Jos W. R. Twisk

Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: 'Establishing normal and reference values'

Aims Carotid–femoral pulse wave velocity (PWV), a direct measure of aortic stiffness, has become increasingly important for total cardiovascular (CV) risk estimation. Its application as a routine tool for clinical patient evaluation has been hampered by the absence of reference values. The aim of the present study is to establish reference and normal values for PWV based on a large European population. Methods and results We gathered data from 16 867 subjects and patients from 13 different centres across eight European countries, in which PWV and basic clinical parameters were measured. Of these, 11 092 individuals were free from overt CV disease, non-diabetic and untreated by either anti-hypertensive or lipid-lowering drugs and constituted the reference value population, of which the subset with optimal/normal blood pressures (BPs) (n = 1455) is the normal value population. Prior to data pooling, PWV values were converted to a common standard using established conversion formulae. Subjects were categorized by age decade and further subdivided according to BP categories. Pulse wave velocity increased with age and BP category; the increase with age being more pronounced for higher BP categories and the increase with BP being more important for older subjects. The distribution of PWV with age and BP category is described and reference values for PWV are established. Normal values are proposed based on the PWV values observed in the non-hypertensive subpopulation who had no additional CV risk factors. Conclusion The present study is the first to establish reference and normal values for PWV, combining a sizeable European population after standardizing results for different methods of PWV measurement.

Intensity of leg and arm training after primary middle-cerebral-artery stroke: a randomised trial

BACKGROUND We investigated the effects of different intensities of arm and leg rehabilitation training on the functional recovery of activities of daily living (ADL), walking ability, and dexterity of the paretic arm, in a single-blind randomised controlled trial. METHODS Within 14 days after stroke onset, 101 severely disabled patients with a primary middle-cerebral-artery stroke were randomly assigned to: a rehabilitation programme with emphasis on arm training; a rehabilitation programme with emphasis on leg training; or a control programme in which the arm and leg were immobilised with an inflatable pressure splint. Each treatment regimen was applied for 30 min, 5 days a week during the first 20 weeks after stroke. In addition, all patients underwent a basic rehabilitation programme. The main outcome measures were ability in ADL (Barthel index), walking ability (functional ambulation categories), and dexterity of the paretic arm (Action Research arm test) at 6, 12, 20, and 26 weeks. Analyses were by intention to treat. FINDINGS At week 20, the leg-training group (n=31) had higher scores than the control group (n=37) for ADL ability (median 19 [IQR 16-20] vs 16 [10-19], p<0.05), walking ability (4 [3-5] vs 3 [1-4], p<0.05), and dexterity (2 [0-56] vs 0 [0-2], p<0.01). The arm-training group (n=33) differed significantly from the control group only in dexterity (9 [0-39] vs 0 [0-2], p<0.01). There were no significant differences in these endpoints at 20 weeks between the arm-training and leg-training groups. INTERPRETATION Greater intensity of leg rehabilitation improves functional recovery and health-related functional status, whereas greater intensity of arm rehabilitation results in small improvements in dexterity, providing further evidence that exercise therapy primarily induces treatment effects on the abilities at which training is specifically aimed.

Depression as a risk factor for the onset of type 2 diabetes mellitus. A meta-analysis

Aims/hypothesisEvidence strongly suggests that depression and type 2 diabetes are associated, but the direction of the association is still unclear. Depression may occur as a consequence of having diabetes, but may also be a risk factor for the onset of type 2 diabetes. This study examined the latter association by reviewing the literature and conducting a meta-analysis of longitudinal studies on this topic.MethodsMedline and PsycInfo were searched for articles published up to January 2005. All studies that examined the relationship between depression and the onset of type 2 diabetes were included. Pooled relative risks were calculated using fixed and random effects models. To explore sources of heterogeneity between studies, subgroup analyses and meta-regression analyses were performed.ResultsNine studies met our inclusion criteria for this meta-analysis. The pooled relative risk was 1.26 (1.13–1.39) using the fixed effects model and 1.37 (1.14–1.63) using the random effects model. Heterogeneity between studies could not be explained by (1) whether studies controlled for undetected diabetes at baseline; (2) the method of diabetes assessment at follow-up; (3) the baseline overall risk of diabetes in the study population; and (4) follow-up duration.Conclusions/interpretationDepressed adults have a 37% increased risk of developing type 2 diabetes mellitus. The pathophysiological mechanisms underlying this relationship are still unclear and warrant further research. A randomised controlled study is needed to test whether effective prevention or treatment of depression can reduce the incidence of type 2 diabetes and its health consequences.

The Effect of Exercise Training Programs on Bone Mass: A Meta- analysis of Published Controlled Trials in Pre- and Postmenopausal Women

Abstract: With the aging of the population, the medical and social costs of skeletal fragility leading to fractures will cause an immense burden on society unless effective prophylactic and therapeutic regimens can be developed. Exercise is suggested as a possible regimen against involutional bone loss. The purpose of the present meta-analysis is to address a quantitative review of the randomized controlled trials (RCTs) and nonrandomized controlled trials (CTs) on the effects of exercise training programs on bone mass, measured as bone mineral density (BMD) or bone mineral content (BMC), of the lumbar spine (LS) and the femoral neck (FN) in pre- and postmenopausal women. The literature from 1966 through December 1996 was searched for published RCTs and CTs. Study treatment effect is defined as the difference between percentage change in bone mass per year in the training group and the control group. Overall treatment effects (OTs) with the 95% confidence intervals of these study treatment effects were calculated using inverse-variance weighting. Of the 62 articles identified, 25 met the inclusion criteria and were maintained for further analyses. The weighted OTs for the RCTs showed very consistently that the exercise training programs prevented or reversed almost 1% of bone loss per year in both LS and FN for both pre- and postmenopausal women. The two OTs that could be calculated for strength training programs did not reach significance. The OTs for the CTs were almost twice as high as those for the RCTs, which gives an indication of the confounding introduced by the nonrandom allocation of the subjects to groups.

Development of Antidrug Antibodies Against Adalimumab and Association With Disease Activity and Treatment Failure During Long-term Follow-up

CONTEXT Short-term data on the immunogenicity of monoclonal antibodies showed associations between the development of antidrug antibodies and diminished serum drug levels, and a diminished treatment response. Little is known about the clinical relevance of antidrug antibodies against these drugs during long-term follow-up. OBJECTIVE To examine the course of antidrug antibody formation against fully human monoclonal antibody adalimumab and its clinical relevance during long-term (3-year) follow-up of patients with rheumatoid arthritis (RA). DESIGN, SETTING, AND PATIENTS Prospective cohort study February 2004-September 2008; end of follow-up was September 2010. All 272 patients were diagnosed with RA and started treatment with adalimumab in an outpatient clinic. MAIN OUTCOME MEASURES Disease activity was monitored and trough serum samples were obtained at baseline and 8 time points to 156 weeks. Serum adalimumab concentrations and antiadalimumab antibody titers were determined after follow-up. Treatment discontinuation, minimal disease activity, and clinical remission were compared for patients with and without antiadalimumab antibodies. RESULTS After 3 years, 76 of 272 patients (28%) developed antiadalimumab antibodies--51 of these (67%) during the first 28 weeks of treatment. Patients without antiadalimumab antibodies had much higher adalimumab concentrations (median, 12 mg/L; IQR, 9-16 mg/L) compared with patients with antibody titers from 13 to 100 AU/mL (median, 5 mg/L; IQR, 3-9 mg/L; regression coefficient, -4.5; 95% CI, -6.0 to -2.9; P < .001) and also those greater than 100 AU/mL (median, 0 mg/L; IQR, 0-3 mg/L; regression coefficient, -7.1; 95% CI, -8.4 to -5.8; P < .001). Patients with antiadalimumab antibodies more often discontinued participation due to treatment failure (n = 29 [38%]; hazard ratio [HR], 3.0; 95% CI, 1.6-5.5; P < .001) compared with antiadalimumab antibody-negative ones (n = 28 [14%]). Ninety-five of 196 patients (48%) without antiadalimumab antibodies had minimal disease activity vs 10 of 76 patients (13%) with antiadalimumab antibodies; patients with antiadalimumab antibodies less often had sustained minimal disease activity score in 28 joints (DAS28) (< 3.2; HR, 3.6; 95% CI, 1.8-7.2; P < .001) compared with antiadalimumab antibody-negative ones. Three of 76 patients (4%) with antiadalimumab antibodies achieved sustained remission compared with 67 of 196 (34%) antiadalimumab antibody-negative ones; patients with antiadalimumab antibodies less often achieved remission (DAS28 < 2.6; HR, 7.1; 95% CI, 2.1-23.4; P < .001) compared with antiadalimumab antibody-negative ones. CONCLUSION Among outpatients with RA in whom adalimumab was started over 3 years, the development of antidrug antibodies was associated with lower adalimumab concentration and lower likelihood of minimal disease activity or clinical remission.

Applied Longitudinal Data Analysis for Epidemiology

Applied longitudinal data analysis for epidemiolog , Applied longitudinal data analysis for epidemiolog , کتابخانه دیجیتال جندی شاپور اهواز

The Effect of a Proprioceptive Balance Board Training Program for the Prevention of Ankle Sprains A Prospective Controlled Trial

Background Ankle sprains are the most common injuries in a variety of sports. Hypothesis A proprioceptive balance board program is effective for prevention of ankle sprains in volleyball players. Study Design Prospective controlled study. Methods There were 116 male and female volleyball teams followed prospectively during the 2001-2002 season. Teams were randomized by 4 geographical regions to an intervention group (66 teams, 641 players) and control group (50 teams, 486 players). Intervention teams followed a prescribed balance board training program; control teams followed their normal training routine. The coaches recorded exposure on a weekly basis for each player. Injuries were registered by the players within 1 week after onset. Results Significantly fewer ankle sprains in the intervention group were found compared to the control group (risk difference = 0.4/1000 playing hours; 95% confidence interval, 0.1-0.7). A significant reduction in ankle sprain risk was found only for players with a history of ankle sprains. The incidence of overuse knee injuries for players with history of knee injury was increased in the intervention group. History of knee injury may be a contraindication for proprioceptive balance board training. Conclusions Use of proprioceptive balance board program is effective for prevention of ankle sprain recurrences.

Attrition in longitudinal studies. How to deal with missing data.

The purpose of this paper was to illustrate the influence of missing data on the results of longitudinal statistical analyses [i.e., MANOVA for repeated measurements and Generalised Estimating Equations (GEE)] and to illustrate the influence of using different imputation methods to replace missing data. Besides a complete dataset, four incomplete datasets were considered: two datasets with 10% missing data and two datasets with 25% missing data. In both situations missingness was considered independent and dependent on observed data. Imputation methods were divided into cross-sectional methods (i.e., mean of series, hot deck, and cross-sectional regression) and longitudinal methods (i.e., last value carried forward, longitudinal interpolation, and longitudinal regression). Besides these, also the multiple imputation method was applied and discussed. The analyses were performed on a particular (observational) longitudinal dataset, with particular missing data patterns and imputation methods. The results of this illustration shows that when MANOVA for repeated measurements is used, imputation methods are highly recommendable (because MANOVA as implemented in the software used, uses listwise deletion of cases with a missing value). Applying GEE analysis, imputation methods were not necessary. When imputation methods were used, longitudinal imputation methods were often preferable above cross-sectional imputation methods, in a way that the point estimates and standard errors were closer to the estimates derived from the complete dataset. Furthermore, this study showed that the theoretically more valid multiple imputation method did not lead to different point estimates than the more simple (longitudinal) imputation methods. However, the estimated standard errors appeared to be theoretically more adequate, because they reflect the uncertainty in estimation caused by missing values.

Type 2 diabetes mellitus as a risk factor for the onset of depression: a systematic review and meta-analysis

Aims/hypothesisAn earlier meta-analysis showed that diabetes is a risk factor for the development and/or recurrence of depression. Yet whether this risk is different for studies using questionnaires than for those relying on diagnostic criteria for depression has not been examined. This study examined the association of diabetes and the onset of depression by reviewing the literature and conducting a meta-analysis of longitudinal studies on this topic.MethodsEMBASE, MEDLINE and PsycInfo were searched for articles published up to September 2009. All studies that examined the relationship between type 2 diabetes and the onset of depression were included. Pooled relative risks were calculated using fixed and random effects models.ResultsEleven studies met our inclusion criteria for this meta-analysis. Based on the pooled data, including 48,808 cases of type 2 diabetes without depression at baseline, the pooled relative risk was 1.24 (95% CI 1.09–1.40) for the random effects model. This risk was significantly higher for studies relying on diagnostic criteria of depression than for studies using questionnaires. However, this difference was no longer significant when controlled for year of publication.Conclusions/interpretationCompared with non-diabetic controls, people with type 2 diabetes have a 24% increased risk of developing depression. The mechanisms underlying this relationship are still unclear and warrant further research.

Physical Activity and Performance at School A Systematic Review of the Literature Including a Methodological Quality Assessment

OBJECTIVE To describe the prospective relationship between physical activity and academic performance. DATA SOURCES Prospective studies were identified from searches in PubMed, PsycINFO, Cochrane Central, and Sportdiscus from 1990 through 2010. STUDY SELECTION We screened the titles and abstracts for eligibility, rated the methodological quality of the studies, and extracted data. MAIN EXPOSURE Studies had to report at least 1 physical activity or physical fitness measurement during childhood or adolescence. MAIN OUTCOME MEASURES Studies had to report at least 1 academic performance or cognition measure during childhood or adolescence. RESULTS We identified 10 observational and 4 intervention studies. The quality score of the studies ranged from 22% to 75%. Two studies were scored as high quality. Methodological quality scores were particularly low for the reliability and validity of the measurement instruments. Based on the results of the best-evidence synthesis, we found evidence of a significant longitudinal positive relationship between physical activity and academic performance. CONCLUSIONS Participation in physical activity is positively related to academic performance in children. Because we found only 2 high-quality studies, future high-quality studies are needed to confirm our findings. These studies should thoroughly examine the dose-response relationship between physical activity and academic performance as well as explanatory mechanisms for this relationship.