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Background: A high number of vitamin K antagonist (VKA) users have a low proportion of time in therapeutic range (TTR) resulting in a high number of bleeding and thromboembolism events., Objective: Can the quality of anticoagulation be improved by dispensing VKAs via multidose drug dispensing (MDD)., Method: A randomized controlled trial in the Netherlands. Patients who used VKAs, ≥65 years of age with a TTR <65% were eligible for inclusion. All oral drugs were dispensed via MDD. In MDD systems, all oral chronic medication intended for one dosing moment is packed in plastic disposable pouches. Controls received VKAs by manual dispensing. The difference in TTR between the 6 months after- and 6 months before the index date. A mixed-effects model with the intervention, TTR before the index date, MDD system at baseline as covariates, and pharmacy as random effect. A per-protocol analysis was performed with all patients who completed the study as intended., Results: One hundred and seventy-nine patients were included. Mean age was 80.0 (SD 6.9) years. Mean TTR during the study was 79.2 ± 18.0% in the intervention group and 72.5 ± 20.1% in the control group. The intervention resulted in a 5.6% (95% CI: 0.1-11.1) increase in TTR compared to the control group. Per-protocol analysis resulted in an 8.3% (95% CI: 0.99-15.61) increase in TTR compared to the control group. No differences in reduction were observed between the intervention and control group., Conclusion: The quality of anticoagulation can be improved with the use of MDD systems., (© 2019 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.)

Aims: Quantitative flow ratio (QFR) is a recently developed technique to calculate fractional flow reserve (FFR) based on 3D quantitative coronary angiography and computational fluid dynamics, obviating the need for a pressure-wire and hyperaemia induction. QFR might be used to guide patient selection for FFR and subsequent percutaneous coronary intervention (PCI) referral in hospitals not capable to perform FFR and PCI. We aimed to investigate the feasibility to use QFR to appropriately select patients for FFR referral., Methods and Results: Patients who underwent invasive coronary angiography in a hospital where FFR and PCI could not be performed and were referred to our hospital for invasive FFR measurement, were included. Angiogram images from the referring hospitals were retrospectively collected for QFR analysis. Based on QFR cut-off values of 0.77 and 0.86, our patient cohort was reclassified to 'no referral' (QFR ≥0.86), referral for 'FFR' (QFR 0.78-0.85), or 'direct PCI' (QFR ≤0.77). In total, 290 patients were included. Overall accuracy of QFR to detect an invasive FFR of ≤0.80 was 86%. Based on a QFR cut-off value of 0.86, a 50% reduction in patient referral for FFR could be obtained, while only 5% of these patients had an invasive FFR of ≤0.80 (thus, these patients were incorrectly reclassified to the 'no referral' group). Furthermore, 22% of the patients that still need to be referred could undergo direct PCI, based on a QFR cut-off value of 0.77., Conclusion: QFR is feasible to use for the selection of patients for FFR referral., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Background: Multidose drug dispensing (MDD) is used to help patients take their medicines appropriately. Little is known about drug regimen changes within these MDD systems and how they are effectuated by the community pharmacist. Manual immediate adjustments of the MDD system could introduce dispensing errors. MDD guidelines therefore recommend to effectuate drug regimen changes at the start of a new MDD system., Objective: The aim of this study was to investigate the frequency, type, procedure followed, immediate necessity, and time taken to make MDD adjustments., Methods: This was a cross-sectional study in eight community pharmacies in the Netherlands. All adjustments to MDD systems were systematically documented for 3 weeks by the community pharmacist., Results: Overall, 261 MDD adjustments involving 364 drug changes were documented for 250 patients: 127 (35%) drug changes involved the addition of a new drug, 124 (34%) a change in dosage, and 95 (26%) drug discontinuation. Of the MDD adjustments, 135 (52%) were effectuated immediately: 81 (31%) by adjusting the MDD system manually, 49 (19%) by temporarily dispensing the drug separately from the MDD system, and 5 (2%) by ordering a new MDD system. Pharmacists considered that 36 (27%) of the immediate MDD adjustments could have been deferred until the next MDD system was produced. Immediate adjustment took significantly longer than deferred adjustment (p < 0.001)., Conclusions: This study shows that in patients using MDD systems, over half of the drug regimen changes are adjusted immediately. The necessity of these immediate changes should be critically evaluated., (Copyright © 2018. Published by Elsevier Inc.)

Background Automated multidose drug dispensing is used to support patients with their medication management. Though multidose drug dispensing systems are frequently used, little is known about patients' experiences with multidose drug dispensing systems. Objective To explore patients' experiences with the initiation and use of multidose drug dispensing systems. Setting A survey was carried out with patients using multidose drug dispensing systems through three community pharmacies. Method A semi-structured interview protocol was designed based on existing literature and a pilot study. Main outcome measures The main outcome measures were (1) patients' experiences with initiating multidose drug dispensing systems and (2) patients' experienced advantages and disadvantages of multidose drug dispensing systems. Results The start of multidose drug dispensing was discussed with 76% of the patients (n = 62). Ninety percent of patients expressed the opinion that the multidose drug dispensing system supported them with their medication management. Sixty patients reported 110 advantages, which can be organized into the following categories: improved medication adherence and medication safety (59%); patient's convenience (40%); and other (1%). Sixty-nine percent of patients reported no disadvantages, 24% had problems opening the bags or outer packaging and 13% had problems with the legibility of the printed text on the bag. Conclusion In concordance with the Dutch guideline, patients are generally involved in the decision to initiate an multidose drug dispensing system. Patients are very satisfied using the system and report multiple advantages. Multidose drug dispensing systems may be further improved by simplifying the manual opening of the bags and improving the legibility of the text on the bags.

Purpose: It is unknown if multidose drug dispensing (MDD) systems are initiated for the appropriate patients. Therefore, the objective of this study was to compare the medication management problems of patients who were about to start with a MDD system (MDD patients) and patients who continued manually dispensed medication (non-MDD users) in order to identify if the appropriate patients receive a MDD system., Methods: Patient interviews (semi-structured) were conducted by 44 community pharmacists at the patient's home. Patients over 65 years of age, home dwelling and using at least five chronic drugs, were eligible for the study. An assessment tool was developed including 22 potential medication management problems, covering four domains: functional (7), organizational (7), medication adherence (6), and medication knowledge (2). Median scores were calculated with the interquartile range. Additionally, cognitive function was assessed with the Mini-Cog and frailty using the Groningen Frailty Indicator., Results: One hundred eighty-eight MDD users and 230 non-MDD users were interviewed. MDD users were older, more often female, and using more drugs. Forty-two percent of the MDD users were possibly cognitively impaired and 63% were assessed as frail compared to 20 and 27% respectively of the non-MDD users. MDD users had more potential organizational problems (3 vs. 1; p < 0.01), functional problems (2 vs. 1; p < 0.01), medication adherence problems (1 vs. 0; p < 0.01), and medication knowledge problems (1 vs. 0; p < 0.01) compared to non-MDD users. Seventy percent of the MDD users scored six or more potential medication management problems while this was 22% among non-MDD users., Conclusions: The majority of MDD systems were initiated for patients who experienced multiple potential medication management problems suggesting a decreased medication management capacity.

The Dutch Sciatica Trial represents a longitudinal study with complex time-varying confounders as patients with poorer health conditions (e.g. more severe pain) are more likely to opt for surgery, which, in turn, may affect future outcomes (pain severity). A straightforward classical as-treated comparison at the end point would lead to biased estimation of the surgery effect. We present several strategies of causal treatment effect estimation that might be applicable for analyzing such data. These include an inverse probability of treatment weighted regression analysis, a marginal weighted analysis, an unweighted regression analysis, and several propensity score-based approaches. In addition, we demonstrate how to evaluate these approaches in a thorough simulation study where we generate various realistic complex confounding patterns akin to the sciatica study.

Aim of the Study: To investigate the seroprevalence of Helicobacter pylori infection in young children from the general population in The Netherlands., Methods: Determination of IgG antibodies against H. pylori, using an enzyme-linked immunosorbent assay technique [cutoff 0.32 Absorption Index (AI)], in serum from 1258 children who were 2-4 years of age. The serum was obtained from a serum bank of 6127 children who attended the community child healthcare centers in the Dutch province of Zuid-Holland., Results: In general, we found a seroprevalence of 1.2% of H. pylori infection, with a significant difference between the children with parents who were both Dutch (0.5%), and the children with at least one non-Dutch parent (2.6%) (P<0.001)., Conclusions: The prevalence of H. pylori infection in young infants in the general population in The Netherlands is low. Children with at least one non-Dutch parent form a risk group, however, for H. pylori infection in The Netherlands.

Background and Objective: In the Netherlands, all procedures in general surgery are categorized into 12 surgery groups by the Association of Surgeons of the Netherlands. The purpose of this study was to assess whether surgery groups differ in adverse outcome probabilities, to decide whether hospital comparisons on adverse outcomes should be adjusted for differences in surgery groups., Methods: All surgical patients in one hospital discharged in 1997-1999 were included. Only the first operation during admission was included, with the assumption that successive operations were treatment of adverse outcomes. To avoid bias, only operations with procedures from the same surgery group were included. A total of 6,025 admissions were included and analyzed by a two-step multilevel analysis., Results: Four surgery groups had fewer admissions with adverse outcomes than expected, and two groups had more. After adjustment for patient and operation characteristics, the remaining variance between surgery groups is still large. Similar results were found when differences in mortality were analyzed., Conclusion: Surgery group can therefore be used to adjust hospital comparisons for differences in surgical procedure mix.

We explore the application of principal component based approaches to pattern recognition in microarray analysis. A comparative assessment is presented, based on predictive evaluation, following a review of some key methodology. On the basis of these results, we select principal component based linear discrimination for a further in-depth analysis. We are particularly interested in studying the use of principal component decomposition for the evaluation of the condition of estimation of the pooled covariance matrix. The results are used to give some guidance as to how principal components may be used as a data exploratory tool in the analysis of microarray data. Opportunities for further development are outlined as well as implications for wider statistical modelling of microarray data., (Copyright 2003 John Wiley & Sons, Ltd.)

Background: Based on different genetic and environmental risk factors and histology, it has been proposed that rheumatoid arthritis (RA) consists of 2 types: autoantibody-positive and autoantibody-negative RA. However, until now, this remained hypothetical. To assess this hypothesis, we studied whether the long-term outcomes differed for these 2 groups of RA patients.Methods and Findings: In the Leiden Early Arthritis Clinic cohort, 1,285 consecutive RA patients were included between 1993 and 2016 and followed yearly. Treatment protocols in routine care improved over time, irrespective of autoantibody status, and 5 inclusion periods were used as instrumental variables: 1993-1996, delayed mild disease-modifying antirheumatic drug (DMARD) initiation (reference period); 1997-2000, early mild DMARDs; 2001-2005, early methotrexate; 2006-2010, early methotrexate followed by treat-to-target adjustments; 2011-2016, similar to 2006-2010 plus additional efforts for very early referral. Three long-term outcomes were studied: sustained DMARD-free remission (SDFR) (persistent absence of clinical synovitis after DMARD cessation), mortality, and functional disability measured by yearly Health Assessment Questionnaire (HAQ). Treatment response in the short term (disease activity) was measured by Disease Activity Score-28 with erythrocyte sedimentation rate (DAS28-ESR). Linear mixed models and Cox regression were used, stratified for autoantibody positivity, defined as IgG anti-CCP2 and/or IgM rheumatoid factor positivity. In total, 823 patients had autoantibody-positive RA (mean age 55 years, 67% female); 462 patients had autoantibody-negative RA (age 60 years, 64% female). Age, gender, and percentage of autoantibody-positive patients were stable throughout the inclusion periods. Disease activity significantly decreased over time within both groups. SDFR rates increased after introduction of treat-to-target (hazard ratio [HR] 2006-2010 relative to 1993-1996: 3.35 [95% CI 1.46 to 7.72; p = 0.004]; HR 2011-2016: 4.57 [95% CI 1.80 to 11.6; p = 0.001]) in autoantibody-positive RA, but not in autoantibody-negative RA. In autoantibody-positive RA, mortality decreased significantly after the introduction of treat-to-target treatment adjustments (HR 2006-2010: 0.56 [95% CI 0.34 to 0.92; p = 0.023]; HR 2011-2016: 0.33 [95% CI 0.14 to 0.77; p = 0.010]), but not in autoantibody-negative RA (HR 2006-2010: 0.79 [95% CI 0.40 to 1.56; p = 0.50]; HR 2011-2016: 0.36 [95% CI 0.10 to 1.34; p = 0.13]). Similarly, functional disability improved in autoantibody-positive RA for the periods after 2000 relative to 1993-1996 (range -0.16 [95% CI -0.29 to -0.03; p = 0.043] to -0.32 [95% CI -0.44 to -0.20; p < 0.001] units of improvement), but not in autoantibody-negative RA (range 0.10 [95% CI -0.12 to 0.31; p = 0.38] to -0.13 [95% CI -0.34 to 0.07; p = 0.20] units of improvement). Limitations to note were that treatment was not randomized-but it was protocolized and instrumental variable analysis was used to obtain comparable groups-and that a limited spread of ethnicities was included.Conclusions: Although disease activity has improved in both autoantibody-positive and autoantibody-negative RA in recent decades, the response in long-term outcomes differed. We propose that it is time to subdivide RA into autoantibody-positive RA (type 1) and autoantibody-negative RA (type 2), in the hope that this leads to stratified treatment in RA. [ABSTRACT FROM AUTHOR]

Aims: We investigated the association between quantified metabolite, lipid and lipoprotein measures and incident heart failure hospitalisation (HFH) in the elderly, and examined whether circulating metabolic measures improve HFH prediction.Methods and Results: Overall, 80 metabolic measures from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial were measured by proton nuclear magnetic resonance spectroscopy (n = 5341; 182 HFH events during 2.7-year follow-up). We repeated the work in FINRISK 1997 (n = 7330; 133 HFH events during 5-year follow-up). In PROSPER, the circulating concentrations of 13 metabolic measures were found to be significantly different in those who were later hospitalised for heart failure after correction for multiple comparisons. These included creatinine, phenylalanine, glycoprotein acetyls, 3-hydroxybutyrate, and various high-density lipoprotein measures. In Cox models, two metabolites were associated with risk of HFH after adjustment for clinical risk factors and N-terminal pro-B-type natriuretic peptide (NT-proBNP): phenylalanine [hazard ratio (HR) 1.29, 95% confidence interval (CI) 1.10-1.53; P = 0.002] and acetate (HR 0.81, 95% CI 0.68-0.98; P = 0.026). Both were retained in the final model after backward elimination. Compared to a model with established risk factors and NT-proBNP, this model did not improve the C-index but did improve the overall continuous net reclassification index (NRI 0.21; 95% CI 0.06-0.35; P = 0.007) due to improvement in classification of non-cases (NRI 0.14; 95% CI 0.12-0.17; P < 0.001). Phenylalanine was replicated as a predictor of HFH in FINRISK 1997 (HR 1.23, 95% CI 1.03-1.48; P = 0.023).Conclusion: Our findings identify phenylalanine as a novel predictor of incident HFH, although prediction gains are low. Further mechanistic studies appear warranted. [ABSTRACT FROM AUTHOR]

The article focuses on the study conducted to examine the clients' perspective regarding the non-use of and dissatisfaction with ankle foot orthoses (AFOs). It is stated that semi-structured interviews were performed with 12 AFO users to find that during the intake and examination phase, activities and environments were seldom inquired about or discussed.

The article discusses a study of rs12212067 minor allele in FOXO3A with respect to the severity of RA (rheumatoid arthritis) in multiple cohorts. Topics discussed include the Leiden Early Arthritis Clinic (EAC) cohort made up of 587 patients with early RA, the Umea cohort consisting of 459 patients with early RA from Sweden and the Wichita cohort consisting of 101 patients from a single practice in Wichita, Kansas and the notion FOXO3A is not a major factor that regulates the severity of RA.

Objective Recently, we discovered a new autoantibody system in rheumatoid arthritis (RA): anti-carbamylated protein (anti-CarP) antibodies. These antibodies have value in predicting joint destruction; however, it is not clear whether they are present before the diagnosis of RA and whether they have value as predictors of RA development. Therefore, we studied whether anti-CarP antibodies are present in patients with arthralgia and whether their presence is associated with the development of RA. Methods Sera from 340 arthralgia patients who did not have clinical signs of arthritis but who were positive for IgM rheumatoid factor (IgM-RF) and/or anti-cyclic citrullinated peptide 2 (anti-CCP-2) and 32 healthy controls were tested for anti-CarP IgG antibodies. Of the patients with arthralgia, 111 were IgM-RF positive/anti-CCP-2 antibody negative and 229 were anti-CCP-2 antibody positive. Patients were observed for the development of RA (based on the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria) during a median followup period of 36 months. Cox proportional hazards regression analysis was performed to compare the risk of developing RA between arthralgia patients who were positive for anti-CarP antibodies and those who were negative for anti-CarP antibodies during followup. Results Anti-CarP antibodies were present in the sera of 39% of the patients. One hundred twenty patients developed RA, after a median of 12 months (interquartile range [IQR] 6-24). The presence of anti-CarP antibodies was associated with the development of RA in the entire arthralgia cohort after correction for RF and anti-CCP-2 antibody status (hazard ratio 1.56 [95% confidence interval 1.06-2.29], P = 0.023), as well as in the anti-CCP-2 antibody-positive subgroup (odds ratio 2.231 [95% confidence interval 1.31-3.79], P = 0.003). Conclusion Anti-CarP antibodies are present in patients with arthralgia, and their presence predicts the development of RA independent of anti-CCP-2 antibodies. [ABSTRACT FROM AUTHOR]

Aim: To compare clinical characteristics and outcome of nonagenarian hip fracture patients with younger patients aged 65-89 years. Methods: This was a cohort follow-up study of admissions for a hip fracture between 2005-2010 (mean follow up of 3.5 years) in two teaching hospitals in the Netherlands; 230 nonagenarians and 1014 patients aged 65-89 years were included. Clinical characteristics, adverse events, mobility and mortality were compared. Results: Nonagenarians were more likely to be female and anemic (both P < 0.001), and had more trochanteric fractures ( P = 0.005). The number of American Society of Anesthesiologists III/VI classified patients did not differ between the two groups. During the hospital stay, adverse events were more frequently observed in nonagenarians compared with younger patients ( P < 0.001). The length of stay was significantly longer in nonagenarians ( P < 0.001), and the 90-day readmission rate was similar. Absolute mortality was higher in nonagenarians ( P < 0.001), excess mortality, however, was comparable. Before admission, 40.0% of the nonagenarians lived in their own home, and 40.9% had returned 3 months postfracture. The rate of returning to their own home was lower compared with younger patients ( P < 0.001). Prefracture mobility was worse in nonagenarians compared with the younger group, but 3 months after discharge, the number of patients that regained prefracture mobility was comparable in both age groups. Conclusions: Nonagenarian hip fracture patients differ significantly from younger patients aged 65-89 years with respect to clinical characteristics and long-term outcome. However, almost half of the nonagenarians returned to their own home and more than half regained their prefracture level of mobility. Given these findings, prevention strategies for hip fracture and adverse events during hospital stay that focus particularly on frail nonagenarians are highly recommended. Geriatr Gerontol Int 2013; 13: 190-197. [ABSTRACT FROM AUTHOR]

Background: The prevalence of Helicobacter pylori has declined over recent decades in developed countries. The increasing prevalence with age is largely because of a birth cohort effect. We previously observed a decline in H. pylori prevalence in 6- to 8-year-old Dutch children from 19% in 1978 to 9% in 1993. Knowledge about birth-cohort-related H. pylori prevalence is relevant as a predictor for the future incidence of H. pylori-associated conditions. Aim: The aim of this study was to investigate whether the birth cohort effect of H. pylori observed between 1978 and 1993 continued in subsequent years. Methods: Anti- H. pylori IgG antibodies and anti-CagA IgG antibodies were determined in serum samples obtained in 2005/2006 from 545 Dutch children aged 7-9 years who participated in the Prevention and Incidence of Asthma and Mite Allergy birth cohort. The H. pylori and CagA antibodies were determined by enzyme-linked immunosorbent assays that have been extensively validated in children, with a 94% sensitivity for H. pylori colonization and a 92.5% sensitivity for colonization with a cagA-positive strain. Results: Of the 545 children (M/F 300/245), most (91.5%) were of Dutch descent. The H. pylori positivity rate was 9% (95% CI 6.6-11.4%). The prevalence of CagA antibodies was 0.9% (95% CI 0.1-1.6%). No significant differences were demonstrated in H. pylori and cagA prevalence in relation to gender or ethnicity. Conclusion: The prevalence of H. pylori in childhood has remained stable in the Netherlands from 1993 to 2005, suggesting a stabilization of the previously decreasing trend in subsequent birth cohorts. This finding may reflect stabilization in determinants such as family size, housing, and hygienic conditions (or offset by day care). If confirmed in other populations in developed countries, it implies that colonization with H. pylori will remain common in the coming decades. Remarkably however, the rate of colonization with cagA+ H. pylori strains has become very low, consistent with prior observations that cagA+ strains are disappearing in Western countries. [ABSTRACT FROM AUTHOR]

The article discusses a study by M. P. M. van der Linden and colleagues to evaluate the items that make up the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria for rheumatoid arthritis (RA), particularly rheumatoid factor (RF) level. The review of the 2010 criteria, which includes anti-citrullinated protein antibodies (ACPA) in addition to RF, ACPA factor contributed substantially to the diagnosis of RA as against RF.

Objective [ABSTRACT FROM AUTHOR]

The article presents a study on use of electronic noses to analyse breath of patients undergoing endovenous laser ablation (EVLA) of varicose veins. The topics discussed include presence of volatile organic compounds in breath, use of gas chromatography and mass spectrometry to analyse breath, and pyrolysis of complex organic molecules in blood and the vein wall tissue.