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1.  Vitamin and Mineral Deficiencies Are Highly Prevalent in Newly Diagnosed Celiac Disease Patients 
Nutrients  2013;5(10):3975-3992.
Malabsorption, weight loss and vitamin/mineral-deficiencies characterize classical celiac disease (CD). This study aimed to assess the nutritional and vitamin/mineral status of current “early diagnosed” untreated adult CD-patients in the Netherlands. Newly diagnosed adult CD-patients were included (n = 80, 42.8 ± 15.1 years) and a comparable sample of 24 healthy Dutch subjects was added to compare vitamin concentrations. Nutritional status and serum concentrations of folic acid, vitamin A, B6, B12, and (25-hydroxy) D, zinc, haemoglobin (Hb) and ferritin were determined (before prescribing gluten free diet). Almost all CD-patients (87%) had at least one value below the lower limit of reference. Specifically, for vitamin A, 7.5% of patients showed deficient levels, for vitamin B6 14.5%, folic acid 20%, and vitamin B12 19%. Likewise, zinc deficiency was observed in 67% of the CD-patients, 46% had decreased iron storage, and 32% had anaemia. Overall, 17% were malnourished (>10% undesired weight loss), 22% of the women were underweight (Body Mass Index (BMI) < 18.5), and 29% of the patients were overweight (BMI > 25). Vitamin deficiencies were barely seen in healthy controls, with the exception of vitamin B12. Vitamin/mineral deficiencies were counter-intuitively not associated with a (higher) grade of histological intestinal damage or (impaired) nutritional status. In conclusion, vitamin/mineral deficiencies are still common in newly “early diagnosed” CD-patients, even though the prevalence of obesity at initial diagnosis is rising. Extensive nutritional assessments seem warranted to guide nutritional advices and follow-up in CD treatment.
doi:10.3390/nu5103975
PMCID: PMC3820055  PMID: 24084055
vitamins; minerals; celiac disease; deficiency; adult; Body Mass Index
2.  Words that make pills easier to swallow: a communication typology to address practical and perceptual barriers to medication intake behavior 
Purpose
The barriers to patients’ successful medication intake behavior could be reduced through tailored communication about these barriers. The aim of this study is therefore (1) to develop a new communication typology to address these barriers to successful medication intake behavior, and (2) to examine the relationship between the use of the typology and the reduction of the barriers to successful medication intake behavior.
Patients and methods
Based on a literature review, the practical and perceptual barriers to successful medication intake behavior typology (PPB-typology) was developed. The PPB-typology addresses four potential types of barriers that can be either practical (memory and daily routine barriers) or perceptual (concern and necessity barriers). The typology describes tailored communication strategies that are organized according to barriers and communication strategies that are organized according to provider and patient roles. Eighty consultations concerning first-time medication use between nurses and inflammatory bowel disease patients were videotaped. The verbal content of the consultations was analyzed using a coding system based on the PPB-typology. The Medication Understanding and Use Self-efficacy Scale and the Beliefs about Medicine Questionnaire Scale were used as indicators of patients’ barriers and correlated with PPB-related scores.
Results
The results showed that nurses generally did not communicate with patients according to the typology. However, when they did, fewer barriers to successful medication intake behavior were identified. A significant association was found between nurses who encouraged question-asking behavior and memory barriers (r = −0.228, P = 0.042) and between nurses who summarized information (r = −0.254, P = 0.023) or used cartoons or pictures (r = −0.249, P = 0.026) and concern barriers. Moreover, a significant relationship between patients’ emotional cues about side effects and perceived concern barriers (r = 0.244, P = 0.029) was found as well.
Conclusion
The PPB-typology provides communication recommendations that are designed to meet patients’ needs and assist providers in the promotion of successful medication intake behavior, and it can be a useful tool for developing effective communication skills training programs.
doi:10.2147/PPA.S36195
PMCID: PMC3526884  PMID: 23271896
interpersonal communication; tailoring; adherence; coding provider-patient interaction; beliefs; self-efficacy
3.  Malabsorption and nutritional balance in the ICU: fecal weight as a biomarker: a prospective observational pilot study 
Critical Care  2011;15(6):R264.
Introduction
Malabsorption, which is frequently underdiagnosed in critically ill patients, is clinically relevant with regard to nutritional balance and nutritional management. We aimed to validate the diagnostic accuracy of fecal weight as a biomarker for fecal loss and additionally to assess fecal macronutrient contents and intestinal absorption capacity in ICU patients.
Methods
This was an observational pilot study in a tertiary mixed medical-surgical ICU in hemodynamically stable adult ICU patients, without clinically evident gastrointestinal malfunction. Fecal weight (grams/day), fecal energy (by bomb calorimetry in kcal/day), and macronutrient content (fat, protein, and carbohydrate in grams/day) were measured. Diagnostic accuracy expressed in terms of test sensitivity, specificity, positive (PPV) and negative predictive value (NPV), and receiver operator curves (ROCs) were calculated for fecal weight as a marker for energy malabsorption. Malabsorption was a priori defined as < 85% intestinal absorption capacity.
Results
Forty-eight patients (63 ± 15 years; 58% men) receiving full enteral feeding were included. A cut-off fecal production of > 350 g/day (that is, diarrhea) was linked to the optimal ROC (0.879), showing a sensitivity and PPV of 80%, respectively. Specificity and NPV were both 96%. Fecal weight (grams/day) and intestinal energy-absorption capacity were inversely correlated (r = -0.69; P < 0.001). Patients with > 350 g feces/day had a significantly more-negative energy balance compared with patients with < 350 g feces/day (loss of 627 kcal/day versus neutral balance; P = 0.012).
Conclusions
A fecal weight > 350 g/day in ICU patients is a biomarker applicable in daily practice, which can act as a surrogate for fecal energy loss and intestinal energy absorption. Daily measurement of fecal weight is a feasible means of monitoring the nutritional status of critically ill patients and, in those identified as having malabsorption, can monitor responses to changes in dietary management.
doi:10.1186/cc10530
PMCID: PMC3388706  PMID: 22071233
4.  Genetic Association Analysis of the Functional c.714T>G Polymorphism and Mucosal Expression of Dectin-1 in Inflammatory Bowel Disease 
PLoS ONE  2009;4(11):e7818.
Background
Dectin-1 is a pattern recognition receptor (PRR) expressed by myeloid cells that specifically recognizes β-1,3 glucan, a polysaccharide and major component of the fungal cell wall. Upon activation, dectin-1 signaling converges, similar to NOD2, on the adaptor molecule CARD9 which is associated with inflammatory bowel disease (IBD). An early stop codon polymorphism (c.714T>G) in DECTIN-1 results in a loss-of-function (p.Y238X) and impaired cytokine responses, including TNF-α, interleukin (IL)-1β and IL-17 upon in vitro stimulation with Candida albicans or β-glucan. The aim of the present study was to test the hypothesis that the DECTIN-1 c.714T>G (p.Y238X) polymorphism is associated with lower disease susceptibility or severity in IBD and to investigate the level of dectin-1 expression in inflamed and non-inflamed colon tissue of IBD patients.
Methodology
Paraffin embedded tissue samples from non-inflamed and inflamed colon of IBD patients and from diverticulitis patients were immunohistochemically stained for dectin-1 and related to CD68 macrophage staining. Genomic DNA of IBD patients (778 patients with Crohn's disease and 759 patients with ulcerative colitis) and healthy controls (n = 772) was genotyped for the c.714T>G polymorphism and genotype-phenotype interactions were investigated.
Principal Findings
Increased expression of dectin-1 was observed in actively inflamed colon tissue, as compared to non-inflamed tissue of the same patients. Also an increase in dectin-1 expression was apparent in diverticulitis tissue. No statistically significant difference in DECTIN-1 c.714T>G allele frequencies was observed between IBD patients and healthy controls. Furthermore, no differences in clinical characteristics could be observed related to DECTIN-1 genotype, neither alone, nor stratified for NOD2 genotype.
Conclusions
Our data demonstrate that dectin-1 expression is elevated on macrophages, neutrophils, and other immune cells involved in the inflammatory reaction in IBD. The DECTIN-1 c.714T>G polymorphism however, is not a major susceptibility factor for developing IBD.
doi:10.1371/journal.pone.0007818
PMCID: PMC2771910  PMID: 19915667
5.  Prototype evaluation of a self-management Internet diary for patients with ulcerative colitis 
Objective:
To evaluate content, navigation, usability, and impact measurability of a prototype Internet-based self-management intervention for patients with ulcerative colitis.
Material and methods:
Analysis of 52 Internet diaries that were used in a six-month test trial. Analysis was done using an evaluation framework for eHealth applications that incorporates goals from theory and empirical studies on living with chronic illness, the software design industry, and health services research.
Results:
Content of the diary covered the intended functions of the Internet-based self-management intervention. The evaluation led to several refinement suggestions concerning navigation, usability, and impact measurability of the Internet diary.
Conclusion:
Psychosocial, medical, and scientific content as well as interface and design are equally important in the development of effective eHealth interventions.
PMCID: PMC2778412  PMID: 19936160
self-management; Internet diary; ulcerative colitis; eHealth; prototype
6.  Safety of anti-tumor necrosis factor therapy in inflammatory bowel disease 
Inflammatory bowel disease (IBD), in particular Crohn’s disease refractory to conventional therapy, fistulizing Crohn’s disease and chronic active ulcerative colitis, generally respond well to anti-tumor necrosis factor (TNF) therapy. However, serious side effects do occur, necessitating careful monitoring of therapy. Potential side effects of anti-TNF therapy include opportunistic infections, which show a higher incidence when concomitant immunosuppression is used. Furthermore, antibody formation against anti-TNF is associated with decreased efficacy and an increased frequency of infusion reactions. The hypothesis of a slightly increased risk of lymphomas in IBD patients treated with anti TNF-therapy is debatable, since most studies lack the specific design to properly address this issue. Alarmingly, the occurrence of hepatosplenic T-cell lymphomas coincides with combined immunosuppressive therapy. Despite the potential serious side effects, anti-TNF therapy is an effective and relatively safe treatment option for refractory IBD. Future research is needed to answer important questions, such as the long-term risk of malignancies, safety during pregnancy, when to discontinue and when to switch anti-TNF therapy, as well as to determine the balance between therapeutic and toxic effects.
doi:10.3748/wjg.15.2067
PMCID: PMC2678575  PMID: 19418577
Anti-tumor necrosis factor; Biologics; Inflammatory bowel diseases; Crohn’s disease; Infliximab
7.  Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial) 
BMC Surgery  2008;8:15.
Background
With the availability of infliximab, nowadays recurrent Crohn's disease, defined as disease refractory to immunomodulatory agents that has been treated with steroids, is generally treated with infliximab. Infliximab is an effective but expensive treatment and once started it is unclear when therapy can be discontinued. Surgical resection has been the golden standard in recurrent Crohn's disease. Laparoscopic ileocolic resection proved to be safe and is characterized by a quick symptom reduction.
The objective of this study is to compare infliximab treatment with laparoscopic ileocolic resection in patients with recurrent Crohn's disease of the distal ileum with respect to quality of life and costs.
Methods/design
The study is designed as a multicenter randomized clinical trial including patients with Crohn's disease located in the terminal ileum that require infliximab treatment following recent consensus statements on inflammatory bowel disease treatment: moderate to severe disease activity in patients that fail to respond to steroid therapy or immunomodulatory therapy. Patients will be randomized to receive either infliximab or undergo a laparoscopic ileocolic resection. Primary outcomes are quality of life and costs. Secondary outcomes are hospital stay, early and late morbidity, sick leave and surgical recurrence. In order to detect an effect size of 0.5 on the Inflammatory Bowel Disease Questionnaire at a 5% two sided significance level with a power of 80%, a sample size of 65 patients per treatment group can be calculated. An economic evaluation will be performed by assessing the marginal direct medical, non-medical and time costs and the costs per Quality Adjusted Life Year (QALY) will be calculated. For both treatment strategies a cost-utility ratio will be calculated. Patients will be included from December 2007.
Discussion
The LIR!C-trial is a randomized multicenter trial that will provide evidence whether infliximab treatment or surgery is the best treatment for recurrent distal ileitis in Crohn's disease.
Trial registration
Nederlands Trial Register NTR1150
doi:10.1186/1471-2482-8-15
PMCID: PMC2533646  PMID: 18721465
8.  Indications for 5-aminosalicylate in inflammatory bowel disease: Is the body of evidence complete? 
Mesalazine is a safe drug, although adverse events may be seen in a minority of patients. This applies also to pregnant women and children. The role of mesalazine in combination therapy to improve efficacy and concomitant drug pharmacokinetics, or in chemoprevention against inflammatory bowel disease (IBD)-related colonic carcinoma has not yet been completely elucidated. Therapeutic success of mesalazine may be optimized by a combination of high dose and low frequency of dosage to improve compliance. Therefore, due to its superior safety profile and pharmacokinetic characteristics, mesalazine is preferable to sulphasalazine. This paper reviews the literature concerning mechanisms of action, indications and off-label use, pharmacokinetic properties and formulations, therapeutic efficacy, compliance, paediatric indications, chemoprevention, and safety issues and adverse event profile of mesalazine treatment versus sulphasalazine. It also highlights these controversies in order to clarify the potential benefits of mesalazines in IBD therapy and evidence for its use.
doi:10.3748/wjg.v12.i38.6115
PMCID: PMC4088103  PMID: 17036381
Mesalazine; Sulphasalazine; Review; Ulcerative colitis; Crohn’s disease; Treatment; Chemoprevention; Pregnancy; Adverse events
9.  Helicobacter pylori Modulates the T Helper Cell 1/T Helper Cell 2 Balance through Phase-variable Interaction between Lipopolysaccharide and DC-SIGN 
The human gastric pathogen Helicobacter pylori spontaneously switches lipopolysaccharide (LPS) Lewis (Le) antigens on and off (phase-variable expression), but the biological significance of this is unclear. Here, we report that Le+ H. pylori variants are able to bind to the C-type lectin DC-SIGN and present on gastric dendritic cells (DCs), and demonstrate that this interaction blocks T helper cell (Th)1 development. In contrast, Le− variants escape binding to DCs and induce a strong Th1 cell response. In addition, in gastric biopsies challenged ex vivo with Le+ variants that bind DC-SIGN, interleukin 6 production is decreased, indicative of increased immune suppression. Our data indicate a role for LPS phase variation and Le antigen expression by H. pylori in suppressing immune responses through DC-SIGN.
doi:10.1084/jem.20041061
PMCID: PMC2211851  PMID: 15492123
Helicobacter pylori; phase variation; DC-SIGN; dendritic cells; Th1/Th2 cell response

Results 1-9 (9)