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ObjectiveTo study changes in retention of first biologic disease-modifying antirheumatic drug (DMARD) therapy over a period of 15 years in an inception cohort of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS).MethodsWe assessed patient and disease characteristics and drug survival of patients starting a biologic (tumor necrosis factor inhibitor [TNFi]) therapy between 2004 and 2019 in routine care at the Amsterdam Rheumatology and Immunology Center, Reade, the Netherlands. Starts were classified as early (2004-2008), intermediate (2009-2013), and recent (2014-2018). Kaplan-Meier plots and log-rank tests assessed the overall difference in drug survival between the 3 observation groups and between diagnoses, followed by Cox regression to estimate hazard ratios (HRs).ResultsWe included 1938 consecutive patients starting TNFi therapy, 63% with RA, 19% with PsA, and 19% with AS; 65% were female. Drug survival decreased significantly over time (overall P< 0.001), mostly caused by decreases in the most recent 4-year period. The HR for drug continuation was 2.04 (95% CI 1.71-2.43, P< 0.001) for the early vs the recent group and 1.92 (95% CI 1.58-2.35, P< 0.001) for the intermediate vs the recent group. Drug survival time was significantly different between diseases (overall P< 0.001), mostly caused by shorter survival in RA. The HR for drug continuation was 0.58 (95% CI 0.47-0.73, P< 0.001) for RA vs PsA and 0.63 (95% CI 0.51-0.78, P< 0.001) for RA vs AS.ConclusionPatients with RA, PsA, and AS currently initiating biologic (TNFi) therapy discontinue the drug much sooner than those starting shortly after the drugs were introduced. This is most likely because of the availability of alternative novel biologic and targeted synthetic DMARD treatments and treat-to-target protocols enabling and necessitating earlier switching.

Background: Body mass index (BMI) during adolescence is predictive of BMI at adult age. However, BMI cannot distinguish between lean and fat body mass. Skinfold thickness may be a better predictor of body fatness. Objective: The objective of this study was to evaluate the relations between BMI and skinfold thickness during adolescence and body fatness during adulthood. Design: We included 168 men and 182 women from the Amsterdam Growth and Health Longitudinal Study, a prospective study that conducted 8 measurements of BMI and skinfold thickness between 1976 and 2000. BMI and skinfold thickness during adolescence were analyzed in relation to adult body fatness measured at a mean age of 37 y with dual-energy X-ray absorptiometry. Results: None of the boys and 1.7% of the girls were overweight at baseline, whereas the prevalence of high body fatness during adulthood was 29% in men and 32% in women. At the ages of 12-16 y, skinfold thickness was more strongly associated with adult body fatness than was BMI. Age-specific relative risks for a high level of adult body fatness varied between 2.3 and 4.0 in boys and between 2.1 and 4.3 in girls in the highest versus the lowest tertile of the sum of 4 skinfold thicknesses. For the highest tertile of BMI, the relative risk varied between 0.8 and 2.1 in boys and between 1.3 and 1.8 in girls. Conclusion: Skinfold thickness during adolescence is a better predictor of high body fatness during adulthood than is BMI during adolescence. KEY WORDS Adolescents, adults, body fatness, body mass index, cohort study, dual-energy X-ray absorptiometry, longitudinal study, skinfold thickness

Background: Glutamine depletion has negative effects on the functional integrity of the gut and leads to immunosuppression. Verylow-birth-weight (VLBW) infants are susceptible to glutamine depletion because nutrition is limited in the first weeks of life. Objective: The objective was to determine the effect of glutamine-enriched enteral nutrition on feeding tolerance, infectious morbidity, and short-term outcome in VLBW infants. Design: In a double-blind randomized controlled trial, VLBW infants (gestational age Results: Baseline patient and nutritional characteristics were not significantly different in the glutamine-supplemented (n = 52) and the control (n = 50) groups. The median time to full enteral feeding was 13 d (range: 7-31 d) in the glutamine-supplemented group and 13 d (range: 6-35 d) in the control group (hazard ratio: 1.19; 95% CI: 0.79, 1.79; P = 0.40). In the glutamine-supplemented group, 26 of 52 infants (50%) had [greater than or equal to] 1 serious infection compared with 38 of 50 (76%) in the control group (odds ratio: 0.32; 95% CI: 0.14, 0.74; P = 0.008). Other variables of feeding tolerance and short-term outcome were not significantly different between groups. Conclusions: Glutamine-enriched enteral nutrition did not improve feeding tolerance or short-term outcome in VLBW infants. However, infectious morbidity was significantly lowered in infants who received glutamine-enriched enteral nutrition. KEY WORDS Infant, very-low-birth-weight, glutamine, enteral nutrition, randomized controlled trial

Objective. To assess differences in diabetes care and patient outcomes by comparing two multifaceted quality improvement programs in two different countries, and to increase knowledge of effective elements of such programs. Study Setting. Primary care in the ExtraMural Clinic (EMC) of the Department of General Practice of the Vrije Universiteit in Amsterdam, the Netherlands, and the Group Health Cooperative (GHC), a group-model health maintenance organization (HMO) in western Washington State in the United States. Data were collected from 1992 to 1997. Study Design. In this observational study two diabetes cohorts in which a quality improvement program was implemented were compared. Both programs included a medical record system, clinical practice guidelines, physician educational meetings, audit, and feedback. Only the Dutch program (EMC) included guidelines on the structure of diabetes care and a recall system. Only the GHC program included educational outreach visits, formation of multidisciplinary teams, and patient self-management support. Data Collection. Included were 379 EMC patients, and 2,119 GHC patients with type 2 diabetes mellitus. Main process outcomes were: annual number of diabetes visits, and number of HbA1c and blood lipid measurements. Main patient outcomes were HbA1c and blood lipid levels. Multilevel analysis was used to adjust for dependency between repeated observations within one patient and for clustering of patients within general practices. Principal Findings. In the EMC process outcomes and glycernic control improved more than at GHC, however, GHC had better baseline measures. There were no differences between programs on blood lipid control. During follow-up, intensification of pharmacotherapy was noted at both sites. Differences noted between programs were in line with differences in diabetes guidelines. Conclusions. Following implementation of guidelines and organizational improvement efforts, change occurred primarily in the process outcomes, rather than in the patient outcomes. Although much effort was put into improving process and patient outcomes, both complex programs still showed only moderate effects. Key Words. Quality of care, type 2 diabetes mellitus, general practice, international comparison, In the last decades, care for patients with type 2 diabetes has shifted away from hospitals and toward general practice (Griffin and Kinmonth 1997; Wood 1990). Numerous general practice guidelines [...]

In 328 type 2 diabetic patients followed for 9.0 years (mean), we investigated whether endothelial dysfunction and chronic inflammation (estimated from plasma markers) can explain the association between (micro)albuminuria and [...]

Activity and fitness and the relationship with cardiovascular disease risk factors have been studied with the finding that the longitudinal development of physical activity and maximal oxygen uptake (VO(sub.2max)) are related to a healthy cardiovascular disease (CVD) risk profile, related to high-density lipoprotein cholesterol and total cholesterol. Less clear is the relationship with the development of neuromotor fitness. Relationships among physical fitness, physical activity, and lipoproteins/blood pressure were seen to be much influenced by how fat the subject is.

Migraine is a common disorder with high social and medical impact. Patients with migraine have a much higher chance of experiencing headache attacks compared with the general population. Recent neuroimaging studies have confirmed that pathophysiology in the brain is not only limited to the moment of the attack but is also present in between attacks, the interictal phase. In this study, we hypothesized that the topology of functional brain networks is also different in the interictal state, compared with people who are not affected by migraine. We also expected that the level of network disturbances scales with the number of years people have suffered from migraine. Functional connectivity between 78 cortical brain regions was estimated for source-level magnetoencephalography data by calculating the phase lag index, in five frequency bands (delta–beta), and compared between healthy controls (n= 24) and patients who had been suffering from migraine for longer than 6 years (n= 12) or shorter than 6 years (n= 12). Moreover, the topology of the functional networks was characterized using the minimum spanning tree. The migraine groups did not differ from each other in functional connectivity. However, the network topology was different compared with healthy controls. The results were frequency specific, and higher average nodal betweenness centrality was specifically evident in higher frequency bands in patients with longer disease duration, while an opposite trend was present for lower frequencies. This study shows that patients with migraine have a different network topology in the resting state compared with healthy controls, whereby specific brain areas have altered topological roles in a frequency-specific manner. Some alterations appear specifically in patients with long-term migraine, which might show the long-term effects of the disease.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2007.06.005 Byline: Franca A. Gerards (a), Jos W.R. Twisk (b), Willem P.F. Fetter (c), Liliane C.D. Wijnaendts (d), John M.G. van Vugt (a) Keywords: fetal lung volume; prenatal diagnosis; pulmonary hypoplasia; 3-dimensional ultrasonography; 2-dimensional ultrasonography Abstract: The aim of this study was to compare 3-dimensional (3D) lung volume measurements with 2-dimensional (2D) biometric parameters in predicting pulmonary hypoplasia in complicated pregnancies. Author Affiliation: (a) Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam, the Netherlands (b) Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands (c) Department of Neonatology, VU University Medical Center, Amsterdam, the Netherlands (d) Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands. Article History: Received 25 January 2006; Revised 14 April 2007; Accepted 5 June 2007 Article Note: (footnote) Cite this article as: Gerards FA, Twisk JWR, Fetter WPF, et al. Predicting pulmonary hypoplasia with 2- or 3-dimensional ultrasonography in complicated pregnancies. Am J Obstet Gynecol 2008;198:140.e1-140.e6.

Results indicate that from adolescence up to age 36, physical activity, as measured in terms of high levels of cardiorespiratory fitness, helps maintain less arterial stiffness leading to mortality reduction from cardiovascular disease.

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Statistical mediation analysis is an often used method in trials, to unravel the pathways underlying the effect of an intervention on a particular outcome variable. Throughout the years, several methods have been proposed, such as ordinary least square (OLS) regression, structural equation modeling (SEM), and the potential outcomes framework. Most applied researchers do not know that these methods are mathematically equivalent when applied to mediation models with a continuous mediator and outcome variable. Therefore, the aim of this paper was to demonstrate the similarities between OLS regression, SEM, and the potential outcomes framework in three mediation models: 1) a crude model, 2) a confounder-adjusted model, and 3) a model with an interaction term for exposure-mediator interaction.

AbstractRecently, a large study demonstrated that lower serum levels of insulin growth factor-1 (IGF-1) relate to brain atrophy and to a greater risk for developing Alzheimer's disease in a healthy elderly population. We set out to test if functional brain networks relate to IGF-1 levels in the middle aged. Hence, we studied the association between IGF-1 and magnetoencephalography-based functional network characteristics in a middle-aged population. The functional connections between brain areas were estimated for six frequency bands (delta, theta, alpha1, alpha2, beta, gamma) using the phase lag index. Subsequently, the topology of the frequency-specific functional networks was characterized using the minimum spanning tree. Our results showed that lower levels of serum IGF-1 relate to a globally less integrated functional network in the beta and theta band. The associations remained significant when correcting for gender and systemic effects of IGF-1 that might indirectly affect the brain. The value of this exploratory study is the demonstration that lower levels of IGF-1 are associated with brain network topology in the middle aged.

In people with low back pain (LBP), altered motor control has been related to reorganization of the primary motor cortex (M1). Sensory impairments in LBP have also been suggested to be associated with reorganization of M1. Little is known about reorganization of M1 over time in people with LBP, and whether it relates to changes in motor control and sensory impairments and recovery. This study aims to investigate 1) differences in organization of M1 of trunk muscles between people with and without LBP, and whether the organization of M1 relates to motor control and sensory impairments (cross-sectional component) and 2) reorganization of M1 over time and its relation with changes in motor control and sensory impairments and experienced recovery (longitudinal component).

Objective.Patients with inflammatory arthritis (IA) have an increased risk of cardiovascular diseases (CVD), suggesting a high rate of CVD-related hospitalizations, but data on this topic are limited. Our study addressed hospital admissions for CVD in a primary care–based population of patients with IA and controls.Methods.All newly diagnosed patients with IA between 2001 and 2010 were selected from electronic medical records of the Netherlands Institute for Health Services Research Primary Care database, representing a national network of general practices. Two control patients matched for age, sex, and practice were selected for each patient with IA. Hospital admission data for all patients was retrieved from the Dutch Hospital Data.Results.There were 2615 patients with IA and 5555 controls included in our study. CVD-related hospital admissions were observed more frequently among patients with IA as compared with control patients: 48% versus 36% (p < 0.001) in a followup period of 4 years. Patients with IA were more often hospitalized because of ischemic heart disease (OR 1.7, 95% CI 1.2–2.2) and for day-care admission because of cerebrovascular disease (OR 2.2, 95% CI 1.0–4.9).Conclusion.Increased hospital admission rates confirm the higher CVD burden among patients with IA compared with controls, and underscore the need for proper CVD risk management in patients with IA.

To evaluate fMRI whole-brain resting-state functional connectivity changes in relation to cognitive decline in Parkinson disease (PD) over a 3-year period.

Tryptophan not only is an amino acid essential to protein synthesis but also serves as a precursor in 2 important metabolic pathways: the serotonin and the kynurenine pathways. Tryptophan is related to sleeping patterns. The objective of the present study was to determine the tryptophan requirement of term infants using the indicator amino acid oxidation (IAAO) method with L-[1-13C]phenylalanine as the indicator. Enterally fed infants were randomly assigned to tryptophan intakes ranging from 0.5 to 73 mg · kg-1· day-1as part of an elemental diet. After 1-day adaptation to the test diet, [13C]bicarbonate and L-[1-13C]phenylalanine tracers were given enterally. Breath samples were collected at baseline and during isotopic plateaus. The mean tryptophan requirement was determined by using the biphasic linear regression crossover analysis on the fraction of 13CO2recovery from L-[1-13C]phenylalanine oxidation (F13CO2). Data are presented as mean ± standard deviation. A total of 30 term neonates (gestational age 39 ± 1 weeks) were studied at 9 ± 4 days. F13CO2decreased until a tryptophan intake of 15 mg · kg-1· day-1; additional increases in tryptophan intake did not affect F13CO2. Mean requirement was determined to be 15 mg · kg-1· day-1. The mean tryptophan requirement for elemental formula-fed term infants is 15 mg · kg-1· day-1. This requirement is lower than the present recommended intake of 29 mg · kg-1· day-1, which is based on the average intake of a breastfed infant.

To assess the ability of neurophysiologic markers in conjunction with cognitive assessment to improve prediction of progression to dementia in Parkinson disease (PD).

Background:We determined the effect of adaptation to the study diet on oxidation of the indicator amino acid and the required tracer washout time in preterms.Methods:Subjects received a study diet for 6 d that entailed a 50% reduction in leucine. Tracer studies using enterally infused [13C]bicarbonate and [1-13C]phenylalanine were performed on days 1, 2, 4, and 6. Breath samples containing 13CO2were collected during steady state and measured by infrared spectrometric analysis, and the fraction of 13CO2recovery from 13C oxidation (F13CO2) was calculated.Results:Preterm infants (n = 11, birth weight 1.9 ± 0.1?kg, gestational age 32.6 ± 1.5?wk) received 166?mg/kg/d of leucine. Baseline enrichment changed significantly at day 1 of the study diet. F13CO2did not change significantly between days 2 and 4 but was significantly lower at day 6. The tracer washout time was determined to be 7.5?h using a biphasic regression analysis.Conclusion:One day of adaptation to a new diet is necessary to adapt to the 13C enrichment of the study formula before starting infant requirement studies. Adaptation for a period of 5 d results in a protein-sparing response. The minimal time between two studies within the same subject is 7.5?h.

To investigate the associations between smoking in adolescence and adulthood, and changes in smoking behaviour between these age periods, with arterial stiffness in young adults; and whether any such associations could be explained by concomitant smoking-related levels of inflammation and endothelial dysfunction.

OBJECTIVE: In rheumatoid arthritis (RA), many genetic markers, such as the shared-epitope (SE) alleles, are described in association with radiographic progression, but limited data are available on undifferentiated arthritis (UA). We investigated whether single-nucleotide polymorphisms (SNP) and haplotypes in immune response genes and HLA class II alleles are associated with radiographic progression in patients with early UA. METHODS: Progression of radiographic damage was determined in white Dutch patients with early UA after 2 years of followup. Severe progression was defined as an increase in Sharp/van der Heijde Score ≥ 5 points after 2 years of followup. The remainder was classified as mild. These SNP were genotyped by Taqman technology: tumor necrosis factor (TNF) –1031, –863, –857, –308, –238; lymphotoxin-α (LTA) +368, +252; interleukin 10 (IL10) –2849, –1082, –819; IL1A –889, IL1B –31, +3953; and IL1RN +2018. Carriage of SE alleles and HLA-DQA1*05-DQB1*02 haplotype was established. These markers were analyzed in relation to radiographic progression. RESULTS: Forty-eight out of 151 patients with early UA had severe radiographic progression. Severe radiographic progression was associated with an increased carrier frequency of SE alleles (OR 5.12, 95% CI 2.0–13.1, p < 0.001) and IL10 GGC haplotype (OR 2.8, 95% CI 1.4–5.8, p = 0.003). Mild radiographic progression was associated with the HLA-DQA1*05-DQB1*02 haplotype (OR 0.3, 95% CI, 0.1–0.8, p = 0.013) and with allele TNF –308A (OR 0.4, 95% CI, 0.2–0.9, p = 0.02). CONCLUSION: The SE and the IL10 GGC haplotype are associated with severe progression of radiographic damage, in contrast to the DQA1*05-DQB1*02 haplotype and the TNF –308A allele, which are associated with mild radiographic progression in early UA.

Aims:Decreased total compliance of the pulmonary vascular bed is associated with increased mortality in patients with pulmonary arterial hypertension (PAH). We investigated whether proximal pulmonary artery stiffness, in terms of area distensibility and noninvasively assessed relative area change (RAC), calculated as relative cross-sectional area change, predicts mortality in patients with PAH.

Objectives: To investigate if birth weight is related to both body mass index (BMI) and distribution of subcutaneous fat at adult age. Research Methods and Procedures: A 9‐year longitudinal study was performed in 229 subjects (192 women) with ages ranging from 27 to 36 years. Birth weight was retrieved by a questionnaire, and adult weight, height, skinfold thicknesses, and waist‐to‐hip ratio (WHR) were repeatedly measured at mean ages 27, 29, 31, and 36 years. BMI, sum of four skinfolds (S4S), the ratio between two truncal skinfolds and S4S (SS/S4S), and the ratio between WHR and the cross‐sectional area of the left thigh were calculated with the available data. Results: The adjusted model showed that in women, birth weight was significantly negatively related to adult S4S [β = −5.211; (−9.768 to −0.654)], waist circumference [β = −1.449; (−2.829 to −0.069)], and SS/S4S ratio [β = −3.579; (−5.296 to −1.862)]. In men, a significant negative association was observed between birth weight and adult WHR [β = −1.096; (−2.092 to −0.100)] only. Other relationships showed, although not significantly, the same negative trend, namely that lower birth weight is related to higher adult body fat mass (S4S) and a more truncal subcutaneous fat distribution (SS/S4S). No associations were found between birth weight and either adult BMI or the cross‐sectional area of the thigh. Discussion: Lower birth weight is, in both adult men and women, related to a higher adult subcutaneous fat mass and a more truncal distribution of subcutaneous fat, indicating a higher risk for obesity.

OBJECTIVES

Background:Mild hyperhomocysteinaemia (HHC) is associated with an increased risk of premature atherothrombotic cerebrovascular disease. We investigated the clinical efficacy with regard to the incidence of cardiovascular events of treatment of mild HHC with vitamin B6plus folic acid.

To assess the development of common carotid artery properties (diameter, distensibility and compliance) in a cohort of 140 subjects (mean age 65.8 years, SD 7.5 years) originally diagnosed as impaired glucose tolerant in a population-based study, and to explore determinants of changes observed.

Background.Tracking analysis of serum cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and the TC/HDL-C ratio was carried out by a new method based on generalized estimating equations (GEE).

BackgroundThe purpose of this study was to analyse which lifestyle parameters (daily physical activity, dietary intake, smoking habits and alcohol consumption) discriminate between participants at high-risk and those at low-risk for coronary heart disease (CHD) [systolic and diastolic blood pressure (SBP/DBP), total serum cholesterol (TC), high-density lipoprotein cholesterol (HDL), the TC:HDL ratio, body fatness (sum of skinfolds [SSF]) and cardiopulmonary fitness (VO2-max)].MethodsThe data were derived from the Amsterdam Growth and Health Study (AGHS); an observational longitudinal study in which six repeated measurements were carried out over a period of 15 years on 181 participants aged 13 years at entry to the study. To assess possible discriminating factors, generalized estimating equations were used. This method makes use of risk group changing behaviour over time by using all available longitudinal data.ResultsFor DBP no significant relationships were found; high risk for SBP was inversely related to smoking habits (OR = 0.52; P< 0.01). No significant relationships were found for TC; high risk for HDL was positively related to the intake of carbohydrates (OR = 1.2; P= 0.02) and to smoking habits (OR = 1.6; P= 0.04); high risk for the TC: HDL ratio was positively related to the intake of carbohydrates (OR = 1.3; P= 0.01). High risk for SSF was positively related to the intake of protein (OR = 1.5; P< 0.01) and smoking habits (OR = 1.8; P= 0.01) and inversely related to daily physical activity (OR = 0.81; P= 0.01). High risk for VO2-max was inversely related to daily physical activity (OR = 0.67; P< 0.01).ConclusionsIn the relative young and healthy population of the AGHS during adolescence and young adulthood, physical inactivity was the most important lifestyle parameter related to high risk for CHD.

Diabetes mellitus (DM) is present in 20-40% of patients with liver cirrhosis. Although DM may predispose to fatal bacterial infections, or may accelerate fibrosis, the prognostic impact of its high prevalence is yet unclear.