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Cutaneous allodynia is a common feature accompanying migraine attacks and considered a clinical marker for central sensitization. In a longitudinal study, we wanted to investigate if allodynia in migraine patients is a predictor of increasing frequency of migraine days. We included 3029 well-defined, web-based migraine patients (86% female, mean age 42.8 ± 11.4 years, 61% migraine without aura). Questionnaires on migraine characteristics (including allodynia), depression and demographic factors were applied. The number of migraine days was measured twice. Multivariate regression models were used, with correction for other factors that are involved in the relation between allodynia and the number of migraine attacks or migraine days, with specific focus on depression. Of all 2331 eligible migraine patients, 1624 (70%) had allodynia. Lifetime depression was an independent risk factor for allodynia (odds ratio 1.52, 95% confidence interval 1.26-1.84), as well as female gender, low age at onset, and high migraine attack frequency. Analysis of the longitudinal data (in migraineurs with a follow-up period of >6 months) showed that, apart from the known risk factors (low age at onset, high baseline number of migraine days, and depression), allodynia was an independent predictor for increase in number of migraine days over a mean follow-up period of 93 ± 30 weeks (median 103 weeks, range 26-160 weeks). Cutaneous allodynia is a risk factor for migraine chronification and may warrant preventive treatment strategies.

Background: Physical inactivity and poor mental wellbeing are associated with poorer prognoses in patients with cardiovascular disease. We aimed to analyse the cross-sectional and prospective associations between physical activity and mental wellbeing in patients with a history of myocardial infarction., Design: Longitudinal, observational study., Methods: We investigated 600 older subjects with a history of myocardial infarction (age range 60-80 years) who participated in the Alpha Omega Trial (AOT). They were tested twice at baseline and at 40 months follow-up for physical activity - with the Physical Activity Scale for the Elderly (PASE); depressive symptoms - with the Geriatric Depression Scale (GDS-15); and dispositional optimism - with the Life Orientation Test (LOT-R). Linear (multilevel) and logistic regression analyses were used to examine cross-sectional and longitudinal associations., Results: Physical activity was cross-sectionally associated with depressive symptoms (adjusted beta = -0.143; p = 0.001), but not with dispositional optimism (adjusted beta = 0.074; p = 0.07). We found a synchrony of change between physical activity and depressive symptoms (adjusted beta = -0.155; p < 0.001), but not with dispositional optimism (adjusted beta = 0.049; p = 0.24). Baseline physical activity did not predict depressive symptoms at 40 months follow-up., Conclusions: Concordant inverse associations were observed for (changes) in physical activity and depressive symptoms. Physical activity did not predict depressive symptoms or low optimism.

Objective: To measure the overall level of adherence to clinical guidelines with a set of cross-diagnostic process indicators in a randomly selected sample of outpatients who started an acute phase treatment for a common mental disorder in a routine clinical setting., Setting and Participants: We developed a generic set of quality measures to asses the implementation of guidelines in daily practice. This set was tested in a retrospective cohort study in a randomly selected sample of 300 outpatients who started an acute phase psychiatric treatment for various psychiatric disorders. Patients were treated with pharmacotherapy, psychotherapy or a combination of both., Main Outcome Measure: Scores on cross-diagnostic process indicators., Results: Most indicators were positive in a high to very high percentage, indicating that most treatment elements in this routine clinical practice setting were delivered according to the guidelines for the acute treatment phase. We observed significant lower scores in the combined treatment group as compared with the two other treatment groups on the indicators 'correct treatment module' and 'stepped care' (P ≤ 0.005). Patients receiving psychotherapy had the best results on the separate indicators. Overall, only a minority of the patients in this sample was treated in complete accordance with the guidelines and treatment manuals., Conclusions: Assessment of guideline adherence is feasible with this cross-diagnostic set of process indicators and hampering factors of implementation could be easily detected. Future research should focus on the relationship with treatment outcomes.

Context: Stress is suggested to lead to metabolic dysregulations as clustered in the metabolic syndrome, but the underlying biological mechanisms are not yet well understood., Objective: We examined the relationship between two main str systems, the autonomic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis, with the metabolic syndrome and its components., Design: The design was baseline data (yr 2004-2007) of a prospective cohort: the Netherlands Study of Depression and Anxiety (NESDA)., Setting: The study comprised general community, primary care, and specialized mental health care., Participants: This study included 1883 participants aged 18-65 yr., Main Outcome Measures: Autonomic nervous system measures included heart rate, respiratory sinus arrhythmia (RSA; high RSA reflecting high parasympathetic activity), and preejection period (PEP; high PEP reflecting low sympathetic activity). HPA axis measures included the cortisol awakening response, evening cortisol, and a 0.5 mg dexamethasone suppression test as measured in saliva. Metabolic syndrome was based on the updated Adult Treatment Panel III criteria and included high waist circumference, serum triglycerides, blood pressure, serum glucose, and low high-density lipoprotein cholesterol., Results: RSA and PEP were both independently negatively associated with the presence of the metabolic syndrome, the number of metabolic dysregulations as well as all individual components except high-density lipoprotein cholesterol (all P < 0.02). Heart rate was positively related to the metabolic syndrome, the number of metabolic dysregulations, and all individual components (all P < 0.001). HPA axis measures were not related to metabolic syndrome or its components., Conclusion: Our findings suggest that increased sympathetic and decreased parasympathetic nervous system activity is associated with metabolic syndrome, whereas HPA axis activity is not.

Background: Whether long-term benzodiazepine users who participate in a family practice-based benzodiazepine discontinuation programme substitute benzodiazepines by other psychotropics is not clear., Objective: To evaluate the impact of a benzodiazepine discontinuation programme on non-benzodiazepine psychotropic prescription in family practice., Methods: In family practices in the Netherlands, 2425 long-term benzodiazepine users participated in a two-step benzodiazepine discontinuation programme. The programme started with a discontinuation letter (Step 1). Subjects unable to stop (N = 1707) were offered participation in Step 2, a three-group randomized trial with a taper procedure with group psychotherapy, a taper without psychotherapy and usual care. Only 156 subjects agreed to participate. The comparison group consisted of 1821 long-term users from family practices not participating in the programme. The main outcome was the change in prescription of non-benzodiazepine psychotropic medication from baseline (3 months before the start of the programme) till 21 months after the start of the programme. Four logistic regression models were performed concerning antidepressant prescription in the follow-up., Results: Only antidepressants were prescribed in relevant numbers. The prescription of antidepressants was not related to the programme. (P-value of experimental versus control group varied between 0.18 and 0.85 in the four models). The most important predictor of antidepressant prescription in follow-up was baseline antidepressant prescription [odds ratio (OR): 67.2; 95% confidence interval (95% CI): 49.8-90.7]. Subjects, of whom the prescription of benzodiazepines had been discontinued completely, had been prescribed less antidepressants (OR: 0.8; 95% CI: 0.6-1.0)., Conclusion: An effective benzodiazepine reduction programme was not accompanied by a substitute use of other psychotropics.

Context: Mineralocorticoid receptors (MR) mediate the action of aldosterone on sodium resorption in kidney tubular cells, but in brain they respond to the glucocorticoid cortisol in stress regulation and cognitive processes., Objective: The objective of the study was to investigate the role of the MR gene variant I180V in the neuroendocrine response to a psychosocial stressor and in electrolyte regulation., Design: Associations between the MRI180V and outcome variables in a healthy cohort subjected to psychosocial challenge (Trier Social Stress Test) and in a mild hypertensive cohort exposed to acute salt loading (Weinberger's test) were investigated. In vitro transactivational assays were applied to compare the effects of cortisol and aldosterone on the MRI180V., Results: Carriers of the MR180V allele showed higher saliva (P < 0.01), plasma cortisol (P < 0.01), and heart rate responses (P < 0.05) to the Trier Social Stress Test than noncarriers (MR180I). After 3 d of a normal salt diet and the Weinberger's test, no association was found with urinary sodium excretion, plasma aldosterone, and plasma renin activity or with changes in blood pressure, aldosterone, and renin responses. In vitro testing of the MR180V allele revealed a mild loss of function using cortisol as a ligand, compared with the MR180I allele. Significantly higher doses of cortisol were needed for half-maximal induction on the TAT-1 (P < 0.002), TAT-3 (P < 0.03), or mouse mammary tumor virus (P < 0.02) promoters, whereas maximal induction was not different. These differences were not observed using aldosterone as a ligand., Conclusion: The findings reveal that cortisol and heart rate responses to a psychosocial stressor are enhanced in carriers of the MR180V variant.

Background: Predictors of benzodiazepine discontinuation after sending a discontinuation letter by the family practitioner have not been established sufficiently., Objective: To identify predictors of short- and long-term discontinuation of benzodiazepine use and relapse in use after a minimal intervention with a discontinuation letter followed by an offer for an evaluation consultation., Methods: Predictors of benzodiazepine discontinuation and relapse in use were studied by logistic regression analysis and survival analysis within a family practice population of long-term benzodiazepine users (n = 1707) addressed by a discontinuation letter and followed for 21 months., Results: A lower baseline prescription, a shorter duration of use, male gender and use of an agent with a half-life time <24 hours were predictive of complete discontinuation in the short (6 months) and long term (21 months). Multiple agent use at baseline, use of antidepressants at 6 months and benzodiazepine type (anxiolytic/hypnotic) at baseline predicted relapse. Attendance at an evaluation consultation 3 months after the letter was sent was not predictive of discontinuation or relapse., Conclusions: Amount of baseline use and duration of use are the main determinative characteristics of successful discontinuation. The discontinuation letter intervention is suitable for use with a broad group of long-term benzodiazepine users in family practice and can be used as a first step within a stepped care approach to decrease long-term benzodiazepine use.

Impairments in memory and psychomotor function appear to be induced by benzodiazepines not only after long-term use, but also after administration of a single dose. Because it is known on which neurotransmitter system the benzodiazepines exert their action, the use of a quantitative radioreceptor assay (RRA) can be a useful tool in studying the interrelationship between the neurochemical and memory processes. The RRA measures the sum of the main compound(s) and all active metabolites present, where it relates the biological activity to the pharmacodynamic effect instead of relating it to the plasma levels of the individual compounds. To correlate the loss of memory with the benzodiazepine concentration, plasma concentrations were determined in suicidal patients. From suicidal patients (n = 84), the benzodiazepines in plasma were measured with a direct radioreceptor assay using tritiated flunitrazepam as the labelled ligand. The receptor material was a lyophilized preparation from calf cortex. Furthermore, the samples were subjected to high-performance liquid chromatographic (HPLC) analysis, and the HPLC data were converted to diazepam equivalents using cross-reactivities of the individual compounds. Patients who had ethanol residues in their plasma were excluded from this correlation experiment. The data (n = 40) obtained with the two analytical techniques were compared and correlated to assess the validity of the radioreceptor assay in establishing the relationship between the loss of memory and the total amount of benzodiazepines present. The cumulative amount of diazepam determined with the RRA and the sum of compounds determined with the HPLC method, after correction using the cross-reactivities, were plotted and correlated using regression analysis. Regression analysis showed an x variable of 0.75 and a correlation coefficient of 0.67. The intercept was not significantly different from zero (P = 0.49, t-test), whereas the slope was significantly different from zero (P < 0.01). Benzodiazepines can be directly determined in plasma using this radioreceptor assay. The data obtained from HPLC analysis were easily converted to diazepam equivalents using the cross-reactivities. A discrepancy between the data obtained from the two analytical techniques, however, indicates that certain metabolites are present, which were not quantitated in the HPLC analysis, but were measured in the radioreceptor assay. Therefore, the radioreceptor assay proved to be a valuable tool for the assessment of clinical effects, such as the demonstration of the loss of memory in suicidal patients after a benzodiazepine overdose.

Background: Contrary to short-term use, long-term benzodiazepine use is undesirable. Nevertheless, its prevalence is high. To prevent long-term use, it is important to know which short-term users are at risk of becoming long-term users., Objectives: The purpose of the present study was to identify patient-related factors of long-term versus short-term use of benzodiazepines., Methods: A cross-sectional study was carried out in family practices among users of benzodiazepines with regard to DSM-IV diagnosis, coping and psychosocial characteristics,. In a multivariate logistic regression analysis, long-term use of benzodiazepines was the dependent variable., Results: A total of 164 short-term and 158 long-term benzodiazepine users participated in the study. Having a DSM-IV disorder and psychiatric co-morbidity, being older, less educated, lonely and using more avoidance coping behaviour was associated with long-term use of benzodiazepines compared with short-term use., Conclusion: The associations found point to possibilities to reduce long-term benzodiazepine use, for example if patients with these characteristics are treated with the alternatives to benzodiazepines or are monitored closely for a short period after being prescribing benzodiazepines.

A group of psychiatric patients with and without orofacial dyskinesia (OFD) were filmed in pairs on videotape and a group of first-year social studies students were asked to select one candidate from each pair to fill a (simulated) job opening. A stationary picture (photograph) in which OFD was not visible and moving images (a video film) in which dyskinesia was visible were shown of each patient. The video effect, which was an indicator of the increase in popularity of a patient on the video film compared with the photograph, differed significantly between the OFD and control patients. Making the movement disability visible caused a relative decrease in the popularity of the OFD patients as opposed to an increase in the popularity of the control patients.