Mismatch between self-perceived and calculated cardiometabolic disease risk among participants in a prevention program for cardiometabolic disease: a cross-sectional study.

BACKGROUND: The rising prevalence of cardiometabolic diseases (CMD) calls for effective prevention programs. Self-assessment of CMD risk, for example through an online risk score (ORS), might induce risk reducing behavior. However, the concept of disease risk is often difficult for people to understand. Therefore, the study objective was to assess the impact of communicating an individualized CMD risk score through an ORS on perceived risk and to identify risk factors and demographic characteristics associated with risk perception among high-risk participants of a prevention program for CMD. METHODS: A cross-sectional analysis of baseline data from a randomized controlled trial conducted in a primary care setting. Seven thousand five hundred forty-seven individuals aged 45-70 years without recorded CMD, hypertension or hypercholesterolemia participated. The main outcome measures were: 1) differences in cognitive and affective risk perception between the intervention group - who used an ORS and received an individualized CMD risk score- and the control group who answered questions about CMD risk, but did not receive an individualized CMD risk score; 2) risk factors and demographic characteristics associated with risk perception. RESULTS: No differences were found in cognitive and affective risk perception between the intervention and control group and risk perception was on average low, even among high-risk participants. A positive family history for diabetes type 2 (ß0.56, CI95% 0.39-0.73) and cardiovascular disease (ß0.28, CI95% 0.13-0.43), BMI ≥25 (ß0.27, CI95% 0.12-0.43), high waist circumference (ß0.25, CI95% 0.02-0.48) and physical inactivity (ß0.30, CI95% 0.16-0.45) were positively associated with cognitive CMD risk perception in high-risk participants. No other risk factors or demographic characteristics were associated with risk perception. CONCLUSIONS: Communicating an individualized CMD risk score did not affect risk perception. A mismatch was found between calculated risk and self-perceived risk in high-risk participants. Family history and BMI seem to affect the level of CMD risk perception more than risk factors such as sex, age and smoking. A dialogue about personal CMD risk between patients and health care professionals might optimize the effect of the provided risk information. TRIAL REGISTRATION: Dutch trial Register number NTR4277, registered 26th Nov 2013.

Prescription patterns of lipid lowering agents among older patients in general practice: an analysis from a national database in the Netherlands.

BACKGROUND: Dutch cardiovascular risk management guidelines state almost every older adult (≥70 years) is eligible for a lipid lowering drug (LLD). However, life expectancy, frailty or comorbidities may influence this treatment decision. OBJECTIVE: investigate how many older adults, according to age, frailty (Drubbel-frailty index) and comorbidities were prescribed LLDs. METHODS: data of 244,328 adults ≥70 years from electronic health records of 415 Dutch general practices from 2011-15 were used. Number of LLD prescriptions in patients with (n = 55,309) and without (n = 189,019) cardiovascular disease (CVD) was evaluated according to age, frailty and comorbidities. RESULTS: about 69% of adults ≥70 years with CVD and 36% without CVD were prescribed a LLD. LLD prescriptions decreased with age; with CVD: 78% aged 70-74 years and 29% aged ≥90 years were prescribed a LLD, without CVD: 37% aged 70-74 years and 12% aged ≥90 years. In patients with CVD and within each age group, percentage of LLD prescriptions was 20% point(pp) higher in frail compared with non-frail. In patients without CVD, percentage of LLD prescriptions in frail patients was 11pp higher in adults aged 70-74 years and 40pp higher in adults aged ≥90 years compared to non-frail. Similar trends were seen in the analyses with number of comorbidities. CONCLUSION: in an older population, LLD prescriptions decreased with age but-contrary to our expectations-LLD prescriptions increased with higher frailty levels.

Cost-Effectiveness of Including a Nurse Specialist in the Treatment of Urinary Incontinence in Primary Care in the Netherlands.

OBJECTIVE: Incontinence is an important health problem. Effectively treating incontinence could lead to important health gains in patients and caregivers. Management of incontinence is currently suboptimal, especially in elderly patients. To optimise the provision of incontinence care a global optimum continence service specification (OCSS) was developed. The current study evaluates the costs and effects of implementing this OCSS for community-dwelling patients older than 65 years with four or more chronic diseases in the Netherlands. METHOD: A decision analytic model was developed comparing the current care pathway for urinary incontinence in the Netherlands with the pathway as described in the OCSS. The new care strategy was operationalised as the appointment of a continence nurse specialist (NS) located with the general practitioner (GP). This was assumed to increase case detection and to include initial assessment and treatment by the NS. The analysis used a societal perspective, including medical costs, containment products (out-of-pocket and paid by insurer), home care, informal care, and implementation costs. RESULTS: With the new care strategy a QALY gain of 0.005 per patient is achieved while saving €402 per patient over a 3 year period from a societal perspective. In interpreting these findings it is important to realise that many patients are undetected, even in the new care situation (36%), or receive care for containment only. In both of these groups no health gains were achieved. CONCLUSION: Implementing the OCSS in the Netherlands by locating a NS in the GP practice is likely to reduce incontinence, improve quality of life, and reduce costs. Furthermore, the study also highlighted that various areas of the continence care process lack data, which would be valuable to collect through the introduction of the NS in a study setting.

Functional MRI correlates of visuospatial planning in out-patient depression and anxiety.

OBJECTIVE: Major depressive disorder (MDD) has been associated with executive dysfunction and related abnormal prefrontal activity, whereas the status of executive function (EF) in frequently co-occurring anxiety disorders and in comorbid depression-anxiety is unclear. We aimed to study functional MRI correlates of (visuospatial) planning in MDD and anxiety disorders and to test for the effects of their comorbidity. METHOD: Functional MRI was employed during performance of a parametric Tower of London task in out-patients with MDD (n = 65), MDD with comorbid anxiety (n = 82) or anxiety disorders without MDD (n = 64), and controls (n = 63). RESULTS: Moderately/severely depressed patients with MDD showed increased left dorsolateral prefrontal activity as a function of task load, together with subtle slowing during task execution. In mildly depressed and remitted MDD patients, in anxiety patients, and in patients with comorbid depression-anxiety, task performance was normal and no activation differences were observed. Medication use and regional brain volume were not associated with altered visuospatial planning. CONCLUSION: Prefrontal hyperactivation during high planning demands is not a trait characteristic, but a state characteristic of MDD without comorbid anxiety, occurring independent of SSRI use. Disturbances in planning or the related activation are probably not a feature of anxiety disorders with or without comorbid MDD, supporting the current distinction between anxiety disorders and depression.

Ankylosing spondylitis: a risk factor for myocardial infarction?

OBJECTIVE: To ascertain the prevalence of myocardial infarction (MI) in ankylosing spondylitis (AS) relative to that in the general population. METHODS: A questionnaire was sent to 593 patients with AS, aged between 50 and 75 years and registered at the Jan van Breemen Institute or VU University Medical Centre. A total of 383 (65%) patients with AS returned their questionnaire that covered the primary outcome, (non-fatal) MI. The prevalence of MI was calculated with data from the general population provided by Netherlands Information Network of General Practice databases as reference. RESULTS: The overall prevalence for MI was 4.4% in patients with AS versus 1.2% in the general population, resulting in an age- and gender-adjusted odds ratio of 3.1 (95% CI 1.9 to 5.1) for patients with AS. When non-responders (35%) were considered as non-MI the odds ratio decreased to 1.9 (95% CI 1.2 to 3.2). CONCLUSIONS: These observations indicate that the prevalence of MI is increased in patients with AS.

DAS-driven therapy versus routine care in patients with recent-onset active rheumatoid arthritis.

OBJECTIVES: To compare the efficacy of Disease Activity Score (DAS)-driven therapy and routine care in patients with recent-onset rheumatoid arthritis. METHODS: Patients with recent-onset rheumatoid arthritis receiving traditional antirheumatic therapy from either the BeSt study, a randomised controlled trial comparing different treatment strategies (group A), or two Early Arthritis Clinics (group B) were included. In group A, systematic DAS-driven treatment adjustments aimed to achieve low disease activity (DAS < or =2.4). In group B, treatment was left to the discretion of the treating doctor. Functional ability (Health Assessment Questionnaire (HAQ)), Disease Activity Score in 28 joints (DAS28) and Sharp/van der Heijde radiographic score (SHS) were evaluated. RESULTS: At baseline, patients in group A (n = 234) and group B (n = 201) had comparable demographic characteristics and a mean HAQ of 1.4. Group A had a longer median disease duration than group B (0.5 vs 0.4 years, p = 0.016), a higher mean DAS28 (6.1 vs 5.7, p<0.001), more rheumatoid factor-positive patients (66% vs 42%, p<0.001) and more patients with erosions (71% vs 53%, p<0.001). After 1 year, the HAQ improvement was 0.7 vs 0.5 (p = 0.029), and the percentage in remission (DAS28 <2.6) 31% vs 18% (p<0.005) in groups A and B, respectively. In group A, the median SHS progression was 2.0 (expected progression 7.0), in group B, the SHS progression was 1.0 (expected progression 4.4). CONCLUSIONS: In patients with recent-onset rheumatoid arthritis receiving traditional treatment, systematic DAS-driven therapy results in significantly better clinical improvement and possibly improves the suppression of joint damage progression.

Distinct brain systems underlie the processing of valence and arousal of affective pictures.

Valence and arousal are thought to be the primary dimensions of human emotion. However, the degree to which valence and arousal interact in determining brain responses to emotional pictures is still elusive. This functional MRI study aimed to delineate neural systems responding to valence and arousal, and their interaction. We measured neural activation in healthy females (N=23) to affective pictures using a 2 (Valence) x 2 (Arousal) design. Results show that arousal was preferentially processed by middle temporal gyrus, hippocampus and ventrolateral prefrontal cortex. Regions responding to negative valence included visual and lateral prefrontal regions, positive valence activated middle temporal and orbitofrontal areas. Importantly, distinct arousal-by-valence interactions were present in anterior insula (negative pictures), and in occipital cortex, parahippocampal gyrus and posterior cingulate (positive pictures). These data demonstrate that the brain not only differentiates between valence and arousal but also responds to specific combinations of these two, thereby highlighting the sophisticated nature of emotion processing in (female) human subjects.

Patients with obsessive-compulsive disorder are impaired in associative learning based on external feedback.

BACKGROUND: Patients with obsessive-compulsive disorder (OCD) have to repeat their actions before feeling satisfied that the action reached its intended goal. Learning theory predicts that this may be due to a failure in the processing of external feedback. METHOD: We examined the performance of 29 OCD patients and 28 healthy volunteers on an associative learning task, in which initial learning is based solely on external feedback signals. Feedback valence was manipulated with monetary gains and losses. RESULTS: As predicted, OCD patients were impaired during initial, external feedback-driven learning but not during later learning stages. The emotional salience of the feedback modulated learning during the initial stage in patients and controls alike. During later learning stages, however, patients approached near-normal performance with rewarding feedback but continued to produce deficient learning with punishing feedback. CONCLUSION: OCD patients have a fundamental impairment in updating behavior based on the external outcome of their actions, possibly mediated by faulty error signals in response selection processes.

Differential frontal-striatal and paralimbic activity during reversal learning in major depressive disorder and obsessive-compulsive disorder.

BACKGROUND: Several lines of research suggest a disturbance of reversal learning (reward and punishment processing, and affective switching) in patients with major depressive disorder (MDD). Obsessive-compulsive disorder (OCD) is also characterized by abnormal reversal learning, and is often co-morbid with MDD. However, neurobiological distinctions between the disorders are unclear. Functional neuroimaging (activation) studies comparing MDD and OCD directly are lacking. METHOD: Twenty non-medicated OCD-free patients with MDD, 20 non-medicated MDD-free patients with OCD, and 27 healthy controls performed a self-paced reversal learning task in an event-related design during functional magnetic resonance imaging (fMRI). RESULTS: Compared with healthy controls, both MDD and OCD patients displayed prolonged mean reaction times (RTs) but normal accuracy. In MDD subjects, mean RTs were correlated with disease severity. Imaging results showed MDD-specific hyperactivity in the anterior insula during punishment processing and in the putamen during reward processing. Moreover, blood oxygen level-dependent (BOLD) responses in the dorsolateral prefrontal cortex (DLPFC) and the anterior PFC during affective switching showed a linear decrease across controls, MDD and OCD. Finally, the OCD group showed blunted responsiveness of the orbitofrontal (OFC)-striatal loop during reward, and in the OFC and anterior insula during affective switching. CONCLUSIONS: This study shows frontal-striatal and (para)limbic functional abnormalities during reversal learning in MDD, in the context of generic psychomotor slowing. These data converge with currently influential models on the neuropathophysiology of MDD. Moreover, this study reports differential neural patterns in frontal-striatal and paralimbic structures on this task between MDD and OCD, confirming previous findings regarding the neural correlates of deficient reversal learning in OCD.

Lipids and inflammation: serial measurements of the lipid profile of blood donors who later developed rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis is characterised by inflammation and an increased cardiovascular risk. It was recently shown that active early rheumatoid arthritis is associated with dyslipidaemia, which may partially explain the enhanced cardiovascular risk. However, it is unknown when this dyslipidaemia starts. OBJECTIVE: To investigate the progression of the lipid profile over time and the influence of inflammatory parameters on this lipid profile, in people who later developed rheumatoid arthritis. METHODS: Levels of total cholesterol, high-density lipoprotein cholesterol (HDLc), triglycerides, apolipoprotein AI (apo AI), apolipoprotein B (apo B) and lipoprotein(a) (Lp(a)) were determined in 1078 stored, deep-frozen, serial blood bank samples, collected between 1984 and 1999, of 79 blood donors who later developed rheumatoid arthritis. These samples were compared with 1071 control samples of unselected blood donors, matched for age, sex and storage time. RESULTS: Samples of patients who later developed rheumatoid arthritis showed, on average, 4% higher total cholesterol, 9% lower HDLc, 17% higher triglyceride and 6% higher apo B levels than matched controls (p< or =0.05). The magnitude of the differences in lipid levels between groups, explained by C reactive protein (CRP), was limited. For example, only 3.6% of the difference in HDLc levels between the groups was explained by the CRP concentrations. CONCLUSION: Patients who later develop rheumatoid arthritis have a considerably more atherogenic lipid profile than matched blood donors at least 10 years before onset of symptoms. As inflammation only marginally explains the differences between the two groups, a modulating effect of lipids on inflammatory processes is hypothesised.

Simultaneous development of acute phase response and autoantibodies in preclinical rheumatoid arthritis.

OBJECTIVE: To investigate the temporal relationship between onset of inflammation (as measured by secretory phospholipase A2 (sPLA2) and C reactive protein (CRP)) and the presence of autoantibodies (IgM rheumatoid factor (IgM RF) and antibodies against citrullinated peptides (anti-CCP)) in the preclinical phase of rheumatoid arthritis (RA). METHODS: For 79 patients with RA who had been blood donors before the onset of disease, a median of 13 serum samples per patient was available. sPLA2 was measured in patient and matched control samples and related to previous CRP, IgM RF, and anti-CCP measurements. The temporal relationship between the increased markers of inflammation and autoantibodies was analysed with time lag analysis. RESULTS: IgM RF and anti-CCP concentrations were significantly associated (p<0.001) with concentrations of sPLA2, CRP, and the combination of sPLA2 and CRP at the same time point. However, we found no stronger association between the two autoantibody tests and the three inflammation measures 1, 2, and 3 years before or after a time point than for measurements at the same time, in the whole group or in subgroups of IgM RF and anti-CCP positive patients. CONCLUSION: Both the acute phase response and autoantibody formation often develop years before the first symptoms of RA occur, and these phenomena are probably closely connected in time.

Antibodies to citrullinated human fibrinogen (ACF) have diagnostic and prognostic value in early arthritis.

BACKGROUND: The anti-cyclic citrullinated peptide (CCP) test has a high sensitivity and specificity for rheumatoid arthritis, although CCP is not the physiological target of the autoantibodies. Citrullinated fibrin is abundant in inflamed synovium OBJECTIVE: To assess the diagnostic and prognostic value of antibodies against citrullinated fibrinogen (ACF), a soluble precursor of fibrin, in comparison with IgM-rheumatoid factor (IgM-RF) and the second generation anti-CCP test. METHODS: In 379 patients with early arthritis (258 rheumatoid and 121 undifferentiated), the sensitivity, specificity, and positive predictive value of ACF, anti-CCP, and IgM-RF for diagnosing rheumatoid arthritis were calculated. Multivariate logistic regression analysis was used to assess the diagnostic and prognostic value (radiographic progression after two years) of the tests. RESULTS: The sensitivities of the ACF, anti-CCP, and IgM-RF tests were 55.8%, 57.8%, and 44.6%, with specificities of 92.6%, 94.2%, and 96.7%, respectively. Approximately 30% of the IgM-RF negative patients were positive for ACF or anti-CCP or both. The ACF and anti-CCP test had a high agreement in early arthritis (kappa = 0.84). Of all baseline characteristics, the ACF test and the anti-CCP test were the best predictors for diagnosing rheumatoid arthritis at one year (odds ratio (OR) = 10.3 and 10.6, respectively) and for radiographic progression after two years (OR = 12.1 and 14.8). CONCLUSIONS: ACF is as sensitive as anti-CCP and more sensitive than IgM-RF in diagnosing rheumatoid arthritis in early arthritis. The ACF test is also a good predictor of radiographic progression, with a performance similar to the anti-CCP test. The ACF test and the anti-CCP test are especially valuable in IgM-RF negative arthritis.

Five-minute recordings of heart rate variability in obsessive-compulsive disorder, panic disorder and healthy volunteers.

BACKGROUND: Recent studies have used spectral analysis of heart rate variability (HRV) to study autonomous nervous system (ANS) function in panic disorder (PD). Most studies reported a reduced HRV in resting PD patients, suggesting increased sympathetic and decreased parasympathetic tone. In obsessive-compulsive disorder (OCD) inconsistent findings have been reported on ANS function and to date no studies have been carried out with spectral analysis of HRV. In this HRV study we compared ANS function in patients with PD, OCD and normal controls. METHODS: Standardized HRV measurement was carried out in 24 PD patients, 26 OCD patients and 24 age-matched normal controls. All patients were drug free. As this comparison yielded unexpected results, the PD and normal control samples were enlarged to 53 and 54 subjects, respectively, to verify our first measurement. RESULTS: OCD patients were not characterized by a reduced HRV, as compared to normal controls. This was also found in PD patients, even in the enlarged sample. CONCLUSIONS: HRV analysis in patients with OCD or PD showed that these patients were not characterized by ANS abnormalities, as no evidence was found of diminished HRV in a large sample of resting OCD and PD patients, measured sitting on a hospital bed.

Neuropsychological performance of OCD patients before and after treatment with fluoxetine: evidence for persistent cognitive deficits.

BACKGROUND: There is an ongoing debate about the nature of executive dysfunction that accompanies obsessive-compulsive disorder (OCD). One reason for this may be that state-related factors, such as use of medication or co-morbid symptoms, confound with task performance. This study tried to isolate trait- from state-dependent cognitive impairments by examining variability of cognition following treatment. METHOD: Nineteen OCD patients were tested on the Cambridge Neuropsychological Test Automated Battery (CANTAB) before and after treatment with fluoxetine. Their pattern of performance was compared to the one observed in healthy volunteers (N = 24). RESULTS: OCD patients displayed impairments in planning ability, spatial memory and motor speed that persisted after clinical improvement. With treatment, OCD performance diverged from that of controls on measures of focused attention and strategic ability. However, these effects were rather mild as they did not entail a significant deterioration of performance within the OCD sample. CONCLUSIONS: Our data suggest that cognitive impairments in OCD are not secondary to symptoms and therefore form a trait feature of the disorder. The nature of the deficits refers to a chronic dysfunction of the dorsolateral-striatal circuit. The minor effects of treatment on task performance is in line with recent evidence that serotonin mediates cognitive functions of orbitofrontal cortex to a greater extent than those associated with dorsolateral prefrontal regions.

Neuropsychological investigation into the carcinoid syndrome.

RATIONALE: In patients suffering from metastatic carcinoid tumors, chronic disturbances of serotonergic metabolism are frequently present. Serotonin is supposed to influence a range of cognitive functions. OBJECTIVES: The present study evaluated the cognitive performance of carcinoid patients. METHODS: In 14 patients with proven carcinoid syndrome, neuropsychological functioning was studied. Visual search, sustained attention, set shifting ability and spatial working memory were assessed using tests from the CANTAB neuropsychological battery. This was compared with the performance of matched healthy controls. RESULTS: Plasma tryptophan levels were lower than controls. Patients showed an enhanced ability to learn new stimulus-response associations. Sustained visual attention, however, was impaired. CONCLUSION: Cognitive patterns were different from those found in depressive patients and partly mimicked those found in tryptophan depletion experiments. Further investigation has to point out the role of serotonergic changes in the accomplishment of affective states.

Decision making performance in obsessive compulsive disorder.

BACKGROUND: Neuro-imaging studies in OCD report the orbitofrontal cortex to be functionally abnormal. As these areas are presumed to be involved in decision making, studying this behavior in OCD may provide further insight into the cognitive deficits accompanying the disorder. METHODS: Performance of 27 drug-free OCD patients and 26 healthy volunteers was compared on the decision making task of Bechara et al. [Cognition, 50 (1994) 7-15]. RESULTS: OCD patients and volunteers displayed comparable decision-making behavior. Within OCD patients, risk taking was independently related to both anxiety and OCD severity. LIMITATIONS: Results must be regarded as preliminary, due to the limited number of OCD patients included and the lack of a clinical control group. CONCLUSIONS: Although VMpfc function is not generally impaired, it seems to be involved in OCD; possibly in another way than could be measured with this task. CLINICAL RELEVANCE: Clarification of cognitive distortions underlying OCD may guide development of new strategies for cognitive-behavioral therapy.