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The European Union is renowned for its ability to transfer certain international norms and values to other countries, including democracy, respect for human rights and peace. This thesis analyzes the EU’s normative influence in the Colombian peace process. It first presents the European Union as a peacebuilding force and the theory of Normative Power Europe (NPE) as coined by Manners. Then, the thesis evaluates the EU’s involvement in the Colombian peace process, along the lines of Manners’ six factors of normative power diffusion. Finally, it indicates to what extent the EU’s policies have been normatively effective. This thesis concludes that despite a number of promising policy initiatives in support of peace, the European Union has not been able to truly establish a normative influence in Colombia, especially when compared to the United States.

The European Union is renowned for its ability to transfer certain international norms and values to other countries, including democracy, respect for human rights and peace. This thesis analyzes the EU’s normative influence in the Colombian peace process. It first presents the European Union as a peacebuilding force and the theory of Normative Power Europe (NPE) as coined by Manners. Then, the thesis evaluates the EU’s involvement in the Colombian peace process, along the lines of Manners’ six factors of normative power diffusion. Finally, it indicates to what extent the EU’s policies have been normatively effective. This thesis concludes that despite a number of promising policy initiatives in support of peace, the European Union has not been able to truly establish a normative influence in Colombia, especially when compared to the United States.

Contains fulltext : 229629.pdf (Publisher’s version ) (Closed access), BACKGROUND: Electronic health records (EHRs) are increasingly used for research; however, multicomponent outcome measures such as daily functioning cannot yet be readily extracted. AIM: To evaluate whether an electronic frailty index based on routine primary care data can be used as a measure for daily functioning in research with community-dwelling older persons (aged ≥75 years). DESIGN AND SETTING: Cohort study among participants of the Integrated Systemic Care for Older People (ISCOPE) trial (11 476 eligible; 7285 in observational cohort; 3141 in trial; over-representation of frail people). METHOD: At baseline (T0) and after 12 months (T12), daily functioning was measured with the Groningen Activities Restriction Scale (GARS, range 18-72). Electronic frailty index scores (range 0-1) at T0 and T12 were computed from the EHRs. The electronic frailty index (electronic Frailty Index - Utrecht) was tested for responsiveness and compared with the GARS as a gold standard for daily functioning. RESULTS: In total, 1390 participants with complete EHR and follow-up data were selected (31.4% male; median age = 81 years, interquartile range = 78-85). The electronic frailty index increased with age, was higher for females, and lower for participants living with a partner. It was responsive after an acute major medical event; however, the correlation between the electronic frailty index and GARS at T0 and over time was limited. CONCLUSION: Because the electronic frailty index does not reflect daily functioning, further research on new methods to measure daily functioning with routine care data (for example, other proxies) is needed before EHRs can be a useful data source for research with older persons.

Contains fulltext : 183824.pdf (publisher's version ) (Open Access)

Purpose: to support older people with several healthcare needs in sustaining adequate functioning and independence, more proactive approaches are needed. This purpose of this study is to summarise the (cost-) effectiveness of proactive, multidisciplinary, integrated care programmes for older people in Dutch primary care. Methods design: individual patient data (IPD) meta-analysis of eight clinically controlled trials. Setting: primary care sector. Interventions: combination of (i) identification of older people with complex problems by means of screening, followed by (ii) a multidisciplinary integrated care programme for those identified. Main outcome: activities of daily living, i.e. a change on modified Katz-15 scale between baseline and 1-year follow-up. Secondary outcomes: quality of life (visual analogue scale 0-10), psychological (mental well-being scale Short Form Health Survey (SF)-36) and social well-being (single item, SF-36), quality-adjusted life years (Euroqol-5dimensions-3level (EQ-5D-3L)), healthcare utilisation and cost-effectiveness. Analysis: intention-to-treat analysis, two-stage IPD and subgroup analysis based on patient and intervention characteristics. Results: included were 8,678 participants: median age of 80.5 (interquartile range 75.3; 85.7) years; 5,496 (63.3%) women. On the modified Katz-15 scale, the pooled difference in change between the intervention and control group was -0.01 (95% confidence interval -0.10 to 0.08). No significant differences were found in the other patient outcomes or subgroup analyses. Compared to usual care, the probability of the intervention group to be cost-effective was less than 5%. Conclusion: compared to usual care at 1-year follow-up, strategies for identification of frail older people in primary care combined with a proactive integrated care intervention are probably not (cost-) effective.

Background: A fundamental issue in elderly care is targeting those older people at risk and in need of care interventions. Frailty is widely used to capture variations in health risks but there is no general consensus on the conceptualization of frailty. Indeed, there is considerable heterogeneity in the group of older people characterized as frail. This research identifies frailty profiles based on the physical, psychological, social and cognitive domains of functioning and the

Objectives: Complex interventions are criticized for being a “black box”, which makes it difficult to determine why they succeed or fail. Recently, nine proactive primary-care programs aiming to prevent functional decline in older adults showed inconclusive effects. The aim of this study was to systematically unravel, compare, and synthesize the development and evaluation of nine primary-care programs within a controlled trial to further improve the development and evaluation of complex interventions. Study Design and Setting: A systematic overview of all written data on the nine proactive primary-care programs was conducted using a validated item list. The nine proactive primary-care programs involved 214 general practices throughout the Netherlands. Results: There was little or no focus on the (1) context surrounding the care program, (2) modeling of processes and outcomes, (3) intervention fidelity and adaptation, and (4) content and evaluation of training for interventionists. Conclusions: An in-depth analysis of the context, modeling of the processes and outcomes, measurement and reporting of intervention fidelity, and implementation of effective training for interventionists is needed to enhance the development and replication of future complex interventions.

Background: As populations age, chronic geriatric conditions linked to progressive organ failure jeopardize health-related quality of life (HRQoL). Thus, this research assessed the validity and applicability of the EQ-5D (a common HRQoL instrument) across four major chronic

Background Preference-weighted multi-faceted endpoints have the potential to facilitate comparative effectiveness research that incorporates patient preferences. The Older Persons and Informal Caregivers Survey Composite endpoint (TOPICS-CEP) is potentially a valuable outcome measure for evaluating interventions in geriatric care as it combines multiple outcomes relevant to older persons in a single metric. The objective of this study was to validate TOPICS-CEP across different study settings (general population, primary care and hospital). Methods Data were extracted from TOPICS Minimum Dataset (MDS), a pooled public-access national database with information on older persons throughout the Netherlands. Data of 1

Contains fulltext : 152010.pdf (Publisher’s version ) (Closed access), BACKGROUND: Guidelines and accompanying risk charts concerning cardiovascular risk management (CVRM) are regularly revised worldwide. OBJECTIVE: To evaluate whether revision of the Dutch CVRM guideline has led to the reclassification of patients and, accordingly, to changes in drug recommendations. METHODS: All medical records (year 2011) of patients aged 40-65 years with no history of cardiovascular disease (CVD) but using antihypertensive and/or lipid-lowering drugs, were selected from the Registration Network of General Practices associated with Leiden University Medical Center. Multiple imputation techniques for missing determinants were used. The individual cardiovascular risk was calculated and the resulting drug recommendation was assessed according to both the 2006 and 2012 versions of the guideline. RESULTS: In total, 2075 patients were selected, of whom 1248 fulfilled the guideline criteria (systolic blood pressure 115-180 mmHg and total cholesterol/high-density-lipoprotein-cholesterol ratio 3.5-8). According to the 2012 guideline, 58.2% of the patients had low risk and 249 patients (20.0%) shifted to a different risk category. For 150 of these patients (12.0%), this category shift implied a shift in drug recommendation. The probability of shifting in drug recommendation increased with increasing age, cholesterol level, and blood pressure, and by being male. CONCLUSION: Guideline revision may have important implications: based on identical values for risk factors, according to the latest revision of the Dutch CVRM guideline 20% of patients shifted in risk category and 12% of the patients shifted in drug recommendation.

Item does not contain fulltext, BACKGROUND: In general practice, it is too time-consuming to invite all patients for cardiovascular risk assessment. OBJECTIVE: To examine how many patients with an indication for treatment with cardiovascular medication can be identified by ad hoc case-finding when all patients with overweight/obesity are invited for risk assessment. METHODS: A cross-sectional analysis of the baseline measurements of the Netherlands Epidemiology of Obesity study, a population-based prospective cohort study in 6673 persons aged 45-65 years. We calculated the proportion of participants with a treatment indication using the risk prediction Systematic COronary Risk Evaluation (SCORE-NL 2011), for lean, overweight and obese participants. Participants with a history of cardiovascular disease, diabetes mellitus or rheumatoid arthritis or using cardiovascular medication were not eligible for ad hoc case-finding because they were already identified as being at risk and/or had been treated. Results : Of the study population, 30% had already been identified and/or treated with cardiovascular medication and were therefore not eligible for ad hoc case-finding. Of the eligible participants, 47% were lean, 41% overweight and 12% obese. Of the participants with overweight, 12% had a treatment indication and of the participants with obesity, 19% had a treatment indication. Of all participants with a treatment indication 24% were not yet treated. Of all participants with a new treatment indication, 70% had overweight or obesity. CONCLUSIONS: Of the participants with a treatment indication, 24% were not yet treated. Inviting patients with overweight/obesity for cardiovascular risk assessment may help to detect 70% of these residual patients with a treatment indication.

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Contains fulltext : 154840.pdf (publisher's version ) (Open Access)

Contains fulltext : 137201.pdf (publisher's version ) (Open Access), BACKGROUND: The outcome measures most frequently used in studies on the effectiveness of migraine treatment are whether the patient is free of pain, nausea, and free of photophobia/phonophobia within two hours. However, no patient-centred outcome measures are available. Therefore, we performed an online Delphi procedure to compile a list of outcome measures deemed most important to migraine patients. METHODS: From a large database of migraine patients, we randomly selected 150 males and 150 females patients. We asked the open-ended question: 'If a new medicine was developed for migraine attacks, what would you wish the effect of this medication to be?' In the second and third rounds, we presented the answers of the first round and asked the patients to rate the importance of each item. RESULTS: The initial response rate was 56% (n = 169). In the subsequent rounds the response rates were 90% (n = 152), and 97% (n = 147), respectively. Patients wanted their attack medication to treat the headache within 30 min, to prevent the attack from getting worse, to ensure they could function properly within 1 h, and prevent the recurrence of symptoms during the same day. CONCLUSIONS: The currently used outcome measures in migraine research do not sufficiently reflect the wishes of patients. Patients want the medication to work faster, to take away pain at an earlier stage, to make them able to function properly quickly, and to prevent recurrence. These aspects should be considered in future evaluation of new attack medication for migraine.

Item does not contain fulltext, BACKGROUND: Clinical trials on the prophylactic effect of propranolol and metoprolol for migraine show that starting this medication leads to a decrease in the use of attack medication of 0.9-8.9 doses per month. However, studies in daily practice are lacking. METHODS: We compared the number of triptans prescribed in the six months before and the six months after the start of propranolol/metoprolol in a Dutch national representative primary care cohort. Results : Of the 168 triptan-using patients who started with propranolol or metoprolol, the number of triptans prescribed before starting was 4.6 doses per month. The number of triptans prescribed six months before compared with six months after starting propranolol/metoprolol decreased with 1.0 dose per month (Wilcoxon rank test; p = 0.000). CONCLUSION: In this primary care population, although the number of triptans prescribed decreased after starting propranolol or metoprolol, the decrease is relatively small compared to data from clinical trials.

Contains fulltext : 139289.pdf (publisher's version ) (Open Access), BACKGROUND: In clinical practice, GPs appeared to have an internalized concept of "vulnerability." This study investigates the variability between general practitioners (GPs) in their vulnerability-assessment of older persons. METHODS: Seventy-seven GPs categorized their 75-plus patients (n = 11392) into non-vulnerable, possibly vulnerable, and vulnerable patients. GPs personal and practice characteristics were collected. From a sample of 2828 patients the following domains were recorded: sociodemographic, functional [instrumental activities in daily living (IADL), basic activities in daily living (BADL)], somatic (number of diseases, polypharmacy), psychological (Mini-Mental State Examination, 15-item Geriatric Depression Scale; GDS-15) and social (De Jong-Gierveld Loneliness Scale; DJG). Variability in GPs' assessment of vulnerability was tested with mixed effects logistic regression. P-values for variability (pvar) were calculated by the log-likelihood ratio test. RESULTS: Participating GPs assessed the vulnerability of 10,361 patients. The median percentage of vulnerable patients was 32.0% (IQR 19.5 to 40.1%). From the somatic and psychological domains, GPs uniformly took into account the patient characteristics 'total number of diseases' (OR 1.7, 90% range = 0, p var = 1), 'polypharmacy' (OR 2.3, 90% range = 0, p var = 1) and 'GDS-15' (OR 1.6, 90% range = 0, p var = 1). GPs vary in the way they assessed their patients' vulnerability in the functional domain (IADL: median OR 2.8, 90% range 1.6, p var < 0.001, BADL: median OR 2.4, 90% range 2.9, p var < 0.001) and the social domain (DJG: median OR 1.2, 90% range = 1.2, p var < 0.001). CONCLUSIONS: GPs seem to share a medical concept of vulnerability, since they take somatic and psychological characteristics uniformly into account in the vulnerability-assessment of older persons. In the functional and social domains, however, variability was found. Vulnerability assessment by GPs might be a promising instrument to

Item does not contain fulltext, OBJECTIVES: To assess the effect of preventive pravastatin treatment on coronary heart disease (CHD) morbidity and mortality in older persons at risk for cardiovascular disease (CVD), stratified according to plasma levels of homocysteine. DESIGN: A post hoc subanalysis in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), started in 1997, which is a double-blind, randomized, placebo-controlled trial with a mean follow-up of 3.2 years. SETTING: Primary care setting in two of the three PROSPER study sites (Netherlands and Scotland). PARTICIPANTS: Individuals (n = 3,522, aged 70-82, 1,765 male) with a history of or risk factors for CVD were ranked in three groups depending on baseline homocysteine level, sex, and study site. INTERVENTION: Pravastatin (40 mg) versus placebo. MEASUREMENTS: Fatal and nonfatal CHD and mortality. RESULTS: In the placebo group, participants with a high homocysteine level (n = 588) had a 1.8 higher risk (95% confidence interval (CI) = 1.2-2.5, P = .001) of fatal and nonfatal CHD than those with a low homocysteine level (n = 597). The absolute risk reduction in fatal and nonfatal CHD with pravastatin treatment was 1.6% (95% CI = -1.6 to 4.7%) in the low homocysteine group and 6.7% (95% CI = 2.7-10.7%) in the high homocysteine group (difference 5.2%, 95% CI = 0.11-10.3, P = .046). Therefore, the number needed to treat (NNT) with pravastatin for 3.2 years for benefit related to fatal and nonfatal CHD events was 14.8 (95% CI = 9.3-36.6) for high homocysteine and 64.5 (95% CI = 21.4-infinity) for low homocysteine. CONCLUSION: In older persons at risk of CVD, those with high homocysteine are at highest risk for fatal and nonfatal CHD. With pravastatin treatment, this group has the highest absolute risk reduction and the lowest NNT to prevent fatal and nonfatal CHD.

Item does not contain fulltext, OBJECTIVE: To interpret questionnaire scores, clinicians and researchers need to know what change in score reflects a meaningful change in the condition of an individual patient, and what difference reflects a meaningful difference between groups. These values differ between different populations. We determined the within-person minimally important change (MIC) and the between-group minimally important difference (MID) of the Headache Impact Test-6 (HIT-6) questionnaire in a primary-care population of migraine patients. METHODS: We included 490 patients who participated in a clinical trial on the treatment of migraine in primary care. We compared their change scores on the HIT-6 questionnaire between baseline and at three-months follow-up with the answers to two anchor questions according to the 'mean change approach' and the 'ROC curve approach'. RESULTS: The within-person MIC was estimated to be between -2.5 points (mean change approach) and -6 points (ROC curve approach). The choice for the within-person MIC value depends on the consequences of false positives and false negatives in a particular setting. The between-group MID was estimated at -1.5 points. CONCLUSIONS: We determined the within-person MIC and between-group MID for the HIT-6 in a primary-care population of migraine patients. We recommend the use of these values for clinical care and for research.

Item does not contain fulltext, AIMS: To investigate whether low systolic blood pressure is predictive for increased mortality risk in 90-year-old subjects without heart failure, defined by low levels of NT-proBNP, as well as in 90-year-old subjects with high levels of NT-proBNP. METHODS AND RESULTS: This study was embedded in the Leiden 85-plus Study, an observational population-based prospective study. All 90-year-old participants (n = 267) were included between 2002 and 2004 and followed up for mortality for at least 5 years. Differences in mortality risks were compared between participants with low systolic blood pressure (150 mmHg) within strata of low NT-proBNP (<284 pg/mL for women and <306 pg/mL for men = lowest tertile) vs. high NT-proBNP (middle and highest tertile) at age 90 years. During maximal follow-up of 7.2 years, 212 participants (79%) died. Among participants with low NT-proBNP, low systolic blood pressure gave a two-fold increased risk (hazard ratio 2.0, 95% confidence interval 1.1-3.4) compared with participants with high systolic blood pressure. For participants with high NT-proBNP, low systolic blood pressure provided a 1.7 increased mortality risk (95% confidence interval 1.2-2.3) compared with high systolic blood pressure. CONCLUSION: Low systolic blood pressure is predictive for increased mortality risk in 90-year-old subjects, irrespective of the NT-proBNP level. Therefore, the absence or presence of heart failure as determined by NT-proBNP does not influence the prognostic value of low systolic blood pressure with regard to mortality in the oldest old.

Item does not contain fulltext, There are indications that in persons of older age, systolic blood pressure (SBP) is no longer associated with mortality. This raises the question whether the predictive value of SBP changes from younger to older age groups. Analysis in the Rotterdam Study, a population-based prospective cohort study among 4,612 participants aged >/=55 years without previous cardiovascular disease and with a median follow-up of 14.9 (interquartile range, 11.1-15.8) years. Within four age groups (55-64, 65-74, 75-84, >/=85 years), the predictive value of baseline SBP for mortality was studied. From age 55 to >/=85 years, risk of all-cause mortality associated with SBP >/=160 mmHg decreased from HR 1.7 (95%CI 1.2-2.2) to HR 0.7 (95%CI 0.4-1.1), p for trend <0.001. For participants with SBP 140-159 mmHg, the risk decreased from HR 1.2 (95%CI 0.9-1.5) to HR 0.7 (95%CI 0.5-1.1), p for trend <0.001. Analyses in the 5-year age groups showed an increased risk with higher SBPs up to age 75 years. After 75 years, a trend towards SBP no longer being associated with an increased mortality risk was seen in our study. These findings need to be considered with recently reported beneficial effects of antihypertensive treatment in this age group.

Item does not contain fulltext, OBJECTIVE: To evaluate the independent contributions of both the trend in SBP and the SBP value at age 90 to the prediction of mortality in nonagenarians. METHODS: The trend in SBP between 85 and 90 years and SBP at age 90 years were assessed in a population-based sample of 271 participants (74 men and 197 women) aged 90 years of the Leiden 85-plus Study, an observational population-based prospective follow-up study (started 1997). Primary endpoint, followed up over 5 years (median 3.6 years), was all-cause mortality. RESULTS: A decreasing trend in SBP between 85 and 90 years (decline >/=2.9 mmHg/year) was associated with increased mortality compared to an average SBP trend (hazard ratio 1.45, 95% confidence interval 1.02-2.06), independent of SBP at age 90. The effect was stronger in institutionalized participants compared to those living independently [hazard ratio 1.87 (1.10-3.19) and hazard ratio 1.30 (0.81-2.09)]. After analysis with a fully adjusted model, the estimate approached unity [hazard ratio 1.08 (0.60-1.86)]. Overall, 90-year-old participants with SBP of 150 mmHg or less had a 1.62 times increased mortality risk compared to those with SBP more than 150 mmHg (1.21-2.20), independent of the SBP trend in preceding years. This applied to those with and without antihypertensive drugs and those with and without history of cardiovascular disease or noncardiovascular disease. In the fully adjusted model, the estimate was 1.47 (0.90-2.40). CONCLUSION: In very old age, both decreasing trend in SBP over the previous 5 years and the current SBP value independently contribute to prediction of all-cause mortality. Therefore, in individual patients, all available preceding SBP measurements should be taken into account.

There are indications that in persons of older age, systolic blood pressure (SBP) is no longer associated with mortality. This raises the question whether the predictive value of SBP changes from younger to older age groups. Analysis in the Rotterdam Study, a population-based prospective cohort study among 4,612 participants aged ≥55 years without previous cardiovascular disease and with a median follow-up of 14.9 (interquartile range, 11.1-15.8) years. Within four age groups (55-64, 65-74, 75-84, ≥85 years), the predictive value of baseline SBP for mortality was studied. From age 55 to ≥85 years, risk of all-cause mortality associated with SBP ≥160 mmHg decreased from HR 1.7 (95%CI 1.2-2.2) to HR 0.7 (95%CI 0.4-1.1), p for trend <0.001. For participants with SBP 140-159 mmHg, the risk decreased from HR 1.2 (95%CI 0.9-1.5) to HR 0.7 (95%CI 0.5-1.1), p for trend <0.001. Analyses in the 5-year age groups showed an increased risk with higher SBPs up to age 75 years. After 75 years, a trend towards SBP no longer being associated with an increased mortality risk was seen in our study. These findings need to be considered with recently reported beneficial effects of antihypertensive treatment in this age group.