Dietary pattern derived by reduced rank regression and depressive symptoms in a multi-ethnic population: the HELIUS study.

BACKGROUND/OBJECTIVES: To investigate the association of dietary patterns derived by reduced rank regression (RRR) with depressive symptoms in a multi-ethnic population. SUBJECTS/METHODS: Cross-sectional data from the HELIUS study were used. In total, 4967 men and women (18-70 years) of Dutch, South-Asian Surinamese, African Surinamese, Turkish and Moroccan origin living in the Netherlands were included. Diet was measured using ethnic-specific food frequency questionnaires. Depressive symptoms were measured with the nine-item patient health questionnaire. RESULTS: By performing RRR in the whole population and per ethnic group, comparable dietary patterns were identified and therefore the dietary pattern for the whole population was used for subsequent analyses. We identified a dietary pattern that was strongly related to eicosapentaenoic acid+docosahexaenoic acid, folate, magnesium and zinc (response variables) and which was characterized by milk products, cheese, whole grains, vegetables, legumes, nuts, potatoes and red meat. After adjustment for confounders, a statistically significant inverse association was observed in the whole population (B: -0.03, 95% CI: -0.06, -0.00, P=0.046) and among Moroccan (B: -0.09, 95% CI: -0.13, -0.04, P=0.027) and South-Asian Surinamese participants (B: -0.05, 95% CI: -0.09, -0.01, P=<0.001), whereas no statistically significant association was found in the remaining ethnic groups. No statistically significant associations were found between the dietary pattern and significant depressed mood in any of the ethnic groups. CONCLUSIONS: No consistent evidence was found that consumption of a dietary pattern, high in nutrients that are hypothesized to protect against depression, was associated with lower depressive symptoms across different ethnic groups.

Feasibility of long-term continuous subcutaneous magnesium supplementation in a patient with irreversible magnesium wasting due to cisplatin.

A 39-year-old woman presented with severe, uncontrolled and irreversible hypomagnesaemia, following cisplatin treatment in her childhood. Because high-dose oral magnesium supplementation therapy was insufficient and not tolerated, continuous subcutaneous magnesium supplementation was successfully instituted and continued in the outpatient setting. This case demonstrates that continuous subcutaneous magnesium supplementation is effective in maintaining magnesium levels within the normal range, is well tolerated and may provide a long-term solution for chronic hypomagnesaemia due to intractable renal losses.

A Randomised Controlled Trial of Consent Procedures for the Use of Residual Tissues for Medical Research: Preferences of and Implications for Patients, Research and Clinical Practice.

BACKGROUND: Despite much debate, there is little evidence on consequences of consent procedures for residual tissue use. Here, we investigated these consequences for the availability of residual tissue for medical research, clinical practice, and patient informedness. METHODS: We conducted a randomised clinical trial with three arms in six hospitals. Participants, patients from whom tissue had been removed for diagnosis or treatment, were randomised to one of three arms: informed consent, an opt-out procedure with active information provision (opt-out plus), and an opt-out procedure without active information provision. Participants received a questionnaire six weeks post-intervention; a subsample of respondents was interviewed. Health care providers completed a pre- and post-intervention questionnaire. We assessed percentage of residual tissue samples available for medical research, and patient and health care provider satisfaction and preference. Health care providers and outcome assessors could not be blinded. RESULTS: We randomised 1,319 patients, 440 in the informed consent, 434 in the opt-out plus, and 445 in the opt-out arm; respectively 60.7%, 100%, and 99.8% of patients' tissue samples could be used for medical research. Of the questionnaire respondents (N = 224, 207, and 214 in the informed consent, opt-out plus, and opt-out arms), 71%, 69%, and 31%, respectively, indicated being (very) well informed. By questionnaire, the majority (53%) indicated a preference for informed consent, whereas by interview, most indicated a preference for opt-out plus (37%). Health care providers (N = 35) were more likely to be (very) satisfied with opt-out plus than with informed consent (p = 0.002) or opt-out (p = 0.039); the majority (66%) preferred opt-out plus. CONCLUSION: We conclude that opt-out with information (opt-out plus) is the best choice to balance the consequences for medical research, patients, and clinical practice, and is therefore the most optimal consent procedure for residual tissue use in Dutch hospitals. TRIAL REGISTRATION: Dutch Trial Register NTR2982.

Opportunities for male involvement during pregnancy in Magu district, rural Tanzania.

BACKGROUND: Male involvement during antenatal care is promoted to be an important intervention to increase positive maternal and new born health outcomes. Despite active promotion to stimulate male involvement during antenatal care, few men in Tanzania accompany women to their antenatal care visits. This study aims to understand perceptions, attitudes and behaviour of men regarding their role and involvement during pregnancy and antenatal care visits in a rural district in Tanzania. METHODS: Data collection took place in Magu District between September 2013 and March 2014, using a mixed method approach. This included observations at six government health facilities, nine focus group discussions (with a total of 76 participants) and 26 semi-structured interviews of participants, included through convenience- and snowball sampling. Additionally, a questionnaire was distributed among 156 women attending antenatal care, regarding their partners' involvement in their pregnancy. Qualitative analysis was done through coding of themes based on the Three Delays Framework. Descriptive analysis was used for quantitative data. RESULTS: Male involvement in pregnancy and antenatal care in Magu district is low. Although men perceived antenatal care as important for pregnant women, most husbands had a passive attitude concerning their own involvement. Barriers for male involvement included: traditional gender roles, lack of knowledge, perceived low accessibility to join antenatal care visits and previous negative experiences in health facilities. CONCLUSION: Although several barriers impede male involvement during antenatal care, men's internal motivation and attitudes towards their role during pregnancy was generally positive. Increasing community awareness and knowledge about the importance of male involvement and increasing accessibility of antenatal clinics can reduce some of the barriers.

Value of allohaemagglutinins in the diagnosis of a polysaccharide antibody deficiency.

Polysaccharide antibody deficiency is characterized by a poor or absent antibody response after vaccination with an unconjugated pneumococcal polysaccharide vaccine. Allohaemagglutinins (AHA) are antibodies to A or B polysaccharide antigens on the red blood cells, and are often used as an additional or alternative measure to assess the polysaccharide antibody response. However, few studies have been conducted to establish the clinical significance of AHA. To investigate the value of AHA to diagnose a polysaccharide antibody deficiency, pneumococcal polysaccharide antibody titres and AHA were studied retrospectively in 180 subjects in whom both tests had been performed. Receiver operating characteristic curves for AHA versus the pneumococcal vaccine response as a marker for the anti-polysaccharide immune response revealed an area under the curve between 0·5 and 0·573. Sensitivity and specificity of AHA to detect a polysaccharide antibody deficiency, as diagnosed by vaccination response, were low (calculated for cut-off 1/4-1/32). In subjects with only low pneumococcal antibody response, the prevalence of bronchiectasis was significantly higher than in subjects with only low AHA (45·5 and 1·3%, respectively) or normal pneumococcal antibody response and AHA (2·4%). A logistic regression model showed that low pneumococcal antibody response but not AHA was associated with bronchiectasis (odds ratio 46·2). The results of this study do not support the routine use of AHA to assess the polysaccharide antibody response in patients with suspected immunodeficiency, but more studies are warranted to clarify the subject further.

Invasive Aspergillus niger complex infections in a Belgian tertiary care hospital.

The incidence of invasive infections caused by the Aspergillus niger species complex was 0.043 cases/10 000 patient-days in a Belgian university hospital (2005-2011). Molecular typing was performed on six available A. niger complex isolates involved in invasive disease from 2010 to 2011, revealing A. tubingensis, which has higher triazole minimal inhibitory concentrations, in five out of six cases.

Azole-resistant Aspergillus fumigatus due to TR46/Y121F/T289A mutation emerging in Belgium, July 2012.

A new azole resistance mechanism in Aspergillus fumigatus consisting of a TR46/Y121F/T289A alteration in the cyp51A gene was recently described in the Netherlands. Strains containing these mutations are associated with invasive infection and therapy failure. This communication describes the first case of fatal invasive aspergillosis caused by TR46/Y121F/T289A outside the Netherlands, in the neighboring country of Belgium, suggesting geographical spread. TR46/Y121F/T289A leads to a recognisable phenotypic susceptibility pattern which should trigger cyp51A genotyping to monitor further spread.

Azole resistance in Aspergillus: an emerging problem?

Reports of Aspergillus' azole resistance are emerging, and resistance is now recognised as a cause of treatment failure. The scope of this article is to describe the problem of resistance in Aspergillus: the epidemiology, clinical impact and the underlying molecular mechanisms. In patients with acute invasive aspergillosis, the probability that the patient harbours a resistant strain depends on the emergence of resistant strains in the environment (acquired resistance due to CYP51A mutations and/or natural resistant Aspergillus species). As environmental pan-azole resistance of Aspergillus fumigatus is reported in increasing numbers in the Netherlands, surveillance is warranted. Voriconazole currently remains the first line therapeutic agent for invasive aspergillosis in Belgium. In chronic (and chronically treated) Aspergillus infections,"in-patient" resistance development is possible, especially in the setting of aspergilloma. Culturing an isolate during therapy should therefore be a trigger to test susceptibility.

High incidence of bloodstream infection detected by surveillance blood cultures in hematology patients on corticosteroid therapy.

PURPOSE: The aim of our study was to evaluate the frequency of "occult" bacteremia/fungemia as well as the diversity of pathogens involved in hematology patients treated with corticosteroids. METHODS: Daily surveillance blood cultures were taken from patients treated with corticosteroids as part of their intensive chemotherapy or during graft-versus-host disease following hematopoietic stem cell transplantation during a 3-year period (2006-2009). We reviewed the frequency of occult bacteremia/fungemia as well as the pathogens involved. RESULTS: During the 3-year period, 3,821 bottles were cultured from 215 patients and 4.9 % of the bottles tested were positive. Surveillance blood cultures revealed bloodstream infection in 24 % of the patients (definite bloodstream infection in 16 %). Seventy-five percent of patients were still afebrile when microorganisms were detected. The main risk group was acute lymphocytic leukemia patients undergoing remission induction chemotherapy. The pathogens cultured most frequently were coagulase-negative staphylococci, enterococci, Escherichia coli, and Pseudomonas aeruginosa. CONCLUSIONS: A high incidence of occult bacteremia was detected by surveillance blood cultures. Further studies are needed to evaluate if a strategy based on surveillance blood cultures can reduce mortality related to bloodstream infections.

Hepcidin as a biomarker for the diagnosis of iron metabolism disorders: a review.

INTRODUCTION: Hepcidin plays a key role in the regulation of plasma iron levels through inhibition of iron export from enterocytes and macrophages. Hepcidin is considered a promising marker in the investigation of iron status, especially in patients that still pose a diagnostic challenge, such as infants and patients with chronic (kidney) disease. OBJECTIVE: To critically review the current evidence for the diagnostic utility of hepcidin, including the (pre) analytical aspects in hepcidin determination. SUMMARY: (Pre)analytical aspects--Since it is doubtful that the prohormone prohepcidin is a relevant biomarker, only the mature peptide hepcidin should be measured. Determinations of serum hepcidin are preferable, as the value of urine concentrations is still unclear. Method harmonization is needed since hepcidin values vary widely between methods. Several (pre-) analytical issues remain unanswered. These barriers hamper the investigation into the diagnostic value of hepcidin. Diagnostic utility--Hepcidin is an acute-phase reactant. The diagnostic potential of hepcidin is controversial in the different settings of iron deficiency as evidence is contradictory (anaemia of chronic disease) or limited (infants). In the setting of haemochromatosis, it has been suggested that hepcidin could be useful to stratify molecular testing, or to optimize the frequency of phlebotomies, but this remains to be investigated.

A trial of consent procedures for future research with clinically derived biological samples.

BACKGROUND: The aims of this study were to determine which consent procedure patients prefer for use of stored tissue for research purposes and what the effects of consent procedures on actual consenting behaviour are. METHODS: We offered 264 cancer patients three different consent procedures: 'one-time general consent' (asked written informed consent), 'opt-out plus' (had the opportunity to opt out by a form), or the standard hospital procedure (control group). The two intervention groups received a specific leaflet about research with residual tissue and verbal information. The control group only received a general hospital leaflet including opt-out information, which is the procedure currently in use. Subsequently, all patients received a questionnaire to examine their preferences for consent procedures. RESULTS: In all, 99% of patients consented to research with their residual tissue. In the 'one-time consent' group 85% sent back their consent form. Patients preferred 'opt-out plus' (43%) above 'one-time consent' (34%) or 'opt-out' (16%), whereas 8% indicated that they did not need to receive information about research with residual tissues or be given the opportunity to make a choice. CONCLUSIONS: The 'opt-out plus' procedure, which places fewer demands on administrative resources than 'one-time consent', can also address the information needs of patients.

Screening for aneurysm of the abdominal aorta: prevalence in patients with stroke or TIA.

BACKGROUND AND PURPOSE: Population screening for aneurysms of the abdominal aorta (AAA) is still not implemented in any country, despite proven benefit both in decreased mortality and in cost effectiveness. Detecting a subpopulation with higher prevalence of AAA may alter this situation. METHODS: Between 2002 and 2005, all patients with a stroke or transient ischaemic attack (TIA) admitted to the department of Neurology of a community-based hospital were classified according to the Toast criteria and enrolled in a prospective study to assess the diameter of the abdominal aorta. The diameter was assessed by ultrasonography. A written questionnaire and blood tests were used to assess risk factors. RESULTS: The prevalence of AAA amongst the 499 screened patients in the study was 5.8% [95% confidence interval (CI) 5.6-6.0%]. Of the risk factors or Toast criteria, only male gender and age over 59 years correlated significantly with AAA. In the subgroup of 235 men aged over 59 years, the prevalence of AAA was 11.1% (95% CI 10.4-11.8%). CONCLUSION: The prevalence of AAA in men over 59 years of age presenting with a stroke or TIA is nearly twofold increased (11.1%) compared with all patients. Therefore, screening for AAA in this subgroup of patients seems beneficial. However, further studies are needed to confirm this finding and to explore the clinical benefit and cost effectiveness.

Opt-out plus, the patients' choice: preferences of cancer patients concerning information and consent regimen for future research with biological samples archived in the context of treatment.

AIMS: The aims of this study were to determine: (1) which consent procedures patients prefer for future medical research with tissue stored following surgery; (2) the percentage of patients who choose not to provide consent for research with their stored tissue; (3) the reasons given for denying such tissue use. METHODS: Patients (n = 103) from the Vrije Universiteit Medical Centre, an academic hospital in The Netherlands, who had recently undergone surgery for breast or colorectal cancer were mailed a questionnaire about preferences for consent regimens. RESULTS: Seventy-six patients (74%) completed the questionnaire. Only two patients (3%) chose not to provide consent for research with their stored tissue. The majority of patients (60%) preferred an "opt-out plus" procedure that included receiving active, verbal information to "one-time general consent" (11%) or to an "opt-out" procedure without verbal notification (5%). Only 3% indicated a wish to be asked for consent for each new research project and 21% did not know what they preferred or had no preference. There were no significant associations observed between preference for the various consent regimens and age, sex, educational level or personal sense of ownership of the stored tissue. CONCLUSION: Patients prefer an opt-out plus procedure that includes the provision of explicit, verbal and written information. Less than 5% of patients decline to consent to the use of their stored tissue for research purposes.

Effect of homocysteine-lowering treatment with folic acid plus vitamin B on cerebrovascular atherosclerosis and white matter abnormalities as determined by MRA and MRI: a placebo-controlled, randomized trial.

BACKGROUND: A high plasma homocysteine concentration is an independent risk factor for large and possibly small vessel disease. We investigated the effects of homocysteine-lowering treatment with folic acid plus vitamin B(6) on markers of cerebrovascular atherosclerosis and cerebral microangiopathy. MATERIALS AND METHODS: Using 158 healthy siblings (mean age 46.0 +/- 7.6 years) of patients with premature atherosclerotic disease, we performed a randomized, placebo-controlled trial using 5 mg of folic acid plus 250 mg of vitamin B(6) daily (n = 78) or placebo medication (n = 80). Participants were followed for 2 years with magnetic resonance angiography (MRA) (carotid stenosis; carotid and/or vertebral elongation) and magnetic resonance imaging (MRI) (white matter abnormalities; cerebral atrophy). RESULTS: Seventeen (10.8%) subjects refused MRA/MRI owing to claustrophobia and were excluded. From the remaining 141 participants, 68 received vitamin and 73 received placebo medication [42 (61.8%) and 48 (65.8%) had postmethionine hyperhomocysteinaemia, respectively]. Twenty-four participants (15.2%; 10 in the treatment and 14 in the placebo group) did not complete both years of the trial. Vitamin treatment was associated with an increase in plasma folate (13-fold vs. placebo; P < 0.001) and vitamin B(6) (8.8-fold; P < 0.001). Fasting and postmethionine total homocysteine concentrations decreased 38.7% (95% CI, 27.4-50.0) and 29.1% (95% CI, 19.2-39.0) vs. placebo (all P < 0.001). During follow up six individuals in the vitamin-treated and 11 in the placebo-treated group deteriorated in their outcome measurements. Vitamin treatment, as compared with placebo, was associated with nonsignificantly improved outcomes on both MRA and MRI outcome measurements (odds ratio 0.48; 95% CI 0.17-1.41; P = 0.18 and 0.48; CI 0.14-1.60; P = 0.23, respectively). CONCLUSIONS: These results could indicate a possible favourable effect of homocysteine-lowering treatment on cerebrovascular atherosclerosis and cerebral microangiopathy among healthy siblings of patients with premature atherosclerotic disease, but larger trials are required to establish this with certainty.

Homocysteine-lowering treatment with folic acid plus vitamin B6 lowers urinary albumin excretion but not plasma markers of endothelial function or C-reactive protein: further analysis of secondary end-points of a randomized clinical trial.

BACKGROUND: Hyperhomocysteinaemia is an independent risk factor for atherosclerosis and is thought to induce its effects through causing endothelial dysfunction. We studied the effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on urinary and plasma markers of endothelial function, and on plasma C-reactive protein, a marker of chronic inflammation. DESIGN: We performed a placebo-controlled 2-year trial among 158 healthy siblings of patients with premature atherosclerotic disease to determine the effect of daily folic acid (5 mg) plus vitamin B6 (250 mg) treatment as compared with placebo medication (n = 80) on markers of endothelial function (urinary albumin-to-creatinine ratio and plasma concentrations of soluble E-selectin, soluble vascular cell adhesion molecule-1, von Willebrand factor, tissue-type plasminogen activator and plasminogen activator inhibitor-1) and inflammation (C-reactive protein). Outcome variables were assessed at baseline and after 1 and 2 years of treatment. RESULTS: Fasting homocysteine concentrations ( micromol L-1) at baseline and after treatment were 14.7 +/- 8.2 and 7.4 +/- 1.9 in the vitamin and 14.7 +/- 8.8 and 12.0 +/- 5.4 for the placebo group, respectively. Vitamin treatment was associated with a decreased urinary albumin-to-creatinine ratio at follow up [regression coefficient (beta) -0.20 mg mmol-1 (CI: -0.43-0.03); P = 0.09]. After adjustment for age, sex, baseline concentrations of postmethionine total homocysteine plus the baseline albumin-to-creatinine ratio, the beta was -0.23 mg mmol-1 (CI: -0.43 to -0.02; P = 0.03), which amounts to a decrease of approximately 20%. There was no apparent effect of vitamin treatment on the other markers. CONCLUSIONS: Homocysteine-lowering vitamin treatment in healthy siblings of patients with premature atherosclerotic disease is associated with a decreased urinary albumin-to-creatinine ratio, but not with other markers of endothelial dysfunction, or in plasma C-reactive protein. The clinical significance of these findings remains to be determined.

Continuing expansion of internal iliac artery aneurysms after surgical exclusion of the inflow. A report of two cases.

Two patients with continuing expansion of an internal iliac artery aneurysm following earlier repair of an aortoiliac aneurysm are described. At the primary operation, inflow to small internal iliac aneurysms had been interrupted by simple proximal ligation only. During follow-up, however, increasing diameter of the by CT-angiography completely thrombosed internal iliac aneurysms required re-operation. The observation of continuing growth of thrombosed internal iliac artery aneurysms following proximal ligation emphasises the danger of persistent collateral circulation and supports the concept of endotension in the absence of endoleak following endovascular AAA repair.

Immune reactivity to mite allergens in nonatopic subjects: immune deviation or immune ignorance.

Most subjects without IgE to Dermatophagoides pteronyssinus do not have IgG to Der p 1 or Der p 2 (as measured by RIA). However, by immunoblot or ELISA, IgG reactivity (mostly IgG1) to mite components is easily detectable. This discrepancy is caused largely by immune reactivity to mite components with a high molecular weight under native conditions (possibly mite gut flora cross-reactive with human gut flora) and partially by the presence of IgG with low affinity for fluid-phase antigen. We conclude that the pattern of IgG antibody in subjects without IgE to mites does not support the notion of immune deviation, but rather indicates a lack of a mite-induced high-affinity immune response.