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Background & aims: Medium chain triglyceride (MCT) supplementation is often recommended as treatment for patients with long-chain fatty acid β-oxidation (lcFAO) disorders, since they can be utilized as an energy source without the use of the defective enzyme. However, studies in mice and preterm infants suggest that not all medium-chain fatty acids (MCFA) are oxidized and may undergo elongation to long-chain fatty acids (LCFA). In this single blinded study, we explored the metabolic fates of MCT in healthy individuals using a 13C-labeled MCT tracer. Method: Three healthy males in rest received on two test days a primed continuous infusion of glyceryl tri[1,2,3,4–13C4]-octanoate with either an isocaloric supplementation of 1) exclusively MCT (MCT-only) or 2) a mixture of MCT, proteins and carbohydrates (MCT-mix). Gas chromatography - combustion - isotope ratio mass spectrometry (GC-C-IRMS) was used to determine 13C-enrichment of long-chain fatty acids in plasma and of 13CO2 in exhaled air. Results: When provided as single energy source, an estimated 42% of administered MCT was converted to CO2. In combination with carbohydrates and proteins in the diet, oxidation of MCT was higher (62%). In both diets

Although Evidence-based medicine (EBM) and Patient-centered medicine (PCM) are often perceived as two conflicting paradigms that speak the language of populations and the language of individuals, respectively, both share the common objective of improving the care of individual patients. As physicians should not practice an EBM that is away from the individual patient nor a PCM that is not based on the best available evidence, it is crucial to connect and combine both movements, promoting the fruitful and natural interaction between research and care. Achieving such interaction requires developing new individual-patient centric research methods. In this commentary, we propose an innovative clinical research design oriented to personalize point-of-care trials -integrating clinical research and medical care -through the incorporation of individual patients' preferences to build personalized research protocols. Building on the framework of N-of-1 studies, in "individual point-of-care trials,"each protocol could be personalized for each patient so that the therapeutic objectives, the outcome variables analyzed, and the (operationalization of the) compared interventions would be based not only on the clinical and biological characteristics of each patient but also on their individual preferences, goals, and values. If patient preferences are being progressively integrated into medical practice, it makes sense that they also are incorporated into clinical trials embedded in care delivery. The proposal to perform individual point of care trials may be an optimal way to combine EBM and PCM while preserving their foundational principles, and to ensure the connection between "personalized"and "personal"care. (c) 2020 Elsevier Inc. All rights reserved.

Knowledge, attitudes and beliefs (KABs) toward influenza vaccination (IV) play a key role in HCWs' decisions to receive vaccination and can strongly influence patients' IV uptake. We examined the knowledge, attitudes and beliefs of GPs toward IV, exploring their opinion on IV in the elderly, mandatory HCW vaccination and the desirability of an IV trial in the elderly with hospitalization/mortality as effect measure. From November 2018 to March 2019, surveys were emailed to GPs and GP-practices (n = 1676) in three regions of the Netherlands. We assessed the self-reported IV in GPs, reasons for (not) advising IV to personnel, (not) supporting mandatory IV for personnel and (not) desiring a trial on IV in the elderly on hospitalization/mortality. Multivariable logistic regression models were used to determine predictors for GP IV. A total of 552 surveys were completed and 71.9% of the GPs reported receiving IV. Determinants for IV in GPs were male sex (aOR 1.62, 95%CI 1.06-2.49, p = .03) and age >= 60 y (aOR 5.25, 95%CI 1.51-18.32, p = .01). Seventy-nine percent of the GPs recommend IV for their practice personnel. Mandatory IV for personnel was supported by 41.2% of the GPs with GP self-reporting IV being the only determinant (aOR 10.03 (95%CI 5.69-17.70 p = .00)). An IV trial on hospitalization and/or mortality was desired by 60.5% of the GPs. We concluded that the majority of Dutch GPs receives IV and recommends IV to their personnel. These high rates along with the hesitancy of GPs toward mandatory HCW IV should be considered when policymakers decide on a mandate for IV in HCW in general.

Participants with a positive faecal immunochemical test (FIT) in screening programs for colorectal cancer (CRC) have a high risk for colorectal cancer and advanced adenomas. They are therefore recommended follow-up by colonoscopy. However, more than ten percent of positively screened persons do not adhere to this advice. To investigate FIT-positive individuals’ motives for non-adherence to colonoscopy advice in the Dutch CRC screening program. Non-adherent FIT-positive participants of the Dutch CRC screening program. We conducted semi structured in-depth interviews with 17 persons who did not undergo colonoscopy within 6 months after a positive FIT. Interviews were undertaken face-to-face and data were analysed thematically with open coding and constant comparison. All participants had multifactorial motives for non-adherence. A preference for more personalised care was described with the following themes: aversion against the design of the screening program, expectations of personalised care, emotions associated with experiences of impersonal care and a desire for counselling where options other than colonoscopy could be discussed. Furthermore, intrinsic motives were: having a perception of low risk for CRC (described by all participants), aversion and fear of colonoscopy, distrust, reluctant attitude to the treatment of cancer and cancer fatalism. Extrinsic motives were: having other health issues or priorities, practical barriers, advice from a general practitioner (GP) and financial reasons. Personalised screening counselling might have helped to improve the interviewees’ experiences with the screening program as well as their knowledge on CRC and CRC screening. Future studies should explore whether personalised screening counselling also has potential to increase adherence rates.Key pointsParticipants with a positive FIT in two-step colorectal cancer (CRC) screening programs are at high risk for colorectal cancer and advanced adenomas. Non-adherence after an unfavourable screening result happens in all CRC programs worldwide with the consequence that many of the participants do not undergo colonoscopy for the definitive assessment of the presence of colorectal cancer. Little qualitative research has been done to study the reasons why individuals participate in the first step of the screening but not in the second step. We found a preference for more personalised care, which was not reported in previous literature on this subject. Furthermore, intrinsic factors, such as a low risk perception and distrust, and extrinsic factors, such as the presence of other health issues and GP advice, may also play a role in non-adherence. A person-centred approach in the form of a screening counselling session may be beneficial for this group of CRC screening participants. Participants with a positive FIT in two-step colorectal cancer (CRC) screening programs are at high risk for colorectal cancer and advanced adenomas. Non-adherence after an unfavourable screening result happens in all CRC programs worldwide with the consequence that many of the participants do not undergo colonoscopy for the definitive assessment of the presence of colorectal cancer. Little qualitative research has been done to study the reasons why individuals participate in the first step of the screening but not in the second step. We found a preference for more personalised care, which was not reported in previous literature on this subject. Furthermore, intrinsic factors, such as a low risk perception and distrust, and extrinsic factors, such as the presence of other health issues and GP advice, may also play a role in non-adherence. A person-centred approach in the form of a screening counselling session may be beneficial for this group of CRC screening participants.

ObjectiveTo investigate whether opportunistic screening in primary care increases the detection of atrial fibrillation compared with usual care.DesignCluster randomised controlled trial.Setting47 intention-to-screen and 49 usual care primary care practices in the Netherlands, not blinded for allocation; the study was carried out from September 2015 to August 2018.ParticipantsIn each practice, a fixed sample of 200 eligible patients, aged 65 or older, with no known history of atrial fibrillation in the electronic medical record system, were randomly selected. In the intention-to-screen group, 9218 patients eligible for screening were included, 55.0% women, mean age 75.2 years. In the usual care group, 9526 patients were eligible for screening, 54.3% women, mean age 75.0 years.InterventionsOpportunistic screening (that is, screening in patients visiting their general practice) consisted of three index tests: pulse palpation, electronic blood pressure measurement with an atrial fibrillation algorithm, and electrocardiography (ECG) with a handheld single lead electrocardiographic device. The reference standard was 12 lead ECG, performed in patients with at least one positive index test and in a sample of patients (10%) with three negative tests. If 12 lead ECG showed no atrial fibrillation, patients were invited for more screening by continuous monitoring with a Holter electrocardiograph for two weeks.Main outcome measuresDifference in the detection rate of newly diagnosed atrial fibrillation over one year in intention-to-screen versus usual care practices.ResultsFollow-up was complete for 8874 patients in the intention-to-screen practices and for 9102 patients in the usual care practices. 144 (1.62%) new diagnoses of atrial fibrillation in the intention-to-screen group versus 139 (1.53%) in the usual care group were found (adjusted odds ratio 1.06 (95% confidence interval 0.84 to 1.35)). Of 9218 eligible patients in the intention-to-screen group, 4106 (44.5%) participated in the screening protocol. In these patients, 12 lead ECG detected newly diagnosed atrial fibrillation in 26 patients (0.63%). In the 266 patients who continued with Holter monitoring, four more diagnoses of atrial fibrillation were found.ConclusionsOpportunistic screening for atrial fibrillation in primary care patients, aged 65 and over, did not increase the detection rate of atrial fibrillation, which implies that opportunistic screening for atrial fibrillation is not useful in this setting.Trial registrationNetherlands Trial Register No NL4776 (old NTR4914).

Background Perception by workers of their health problems as work-related is possibly associated with sickness absence (SA). The aim of this study was to to study the relationship between perceived work-relatedness of health problems and SA among workers who visit their GP, taking the influence of other potential determinants into account and to study the influence of these determinants on SA. Design and setting prospective cohort study in 32 Dutch GP practices. Methods A secondary analysis of RCT data among workers, aged 18–63 years, who visited their GP. We measured self-reported SA days in 12 months and high SA (>20 days in 12 months) and compared workers who perceived work-relatedness (WR+) with workers who did not (WR−). With multivariable linear and logistic regression models, we analyzed the influence of age, gender, experienced health, chronic illness, prior SA, number of GP consultations and perceived work ability. Results We analyzed data of 209 workers, 31% perceived work-relatedness. Geometric mean of SA days was 1.6 (95% CI: 0.9–3.0) for WR+− workers and 1.2 (95% CI: 0.8–1.8) for WR− workers (P = 0.42). Incidence of high SA was 21.5 and 13.3%, respectively (odds ratio 1.79; 95% CI: 0.84–3.84). SA was positively associated with chronic illness, prior SA, low perceived work ability and age over 50. Conclusions Perceived work-relatedness was not associated with SA. SA was associated with chronic illness, prior SA, low perceived work ability and age over 50.

Background Multimorbidity in primary care is a challenge not only for developing countries but also for low and medium income countries (LMIC). Health services in LMIC countries are being provided by both public and private health care providers. However, a critical knowledge gap exists on understanding the true extent of multimorbidity in both types of primary care settings. Methods We undertook a study to identify multimorbidity prevalence and healthcare utilization among both public and private primary care attendees in Odisha state of India. A total of 1649 patients attending 40 primary care facilities were interviewed using a structured multimorbidity assessment questionnaire collecting information on 22 chronic diseases, medication use, number of hospitalization and number of outpatient visits. Result The overall prevalence of multimorbidity was 28.3% and nearly one third of patients of public facilities and one fourth from private facilities had multimorbidity. Leading diseases among patients visiting public facilities included acid peptic diseases, arthritis and chronic back pain. No significant difference in reporting of hypertension and diabetes across the facilities was seen. Besides age, predictors of multimorbidity among patients attending public facilities were, females [AOR: 1.6; 95% CI 1.1–1.3] and non-aboriginal groups [AOR: 1.6; 95%CI 1.1–2.3] whereas, in private females [AOR: 1.6; 95%CI 1.1–2.4], better socioeconomic conditions [AOR 1.4; 95% CI 1.0–2.1] and higher educational status [primary school completed [AOR 2.6; 95%CI 1.6–4.2] and secondary schooling and above [AOR 2.0; 95%CI 1.1–3.6] with reference to no education were seen to be the determinants of multimorbidity. Increased number of hospital visits to public facilities were higher among lower educational status patients [IRR: 1.57; 95% CI 1.13–2.18] whereas, among private patients, the mean number of hospital visits was 1.70 times more in higher educational status [IRR: 1.70; 95%CI 1.01–3.69]. The mean number of medicines taken per day was higher among patients attending private hospitals. Conclusion Our findings suggest that, multimorbidity is being more reported in public primary care facilities. The pattern and health care utilization in both types of settings are different. A comprehensive care approach must be designed for private care providers.

We aimed to disprove an in-hospital off-hour effect in stroke patients by adjusting for disease severity and poor prognostic findings on imaging. Our study included 5378 patients from a single center prospective stroke registry of a large teaching hospital in the Netherlands, admitted between January 2003 and June 2015. Patients were categorized by admission time, off-hours (OH) or working hours (WH). The in-hospital mortality, 7-day mortality, unfavorable functional outcome (modified Rankin scale > 2) and discharge to home were analyzed. Results were adjusted for age, sex, stroke severity (NIHSS score) and unfavorable findings on imaging of the brain (midline shift and dense vessel sign). Overall, 2796 patients (52%) were admitted during OH, which had a higher NIHSS score [3 (IQR 2–8) vs. 3 (IQR 2–6): p

Funding Information: This work was supported by the University of Melbourne, Melbourne School of Population and Global Health, Human Ethics Advisory Group. Project title: “Consultation to understand international differences in bowel cancer screening participation,” ID 2057312.1 Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Engagement Research Funding from the Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Australia. Publisher Copyright: © The Author(s) 2022. Background: Colorectal cancer (CRC) is the second most diagnosed cancer in men and women and second most common cause of cancer death in Australia; Australia’s CRC incidence and mortality are among the world’s highest. The Australian National Bowel Cancer Screening Program began in 2006; however, only 33% of those approached for the first time by the Program between 2018 and 2019 returned the kit. Of the 5.7 million kits sent during this period, only 44% were returned. Our aim was to identify practices and features of national bowel cancer screening programs in countries with similar programs but higher screening participation, to identify potential interventions for optimising Australian CRC screening participation. Methods: We searched published and grey literature for CRC screening programs reporting at least 50% screening participation using postal invitation and free return of iFOBT home kits. Interviews were conducted with cancer registry staff and academic researchers, focused on participant and practitioner engagement in screening. Results: National programs in Netherlands, Scotland, Denmark, and Finland reported over 50% screening participation rates for all invitation rounds. Shared characteristics include small populations within small geographic areas relative to Australia; relatively high literacy; a one-sample iFOBT kit; national registration systems for population cancer screening research; and screening program research including randomised trials of program features. Conclusions: Apart from the one-sample kit, we identified no single solution to persistent Australian low uptake of screening. Research including randomised trials within the program promises to increase participation. Impact: This screening program comparison suggests that within-program intervention trials will lead to increased Australian screening participation.

Background: Paying attention to their patients’ work and recognizing work-related problems is challenging for many general practitioners (GPs). Objectives: To assess the effect of training designed to improve the care for patients with work-related problems in general practice. Methods: A cluster randomized controlled trial among 32 Dutch GPs. GPs in the intervention group received five-hour training. GPs in the control group were not trained. Included patients (age 18–63, working ≥12 h per week) completed baseline questionnaires and follow-up questionnaires planned after one year. Primary outcome at patient level was patients’ expectations about their ability to work, measured using the return-to-work self-efficacy scale (RTW-SE). Primary outcomes on GP level were their use of ICPC-code Z05 (‘work-related problem’) per 1000 working-age patients and percentage of the electronic medical files of working-age patients in which information about occupation had been recorded. Results: A total of 640 patients completed the baseline questionnaire and 281 the follow-up questionnaire. We found no statistically significant differences in patients’ RTW-SE scores: intervention 4.6 (95%CI: 4.2–5.0); control 4.5 (95%CI: 4.1–4.9). Twenty-nine GPs provided data about the GP-level outcomes, which showed no statistically significant differences: use of ICPC code Z05 11.6 (95%CI: 4.7–18.6) versus 6.0 (95%CI: –1.2 to 13.2) per 1000 working-age patients; recording of occupation 28.8% (95%CI: 25.8–31.7) versus 28.6% (95%CI: 25.6–31.6). Conclusion: Training GPs did not improve patients’ work-related self-efficacy or GPs’ registration of work-related problems and occupation.

Background Detection and treatment of atrial fibrillation (AF) are important given the serious health consequences. AF may be silent or paroxysmal and remain undetected. It is unclear whether general practitioners (GPs) have appropriate equipment and optimally utilise it to detect AF. This case vignette study aimed to describe current practice and to explore possible improvements to optimise AF detection. Methods Between June and July 2017, we performed an online case vignette study among Dutch GPs. We aimed at obtaining at least 75 responses to the questionnaire. We collected demographics and asked GPs’ opinion on their knowledge and experience in diagnosing AF. GPs could indicate which diagnostic tools they have for AF. In six case vignettes with varying symptom frequency and physical signs, they could make diagnostic choices. The last questions covered screening and actions after diagnosing AF. We compared the answers to the Dutch guideline for GPs on AF. Results Seventy-six GPs completed the questionnaire. Seventy-four GPs (97%) thought they have enough knowledge and 72 (95%) enough experience to diagnose AF. Seventy-four GPs (97%) could order or perform ECGs without the interference of a cardiologist. In case of frequent symptoms of AF, 36–40% would choose short-term (i.e. 24–48 h) and 11–19% long-term (i.e. 7 days, 14 days or 1 month) monitoring. In case of non-frequent symptoms, 29–31% would choose short-term and 21–30% long-term monitoring. If opportunistic screening in primary care proves to be effective, 83% (58/70) will support it. Conclusions Responding GPs report to have adequate equipment, knowledge, and experience to detect and diagnose AF. Almost all participants can order ECGs. Reported monitoring duration was shorter than recommended by the guideline. AF detection could improve by increasing the monitoring duration.

Background Multimorbidity, the coexistence of two or more chronic conditions is increasingly prevalent in primary care populations. Despite reports on its adverse impact on health outcomes, functioning and well-being, it’s association with quality of life is not well known in low and middle income countries. We assessed the health-related quality of life (HRQoL) of primary care patients with multimorbidity and identified the influencing factors. Methods This cross-sectional study was done across 20 public and 20 private primary care facilities in Odisha, India. Data were collected from 1649 adult out-patients using a structured multimorbidity assessment questionnaire for primary care (MAQ-PC). HRQoL was assessed by the 12-item short-form health survey (SF-12). Both physical (PCS) and mental components scores (MCS) were calculated. Multiple regression analysis was performed to determine the association of HRQoL with socio-demographics, number, severity and typology of chronic conditions. Results Around 28.3% [95% CI: 25.9–30.7] of patients had multimorbidity. Mean physical component scope (PCS) and mental component score (MCS) of QoL in the study population was 43.56 [95% CI: 43.26–43.86] and 43.69 [95% CI: 43.22–44.16], respectively. Patients with multimorbidity reported poorer mean PCS [43.23, 95% CI: 42.62–43.84] and MCS [41.58, 95% CI: 40.74–42.43] compared to those without. After adjusting for other variables, morbidity severity burden score was found to be negatively associated with MCS [adjusted coefficient: -0.24, 95% CI − 0.41 to − 0.08], whereas no significant association was seen with PCS. Hypertension and diabetes with arthritis and acid peptic diseases were found to be negatively related with MCS. Within multimorbidity, lower education was inversely associated with mental QoL and positively associated with physical QoL score after adjusting for other variables. Conclusion Our findings demonstrate the diverse negative effects of multimorbidity on HRQoL and reveal that apart from count of chronic conditions, severity and pattern also influence HRQoL negatively. Health care providers should consider severity as an outcome measure to improve QoL especially in individuals with physical multimorbidity. Given the differences observed between age groups, it is important to identify specific care needs for each group. Musculoskeletal clusters need prioritised attention while designing clinical guidelines for multimorbidity. Electronic supplementary material The online version of this article (10.1186/s12955-019-1180-3) contains supplementary material, which is available to authorized users.

Influenza vaccination is proven effective in preventing influenza. However, long-term effects on mortality have never been supported by direct evidence. In this study we assessed the long-term outcome of influenza vaccination on mortality in the elderly by conducting a 25-year follow-up study of a RCT on the efficacy of influenza vaccination as baseline. The RCT had been conducted in the Netherlands 5 years before vaccination was recommended for those aged >65 and 17 years before recommending it for those aged >60. The RCT included 1838 community-dwelling elderly aged ≥ 60 that had received an intramuscular injection with the inactivated quadrivalent influenza vaccine (n = 927) or placebo (n = 911) during the 1991/1992 winter. In our follow-up study, outcomes included all-cause mortality, influenza-related mortality and seasonal mortality. Unadjusted and adjusted hazard ratios (HRs) were estimated by Cox regression and sub-hazard ratios (SHRs) by competing risk models. Secondary analyses included subgroup analyses by age and disease status. The vital status up to January 1, 2017 was provided in 1800/1838 (98%) of the cases. Single influenza vaccination did not reduce all-cause mortality when compared to placebo (adjusted HR 0.95, 95% CI 0.85−1.05). Also, no differences between vaccination and placebo group were shown for underlying causes of death or seasonal mortality. In those aged 60–64, median survival increased with 20.1 months (95% CI 2.4–37.9), although no effects on all-cause mortality (adjusted HR 0.86, 95% CI 0.72−1.03) could be demonstrated in survival analysis. In conclusion, this study did not demonstrate a statistically significant effect following single influenza vaccination on long-term mortality in community-dwelling elderly in general. We propose researchers designing future studies on influenza vaccination in the elderly to fit these studies for longer-term follow-up, and suggest age-group comparisons in observational research. Clinical trial registry number: NTR6179.

Background Assessing the cost effectiveness of training aimed at increasing general practitioners’ (GP) work awareness and patients’ work-related self-efficacy and quality of life. Methods A cluster randomized controlled trial in twenty-six GP practices in the southeast of the Netherlands with 32 participating GPs. GPs working in an intervention group practice received training and GPs working in a control group practice delivered usual care. The training intervention consisted of lectures and workshops aimed at increasing GPs’ work awareness and more proactive counseling for patients with work-related problems (WRP). Subjects were working age patients with paid work for at least 12 h per week, who visited one of the participating GPs during the study period. As outcome measures we used the Return to Work Self Efficacy scale to assess patients’ work-related self-efficacy and the Euroquol to assess quality of life. We also measured health care costs and productivity costs. With a 4-item questionnaire we asked patients to assess their GPs’ work awareness. Data were collected at baseline, after 6 and 12 months. Results Data of 280 patients could be analyzed. The patient related outcomes did not improve after GP training. The change in GP work awareness and the overall mean cost difference (of €770) in favor of the intervention group were not significant. Conclusions The training intervention presented in this paper was not cost-effective. Training which is further personalized and targeted at high risk groups with respect to WRP, is more likely to be cost effective. Electronic supplementary material The online version of this article (10.1186/s12875-019-0924-9) contains supplementary material, which is available to authorized users.

Objective: To construct a clinical prediction rule for coronary artery disease (CAD) presenting with chest pain in primary care. Study Design and Setting: Meta-Analysis using 3,099 patients from five studies. To identify candidate predictors, we used random forest trees, multiple imputation of missing values, and logistic regression within individual studies. To generate a prediction rule on the pooled data, we applied a regression model that took account of the differing standard data sets collected by the five studies. Results: The most parsimonious rule included six equally weighted predictors: age >= 55 (males) or >= 65 (females) (+1); attending physician suspected a serious diagnosis (+1); history of CAD (+1); pain brought on by exertion (+1); pain feels like "pressure" (+1); pain reproducible by palpation (-1). CAD was considered absent if the prediction score is = 2, it was 43.0% (95% CI: 35.8-50.4%). Conclusions: Clinical prediction rules are a key strategy for individualizing care. Large data sets based on electronic health records from diverse sites create opportunities for improving their internal and external validity. Our patient-level meta-analysis from five primary care sites should improve external validity. Our strategy for addressing site-to-site systematic variation in missing data should improve internal validity. Using principles derived from decision theory, we also discuss the problem of setting the cutoff prediction score for taking action. (C) 2016 Elsevier Inc. All rights reserved. This study was funded by Federal Ministry of Education and Research, Germany (BMBF grant no. FKZ 01GK0920).

Contains fulltext : 172695.pdf (Publisher’s version ) (Open Access) BACKGROUND: In the Netherlands, there is a lack of knowledge about general practitioners' (GPs) perception of their role regarding patients' occupation and work related problems (WRP). As work and health are closely related, and patients expect help from their GPs in this area, a better understanding is needed of GPs' motivation to address WRP. OBJECTIVES: To explore GPs' opinions on their role in the area of work and health. METHODS: This is a qualitative study using three focus groups with Dutch GPs from the catchment area of a hospital in the Southeast of the Netherlands. The group was heterogeneous in characteristics such as sex, age, and practice setting. Three focus groups were convened with 18 GPs. The moderator used an interview guide. Two researchers analysed verbatim transcripts using constant comparative analysis. RESULTS: We distinguished three items: (a) work context in a GP's integrated consultation style; (b) counselling about sick leave; (c) cooperation with occupational physicians (OPs). The participants are willing to address the topic and counsel about sick leave. They consider WRP in patients with medically unexplained symptoms (MUS) challenging. They tend to advise these patients to continue working as they think this will ultimately benefit them. CONCLUSION: The participating GPs seemed well aware of the relation between work and health but need more knowledge, communication skills and better cooperation with occupational physicians to manage work-related problems. [Box: see text].

Background: polypharmacy contributes to patients' non-adherence with physicians' prescriptions. Patients' knowledge about the indications for their medicines is one of the factors influencing adherence. Objective: to identify factors associated with appropriate knowledge about the indications for drugs prescribed to older patients with polypharmacy. Methods: in a primary care setting, using home interviews and postal questionnaires, patients aged 60 and over who were taking five or more prescribed drugs simultaneously were asked about their medication. Multiple logistic regression analysis was used to evaluate the association (odds ratio, OR) between medication knowledge and explanatory variables like medication use, sex, age, living situation and educational level. Results: seven hundred and fifty-four participants (mean age 73.2 years) reported an average daily intake of nine (SD 3.0) prescribed drugs. Only 15% of the patients were able to recall the indication for each of their prescribed drugs. Variables that were negatively associated with correct reporting of all indications were taking many prescribed drugs (e.g. a parts per thousand yen10 versus a parts per thousand currency sign5: OR 0.05), age 80 years or over (versus 60-69 years: OR 0.47) and male sex (OR 0.53). Patients living with a partner were more knowledgeable than patients living alone (OR 2.11). We did not find an association with educational level. Conclusion: among older patients using five or more prescribed drugs, there was little understanding of the indications for their drugs, especially among patients taking the highest number of drugs, patients aged 80 or over, and men. Patients living independently with a partner were more knowledgeable than others.

Objective To improve the effectiveness of treatment in patients with chronic fatigue syndrome it is worthwhile studying factors influencing outcomes. The aims of this study were (1) to assess the association of expectancy and credibility on treatment outcomes, and (2) to identify baseline variables associated with treatment expectancy and credibility. Methods 122 patients were included in a randomized controlled trial of whom 60 received cognitive behavioural therapy (CBT) and 62 multidisciplinary rehabilitation treatment (MRT). Expectancy and credibility were measured with the credibility and expectancy questionnaire. Outcomes of treatment, fatigue, and quality of life (QoL), were measured at baseline and post-treatment. Multiple linear regressions were performed to analyse associations. Results In explaining fatigue and the physical component of the QoL, the effect of expectancy was significant for MRT, whereas in CBT no such associations were found. The main effect of expectancy on the mental component of QoL was not significant. For credibility, the overall effect on fatigue and the physical component of QoL was not significant. In explaining the mental component of QoL, the interaction between treatment and credibility was significant. However, the effects within each group were not significant. In the regression model with expectancy as dependent variable, only treatment centre appeared significantly associated. In explaining credibility, treatment centre, treatment allocation and depression contributed significantly. Conclusions For clinical practice it seems important to check the expectations of the patient, since expectations influence the outcome after MRT.

Aim It is unknown to what extend patients with type 2 diabetes mellitus (T2DM) in primary care are motivated to change their lifestyle. We assessed the level of motivation to change lifestyle and the agreement for that level between patients and healthcare professionals. Methods Patients with T2DM (150) filled in a questionnaire to assess the level of motivation to change their lifestyle, using a single question with three answer options. We investigated the agreement for this level between these patients and their healthcare professionals (12 professionals). In addition, we investigated and compared the level of physical activity as indicated by the patients and the healthcare professionals. Results A large part of the patients reported to have a deficient physical activity level (35% according to patients, 47% according to healthcare professionals, kappa 0.32) and were not motivated to change their lifestyle level (29% according to patients, 43% according to healthcare professionals, kappa 0.13). Patients tended to overestimate their physical activity and their motivation to change in comparison with their healthcare professionals. Conclusions Patients with T2DM in primary care should increase their physical activity level. Healthcare professionals often do not know whether patients are motivated to change their lifestyle, and should therefore assess motivation regularly to optimize lifestyle management.

Purpose Uncertainty about recurrence after a first unprovoked seizure is a significant psychological burden for patients, and motivates the need for diagnostic tools with high sensitivity and specificity to assess recurrence risk. As the sensitivity of a routine EEG after a first unprovoked seizure is limited, patients often require further diagnostics. Here, we study if ambulatory EEG (aEEG) has similar diagnostic accuracy as sleep deprived EEG (sdEEG). Methods In this retrospective cohort, we included patients with an unprovoked first seizure and a normal routine EEG who subsequently underwent an sdEEG or aEEG. All EEGs were reviewed for the presence of interictal epileptiform discharges (IEDs). We calculated specificity and sensitivity of sdEEG and aEEG, using the clinical diagnosis of epilepsy as golden standard. All patients had a follow-up of one year. Results We included 104 patients. Sensitivities for sdEEG and aEEG were 45% (specificity 91%) and 63% (specificity 95%), respectively. Independent risk factor for recurrent seizure were IEDs on the additional EEG, with a relative risk of 1.5 of having a recurrent seizure within a year. Conclusion Diagnostic accuracies of sdEEG and aEEG are similar and depending on patients' and clinicians' preference both can be considered in patients with a first seizure and a normal routine EEG to determine recurrence risk.

Objective Mucopolysaccharidosis IIIA or Sanfilippo disease type A is a progressive neurodegenerative disorder presenting in early childhood, caused by an inherited deficiency of the lysosomal hydrolase sulfamidase. New missense mutations, for which genotype–phenotype correlations are currently unknown, are frequently reported, hampering early prediction of phenotypic severity and efficacy assessment of new disease‐modifying treatments. We aimed to design a method to determine phenotypic severity early in the disease course. Methods Fifty‐three patients were included for whom skin fibroblasts and data on disease course and mutation analysis were available. Patients were phenotypically characterized on clinical data as rapidly progressing or slowly progressing. Sulfamidase activity was measured in fibroblasts cultured at 37 °C and at 30 °C. Results Sulfamidase activity in fibroblasts from patients homozygous or compound heterozygous for a combination of known severe mutations remained below the limit of quantification under both culture conditions. In contrast, sulfamidase activity in fibroblasts from patients homozygous or compound heterozygous for a known mild mutation increased above the limit of quantification when cultured at 30 °C. With division on the basis of the patients' phenotype, fibroblasts from slowly progressing patients could be separated from rapidly progressing patients by increase in sulfamidase activity when cultured at 30 °C (p

The aim of the study was to examine self- efficacy, attitudes, and perceptions of pediatricians in the management of children with MUPS. Our hypothesis was that pediatricians with more experience had a greater exposure to children with MUPS. More exposure could have a positive effect on the self-efficacy scores and attitudes toward the management of children with MUPS.

Background and Purpose— Asymptomatic lacunar infarcts, white matter lesions, cerebral microbleeds, and enlarged perivascular spaces are MRI markers of cerebral small vessel disease (cSVD). Higher blood pressure (BP) levels are associated with the presence of these markers separately, but the association with the total burden of cSVD on brain MRI, expressed by the simultaneous presence of multiple markers of cSVD (a compound score), has not been investigated. Methods— We performed 24-hour ambulatory BP monitoring in 122 patients with first-ever lacunar stroke. On brain MRI, we scored the presence of each marker of cSVD. One point was awarded for the presence of each marker, producing a score between 0 and 4. Associations with BP levels were tested with ordinal regression analyses. Results— Eighteen (15%) patients had no markers of cSVD, and 6 (5%) patients had 4 markers. Most patients (45; 37%) had 2 different markers. After correction for age and sex, higher 24-hour, day, and night systolic (24-hour odds ratio, 1.25; 95% confidence interval, 1.02–1.52 per 10 mm Hg) and diastolic (24-hour odds ratio, 1.32; 95% confidence interval, 1.12–1.56 per 5 mm Hg) BP were all significantly associated with an increasing total burden of cSVD. Conclusions— We found a positive association of ambulatory BP levels with total burden of cSVD on brain MRI. With increasing BP levels, there is a piling up of damage in the brain. We suggest that further cSVD studies also consider viewing the total burden in addition to each of the MRI markers separately.

Infants of parents with a history of asthma could benefit from exclusive breastfeeding during the first 6 months of life to reduce the chance of developing childhood asthma. Continuing to breastfeed for 6 months seemed difficult to perform for many Dutch women. Therefore, an educational breastfeeding program was developed and implemented. The program (a theory-based booklet and pre- and postnatal home visits by trained assistants) significantly improved exclusive breastfeeding rates at 6 months postpartum (48% for intervention vs. 27% for control). Repeated-measurements analyses showed significant increases in knowledge and more positive attitudinal beliefs regarding breastfeeding for 6 months, in particular immediately after exposure to the program, compared with the controls. As expected, over time perceived self-efficacy and women's positive emotions toward breastfeeding increased, and support for breastfeeding diminished in both groups. The intervention group was reported to perceive more pressure to bottle feed and to know more breastfeeding models than the control group. Implications for practice are discussed.

Multimorbidity is increasingly the primary concern of healthcare systems globally with substantial implications for patient outcomes and resource cost. A critical knowledge gap exists as to the magnitude of multimorbidity in primary care practice in low and middle income countries with available information limited to prevalence. In India, primary care forms the bulk of the health care delivery being provided through both public (community health center) and private general practice setting. We undertook a study to identify multimorbidity patterns and relate these patterns to severity among primary care attendees in Odisha state of India. A total of 1649 patients attending 40 primary care facilities were interviewed using a structured multimorbidity assessment questionnaire. Multimorbidity patterns (dyad and triad) were identified for 21 chronic conditions, functional limitation was assessed as a proxy measure of severity and the mean severity score for each pattern, was determined after adjusting for age. The leading dyads in younger age group i.e. 18–29 years were acid peptic disease with arthritis/ chronic back ache/tuberculosis /chronic lung disease, while older age groups had more frequent combinations of hypertension + arthritis/ chronic lung disease/vision difficulty, and arthritis + chronic back ache. The triad of acid peptic disease + arthritis + chronic backache was common in men in all age groups. Tuberculosis and lung diseases were associated with significantly higher age-adjusted mean severity score (poorer functional ability). Among men, arthritis, chronic backache, chronic lung disease and vision impairment were observed to have highest severity) whereas women reported higher severity for combinations of hypertension, chronic back ache and arthritis. Given the paucity of studies on multimorbidity patterns in low and middle income countries, future studies should seek to assess the reproducibility of our findings in other populations and settings. Another task is the potential implications of different multimorbidity clusters for designing care protocols, as currently the protocols are disease specific, hardly taking comorbidity into account.

Enlarged Virchow-Robin spaces (EVRS) are considered to be a sign of cerebral small vessel disease. Hypertension is an important risk factor for cerebral small vessel disease, whereas ambulatory blood pressure (BP) is the strongest predictor of hypertension-related brain damage. However, the association between ambulatory BP levels and EVRS has never been investigated. The aim of this study was to determine the association between ambulatory BP levels and EVRS. In 143 first-ever lacunar stroke patients, we performed 24-h ambulatory BP monitoring after the acute stroke phase. On brain MRI we counted EVRS in the basal ganglia and the centrum semiovale. We graded the number of EVRS at each level into a three-category severity scale. We assessed the association between BP levels and EVRS by ordinal regression analysis. After adjusting for age, sex, extensive white matter lesions, and asymptomatic lacunar infarcts, higher day systolic (OR 1.21; 95 % CI 1.00-1.46 per 10 mmHg), day diastolic (1.18; 95 % CI 1.02-1.37 per 5 mmHg) and 24-h diastolic (OR 1.18; 95 % CI 1.01-1.37 per 5 mmHg) ambulatory BP levels were associated with EVRS at the basal ganglia level. No relation was found between ambulatory BP levels and EVRS in the centrum semiovale. Higher day ambulatory BP levels are associated with EVRS in the basal ganglia. This association was independent of the presence of extensive white matter lesions and asymptomatic lacunar infarcts. Our results imply that basal ganglia EVRS should be regarded as a separate manifestation of BP-related brain damage.

To identify factors associated with appropriate knowledge about the indications for drugs prescribed to older patients on polypharmacy.Cross-sectional study.In a primary care setting, patients aged 60 years and over who were taking five or more prescribed drugs simultaneously were asked about their medication by conducting home interviews and postal questionnaires. Multiple logistic regression analysis was used to evaluate the association between medication knowledge and explanatory variables such as medication use, sex, age, residential status and educational level.Seven hundred and fifty-four participants, mean age 73.2 years, reported an average daily intake of nine (SD 3.0) prescribed drugs. Only 15% of the patients were able to recall the indication for each of their prescribed drugs. Variables that were negatively associated with correct reporting of all indications were: taking many prescribed drugs (≥ 10 vs. ≤ 5 drugs: odds ratio (OR) 0.05), age 80 years or over (vs. 60-69 years: OR 0.47) and male sex (vs. females: OR 0.53). Patients living with a partner were more knowledgeable than patients living alone (OR 2.11). We did not find an association with educational level.Among older patients using five or more prescribed drugs, there was little understanding of the indications for their drugs, especially among patients taking the highest number of drugs, patients aged 80 years or over, and men. Patients living independently with a partner were more knowledgeable than others.

ObjectiveTo improve medication appropriateness and adherence in elderly patients with multimorbidity, we developed a complex intervention involving general practitioners (GPs) and their healthcare assistants (HCA). In accordance with the Medical Research Council guidance on developing and evaluating complex interventions, we prepared for the main study by testing the feasibility of the intervention and study design in a cluster randomised pilot study. Setting20 general practices in Hesse, Germany. Participants100 cognitively intact patients ≥65 years with ≥3 chronic conditions, ≥5 chronic prescriptions and capable of participating in telephone interviews; 94 patients completed the study. InterventionThe HCA conducted a checklist-based interview with patients on medication-related problems and reconciled their medications. Assisted by a computerised decision-support system (CDSS), the GPs discussed medication intake with patients and adjusted their medication regimens. The control group continued with usual care. Outcome measuresFeasibility of the intervention and required time were assessed for GPs, HCAs and patients using mixed methods (questionnaires, interviews and case vignettes after completion of the study). The feasibility of the study was assessed concerning success of achieving recruitment targets, balancing cluster sizes and minimising drop-out rates. Exploratory outcomes included the medication appropriateness index (MAI), quality of life, functional status and adherence-related measures. MAI was evaluated blinded to group assignment, and intra-rater/inter-rater reliability was assessed for a subsample of prescriptions. Results10 practices were randomised and analysed per group. GPs/HCAs were satisfied with the interventions despite the time required (35/45 min/patient). In case vignettes, GPs/HCAs needed help using the CDSS. The study made no patients feel uneasy. Intra-rater/inter-rater reliability for MAI was excellent. Inclusion criteria were challenging and potentially inadequate, and should therefore be adjusted. Outcome measures on pain, functionality and self-reported adherence were unfeasible due to frequent missing values, an incorrect manual or potentially invalid results. ConclusionsIntervention and trial design were feasible. The pilot study revealed important limitations that influenced the design and conduct of the main study, thus highlighting the value of piloting complex interventions. Trial registration numberISRCTN99691973; Results.

Objectives The aim of this trial was to evaluate the difference in treatment effect, at 26 and 52 weeks after the start of treatment, between cognitive behavioural therapy (CBT) and multidisciplinary rehabilitation treatment (MRT) for patients with chronic fatigue syndrome (CFS). Design Multicentre, randomized controlled trial of patients with CFS. Participants were randomly assigned to MRT or CBT. Setting Four rehabilitation centres in the Netherlands. Subjects A total of 122 patients participated in the trial. Main outcome measures Primary outcomes were fatigue measured by the fatigue subscale of the Checklist Individual Strength and health-related quality of life measured by the Short-Form 36. Outcomes were assessed prior to treatment and at 26 and 52 weeks after treatment initiation. Results A total of 114 participants completed the assessment at 26 weeks, and 112 completed the assessment at 52 weeks. MRT was significantly more effective than CBT in reducing fatigue at 52 weeks. The estimated difference in fatigue between the two treatments was −3.02 [95% confidence interval (CI) −8.07 to 2.03; P = 0.24] at 26 weeks and −5.69 (95% CI −10.62 to −0.76; P = 0.02) at 52 weeks. Patients showed an improvement in quality of life over time, but between-group differences were not significant. Conclusion This study provides evidence that MRT is more effective in reducing long-term fatigue severity than CBT in patients with CFS. Although implementation in comparable populations can be recommended based on clinical effectiveness, it is advisable to analyse the cost-effectiveness and replicate these findings in another multicentre trial. Click here to view the Editorial Comment by J. Nijs et al.

Background: Hypoglycemia is a frequent phenomenon in people being treated for diabetes mellitus, which can acutely disrupt driving performance. For the benefit of personal and public traffic safety, we decided to identify successful diabetes-related (SDR) behaviors to support safe driving for people with diabetes, from the perspective of experiential experts with diabetes mellitus. Experiential experts are people who can manage their own illness and conditions by developing expertise relevant to maintaining health and countering illness, and who are able to use this expertise to the benefit of peers. Objective: The aim of our study was to objectify and systematize experiential expertise in terms of SDR behaviors, based on reports by experiential experts, to support safe driving for people with type 1 and type 2 diabetes mellitus. The emphasis was on preventing hypoglycemia as a short-term complication during driving. Methods: We performed a mixed-methods study involving (i) semi-structured in-depth interviews with 33 experiential experts with diabetes mellitus from the Dutch Diabetes Association (DVN; Diabetesvereniging Nederland), in order to identify SDR behaviors regarding safe driving, and (ii) a validation study by means of a survey among a panel of 98 experiential experts (peers) from the DVN, to determine the extent to which they agreed with the communicability, importance, and feasibility of these behaviors for drivers with diabetes mellitus. Results: We identified a comprehensive set of 11 SDR behaviors, differentiated into seven general and four specific behaviors, to support safe driving. The general behaviors concern the following topics: (i) acquiring knowledge and information; (ii) acquiring and using self-measuring of blood glucose (SMBG) equipment; (iii) knowing one's physical response pattern; (iv) obtaining knowledge about the medication used; (v) preventing long-term eye complications; (vi) influencing factors that can affect blood glucose; and (vii) renewal procedure for driving license. The four specific behaviors refer to the following topics: (i) measures to be taken before driving; (ii) responding effectively to hypoglycemia while driving; (iii) informing and instructing passengers; and (iv) preventing hypoglycemia in drivers with type 2 diabetes mellitus not using SMBG equipment. Key factors for safe driving proved to be the ability of drivers to anticipate and respond effectively to hypoglycemia while driving and to inform and instruct fellow passengers. Participants of the validation survey agreed to a considerable degree with the communicability, importance, and feasibility of these behaviors to support safe driving for people with diabetes mellitus. Conclusions: This study resulted in the identification and description of SDR behaviors to support safe driving. It proved possible to operationalize experiential expertise in terms of such behaviors. The next step is to have these behaviors validated by professional care providers in the field of diabetes, followed by translation into recommendations in self-management programs. Language: en

Background. Previously published investigations suggest a positive effect of increased water intake on headache, but a randomised controlled trial has not been done. Objective. To investigate the effects of increased water intake on headache. Methods. Randomised controlled trial in primary care with two groups and a follow-up period of 3 months. Patients were included if they had at least two episodes of moderately intense headache or at least five mildly intense episodes per month and a total fluid intake of less than 2.5 l/day. Both groups received written instructions about stress reduction and sleep improvement strategies. The intervention group additionally received the instruction to increase the daily water intake by 1.5 l. The main outcome measures were Migraine-Specific Quality of Life (MSQOL) and days with at least moderate headache per month. Results. We randomised 50 patients to the control group and 52 patients to the intervention group. Drinking more water resulted in a statistically significant improvement of 4.5 (confidence interval: 1.3-7.8) points on MSQOL. In addition, 47% in the water group reported much improvement (6 or higher on a 10-point scale) on perceived intervention effect against 25% in the control group. However, drinking more water did not result in relevant changes in days with at least moderate headache. Conclusions. Considering the observed positive subjective effects, it seems reasonable to recommend headache patients to try this non-invasive intervention for a short period of time to see whether they experience improvement.

Background. Cardiometabolic health checks are currently introduced in several countries in an attempt to reduce the population-wide increase of cardiometabolic disease. Objective. Developing and implementing a health check for cardiometabolic disorders in a medium-sized primary health care centre and describing the participation rate and the numbers of disorders requiring treatment that are identified. Methods. Observational research in Eindhoven, The Netherlands. All registered patients aged 40-75 years without known cardiometabolic disease (i.e. cardiovascular diseases, diabetes and chronic kidney disease) (n = 1704) were sent a written invitation to participate in a health check. A three-step procedure was used to determine whether a participant was at increased risk of developing cardiometabolic disease. Treatment was started if necessary, according to current guidelines. We recorded the numbers of patients proceeding through each step and the numbers of disorders identified. Results. A total of 1270 patients (75%) returned the first screening questionnaire. Based on the information from this questionnaire, 952 were invited to visit the health care centre for further assessment. A total of 145 patients (11% of the 1270) were found to have at least one disorder for which treatment was indicated (e.g. increased cardiovascular risk, isolated systolic hypertension, diabetes mellitus, suspected familial hypercholesterolaemia or kidney disease). Conclusions. The response rate and the number of cases identified demonstrate that cardiometabolic disorders can be effectively detected at a primary health care centre. Further research is needed to assess the long-term effects and efficacy of health checks in general practice.

Objectives: New insights in the pathophysiology of lacunar stroke (LS) suggest that it is caused by increased permeability of the blood-brain barrier due to endothelial activation. Because endothelial cells are the major production and storage site of tissue factor pathway inhibitor (TFPI), this protein can be used as marker of endothelial activation. In this observational study we measured the different pools of TFPI, as a marker of endothelial function, in first-ever lacunar stroke patients. Methods: We determined antigen levels of total and free full-length (FL) TFPI using ELISA in 149 patients and 42 controls. Heparin-releasable free FL TFPI was determined in a random subset of 17 patients and 15 controls. By brain MRI, we classified LS patients as having isolated lacunar infarct (ILA) or silent ischemic lesions (SILs). Results: Plasma levels of total TFPI were highest in patients with SILs compared with those with ILA, but this association disappeared after correction for age and levels of low-density lipoprotein cholesterol. However, levels of heparin-releasable free FL TFPI were higher in patients than in controls. Conclusions: Although ambient plasma levels of total TFPI were not different in subtypes of LS, the increased levels of heparin-releasable TFPI in patients suggest a role of endothelial activation in the pathogenesis of LS. Neurology (R) 2012;78:493-498

Background and Purpose— Results from case-control and case-case studies indicate that a positive family history of stroke (FHstroke) is an independent risk factor for lacunar stroke. Different lacunar stroke phenotypes can be distinguished on the basis of the presence of asymptomatic lacunar infarcts (aLACs), ischemic white-matter lesions, or brain microbleeds. The aim of the present study was to determine whether familial aggregation of stroke was different for lacunar stroke phenotypes. Methods— In 157 patients with a first-ever lacunar stroke, a complete first-degree FHstroke was obtained by a standardized questionnaire and additional interview. Lacunar stroke patients were categorized successively into groups, depending on the presence of aLACs, ischemic white-matter lesions, and brain microbleeds on magnetic resonance imaging. Results— Fifty-two percent of patients reported a positive FHstroke in at least one of their first-degree relatives. In younger (P Conclusions— A family history of stroke might be an independent risk factor for the lacunar stroke phenotype with aLACs at younger ages, suggesting a role for genetic factors in this phenotype caused by diffuse vasculopathy.

Background: A striatocapsular infarct (SCI) is a subcortical infarct in the territory of the lenticulostriate arteries, most likely due to transient occlusion of the main stem of the middle cerebral artery (MCA). Presence of the hyperdense middle cerebral artery sign (HMCAS) is a reliable marker of occlusion of the MCA. We hypothesized that SCIs are related to HMCAS at baseline, which subsequently disappears (HMCAS-D) on follow-up CT in stroke patients treated with intravenous rtPA. Methods: Baseline and 24-hour follow-up CTs were evaluated for HMCAS in acute ischemic stroke patients treated with intravenous rtPA and follow-up scans were also reviewed for the presence of isolated cortical (CIn), SCI, cortical and striatocapsular (CI-SCI) or lacunar infarct. We determined the incidence of SCI and the association between SCI and HMCAS on baseline and follow-up CT. Results: Of the 247 patients, 43 had an SCI (17.4%; 95% CI: 13.1–22.5). The presence of HMCAS at baseline was related to the occurrence of infarction with involvement of the striatocapsular region (SCI or CI-SCI) on follow-up CT (OR: 11.6; 95% CI: 5.9–22.8). HMCAS-D on follow-up scans was significantly related to SCI on follow-up CT compared to CI-SCI (OR: 4.9; 95% CI: 3.7–6.1). Conclusions: Occurrence of SCI and CI-SCI is associated with the presence of HMCAS on CT before thrombolysis, whereas HMCAS-D on follow-up CT is strongly related to the occurrence of SCI. Our findings support the causative role of transient occlusion of the MCA main stem in the pathogenesis of SCI.

Background: Metabolic syndrome (MetS) is a cluster of three or more of the following risk factors: obesity, elevated blood pressure, elevated triglyceride level, elevated glucose level, and low high-density lipoprotein level. Lacunar infarcts (LS) account for 25% of all ischemic strokes and are small, deeply located brain infarcts. Two different subtypes exist, which are distinguished by the presence of concomitant white matter lesions (WML) on brain imaging. We determined the prevalence of MetS in LS and the association between MetS with LS subtypes in a series of first-ever LS patients. Methods: We included 92 patients with a first-ever LS, and 92 patients with a first-ever atheroslerotic cortical stroke (CS) matched for age and sex. LS subtypes were defined according to presence of concomitant WML. We defined MetS retrospectively according to previously defined standards. Results: 35.9% of LS patients and 45.7% of CS patients had MetS (OR 0.67; 95% CI 0.37–1.20). MetS was more prevalent in LS without WML than in LS with WML (44.4 and 23.7%, respectively; OR 2.98; 95% CI 1.04–8.47). Similarly, MetS related more to CS compared to LS with WML (OR 2.56; 95% CI 1.03–6.37). Conclusion: MetS relates more strongly to LS without WML and to CS, than to LS with WML. Our results suggest a different underlying mechanism between LS without WML and CS, and lacunar stroke with WML.

Although the Roland disability questionnaire (RDQ) is a commonly used questionnaire for patients with low back pain (LBP), several important issues remain understudied. The purposes of this study were to investigate the impact that several parameters (length of test-retest interval, interpretation of the global perceived effect (GPE) scores, methods to estimate standard error of measurement (SEM), intervention and baseline scores) have on various measurement properties, such as agreement (Limits of Agreement (LOA), SEMagreement), responsiveness (area under the ROC curve, sensitivity, specificity) and interpretability (optimal cut-off point, Minimal Detectable Change), of the RDQ. RDQ was administered four times to 212 patients with chronic non-specific LBP (first consultation (T-1), eligibility check (T0), randomization/start of treatment (T1) and end of treatment (T2)). They also completed a GPE scale at T2. To study the influence of length of test interval between T-1, T0 and T1, six time intervals were assessed. Analyses of the impact of parameters on responsiveness and interpretability were based on the GPE score and on RDQ score changes (T1 versus T2). Results revealed that agreement parameters decreased with increasing time interval between test-retest. They confirmed the influence of the interpretation of the GPE as well as of the method to calculate the SEM on the magnitude of the Minimal Detectable Change and ROC parameters. Baseline RDQ scores and the way to cluster patients with regard to baseline scores influenced mainly the optimal cut-off point and responsiveness parameters; intervention did not affect the magnitude of the Minimal Detectable Change.

Purpose. Firstly, to examine whether heart rate (HR) can be predicted based on the Borg-scale for perceived exertion in patients with chronic low back pain (CLBP) and secondly, to assess changes in HR, Borg-scores and workload to study the relevance of a stepwise increase of workload based on the Borg-score and HR. Methods. Ninety-nine patients with CLBP and a mean disability-score (Roland Morris Disability Questionnaire) of 13.8 (SD = 3.7) participated in a 10-week aerobic training programme (20 min, 3 times/week). HR, ratings of perceived exertion (RPE), and workload were monitored. Prior to treatment, patients completed questionnaires on pain, disability, and several psychological factors (catastrophizing, kinesiophobia, and depression). Results. The original Borg-equation (i.e. 'HR Borg x 10') appears accurate in predicting HR on a group-level. Pain-related and psychological factors were not significantly related to the accuracy of the Borg equation. Whereas mean workload increased significantly (from 93.8 (SD = 29.9) to 129.5 W (SD = 39.7), p

Background and Purpose— Hypertension is an important risk factor for brain microbleeds (BMBs) in lacunar stroke patients. However, beyond the qualitative label “hypertension,” little is known about the association with ambulatory blood pressure (BP) levels. Methods— In 123 first-ever lacunar stroke patients we performed 24-hour ambulatory BP monitoring after the acute stroke-phase. We counted BMBs on T2*-weighted gradient-echo MR images. Because a different etiology for BMBs according to location has been suggested, we distinguished between BMBs in deep and lobar location. Results— BMBs were seen in 36 (29.3%) patients. After adjusting for age, sex, number of antihypertensive drugs, asymptomatic lacunar infarcts, and white matter lesions, we found 24-hour, day, and night systolic and diastolic BP levels to be significantly associated with the presence and number of BMBs (odds ratios 1.6 to 2.3 per standard deviation increase in BP). Distinguishing between different locations, various BP characteristics were significantly associated with the presence of deep (or combined deep and lobar) BMBs, but not with purely lobar BMBs. Conclusions— Our results underline the role of a high 24-hour BP load as an important risk factor for BMBs. The association of BP levels with deep but not purely lobar BMBs is in line with the idea that different vasculopathies might be involved. Deep BMBs may be a particular marker of BP-related small vessel disease, but longitudinal and larger studies are now warranted to substantiate these findings.

Background and Purpose— Blood–brain barrier dysfunction may be an early phenomenon in the development of the small vessel disease, which underlies white matter lesions. Because vitamin B12 plays a role in maintaining the integrity of the blood–brain barrier, we studied serum vitamin B12 level in relation to such lesions. Methods— In 124 patients with first lacunar stroke, we measured serum vitamin B12 level and rated the degree of white matter lesions on MRI. Results— Mean vitamin B12 level was 202 pmol/L (SD, 68.9). Thirty-nine patients (31.5%) had a vitamin B12 level less than the lower reference value of 150 pmol/L. Lower vitamin B12 level was (statistically significant) associated with more severe periventricular white matter lesions (odds ratio/100 pmol/L decrease, 1.773; 95% CI, 1.001–3.003), but not with deep white matter lesions (odds ratio/100 pmol/L decrease, 1.441; 95% CI, 0.881–2.358; ordered multivariate regression analysis). Conclusions— More severe periventricular white matter lesions in lacunar stroke patients relate to lower vitamin B12 levels. A possible causal relationship should now be studied prospectively.

Cerebral small vessel disease results in silent ischemic lesions (SIL) among which is leukoaraiosis. In this process, endothelial damage is probably involved. Endothelial progenitor cells (EPC), are involved in endothelial repair. By restoring the damaged endothelium, EPC could mitigate SIL and cerebral small vessel disease. Haptoglobin 1-1, one of three phenotypes of haptoglobin, relates to SIL and may therefore attenuate the endothelial repair by EPC. Our aim was to quantify EPC number and function and to assess haptoglobin phenotype and its effect on EPC function in patients with a high prevalence of SIL: lacunar stroke patients. We assessed EPC In 42 lacunar stroke patients and 18 controls by flow cytometry and culture with fetal calf serum, patient and control serum. We determined haptoglobin phenotype and cultured EPC with the three different haptoglobin phenotypes. We found that EPC cluster counts were lower in patients (96.9 clusters/well +/- 83.4 (mean +/- SD)), especially in those with SIL (85.0 +/- 64.3), than in controls (174.4 +/- 112.2). Cluster formation was inhibited by patient serum, especially by SIL patient serum, but not by control serum. Patients with haptoglobin 1-1 had less clusters in culture, and when haptoglobin 1-1 was added to EPC cultures, cluster numbers were lower than with the other haptoglobin phenotypes. We conclude that lacunar stroke patients, especially those with SIL, have impaired EPC cluster formation, which may point at decreased endothelial repair potential. The haptoglobin 1-1 phenotype is likely a causative factor in this impairment.

Contains fulltext : 79835.pdf (Publisher’s version ) (Closed access) Patient adherence to medical treatment for dyspepsia is disappointing, whereas adherence is crucial for a proper evaluation of treatment. This prospective study used elements of the Integrated Change Model and Weiner's Attribution Theory to describe patients' important cognitions and their interrelationships regarding self-perceived adherence to short-term medical treatment for dyspepsia. Patient questionnaires measured the predictors before treatment and self-perceived adherence after treatment. Approximately one-quarter of the patients indicated that they were non-adherent (n = 347). Univariate and multiple linear regression analyses revealed several significant predictors that explained 44% of the variance in self-perceived adherence. Patients with a low educational level, patients who claimed to regularly forget their medication in general, patients with a low self-efficacy or a low intention were less likely to be adherent. These results may indicate targets for interventions designed to improve adherence to medical treatment for dyspepsia. For instance, asking about expected difficulties in taking acid suppressants (e.g. forgetfulness or medication use at weekends) and making action plans to overcome these difficulties (e.g. using reminders) may result in improved adherence rates. Such an approach may reach a substantial number of patients since one in five patients in our study experienced some difficulties in taking medication.

Contains fulltext : 80182.pdf (Publisher’s version ) (Closed access) BACKGROUND: The most effective initial treatment strategy of dyspepsia is still under debate. Individual biological characteristics, such as condition of gastric mucosa, might contribute to selection of the most appropriate acid suppression treatment strategy. AIM: To assess whether pre-treatment testing of gastric mucosal status is relevant for treatment success in an RCT comparing step-up and step-down therapies in newly diagnosed dyspepsia patients. METHODS: Baseline serum samples were collected to assess gastric mucosal status using serum levels of pepsinogens-I&II, gastrin-17, and Helicobacter pylori IgA/IgG-antibodies. The 6-month treatment success was compared between step-up and step-down for patients with serum diagnoses: normal; gastritis; corpus atrophy or antrum atrophy. RESULTS: In all, 519 patients (M/F: 249/270, age: 47 (18-85) years, 29%H. pylori+) were randomized to step-up (n = 293) or step-down (n = 226). Normal mucosa, gastritis and corpus atrophy were diagnosed serologically in 70%, 28% and 2% of the patients, evenly distributed between the strategies (P = 0.65). Treatment success was achieved in respectively, 69%, 70% and 70% for the serum diagnosis groups, and did not differ between the strategies. CONCLUSIONS: Dyspepsia treatment success could not be predicted by gastric mucosal status. Therefore, serum diagnosis of gastric mucosal status is no useful tool for patient allocation to acid suppressive treatment strategies.

Several treatment principles for the reduction of chronic low back pain associated disability have been postulated. To examine whether a combination of a physical training and operant-behavioral graded activity with problem solving training is cost-effective compared to either alone one year post-treatment, a full economic analysis alongside a randomized controlled trial was conducted. in total 172 patients with chronic disabling non-specific low back pain referred for rehabilitation treatment, were randomized to 10 weeks of aerobic training and muscle strengthening of back extensors (active physical treatment; APT), 10 weeks of gradual assumption of patient relevant activities based on operant-behavioral principles and problem solving training (graded activity Plus problem solving training; GAP), or APT combined with GAP (combination treatment; CT). Total costs, existing of direct health and non-health costs and indirect costs due to absence of paid work were Calculated by using cost diaries and treatment attendance lists. The Roland Disability Questionnaire was used to calculate the cost-effectiveness to reduce disability and the gain in quality adjusted life year (QALY) by using the EuroQol-5D. APT, followed by CT showed, although not significant, higher total costs than GAP. Reduction of disability and gain in QALY did not differ significantly between CT and the single treatment modalities. Based on the incremental cost effectiveness ratios (ICERs) and cost-effectiveness acceptability curves CT is not cost-effective at all. However, GAP is cost-effective regarding the reduction of disability and gain in QALY, and to a lesser degree APT is more cost-effective than CT in reducing disability.

Haptoglobin (Hp) 2-2 phenotype has been associated with peripheral and coronary artery disease and risk of vascular complications in diabetic patients, but any association of Hp polymorphism with cerebrovascular disease has not been explored so far. We aimed to study Hp polymorphism in a sample of 124 patients with a rather homogeneous type of cerebrovascular disease, namely first symptomatic lacunar stroke due to small vessel disease, in comparison with a large (n=918) control group. Hp phenotypes were determined using starch gel electrophoresis. Hp1 allele frequency was significantly higher in patients than in controls (0.480 vs. 0.395, p < 0.05), mainly due to a lower Hp2-2 phenotype frequency (25.0 vs. 36.3 %; OR 0.59; 95%CI 0.38-0.90; p < 0.05). This was even more pronounced in younger (60 years) patients (Hp1 allele frequency 0.539). Concomitant asymptomatic lacunar lesions were present in 82 patients, extensive white matter lesions in 47 patients. The association between Hp1 and lacunar stroke suggests that Hp may serve different functions depending on the pathological processes in various types of vascular disease in different organs. The association between Hp1 and lacunar stroke may relate to blood-brain barrier dysfunction, to the association between hypertension and cerebral small vessel disease, or a special dependence of small vessel wall integrity on Hp2-2 related angiogenic potential. The presence of concomitant signs of cerebral small vessel disease weakened the association between Hp1 and lacunar stroke, which could reflect a difference in underlying vascular pathophysiology in which Hp phenotype may play a different role.

Background: Current alcohol intake has been associated with cardiovascular morbidity and mortality. The effect of past and lifetime drinking has received less attention. In the present study, the impact of current, past and lifetime drinking on cardiovascular events and all-cause mortality has been assessed. Secondly, the effect of accounting for covariates within these relationships has been studied. Methods: The Lifestyle and Health study is a prospective cohort study in 2 regions of the Netherlands. Men and women aged 45 to 70 years registered in 34 general practices were followed over the period July 1996 to June 2001. At baseline, an extensive questionnaire had to be filled in. It included 3 questionnaires about alcohol intake: a Weekly Recall, a Quantity-Frequency about last year, and the Lifetime Drinking History questionnaire. Health problems were registered by the general practitioners. Results: During follow-up, 679 men and 397 women had a cardiovascular event and 330 men and 204 women died. Current drinking was associated with lower risks of cardiovascular events (women) and all-cause mortality (men and women) compared with never drinkers. The relationships were strongest for alcohol intake measured with the Weekly Recall. Lifetime alcohol intake and alcohol intake in the distant past did not seem to be related to all-cause mortality or cardiovascular events. Adjustments for covariates weakened the relationships. Conclusions: Potential positive effects of drinking seem to be of a transient nature, as lifetime drinking and drinking in the past could not be related to all-cause mortality or cardiovascular events. The alleged benefits of current drinking at baseline diminished with increasing methodological quality and rigor.

Introduction: Patients' initial beliefs about the success of a given pain treatment are shown to affect final treatment outcome. The Credibility/Expectancy Questionnaire (CEQ) has recently been developed as measure of treatment credibility and expectancy. Objective: The objectives of this study were (1) to investigate the factor structure of the CEQ in a sample of chronic low back pain (CLBP) patients by means of a confirmatory factor analysis, (2) to examine the association between treatment credibility and expectancy and patient characteristics, and (3) to assess whether treatment expectancy and credibility are associated with the outcome of rehabilitation treatment. Methods: CLBP patients (n = 167) were randomized to either active physical therapy (n = 51), cognitive-behavioral therapy (n = 57), or a combination therapy (n 59), and completed the CEQ after a careful explanation of the treatment rationale. Results: Confirmatory factor analysis supported the 2-factor structure (credibility/expectancy) of the CEQ. Lower credibility was associated with higher pain-related fear and lower internal control of pain, and lower expectancy with higher levels of pain-related fear and no radiating pain. Multiple linear regression analyses revealed that after controlling for age, sex, treatment center, pain-intensity at baseline, duration of disability, and irrespective of the treatment offered, expectancy was significantly associated with disability and satisfaction. Credibility was significantly associated with patient-specific symptoms and satisfaction. For global perceived effect, treatment expectancy was predictive in active physical therapy only, and treatment credibility was a significant predictor in combination therapy only. Discussion: Although the associations found were low to modest, these results underscore the importance of expectancy and credibility for the outcome of different active interventions for CLBP and might contribute to the development of more effective treatments.

Bed rest has been shown to be an ineffective treatment for non-specific low back pain (LBP). Despite this, during a new episode of pain some patients still rely on bed rest. Which patients choose bed rest is however unknown. The objectives of the present study were, firstly, to assess characteristics of patients choosing bed rest in (sub)acute pain and secondly to study whether prolonged bed rest in the (sub)acute phase of pain will result in long term disability. A prospective longitudinal cohort study included 282 patients with non-specific LBP for less than 7 weeks. Main outcome measures were duration of bed rest (in three categories) and disability. Results showed that 33% of patients with (sub)acute LBP had bed rest, but only 8% stayed in bed for more than four days. An ordinal regression analysis revealed that behavioural factors (catastrophizing (OR = 1.05 per bed rest category p