The assessment of resting-state functional connectivity has become an important tool in studying brain disease mechanisms. Here we use magnetoencephalography to longitudinally evaluate functional connectivity changes in relation to clinical measures of disease progression in Parkinson's disease (PD).
Using a source-space based approach with detailed anatomical mapping, functional connectivity was assessed for temporal, prefrontal and high order sensory association areas known to show neuropathological changes in early clinical disease stages.
At baseline, early stage, untreated PD patients (n = 12) had lower parahippocampal and temporal delta band connectivity and higher temporal alpha1 band connectivity compared to controls. Longitudinal analyses over a 4-year period in a larger patient group (n = 43) revealed decreases in alpha1 and alpha2 band connectivity for multiple seed regions that were associated with motor or cognitive deterioration.
In the earliest clinical stages of PD, delta and alpha1 band resting-state functional connectivity is altered in temporal cortical regions. With disease progression, a reversal of the initial changes in alpha1 and additional decreases in alpha2 band connectivity evolving in a more widespread cortical pattern. These changes in functional connectivity appear to reflect clinically relevant phenomena and therefore hold promise as a marker of disease progression, with potential predictive value for clinical outcome.
•We use MEG to longitudinally evaluate resting-state functional connectivity in PD.•We report alterations in delta and alpha1 band connectivity in early-stage PD.•These changes evolve over the disease course in relation to clinical deterioration.•Connectivity changes hold promise as a marker of disease progression in PD.•They may also have potential predictive value for clinical outcome.
Parkinson's disease; Functional connectivity; Cognitive decline; Magnetoencephalography (MEG); Longitudinal
Within longitudinal epidemiological research, ‘count’ outcome variables with an excess of zeros frequently occur. Although these outcomes are frequently analysed with a linear mixed model, or a Poisson mixed model, a two-part mixed model would be better in analysing outcome variables with an excess of zeros. Therefore, objective of this paper was to introduce the relatively ‘new’ method of two-part joint regression modelling in longitudinal data analysis for outcome variables with an excess of zeros, and to compare the performance of this method to current approaches.
Within an observational longitudinal dataset, we compared three techniques; two ‘standard’ approaches (a linear mixed model, and a Poisson mixed model), and a two-part joint mixed model (a binomial/Poisson mixed distribution model), including random intercepts and random slopes. Model fit indicators, and differences between predicted and observed values were used for comparisons. The analyses were performed with STATA using the GLLAMM procedure.
Regarding the random intercept models, the two-part joint mixed model (binomial/Poisson) performed best. Adding random slopes for time to the models changed the sign of the regression coefficient for both the Poisson mixed model and the two-part joint mixed model (binomial/Poisson) and resulted into a much better fit.
This paper showed that a two-part joint mixed model is a more appropriate method to analyse longitudinal data with an excess of zeros compared to a linear mixed model and a Poisson mixed model. However, in a model with random slopes for time a Poisson mixed model also performed remarkably well.
Two-part joint model; Excess of zeros; Count; Mixed modelling; Longitudinal; Statistical methods
When study data are clustered, standard regression analysis is considered inappropriate and analytical techniques for clustered data need to be used. For prediction research in which the interest of predictor effects is on the patient level, random effect regression models are probably preferred over standard regression analysis. It is well known that the random effect parameter estimates and the standard logistic regression parameter estimates are different. Here, we compared random effect and standard logistic regression models for their ability to provide accurate predictions.
Using an empirical study on 1642 surgical patients at risk of postoperative nausea and vomiting, who were treated by one of 19 anesthesiologists (clusters), we developed prognostic models either with standard or random intercept logistic regression. External validity of these models was assessed in new patients from other anesthesiologists. We supported our results with simulation studies using intra-class correlation coefficients (ICC) of 5%, 15%, or 30%. Standard performance measures and measures adapted for the clustered data structure were estimated.
The model developed with random effect analysis showed better discrimination than the standard approach, if the cluster effects were used for risk prediction (standard c-index of 0.69 versus 0.66). In the external validation set, both models showed similar discrimination (standard c-index 0.68 versus 0.67). The simulation study confirmed these results. For datasets with a high ICC (≥15%), model calibration was only adequate in external subjects, if the used performance measure assumed the same data structure as the model development method: standard calibration measures showed good calibration for the standard developed model, calibration measures adapting the clustered data structure showed good calibration for the prediction model with random intercept.
The models with random intercept discriminate better than the standard model only if the cluster effect is used for predictions. The prediction model with random intercept had good calibration within clusters.
Logistic regression analysis; Prediction model with random intercept; Validation
Two models including age, self-rated health (SRH) and prior sickness absence (SA) were found to predict high SA in health care workers. The present study externally validated these prediction models in a population of office workers and investigated the effect of adding gender as a predictor.
SRH was assessed at baseline in a convenience sample of office workers. Age, gender and prior SA were retrieved from an occupational health service register. Two pre-defined prediction models were externally validated: a model identifying employees with high (i.e. ≥30) SA days and a model identifying employees with high (i.e. ≥3) SA episodes during 1-year follow-up. Calibration was investigated by plotting the predicted and observed probabilities and calculating the calibration slope. Discrimination was examined by receiver operating characteristic (ROC) analysis and the area under the ROC-curve (AUC).
A total of 593 office workers had complete data and were eligible for analysis. Although the SA days model showed acceptable calibration (slope = 0.89), it poorly discriminated office workers with high SA days from those without high SA days (AUC = 0.65; 95% CI 0.58–0.71). The SA episodes model showed acceptable discrimination (AUC = 0.76, 95% CI 0.70–0.82) and calibration (slope = 0.96). The prognostic performance of the prediction models did not improve in the population of office workers after adding gender.
The SA episodes model accurately predicted the risk of high SA episodes in office workers, but needs further multisite validation and requires a simpler presentation format before it can be used to select high-risk employees for interventions to prevent or reduce SA.
Absenteeism; Forecasting; Generalization; Office workers; Regression prognostics; Sick leave; Transportability
In 2012, in The Netherlands a multidisciplinary practice guideline for the assessment and treatment of suicidal behavior was issued. The release of guidelines often fails to change professional behavior due to multiple barriers. Structured implementation may improve adherence to guidelines. This article describes the design of a study measuring the effect of an e-learning supported Train-the-Trainer program aiming at the training of the full staff of departments in the application of the guideline. We hypothesize that both professionals and departments will benefit from the program.
In a multicenter cluster randomized controlled trial, 43 psychiatric departments spread over 10 regional mental health institutions throughout The Netherlands will be clustered in pairs with respect to the most prevalent diagnostic category of patients and average duration of treatment. Pair members are randomly allocated to either the experimental or the control condition. In the experimental condition, the full staff of departments, that is, all registered nurses, psychologists, physicians and psychiatrists (n = 532, 21 departments) will be trained in the application of the guideline, in a one-day small interactive group Train-the-Trainer program. The program is supported by a 60-minute e-learning module with video vignettes of suicidal patients and additional instruction. In the control condition (22 departments, 404 professionals), the guideline shall be disseminated in the traditional way: through manuals, books, conferences, internet, reviews and so on. The effectiveness of the program will be assessed at the level of both health care professionals and departments.
We aim to demonstrate the effect of training of the full staff of departments with an e-learning supported Train-the-Trainer program in the application of a new clinical guideline. Strengths of the study are the natural setting, the training of full staff, the random allocation to the conditions, the large scale of the study and the willingness of both staff and management to participate in the study.
Dutch trial register: NTR3092
Guideline; Implementation; Suicide prevention; Train-the-trainer; E-learning; Healthcare professionals
The high burden of diabetes for healthcare costs and their impact on quality of life and management of the disease have triggered the design and introduction of disease management programmes (DMPs) in many countries. The extent to which diabetes patients vary with regard to their healthcare utilisation and costs is largely unknown and could impact on the design of DMPs. The objectives of this study are to develop profiles based on both the diabetes-related healthcare utilisation and total healthcare utilisation in primary care, to investigate which patient and disease characteristics determine ‘membership’ of each profile, and to investigate the association between these profiles.
Data were used from electronic medical records of 6721 known type II diabetes patients listed in 48 Dutch general practices. Latent Class Analyses were conducted to identify profiles of healthcare and regression analyses were used to analyse the characteristics of the profiles.
For both diabetes-related healthcare utilisation and total healthcare utilisation three profiles could be distinguished: for the diabetes-related healthcare utilisation these were characterised as ‘high utilisation and frequent home visits’ (n=393), ‘low utilisation, GP only’ (n=3231) and ‘high utilisation, GP and nurse’ (n=3097). Profiles differed with respect to the patients’ age and type of medication; the oldest patients using insulin were dominant in the ‘high utilisation, GP and nurse’ profile. High total healthcare utilisation was not associated with high diabetes-related healthcare utilisation.
Healthcare utilisation of diabetes patients is heterogeneous. This challenges the development of distinguishable DMPs.
Type II diabetes mellitus; Healthcare utilisation profiles; Primary care; Latent Class Analyses
Children are especially vulnerable during periods of resource shortage such as economic embargoes. They are likely to suffer most from poor nutrition, infectious diseases, and other ensuing short-term threats. Moreover, early life circumstances can have important consequences for long-term health. We examined the relationship between early childhood exposure to the Cuban economic situation in the nineties and the occurrence of atopic diseases later in childhood.
A cross-sectional study of 1321 primary schoolchildren aged 4–14 was conducted in two Cuban municipalities. Asthma, allergic rhinoconjunctivitis and atopic dermatitis were diagnosed using the International Study of Asthma and Allergies in Childhood questionnaire. Children were divided into three groups of exposure to the economic situation in the nineties according to birth date: (1) unexposed; (2) exposed during infancy; (3) exposed during infancy and early childhood. Associations were assessed using multiple logistic regression models. Exposure during infancy had a significant inverse association with the occurrence of asthma (OR 0.56, 95%CI 0.33–0.94) and allergic rhinoconjunctivitis (OR 0.46, 95%CI 0.25–0.85). The associations were stronger after longer exposure, i.e. during infancy and early childhood, for asthma (OR 0.40, 95% CI 0.17–0.95) and allergic rhinoconjunctivitis (OR 0.29, 95%CI 0.11–0.77). No significant associations were found for atopic dermatitis.
Exposure to the economic situation in the nineties during infancy and early childhood was inversely associated with asthma and allergic rhinoconjunctivitis occurrence later in childhood. We hypothesize that factors related to this period, such as infectious diseases and undernutrition, may have an attenuating effect on atopic disease development. The exact cause and underlying mechanisms need to be further elucidated.
Purpose Much research has been performed on physical exposures during work (e.g. lifting, trunk flexion or body vibrations) as risk factors for low back pain (LBP), however results are inconsistent. Information on the effect of doses (e.g. spinal force or low back moments) on LBP may be more reliable but is lacking yet. The aim of the present study was to investigate the prospective relationship of cumulative low back loads (CLBL) with LBP and to compare the association of this mechanical load measure to exposure measures used previously. Methods The current study was part of the Study on Musculoskeletal disorders, Absenteeism and Health (SMASH) study in which 1,745 workers completed questionnaires. Physical load at the workplace was assessed by video-observations and force measurements. These measures were used to calculate CLBL. Furthermore, a 3-year follow-up was conducted to assess the occurrence of LBP. Logistic regressions were performed to assess associations of CLBL and physical risk factors established earlier (i.e. lifting and working in a flexed posture) with LBP. Furthermore, CLBL and the risk factors combined were assessed as predictors in logistic regression analyses to assess the association with LBP. Results Results showed that CLBL is a significant risk factor for LBP (OR: 2.06 (1.32–3.20)). Furthermore, CLBL had a more consistent association with LBP than two of the three risk factors reported earlier. Conclusions From these results it can be concluded that CLBL is a risk factor for the occurrence of LBP, having a more consistent association with LBP compared to most risk factors reported earlier.
Low back loading; Ergonomics; Workers; Longitudinal studies; Observational studies
Little is known about the relationship between body composition and physical fitness in 14 year-old high school adolescents of South Africa. Baseline data from a longitudinal study on physical activity and health (PAHLS) may provide valuable information for future studies, hence to inform public health policy makers. The objectives of this study are to determine the prevalence of underweight, normal weight and overweight among adolescents aged 14 years in the Tlokwe Local Municipality of the North West Province of South Africa, and to assess the association between physical fitness and body composition separately for boys and girls, adjusted for race and locality.
Body weight, height and triceps, and subscapular skinfolds of 256 adolescents (100 boys and 156 girls) aged 14 years were measured, and percentage body fat and body mass index (BMI) were calculated. BMI was used to determine underweight, normal weight and overweight based on the standard criterion. Physical fitness was assessed by standing broad jump, bent arm hang and sit-ups according to the EUROFIT fitness standard procedures. Multinomial logistic regression analyses stratified for gender and adjusted for race (black or white), and the locality (urban or township) of the schools were used to analyze the data.
In the total group 35.9% were underweight and 13.7% overweight. Boys were more underweight (44%) than girls (30.7%). The prevalence of overweight was 8% in boys and 17.3% in girls. BMI was strongly (p = 0.01) related with percentage body fat. Strong and significant positive associations between physical fitness and BMI for the underweight girls with high physical fitness scores (OR, 10.69 [95%CI: 2.81-40.73], and overweight girls with high physical fitness scores (OR, 0.11 [95%CI: 0.03-0.50]) were found. Non-significant weaker positive relationship between physical fitness and BMI for the underweight boys with high physical fitness scores (OR, 1.80 [95%CI: 0.63-5.09]), and the overweight boys with high physical fitness scores (OR, 0.18 [95%CI: 0.02-1.78]) were found.
Both underweight and overweight among boys and girls in Tlokwe Local Municipality exist, and their effects on physical fitness performances were also noticed. As such, strategic physical activity, interventions or follow-up studies recognizing this relationship particularly in the overweight adolescents are needed. In addition, authorities in health and education departments dealing with adolescents should make use of this evidence base information in policies development.
Physical fitness; Body composition; Underweight; Overweight; Adolescents; PAHL study
Care for older adults is facing a number of challenges: health problems are not consistently identified at a timely stage, older adults report a lack of autonomy in their care process, and care systems are often confronted with the need for better coordination between health care professionals. We aim to address these challenges by introducing the geriatric care model, based on the chronic care model, and to evaluate its effects on the quality of life of community-dwelling frail older adults.
In a 2-year stepped-wedge cluster randomised clinical trial with 6-monthly measurements, the chronic care model will be compared with usual care. The trial will be carried out among 35 primary care practices in two regions in the Netherlands. Per region, practices will be randomly allocated to four allocation arms designating the starting point of the intervention. Participants: 1200 community-dwelling older adults aged 65 or over and their primary informal caregivers. Primary care physicians will identify frail individuals based on a composite definition of frailty and a polypharmacy criterion. Final inclusion criterion: scoring 3 or more on a disability case-finding tool. Intervention: Every 6 months patients will receive a geriatric in-home assessment by a practice nurse, followed by a tailored care plan. Expert teams will manage and train practice nurses. Patients with complex care needs will be reviewed in interdisciplinary consultations. Evaluation: We will perform an effect evaluation, an economic evaluation, and a process evaluation. Primary outcome is quality of life as measured with the Short Form-12 questionnaire. Effect analyses will be based on the “intention-to-treat” principle, using multilevel regression analysis. Cost measurements will be administered continually during the study period. A cost-effectiveness analysis and cost-utility analysis will be conducted comparing mean total costs to functional status, care needs and QALYs. We will investigate the level of implementation, barriers and facilitators to successful implementation and the extent to which the intervention manages to achieve the transition necessary to overcome challenges in elderly care.
This is one of the first studies assessing the effectiveness, cost-effectiveness and implementation process of the chronic care model for frail community-dwelling older adults.
The Netherlands National Trial Register NTR2160.
Chronic care model; Frailty; Elderly; Primary care; Stepped wedge cluster randomised controlled clinical trial
Depression and diabetes are two highly prevalent and co-occurring health problems. Web-based, diabetes-specific cognitive behavioral therapy (CBT) depression treatment is effective in diabetes patients, and has the potential to be cost effective and to have large reach. A remaining question is whether the effectiveness differs between patients with seriously impaired mental health and patients with less severe mental health problems.
To test whether the effectiveness of an eight-lesson Web-based, diabetes-specific CBT for depression, with minimal therapist support, differs in patients with or without diagnosed major depressive disorder (MDD), diagnosed anxiety disorder, or elevated diabetes-specific emotional distress (DM-distress).
We used data of 255 patients with diabetes with elevated depression scores, who were recruited via an open access website for participation in a randomized controlled trial, conducted in 2008–2009, comparing a diabetes-specific, Web-based, therapist-supported CBT with a 12-week waiting-list control group. We performed secondary analyses on these data to study whether MDD or anxiety disorder (measured using a telephone-administered diagnostic interview) and elevated DM-distress (online self-reported) are effect modifiers in the treatment of depressive symptoms (online self-reported) with Web-based diabetes-specific CBT.
MDD, anxiety disorder, and elevated DM-distress were not significant effect modifiers in the treatment of self-assessed depressive symptoms with Web-based diabetes-specific CBT.
This Web-based diabetes-specific CBT depression treatment is suitable for use in patients with severe mental health problems and those with a less severe clinical profile.
International Standard Randomized Controlled Trial Number (ISRCTN): 24874457; http://www.controlled-trials.com/ISRCTN24874457 (Archived by WebCite at http://www.webcitation.org/63hwdviYr)
Diabetes mellitus, type 1; diabetes mellitus, type 2; depression; behavior therapy; cognitive therapy; depressive disorder; adults; psychology
Patients with ST-elevation myocardial infarction (STEMI) not treated with primary or rescue percutaneous coronary intervention (PCI) are at risk for recurrent ischemia, especially when viability in the infarct-area is present. Therefore, an invasive strategy with PCI of the infarct-related coronary artery in patients with viability would reduce the occurrence of a composite end point of death, reinfarction, or unstable angina (UA).
Patients admitted with an (sub)acute myocardial infarction, who were not treated by primary or rescue PCI, and who were stable during the first 48 hours after the acute event, were screened for the study. Eventually, we randomly assigned 216 patients with viability (demonstrated with low-dose dobutamine echocardiography) to an invasive or a conservative strategy. In the invasive strategy stenting of the infarct-related coronary artery was intended with abciximab as adjunct treatment. Seventy-five (75) patients without viability served as registry group. The primary endpoint was the composite of death from any cause, recurrent myocardial infarction (MI) and unstable angina at one year. As secondary endpoint the need for (repeat) revascularization procedures and anginal status were recorded.
The primary combined endpoint of death, recurrent MI and unstable angina was 7.5% (8/106) in the invasive group and 17.3% (19/110) in the conservative group (Hazard ratio 0.42; 95% confidence interval [CI] 0.18-0.96; p = 0.032). During follow up revascularization-procedures were performed in 6.6% (7/106) in the invasive group and 31.8% (35/110) in the conservative group (Hazard ratio 0.18; 95% CI 0.13-0.43; p < 0.0001). A low rate of recurrent ischemia was found in the non-viable group (5.4%) in comparison to the viable-conservative group (14.5%). (Hazard-ratio 0.35; 95% CI 0.17-1.00; p = 0.051).
We demonstrated that after acute MI (treated with thrombolysis or without reperfusion therapy) patients with viability in the infarct-area benefit from a strategy of early in-hospital stenting of the infarct-related coronary artery. This treatment results in a long-term uneventful clinical course. The study confirmed the low risk of recurrent ischemia in patients without viability.
Hepatic steatosis is common in type 2 diabetes. It is causally linked to the features of the metabolic syndrome, liver cirrhosis, and cardiovascular disease. Experimental data have indicated that increased liver fat may impair hepatic perfusion and metabolism. The aim of the current study was to assess hepatic parenchymal perfusion, together with glucose and fatty acid metabolism, in relation to hepatic triglyceride content.
RESEARCH DESIGN AND METHODS
Fifty-nine men with well controlled type 2 diabetes and 18 age-matched healthy normoglycemic men were studied using positron emission tomography to assess hepatic tissue perfusion, insulin-stimulated glucose, and fasting fatty acid metabolism, respectively, in relation to hepatic triglyceride content, quantified by proton magnetic resonance spectroscopy. Patients were divided into two groups with hepatic triglyceride content below (type 2 diabetes-low) or above (type 2 diabetes-high) the median of 8.6%.
Type 2 diabetes-high patients had the highest BMI and A1C and lowest whole-body insulin sensitivity (ANOVA, all P < 0.001). Compared with control subjects and type 2 diabetes-low patients, type 2 diabetes-high patients had the lowest hepatic parenchymal perfusion (P = 0.004) and insulin-stimulated hepatic glucose uptake (P = 0.013). The observed decrease in hepatic fatty acid influx rate constant, however, only reached borderline significance (P = 0.088). In type 2 diabetic patients, hepatic parenchymal perfusion (r = −0.360, P = 0.007) and hepatic fatty acid influx rate constant (r = −0.407, P = 0.007) correlated inversely with hepatic triglyceride content. In a pooled analysis, hepatic fat correlated with hepatic glucose uptake (r = −0.329, P = 0.004).
In conclusion, type 2 diabetic patients with increased hepatic triglyceride content showed decreased hepatic parenchymal perfusion and hepatic insulin mediated glucose uptake, suggesting a potential modulating effect of hepatic fat on hepatic physiology.
The aim of this review was to systematically review the results and quality of studies investigating the moderators of school-based interventions aimed at energy balance-related behaviors. We systematically searched the electronic databases of Pubmed, EMBASE, Cochrane, PsycInfo, ERIC and Sportdiscus. In total 61 articles were included. Gender, ethnicity, age, baseline values of outcomes, initial weight status and socioeconomic status were the most frequently studied potential moderators. The moderator with the most convincing evidence was gender. School-based interventions appear to work better for girls than for boys. Due to the inconsistent results, many studies reporting non-significant moderating effects, and the moderate methodological quality of most studies, no further consistent results were found. Consequently, there is lack of insight into what interventions work for whom. Future studies should apply stronger methodology to test moderating effects of important potential target group segmentations.
Children; diet; intervention; moderator; overweight; physical activity
This study investigated the associations of physical characteristics and personality in adolescence with physical activity and sedentary behaviour in adulthood.
Physical characteristics (i.e. objectively measured BMI, sum of skin folds, MOPER test battery performance), and personality (i.e. self-reported inadequacy, social inadequacy, rigidity, self-sufficiency/recalcitrance, dominance, achievement motivation, facilitating anxiety, debilitating anxiety, and social desirability) were assessed in 217 adolescent boys (Mean 13.0, SD 0.6) and girls (Mean 12.9, SD 0.6). Twenty-nine years later, at the age of 42, their physical activity and sedentary behaviour were assessed by means of accelerometry. Boys who scored lower on self-sufficiency/recalcitrance and higher on facilitating anxiety spent more time sedentary in adulthood. Girls with a superior standing high jump performance, and a lower score on social desirability spent more time sedentary in adulthood. In contrast with sedentary behaviour, physical activity at age 42 year could not be predicted by physical characteristics or personality in adolescence.
Sedentary behaviour in adulthood was partly explained by physical characteristics and/or personality in adolescence. Thus, our results suggest that it may be possible to identify people who are at risk of becoming sedentary at a rather young age.
Accelerometry; Aerobic fitness; Longitudinal; Motor fitness; Personality
Family history is a known risk factor for type 2 diabetes (T2DM), and more so in the presence of overweight. This study aims to develop and evaluate the effectiveness of a new lifestyle education programme 'DiAlert' targeted at 1st degree relatives of people with T2DM and overweight. In view of the high risk for diabetes and cardiovascular disease in immigrants from Turkish origin living in Western Europe, a culturally appropriate Turkish version of DiAlert will be developed and tested.
In this RCT, 268 (134 Dutch and 134 Turkish) overweight 1st degree relatives of patients with T2DM will be allocated to either the intervention or control group (leaflet). The intervention DiAlert aims to promote intrinsic motivation to change lifestyle, and sustain achieved behaviour changes during follow-up. Primary outcome is weight loss. Secondary outcomes include biological, behavioural and psychological indices, along with process indicators. Measurements will take place at baseline and after 3 and 9 months. Changes in outcomes are tested between intervention and control group at 3 months; effects over time are tested within and between both ethnic groups at 3 and 9 months.
The DiAlert intervention is expected to be more effective than the control condition in achieving significant weight loss at 3 months, in both Dutch and Turkish Dutch participants.
Netherlands National Trial Register (NTR): NTR2036
The traditional approach for identifying subjects at risk from cardiovascular diseases (CVD) is to determine the extent of clustering of biological risk factors adjusted for lifestyle. Recently, markers of endothelial dysfunction and low grade inflammation, including high sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecules (sICAM), and soluble vascular adhesion molecules (sVCAM), have been included in the detection for high risk individuals. However, the relationship of these novel biomarkers with CVD risk in adolescents remains unclear. The purpose of this study, therefore, was to establish the association of hsCRP, sICAM, and sVCAM with CVD risk in an adolescent population.
Data from the Young Hearts 2000 cross-sectional cohort study, carried out in 1999–2001, were used. From a total of 2,017 male and female participants, 95 obese subjects were identified and matched according to age, sex, and cigarette smoking, with 95 overweight and 95 normal-weight adolescents. Clustered CVD risk was computed using a sum of Z-scores of biological risk factors. The relationship was described using multiple linear regression analyses.
hsCRP, sICAM, and sVCAM showed significant associations with CVD risk. hsCRP and sICAM had a positive relation with CVD risk, whereas sVCAM showed an inverse relationship. In this study, lifestyle factors showed no relation with CVD risk.
The results fit the hypothesized role of low grade inflammation and endothelial dysfunction in CVD risk in asymptomatic adolescents. The inverse relationship of VCAM, however, is hard to explain and indicates the complex mechanisms underlying CVD. Further research is needed to draw firm conclusions on the biomarkers used.
Cardiovascular diseases; Adolescence; hsCRP; sICAM; sVCAM
Low body mass index is a general measure of thinness. However, its measurement can be cumbersome in older persons and other simple anthropometric measures may be more strongly associated with mortality. Therefore, associations of low mid-upper arm circumference, calf circumference, and body mass index with mortality were examined in older persons.
Data of the Longitudinal Aging Study Amsterdam, a population-based cohort study in the Netherlands, were used. The present study included community-dwelling persons 65 years and older in 1992–1993 (n = 1,667), who were followed until 2007 for their vital status. Associations between anthropometric measures and 15-year mortality were examined by spline regression models and, below the nadir, Cox regression models, transforming all measures to sex-specific Z scores.
Mortality rates were 599 of 826 (73%) in men and 479 of 841 (57%) in women. Below the nadir, the hazard ratio of mortality per 1 standard deviation lower mid-upper arm circumference was 1.79 (95% confidence interval, 1.48–2.16) in men and 2.26 (1.71–3.00) in women. For calf circumference, the hazard ratio was 1.45 (1.22–1.71) in men and 1.30 (1.15–1.48) in women and for body mass index 1.38 (1.17–1.61) in men and 1.56 (1.10–2.21) in women. Excluding deaths within the first 3 years after baseline did not change these associations. Excluding those with a smoking history, obstructive lung disease, or cancer attenuated the associations of calf circumference (men) and body mass index (women).
Based on the stronger association with mortality and given a more easy assessment in older persons, mid-upper arm circumference seems a more feasible and valid anthropometric measure of thinness than body mass index in older men and women.
Aged; Anthropometry; Body mass index; Mortality; Thinness
Background and objective
The haemodynamics of crystalloid and colloid fluid loading may depend on underlying disease, i.e. sepsis versus non-sepsis.
Design and setting
A single-centre, single-blinded, randomized clinical trial was carried out on 24 critically ill sepsis and 24 non-sepsis patients with clinical hypovolaemia, assigned to loading with normal saline, gelatin 4%, hydroxyethyl starch 6% or albumin 5% in a 90-min (delta) central venous pressure (CVP)-guided fluid loading protocol. Transpulmonary thermodilution was done each 30 min, yielding, among others, global end-diastolic volume and cardiac indices (GEDVI, CI).
Sepsis patients had hyperdynamic hypotension in spite of myocardial depression and dilatation, and greater inotropic/vasopressor requirements than non-sepsis patients. Independent of underlying disease, CVP and GEDVI increased more after colloid than saline loading (P < 0.018), so that CI increased by about 2% after saline and 12% after colloid loading (P = 0.029). The increase in preload-recruitable stroke work was also greater with colloids and did not differ among conditions.
Fluid loading with colloids results in a greater linear increase in cardiac filling, output and stroke work than does saline loading, in both septic and non-septic clinical hypovolaemia, in spite of myocardial depression and presumably increased vasopermeability potentially decreasing the effects of colloid fluid loading in the former.
Electronic supplementary material
The online version of this article (doi:10.1007/s00134-010-1776-x) contains supplementary material, which is available to authorized users.
Colloids; Crystalloids; Sepsis; Preload-recruitable stroke work; Hypovolaemia; Global end-diastolic volume; Fluid challenge
To study whether the methods used to select participants in research on prevalence rates of the health effects of exposure to a disaster may cause bias. This study compared background characteristics, disaster exposure, and complaints reported by (1) police officers who participated in an epidemiological study and underwent a medical examination, and (2) police officers who only participated in an epidemiological study.
Design and Setting
In 2000, an epidemiological study was started to investigate the health status among police officers who were involved in assistance work related to the air disaster in Amsterdam: the epidemiological study air disaster Amsterdam (ESADA). These police officers were personally invited to participate in the epidemiological study and were additionally offered a medical examination, providing them with the opportunity to have their health checked by a medical doctor.
Of the total group of involved police officers who were invited, 834 (70%) participated in the ESADA: 224 (26.9%) only participated in the study, but 610 (73.1%) also underwent the medical examination.
Police officers who underwent a medical examination significantly more often reported one or more musculoskeletal complaints, skin complaints, general or non‐specific complaints, had more often experienced an event with potentially traumatic impact, or had performed one or more potentially traumatic tasks.
The methods of selection of participants are important in research on health effects after disasters and can result in an overestimation of some of the effects, on average, by a factor of 1.5 to 2.
selection bias; disaster research
The purpose of the study was to compare early changes in blood flow (BF) and glucose metabolism (MRglu) in metastatic breast cancer lesions of patients treated with chemotherapy.
Eleven women with stage IV cancer and lesions in breast, lymph nodes, liver, and bone were scanned before treatment and after the first course of chemotherapy. BF, distribution volume of water (Vd), MRglu/BF ratio, MRglu and its corresponding rate constants K1 and k3 were compared per tumor lesion before and during therapy.
At baseline, mean BF and MRglu varied among different tumor lesions, but mean Vd was comparable in all lesions. After one course of chemotherapy, mean MRglu decreased in all lesions. Mean BF decreased in breast and node lesions and increased in bone lesions. Vd decreased in breast and nodes, but did not change in bone lesions. The MRglu/BF ratio decreased in breast and bone lesions and increased in node lesions. In patients with multiple tumor lesions BF and MRglu response could be very heterogeneous, even within similar types of metastases. BF and MRglu increased in lesions of patients who experienced early disease progression or showed no response during clinical follow-up.
BF and MRglu changes separately give unique information on different aspects of tumor response to chemotherapy. Changes in BF and MRglu parameters can be remarkably heterogeneous in patients with multiple lesions.
Positron emission tomography; Blood flow; Glucose metabolism; Breast cancer; Metastases
Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of mechanical ventilation with heliox in these patients is unclear. The objective of this prospective cross-over study was to determine the effects of mechanical ventilation with heliox 60/40 versus conventional gas on respiratory system resistance, air-trapping and CO2 removal.
Mechanically ventilated, sedated and paralyzed infants with proven RSV were enrolled within 24 hours after paediatric intensive care unit (PICU)admission. At T = 0, respiratory system mechanics including respiratory system compliance and resistance, and peak expiratory flow rate were measured with the AVEA ventilator. The measurements were repeated at each interval (after 30 minutes of ventilation with heliox, after 30 minutes of ventilation with nitrox and again after 30 minutes of ventilation with heliox). Indices of gas exchange (ventilation and oxygenation index) were calculated at each interval. Air-trapping (defined by relative change in end-expiratory lung volume) was determined by electrical impedance tomography (EIT) at each interval.
Thirteen infants were enrolled. In nine, EIT measurements were performed. Mechanical ventilation with heliox significantly decreased respiratory system resistance. This was not accompanied by an improved CO2 elimination, decreased peak expiratory flow rate or decreased end-expiratory lung volume. Importantly, oxygenation remained unaltered throughout the experimental protocol.
Respiratory system resistance is significantly decreased by mechanical ventilation with heliox (ISCRTN98152468).
Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival.
Two sample sets of high-risk primary breast cancer patients participating in a randomised national trial investigating the effectiveness of high-dose chemotherapy were analysed. Sera in set I (n = 63) were analysed by surface enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS) for biomarker finding. Initial results were validated by analysis of sample set II (n = 371), using one-dimensional gel-electrophoresis.
In sample set I, the expression of a peak at mass-to-charge ratio 9198 (relative intensity ≤ 20 or > 20), identified as haptoglobin (Hp) alpha-1 chain, was strongly associated with recurrence free survival (global Log-rank test; p = 0.0014). Haptoglobin is present in three distinct phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2), of which only individuals with phenotype Hp 1-1 or Hp 2-1 express the haptoglobin alpha-1 chain. As the expression of the haptoglobin alpha-1 chain, determined by SELDI-TOF MS, corresponds to the phenotype, initial results were validated by haptoglobin phenotyping of the independent sample set II by native one-dimensional gel-electrophoresis. With the Hp 1-1 phenotype as the reference category, the univariate hazard ratio for recurrence was 0.87 (95% CI: 0.56 – 1.34, p = 0.5221) and 1.03 (95% CI: 0.65 – 1.64, p = 0.8966) for the Hp 2-1 and Hp 2-2 phenotypes, respectively, in sample set II.
In contrast to our initial results, the haptoglobin phenotype was not identified as a predictor of recurrence free survival in high-risk primary breast cancer in our validation set. Our initial observation in the discovery set was probably the result of a type I error (i.e. false positive). This study illustrates the importance of validation in obtaining the true clinical applicability of a potential biomarker.
AIM: To investigate the effects of an enteral supple-ment containing antioxidants on circulating levels of antioxidants and indicators of oxidative stress after major gastrointestinal surgery.
METHODS: Twenty-one patients undergoing major upper gastrointestinal tract surgery were randomised in a single centre, open label study on the effect of postoperative enteral nutrition supplemented with antioxidants. The effect on circulating levels of antioxidants and indicators of oxidative stress, such as F2-isoprostane, was studied.
RESULTS: The antioxidant enteral supplement showed no adverse effects and was well tolerated. After surgery a decrease in the circulating levels of antioxidant parameters was observed. Only selenium and glutamine levels were restored to pre-operative values one week after surgery. F2-isoprostane increased in the first three postoperative days only in the antioxidant supplemented group. Lipopolysaccharide binding protein (LBP) levels decreased faster in the antioxidant group after surgery.
CONCLUSION: Despite lower antioxidant levels there was no increase in the circulating markers of oxidative stress on the first day after major abdominal surgery. The rise in F2-isoprostane in patients receiving the antioxidant supplement may be related to the conversion of antioxidants to oxidants which raises questions on antioxidant supplementation. Module AOX restored the postoperative decrease in selenium levels. The rapid decrease in LBP levels in the antioxidant group suggests a possible protective effect on gut wall integrity. Further studies are needed on the role of oxidative stress on outcome and the use of antioxidants in patients undergoing major abdominal surgery.
Antioxidants; Critical illness; Enteral nutrition; Oxidative stress; Surgery; Upper gastrointe-stinal tract
Many depressed people do not receive help for their symptoms, and there are various barriers that impede help-seeking. The Internet may offer interesting alternatives for reaching and helping people with depression. Depression can be treated effectively with Internet-based cognitive behavioral therapy (CBT), but a short intervention based on problem solving therapy (PST) could constitute a worthwhile alternative to CBT.
In this study we evaluated the effectiveness of Internet-based CBT and Internet-based PST in comparison to a waiting list control group (WL), and we determined the differences between the two treatments.
We conducted a 3-arm randomized controlled trial to compare CBT, PST, and WL. The main inclusion criterion was presence of depressive symptoms (≥ 16 on the Center for Epidemiological Studies Depression scale). CBT and PST consisted of eight and five weekly lessons respectively. Participants were supported by email. Self-report measures of depression, anxiety, and quality of life were completed at pretest and after 5, 8, and 12 weeks.
A total of 263 participants were randomized to the three conditions (CBT: n=88; PST: n=88; WL: n=87). Of the 263 participants, 184 (70%) completed questionnaires after 5 weeks, 173 (66%) after 8 weeks, and 151 (57%) after 12 weeks. Between-group effect sizes for depressive symptoms were 0.54 for CBT after 8 weeks (95% confidence interval (CI): 0.25 - 0.84) and 0.47 for PST after 5 weeks (95% CI: 0.17 - 0.77). These effects were further improved at 12 weeks (CBT: 0.69, 95% CI: 0.41 - 0.98; PST: 0.65, 95% CI: 0.36 - 0.95). For anxiety, effect sizes were also at a medium level. Effect sizes for quality of life were low. The number of participants showing clinically significant change at 12 weeks was significantly higher for CBT (n = 34, 38.6%) and PST (n = 30, 34.1%), compared to WL (n = 0).
Both Internet-based treatments are effective in reducing depressive symptoms, although the effect of PST is realized more quickly.
International Standard Randomized Controlled Trial Number (ISRCTN): 16823487; http://www.controlled-trials.com/ISRCTN16823487/16823487 (Archived by WebCite at http://www.webcitation.org/5cQsOj7xf).
Internet; depression; self-help; cognitive therapy; problem solving; randomized trial