I (N = 492 and 503). The associations of vitamin D status with BUA and BMD were modified by BMI. Only in persons with low-to-normal BMI (<25 kg/m(2)) and serum 25(OH)D <25 nmol/L was associated with lower BUA as compared to the reference group (≥50 nmol/L) in LASA-I and B-PROOF. Furthermore, in LASA-I, these individuals had lower BMD at the hip and lumbar spine. In LASA-II, no associations with BUA were observed. Vitamin D status was not associated with SOS, and these associations were not modified by the effect modifiers tested. The association between vitamin D status and BUA and BMD was modified by BMI in the older-aged cohorts: there was only an association in individuals with BMI <25 kg/m(2).

[INTEGRATED APPROACH TO PREVENT FUNCTIONAL DECLINE IN HOSPITALIZED ELDERLY]. / Integrale interventie ter voorkoming van functieverlies bij ouderen tijdens ziekenhuisopname: het Zorgprogramma voor Preventie en Herstel.

BACKGROUND: Hospital related functional decline in older patients is an underestimated problem. Thirty-five procent of 70-year old patients experience functional decline during hospital admission in comparison with pre-illness baseline. This percentage increases considerably with age. METHODS/DESIGN: To address this issue, the Vlietland Ziekenhuis in The Netherlands has implemented the Prevention and Reactivation Care Programme (PReCaP), an innovative program aimed at reducing hospital related functional decline among elderly patients by offering interventions that are multidisciplinary, integrated and goal-oriented at the physical, social, and psychological domains of functional decline. DISCUSSION: This paper presents a detailed description of the intervention, which incorporates five distinctive elements: (1) Early identification of elderly patients with a high risk of functional decline, and if necessary followed by the start of the reactivation treatment within 48 h after hospital admission; (2) Intensive follow-up treatment for a selected patient group at the prevention and Reactivation Centre; (3) Availability of multidisciplinary geriatric expertise; (4) Provision of support and consultation of relevant professionals to informal caregivers; (5) Intensive follow-up throughout the entire chain of care by a casemanager with geriatric expertise. Outcome and process evaluations are ongoing and results will be published in a series of forthcoming papers. This article is an edited translation of the previously published article 'Integrated approach to prevent functional decline in hospitalized elderly: the Prevention and Reactivation Care Program (PReCaP), BMC Geriatrics 2012;12:7, AJBM de Vos, KJE Asmus-Szepesi, TJEM Bakker, PL de Vreede, JDH van Wijngaarden, EW Steyerberg, JP Mackenbach, AP Nieboer.

B-vitamin levels and genetics of hyperhomocysteinemia are not associated with arterial stiffness.

BACKGROUND AND AIMS: Hyperhomocysteinemia is associated with arterial stiffness, but underlying pathophysiological mechanisms explaining this association are to be revealed. This study was aimed to explore two potential pathways concerning the one-carbon metabolism. A potential causal effect of homocysteine was explored using a genetic risk score reflecting an individual's risk of having a long-term elevated plasma homocysteine level and also associations with B-vitamin levels were investigated. METHODS AND RESULTS: Baseline cross-sectional data of the B-PROOF study were used. In the cardiovascular subgroup (n = 567, 56% male, age 72.6 ± 5.6 yrs) pulse wave velocity (PWV) was determined using applanation tonometry. Plasma concentrations of vitamin B12, folate, methylmalonic acid (MMA) and holo transcobalamin (holoTC) were assessed and the genetic risk score was based on 13 SNPs being associated with elevated plasma homocysteine. Associations were examined using multivariable linear regression analysis. B-vitamin levels were not associated with PWV. The genetic risk score was also not associated with PWV. However, the homocysteine-gene interaction was significant (p < 0.001) in the association of the genetic risk score and PWV. Participants with the lowest genetic risk of having long-term elevated homocysteine levels, but with higher measured homocysteine levels, had the highest PWV levels. CONCLUSION: Homocysteine is unlikely to be causally related to arterial stiffness, because there was no association with genetic variants causing hyperhomocysteinemia, whereas non-genetically determined hyperhomocysteinemia was associated with arterial stiffness. Moreover, the association between homocysteine and arterial stiffness was not mediated by B-vitamins. Possibly, high plasma homocysteine levels reflect an unidentified factor, that causes increased arterial stiffness.

An argument-based approach to the validation of UHTRUST: can we measure how recent graduates can be trusted with unfamiliar tasks?

There is a need for valid methods to assess the readiness for clinical practice of medical graduates. This study evaluates the validity of Utrecht Hamburg Trainee Responsibility for Unfamiliar Situations Test (UHTRUST), an authentic simulation procedure to assess whether medical trainees are ready to be entrusted with unfamiliar clinical tasks near the highest level of Miller's pyramid. This assessment, in which candidates were judged by clinicians, nurses and standardized patients, addresses the question: can this trainee be trusted with unfamiliar clinical tasks? The aim of this paper is to provide a validity argument for this assessment procedure. We collected data from various sources during preparation and administration of a UHTRUST-assessment. In total, 60 candidates (30 from the Netherlands and 30 from Germany) participated. To provide a validity argument for the UHTRUST-assessment, we followed Kane's argument-based approach for validation. All available data were used to design a coherent and plausible argument. Considerable data was collected during the development of the assessment procedure. In addition, a generalizability study was conducted to evaluate the reliability of the scores given by assessors and to determine the proportion of variance accounted by candidates and assessors. It was found that most of Kane's validity assumptions were defendable with accurate and often parallel lines of backing. UHTRUST can be used to compare the readiness for clinical practice of medical graduates. Further exploration of the procedures for entrustment decisions is recommended.

Moving Beyond the Status Quo of Integrated Inpatient Medical and Psychiatric Care Units: The Path to Real-World Evaluation.

Integrated inpatient medical and psychiatric care units (IMPUs) are hospital wards that care for inpatients with both acute general medical and psychiatric disorders. IMPU development has stalled, and wide variation in IMPU designs may reflect the fact that IMPUs are still in an early evolutionary stage. High-quality evidence concerning the costs and effectiveness of IMPUs is sparse, because IMPUs do not lend themselves well to traditional evidence-based medicine methods. As a result, most studies of IMPUs have been only observational. Therefore, it is time for a different approach, in which goals for IMPUs are explicitly formulated and IMPU research is incorporated into evidence-based practice (EBP) instead of evidence-based medicine. EBP can be viewed as integrating best available evidence into organizational practices by using four pillars of evidence: organizational, experiential, stakeholder, and scientific. Such types of evidence require an investment in describing the field more precisely. When pragmatic reasoning, where clinical expertise and organizational needs determine IMPU designs, is replaced with EBP, researchers can more effectively perform studies that may convince health care policy makers that IMPUs represent a cost-effective way to improve patients' health and that they increase the well-being of both patients and hospital staff.

Making knowledge clips with patients: What learning mechanisms are triggered in medical students?

OBJECTIVE: To prepare medical students for a rapidly changing healthcare landscape, where new means of communication emerge, innovative teaching methods are needed. We developed a project-based learning course in which medical students design audiovisual patient information in collaboration with patients and with students in Communication and Information Sciences (CIS). We studied what learning mechanisms are triggered in medical students by elements of a project-based-learning course. METHODS: In this qualitative study, twelve sixth year medical students that participated in the course were individually interviewed. Data were analyzed according to the principles of qualitative template analysis. RESULTS: We identified four learning mechanisms: Challenging assumptions about patients' information needs; Becoming aware of the origin of patients' information needs; Taking a patient's perspective; Analyzing language to adapt to patients' needs. These learning mechanisms were activated by making a knowledge clip, collaborating with patients, and collaborating with CIS students. CONCLUSION: Collaborating with patients helped students to recognize and understand patients' perspectives. Working on a tangible product in partnership with patients and CIS students, triggered students to apply their understanding in conveying information back to patients. PRACTICE IMPLICATION: Based on our findings we encourage educators to involve patients as collaborators in authentic assignments for students so they can apply what they learned from taking patients' perspectives.

Discrepant perceptions of communication, teamwork and situation awareness among surgical team members.

OBJECTIVE: To assess surgical team members' differences in perception of non-technical skills. DESIGN: Questionnaire design. SETTING: Operating theatres (OTs) at one university hospital, three teaching hospitals and one general hospital in the Netherlands. PARTICIPANTS: Sixty-six surgeons, 97 OT nurses, 18 anaesthetists and 40 nurse anaesthetists. METHODS: All surgical team members, of five hospitals, were asked to complete a questionnaire and state their opinion on the current state of communication, teamwork and situation awareness at the OT. RESULTS: Ratings for 'communication' were significantly different, particularly between surgeons and all other team members (P ≤ 0.001). The ratings for 'teamwork' differed significantly between all team members (P ≤ 0.005). Within 'situation awareness' significant differences were mainly observed for 'gathering information' between surgeons and other team members (P < 0.001). Finally, 72-90% of anaesthetists, OT nurses and nurse anaesthetists rated routine team briefings and debriefings as inadequate. CONCLUSIONS: This study shows discrepancies on many aspects in perception between surgeons and other surgical team members concerning communication, teamwork and situation awareness. Future research needs to ascertain whether these discrepancies are linked to greater risk of adverse events or to process as well as systems failures. Establishing this link would support implementation and use of complex team interventions that intervene at multiple levels of the healthcare system.

Association between malnutrition and stages of sarcopenia in geriatric rehabilitation inpatients: RESORT.

BACKGROUND & AIMS: Malnutrition and sarcopenia coexist in older adults, yet they remain largely undiagnosed and untreated, despite available interventions. This study aimed to assess the prevalence, the coexistence of, and the association between malnutrition and sarcopenia in geriatric rehabilitation inpatients. METHODS: REStORing health of acutely unwell adulTs (RESORT) is an observational, longitudinal cohort of geriatric rehabilitation inpatients. The association between malnutrition, diagnosed according to the Global Leadership Initiative on Malnutrition (GLIM) criteria and sarcopenia according to the revised definition of the European Working Group on Sarcopenia in Older People (EWGSOP2) (no sarcopenia, probable sarcopenia, confirmed sarcopenia and severe sarcopenia) was determined using multinomial logistic regression analyses, adjusted for age, sex, comorbidities and cognitive impairment. RESULTS: Out of 506 geriatric rehabilitation inpatients, 51% were malnourished, 49% had probable sarcopenia, 0.4% had confirmed sarcopenia (non-severe) and 19% had severe sarcopenia. Malnutrition and probable sarcopenia and malnutrition and confirmed/severe sarcopenia coexisted in 23% and 13% of the 506 patients respectively. Malnutrition was not associated with probable sarcopenia (OR = 0.91, 95% CI = 0.58-1.42, p = 0.674) but with severe sarcopenia (OR = 2.07, 95% CI = 1.13-3.81, p = 0.019). CONCLUSION: The prevalence, coexistence of, and the association between malnutrition and severe sarcopenia in geriatric rehabilitation inpatients warrant diagnosis at admission. Further research into feasible and effective interventions to counteract both conditions to improve geriatric rehabilitation outcomes is needed.

Synergistic effect of bisphosphonate and docetaxel on the growth of bone metastasis in an animal model of established metastatic bone disease.

Bisphosphonates decrease bone resorption and reduce significantly the rate of skeletal complications in patients with metastatic bone disease. Bisphosphonates have also been shown to exhibit antitumor activity in vitro but in vivo results have been equivocal. In the present study, we investigated the effects of bisphosphonate treatment alone or in combination with the cytostatic docetaxel on the growth of breast cancer cells in bone. Tumor gowth was studied in an athymic nude mice model inoculated with MDA-231-B/luc+ breast cancer cells. Two days after the inoculation, mice were treated with risedronate, zolendronate or docetaxel alone or with a combination of risedronate and docetaxel. Bone destruction and tumor growth were evaluated radiographically, histologically and by whole-body bioiluminescent reporter imaging (BLI). Five week treatment with high doses risedronate or zoledronate (37.5-150 microg/kg, 5 times/week), fully protected the bones from osteolysis, but did not affect tumour growth. Docetaxel (2, 4, and 8 mg/kg, 2 times/week) inhibited tumour growth dose-dependently and after 5 weeks treatment with the highest dose, there was no detectable tumour in bone. The combination of a dose of docetaxel (4 mg/kg) that demonstrated only a minimal effect on tumour growth, with risedronate (150 microg/kg), protected bone integrity and nearly completely inhibited the growth of the cancer cells. Risedronate and docetaxel act synergistically to protect bone and decrease tumour burden in an animal model of established bone metastases from breast cancer cells.

[Increase in preventive screening: need for revision of the Dutch 'Wet op het Bevolkingsonderzoek' (Population Screening Act)]. / Toename van het preventiefonderzoek: noodzaak tot revisie van de Wet op het Bevolkingsonderzoek.

A growing number of institutions offer health checks to the public. These preventive checks have to comply with the Dutch 'Wet op het Bevolkingsonderzoek' (Population Screening Act), in order to protect citizens from harmful investigations and the detection of diseases for which there is no cure. However, for some of the investigations it is not clear whether a license is needed or what diseases may be detected. In addition, institutions are allowed to sell self-tests of prohibited investigations. The Act therefore needs revision. Moreover the 'Kwaliteitswet Zorginstellingen' (Care Institutions Quality Act) should also apply to institutions that offer preventive investigations so as to ensure that unwarranted screening is no longer possible.

Muscle Measures and Nutritional Status at Hospital Admission Predict Survival and Independent Living of Older Patients - the EMPOWER Study.

OBJECTIVES: Older adults with sarcopenia and malnutrition are at risk for co-morbidities, hospitalization, institutionalization, and mortality. In case of hospitalization, risks may be further increased, especially in case of suboptimal dietary intake. The aim of our study was to assess whether muscle mass, muscle strength, functional performance, and nutritional status at hospital admission were associated with survival and independent living among older patients three months after discharge. DESIGN, SETTING, PARTICIPANTS: The EMPOWER study was an observational, prospective and longitudinal inception cohort of patients older than 70 years admitted to the VU University Medical Centre in Amsterdam, the Netherlands. MEASUREMENTS: Patients were assessed for demographic and clinical characteristics, measurements of muscle mass (by bioelectrical impedance analysis), handgrip strength (by dynamometry), functional performance (self-reported ability to walk), and screened for risk of malnutrition (by SNAQ). Three months after hospital discharge, survival and living situation were assessed by a follow-up telephone interview. RESULTS: The majority of the 378 patients enrolled were living independently at the time of hospitalization (90%) and three months post-discharge (83%). Fifty-two patients died in the period from hospital admission to three months after discharge (survival rate 86%). Higher absolute muscle mass measures and not being malnourished at admission were significantly associated with the likelihood of survival. Handgrip strength and self-reported ability to walk were positively associated with a higher chance of living independently three months after discharge, but not with survival. CONCLUSIONS: Older patients with greater muscle mass and without malnutrition at hospital admission had a higher survival rate, while measures of muscle strength and functional performance were predictive for living independently three months after hospital discharge. Different components of muscle health relate to different relevant outcomes and therefore require investigation of specifically targeted interventions in the hospitalized older population.

[Medical Psychiatric Units in the Netherlands: an investigation into distribution and quality]. / Medisch-psychiatrische units in Nederland.

OBJECTIVE: One of the spearheads of psychiatric healthcare in the Netherlands is hospital care for patients with a psychiatric comorbidity. In 2014, the Netherlands Psychiatric Association published ten field standards for Medical Psychiatric Units (MPUs). We catalogued healthcare in the Netherlands on the basis of these field standards. DESIGN: Telephone screening, followed by a questionnaire investigation. METHOD: In the period May-August 2015, psychiatrists in 90 hospitals in the Netherlands were approached by telephone with 4 screening questions. If the department complied with the screening criteria for an MPU, a structured interview comprising 51 questions followed. The interview script was tested against the field standards using the Delphi method. RESULTS: The screening identified 40 potential MPUs; 37 (92.5%) wards participated in the complete interview. CONCLUSION: MPUs are unevenly distributed across the country; care content is adequate, but education, tighter multidisciplinary cooperation and availability of somatic nursing expertise on every shift could improve care on MPUs. The departments should also pay more attention to care chain arrangements. The field standards are too stringent; these could be improved by defining 'essential care' and application of differentiated assessment of subcriteria.

Food sources of vitamin D and their association with 25-hydroxyvitamin D status in Dutch older adults.

Various populations are at increased risk of developing a low vitamin D status, in particular older adults. Whereas sun exposure is considered the main source of vitamin D, especially during summer, dietary contributions should not be underestimated. This study aims to identify food sources of vitamin D that associate most strongly with serum vitamin D concentration. Data of 595 Dutch adults, aged ≥65 years, were analysed. Vitamin D intake was assessed with a food frequency questionnaire and 25-hydroxyvitamin D (25(OH)D) was determined in serum. Associations of total vitamin D intake and vitamin D intake from specific food groups with serum 25(OH)D status were examined by P-for trend analyses over tertiles of vitamin D intake, prevalence ratios (PRs), and spline regression. The prevalence of vitamin D deficiency was high, with 36% of the participants having a 25(OH)D status <50nmol/L. Participants with adequate 25(OH)D concentrations were more likely to be men and more likely to be younger than participants with vitamin D deficiency. Total median vitamin D intake was 4.3µg/day, of which 4.0µg/day was provided by foods. Butter and margarine were the leading contributors to total vitamin D intake with 1.8µg/day, followed by the intake of fish and shellfish with 0.56µg/day. Participants with higher intakes of butter and margarine were 21% more likely to have a sufficient 25(OH)D status after adjustment for covariates (T1 vs. T3: PR 1.0 vs. 1.21 (95%CI: 1.03-1.42), P-for trend 0.02). None of the other food groups showed a significant association with the probability of having a sufficient 25(OH)D status. This study shows that vitamin D intake was positively associated with total serum 25(OH)D concentration, with butter and margarine being the most important contributors to total vitamin D intake.

Vitamin B12 Intake and Related Biomarkers: Associations in a Dutch Elderly Population.

BACKGROUND: Vitamin B12 status is measured by four plasma/ serum biomarkers: total vitamin B12 (total B12), holotranscobalamin (holoTC), methylmalonic acid (MMA) and homocysteine (tHcy). Associations of B12 intake with holoTC and tHcy and associations between all four biomarkers have not been extensively studied. A better insight in these associations may contribute to an improved differentiation between vitamin B12 deficiency and a normal vitamin B12 status. OBJECTIVE: This study investigates associations between vitamin B12 intake and biomarkers and associations between biomarkers. DESIGN: In this cross-sectional observational study, levels of total B12, HoloTC, MMA and tHcy were determined in participants of the B-PROOF study: 2919 elderly people (≥65 years, with a mean age of 74.1 years, a mean BMI of 27.1 and 50% women) with elevated tHcy levels (≥12 µmol/L). B12 intake was assessed in a subsample. We assessed the association between intake and status with multivariate regression analysis. We explored the dose-response association between B12 intake and biomarkers and the association of total B12 and holoTC with tHcy and MMA with restricted cubic spline plots. RESULTS: A doubling of B12 intake was associated with 9% higher total B12, 15% higher HoloTC, 9% lower MMA and 2% lower tHcy. Saturation of biomarkers occurs with dietary intakes of >5 µg B12. Spline regression showed that levels of MMA and tHcy started to rise when vitamin B12 levels fall below 330 pmol/L and with HoloTC levels below 100 pmol/L, with a sharp increase with levels of B12 and HoloTC below 220 and 50 pmol/L respectively. CONCLUSIONS: In this study we observed a significant association between vitamin B12 intake and vitamin B12 biomarkers and between the biomarkers. The observed inflections for total B12 and holoTC with MMA and tHcy could indicate cut-off levels for further testing for B12 deficiency and determining subclinical B12 deficiency.

Converting enzyme inhibition after experimental myocardial infarction in rats: comparative study between spirapril and zofenopril.

STUDY OBJECTIVE: The aim was to compare the effects of two novel angiotensin converting enzyme (ACE) inhibitors, spirapril and zofenopril, on cardiac remodelling in rats with congestive heart failure after myocardial infarction. Spirapril contains no sulphydryl group, whereas zofenopril is a sulphydryl containing ACE inhibitor. DESIGN: Experimental myocardial infarction was induced by ligation of the left coronary artery. Sham operated animals served as controls. Treatment with spirapril (2-2.5 mg.kg-1.d-1) or zofenopril (12-15 mg.kg-1.d-1) added to the drinking water was started immediately after myocardial infarction or sham operation and continued for six weeks. After the treatment period, all rats were killed. The heart was rapidly removed and perfused as described by Langendorff. Heart rate and left ventricular pressure were measured both at baseline and during stimulation with isoprenaline (6 nM). Heart and lung weights were determined. SUBJECTS: Normotensive male Wistar rats (220-240 g) were used. MEASUREMENTS AND MAIN RESULTS: Experimental myocardial infarction considerably increased left ventricular cavity volume. Chronic treatment with either spirapril or zofenopril significantly attenuated this increase in volume. In infarcted rats, the increase in total heart and lung weight was also significantly reduced by chronic treatment with spirapril and zofenopril, indicating that these compounds reduce cardiac mass and pulmonary congestion in congestive heart failure due to myocardial infarction. There were no significant differences between treatment with spirapril and zofenopril. In the isolated and perfused rat heart, myocardial infarction significantly decreased both heart rate and left ventricular pressure. Converting enzyme inhibition only affected heart rate. Heart rate was significantly higher in infarcted animals treated with spirapril and zofenopril than in untreated infarcted animals. CONCLUSIONS: Both spirapril and zofenopril attenuated ventricular enlargement and cardiac hypertrophy in rats with congestive heart failure after myocardial infarction when treatment was started in the acute phase of myocardial infarction. No additional role could be attributed to the sulphydryl moiety of zofenopril. It is also suggested that these two ACE inhibitors modify cardiac sympathetic activity in rats with congestive heart failure, but more studies are needed to confirm these findings.

BMI and Body Fat Mass Is Inversely Associated with Vitamin D Levels in Older Individuals.

OBJECTIVE: To assess the association between obesity (measured by Body Mass Index (BMI) and fat percentage) and serum 25(OH)D levels in older persons. DESIGN: Cross-sectional analysis of data from 'the B-PROOF study' (B-vitamins for the Prevention Of Osteoporotic Fractures). PARTICIPANTS: 2842 participants aged 65 years and older. MEASUREMENTS: BMI and fat percentage, measured by Dual Energy X-ray, and serum 25(OH)D levels. RESULTS: Mean age was 74 years (6.5 SD), with 50% women. Mean serum 25(OH)D levels were 55.8 nmol/L (25 SD). BMI and total body fat percentage were significant inversely associated with serum 25(OH)D levels after adjustment for confouders (ß-0.93; 95% CI [-1.15; -0.71], p<0.001 and ß-0.84; 95% CI [-1.04; -0.64], p<0.001). This association was most prominent in individuals with a BMI in the 'overweight' and 'obesity' range (ß -1.25 and -0.96 respectively) and fat percentage in the last two upper quartiles (ß-1.86 and -1.37 respectively). CONCLUSION: In this study, higher BMI and higher body fat percentage were significantly associated with lower serum 25(OH)D levels in older persons. This association was particularly present in individuals with overweight, and higher fat percentages, suggesting that these persons are at increased risk of vitamin D insufficiency.