Effect of a Dietary Supplement Combining Bioactive Peptides and Magnesium on Adjustment Disorder with Anxiety: A Clinical Trial in General Practice.

Anxiety is a high frequency disorder in the general population. It is usually treated with benzodiazepines, which cause side effects and a dependence that could make withdrawal difficult. Alternative treatments are therefore needed to reduce the use of anxiolytics, particularly for adjustment disorder with anxiety. An observational, multicentre, prospective, longitudinal study has been conducted by general practitioners and one gynaecologist to evaluate the efficacy of a dietary supplement on adjustment disorder with anxiety (Stress 2 study). Patients diagnosed as anxious with a score of ≥20 on the Hamilton Anxiety Rating Scale (Ham-A, first visit on Day 0 (V0)) were offered a 28-day treatment with a dietary supplement formulated with bioactive peptides from a fish protein hydrolysate (Gabolysat®), magnesium and vitamin B6. At the second visit (V1), the Ham-A Rating Scale, the Patient Global Impression scale (PGI) and the Clinical Global Impressions scale (CGI) were administered. A 50% reduction in the Ham-A score, was achieved for 41.9% of the patients. The mean Ham-A score decreased by 12.1 ± 5.7 points (p < 0.001) between V0 (25.6 ± 3.8) and V1 (13.6 ± 6.0). Furthermore, according to the CGI scale, the anxiety of 75.3% of patients improved significantly and very significantly, with limited side effects and a negligible rebound effect. In conclusion, adjustment disorder with anxiety seems to be effectively managed by an alternative and safer solution than benzodiazepines.

Effect of an Institutional Medication Adherence Program for Long-Acting Injectable Risperidone on Adherence and Psychiatric Hospitalizations: Evidence from a Prospective Cohort Study.

BACKGROUND: Long-acting injectable (LAI) atypical antipsychotics are associated with improved adherence and reduced relapse rates in schizophrenia but reminder-based interventions may further improve outcomes. OBJECTIVES: To assess an institutional medication adherence program's (IMAP) effectiveness on adherence and psychiatric hospitalizations among schizophrenia patients taking risperidone LAI (RLAI). METHODS: Between 2009 and 2010, we recruited patients meeting DSM-IV criteria for schizophrenia treated with RLAI receiving outpatient care from psychiatric centres in France. The IMAP consisted of calling patients 48 hours prior to their scheduled RLAI injections and within 3 days of a missed appointment. Centres applying the IMAP to ≥50% of scheduled patient injections were deemed compliant. Patients were followed up to one year for adherence (≥80% of scheduled RLAI injections received within 5 days of the scheduled date) and psychiatric hospitalizations. RESULTS: Among 506 patients recruited from 36 centres, the hospitalization rate was 32.5 per 100 person-years. 15 centres treating 243 patients were IMAP compliant and 21 centres treating 263 patients were not. IMAP compliance was associated with lower psychiatric hospitalization rates (crude RR: 0.64 [95% CI: 0.44-0.93]; adjusted RR: 0.78 [95% CI: 0.47-1.27]). Nearly 75% of patients were adherent to RLAI. While patient adherence had little impact on hospitalization rates (adjusted RR: 0.92 [95% CI: 0.59-1.44]), IMAP compliance was more effective among non-adherent (adjusted RR: 0.45 [95% CI: 0.16-1.28]) than adherent (adjusted RR: 0.88 [95% CI: 0.51-1.53]) patients. CONCLUSIONS: IMAPs may improve patient adherence and reduce psychiatric hospitalizations, particularly among patients with difficulties adhering to LAI antipsychotics.

Antiepileptic drugs and risk of suicide attempts: a case-control study exploring the impact of underlying medical conditions.

PURPOSE: Randomized-controlled trials and claims databases suggest that antiepileptic drug (AED) use may increase the risk of suicide attempts (SA). The present case-control study explores the impact of underlying indications on this potential association. METHODS: Physicians collected the medical history; prior 12-month drug use was obtained from standardized telephone interviews with patients. The association between AED use and SA was explored using multivariate conditional logistic regression. The analyses were replicated after stratification on depression and neurological disorders (epilepsy, migraine, and chronic neuropathic pain). RESULTS: Between 2008 and 2012, 506 adults with an incident SA were recruited in suicide treatment centers from across France and socio-demographically matched to 2829 controls from primary care settings. The association between AED use and odds of SA was not significant overall (odds ratio [OR], 1.5; 95% confidence interval [CI], 0.9-2.4). No association was observed for patients with neurological disorders (OR, 1.1; 95%CI, 0.5-2.4) as opposed to patients with depression (OR, 1.6; 95%CI, 1.0-2.5), but unmeasured confounding was suspected. CONCLUSIONS: Our results suggest that the association observed between AED use and increased odds of non-fatal SA in patients with either a lifetime history of depression or no neurological disorder may be explained by the presence of an underlying psychiatric disorder. Accounting for underlying indications is crucial in drug safety studies, as these can cause a reported association (or lack thereof) to be misleading. This may require the prospective collection of medical data at a patient level. Copyright © 2017 John Wiley & Sons, Ltd.

Homeopathic medical practice for anxiety and depression in primary care: the EPI3 cohort study.

BACKGROUND: The purpose of the study was to compare utilization of conventional psychotropic drugs among patients seeking care for anxiety and depression disorders (ADDs) from general practitioners (GPs) who strictly prescribe conventional medicines (GP-CM), regularly prescribe homeopathy in a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho). METHODS: This was one of three epidemiological cohort studies (EPI3) on general practice in France, which included GPs and their patients consulting for ADDs (scoring 9 or more in the Hospital Anxiety and Depression Scale, HADS). Information on all medication utilization was obtained by a standardised telephone interview at inclusion, 1, 3 and 12 months. RESULTS: Of 1562 eligible patients consulting for ADDs, 710 (45.5 %) agreed to participate. Adjusted multivariate analyses showed that GP-Ho and GP-Mx patients were less likely to use psychotropic drugs over 12 months, with Odds ratio (OR) = 0.29; 95 % confidence interval (CI): 0.19 to 0.44, and OR = 0.62; 95 % CI: 0.41 to 0.94 respectively, compared to GP-CM patients. The rate of clinical improvement (HADS <9) was marginally superior for the GP-Ho group as compared to the GP-CM group (OR = 1.70; 95 % CI: 1.00 to 2.87), but not for the GP-Mx group (OR = 1.49; 95 % CI: 0.89 to 2.50). CONCLUSIONS: Patients with ADD, who chose to consult GPs prescribing homeopathy reported less use of psychotropic drugs, and were marginally more likely to experience clinical improvement, than patients managed with conventional care. Results may reflect differences in physicians' management and patients' preferences as well as statistical regression to the mean.

Depression predictors within six months of ischemic stroke: The DEPRESS Study.

BACKGROUND: Depression negatively affects rehabilitation and quality of life after stroke. Identifying in the acute phase patients at high risk for post-stroke depression would facilitate early detection of depressive symptoms. METHODS: The DEPRESS (Depression Predictors after Ischemic Stroke) study was a prospective cohort study designed to identify baseline predictors of depression occurring within six months after ischemic stroke and high-risk patients for post-stroke depression. All patients without aphasia were screened for depression by a neurologist using the Patient Health Questionnaire, and the diagnosis was confirmed by a psychiatrist with the Mini International Neuropsychiatric Interview. In severely aphasic patients, depression was diagnosed using the Aphasic Depression Rating Scale and the Visual Analog Mood Scale. RESULTS: Depression was present in 61 of 251 (24%) patients enrolled in the DEPRESS study. Female gender, prior history of depression, major physical disability, prior history of stroke, stressful life event exposure in the month preceding stroke onset, and pathologic crying were significant predictors of depression within six months after ischemic stroke. Depression was more frequent in patients with left caudate and/or lenticular nucleus lesion (OR = 2.4, 95% confidence interval, 0.97-5.91), but the difference was not significant. The presence of ≥2 predictors identified the largest proportion of depressed patients (62%) in the smallest proportion of the cohort (36%). CONCLUSION: Female gender, prior history of depression, major physical disability, prior history of stroke, recent stressful life event exposure before stroke, and pathologic crying were significant predictors of post-stroke depression occurring within six months after stroke onset.

Utilization of psychotropic drugs by patients consulting for sleeping disorders in homeopathic and conventional primary care settings: the EPI3 cohort study.

BACKGROUND: Utilization of sedative hypnotic drugs for sleeping disorders (SD) raises concerns, particularly among older people. This study compared utilization of conventional psychotropic drugs for SD among patients seeking care from general practitioners (GPs) who strictly prescribe conventional medications (GP-CM), regularly prescribe homeopathy in a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho). METHODS: This was a French population-based cohort study of GPs and their patients consulting for SD, informed through the Pittsburgh sleep quality index (PSQI) questionnaire. Information on psychotropic drugs utilization was obtained from a standardized telephone interview at inclusion, one, three and 12 months. RESULTS: 346 patients consulting for SD were included. Patients in the GP-Ho group experienced more often severe SD (41.3%) than patients in the GP-CM group (24.3%). Adjusted multivariate analyses showed that patients who chose to be managed by GP-Ho were less likely to use psychotropic drugs over 12 months as opposed to the GP-CM group, with Odds ratio (OR) = 0.25; 95% confidence interval (CI): 0.14 to 0.42. Patients in the GP-Mx group also used less psychotropic drugs but the result was not statistically significant (OR = 0.67; 95% CI: 0.39-1.16). Rates of clinical improvement of the SD did not differ between groups. CONCLUSIONS: Patients with SD who chose to consult GPs certified in homeopathy consumed less psychotropic drugs and had a similar evolution of their condition to patients treated with conventional medical management. This result may translate in a net advantage with reduction of adverse events related to psychotropic drugs.

Latent classes of nonresponders, rapid responders, and gradual responders in depressed outpatients receiving antidepressant medication and psychotherapy.

BACKGROUND: We used growth mixture modeling (GMM) to identify subsets of patients with qualitatively distinct symptom trajectories resulting from treatment. Existing studies have focused on 12-week antidepressant trials. We used data from a concurrent antidepressant and psychotherapy trial over a 6-month period. METHOD: Eight hundred twenty-one patients were randomized to receive either fluoxetine or tianepine and received cognitive-behavioral therapy, supportive therapy, or psychodynamic therapy. Patients completed the Montgomery-Åsberg depression rating scale (MADRS) at the 0, 1, 3, and 6-month periods. Patients also completed measures of dysfunctional attitudes, functioning, and personality. GMM was conducted using MADRS scores and the number of growth classes to be retained was based on the Bayesian information criterion. RESULTS: Criteria supported the presence of four distinct latent growth classes representing gradual responders of high severity (42% of sample), gradual responders of moderate severity (31%), nonresponders (15%), and rapid responders (11%). Initial severity, greater use of emotional coping strategies, less use of avoidance coping strategies, introversion, and less emotional stability predicted nonresponder status. Growth classes were not associated with different treatments or with proportion of dropouts. CONCLUSIONS: The longer time period used in this study highlights potential overestimates of nonresponders in previous research and the need for continued assessments. Our findings demonstrate distinct growth trajectories that are independent of treatment modality and generalizable to most psychotherapy patients. The correlates of class membership provide directions for future studies, which can refine methods to predict likely nonresponders as a means to facilitate personalized treatments.

Management of upper respiratory tract infections by different medical practices, including homeopathy, and consumption of antibiotics in primary care: the EPI3 cohort study in France 2007-2008.

BACKGROUND: Prescribing of antibiotics for upper respiratory tract infections (URTI) varies substantially in primary care. OBJECTIVES: To describe and compare antibiotic and antipyretic/anti-inflammatory drugs use, URTI symptoms' resolution and occurrence of potentially-associated infections in patients seeking care from general practitioners (GPs) who exclusively prescribe conventional medications (GP-CM), regularly prescribe homeopathy within a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho). METHOD: The EPI3 survey was a nationwide population-based study of a representative sample of 825 GPs and their patients in France (2007-2008). GP recruitment was stratified by self-declared homeopathic prescribing preferences. Adults and children with confirmed URTI were asked to participate in a standardized telephone interview at inclusion, one-, three- and twelve-month follow up. Study outcomes included medication consumption, URTI symptoms' resolution and potentially-associated infections (sinusitis or otitis media/externa) as reported by patients. Analyses included calibration to account for non-respondents and groups were compared using multivate analyses adjusting for baseline differences with a propensity score. RESULTS: 518 adults and children with URTI (79.3% rhinopharyngitis) were included (36.9% response rate comparable between groups). As opposed to GP-CM patients, patients in the GP-Ho group showed significantly lower consumption of antibiotics (Odds ratio (OR) = 0.43, 95% confidence interval (CI): 0.27-0.68) and antipyretic/anti-inflammatory drugs (OR = 0.54, 95% CI: 0.38-0.76) with similar evolution in related symptoms (OR = 1.16, 95% CI: 0.64-2.10). An excess of potentially-associated infections (OR = 1.70, 95% CI: 0.90-3.20) was observed in the GP-Ho group (not statistically significant). No difference was found between GP-CM and GP-Mx patients. CONCLUSION: Patients who chose to consult GPs certified in homeopathy used less antibiotics and antipyretic/anti-inflammatory drugs for URTI than those seen by GPs prescribing conventional medications. No difference was observed in patients consulting GPs within mixed-practice. A non-statistically significant excess was estimated through modelling for associated infections in the GP-Ho group and needs to be further studied.

Characteristics of patients consulting their regular primary care physician according to their prescribing preferences for homeopathy and complementary medicine.

BACKGROUND: Homeopathic care has not been well documented in terms of its impact on patients' utilization of drugs or other complementary and alternative medicines (CAM). The objective of this study was to describe and compare patients who visit physicians in general practice (GPs) who prescribe only conventional medicines (GP-CM), regularly prescribe homeopathy within a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho). MATERIAL AND METHODS: The EPI3-LASER study was a nationwide observational survey of a representative sample of GPs and their patients from across France. Physicians recorded their diagnoses and prescriptions on participating patients who completed a self-questionnaire on socio-demographics, lifestyle, quality of life Short Form 12 (SF-12) and the complementary and alternative medicine beliefs inventory (CAMBI). RESULTS: A total of 6379 patients (participation rate 73.1%) recruited from 804 GP practices participated in this survey. Patients attending a GP-Ho were slightly more often female with higher education than in the GP-CM group and had markedly healthier lifestyle. They did not differ greatly in their comorbidities or quality of life but exhibited large differences in their beliefs in holistic medicine and natural treatments, and in their attitude toward participating to their own care. Similar but less striking observations were made in patients of the GP-Mx group. CONCLUSION: Patients seeking care with a homeopathic GP did not differ greatly in their socio-demographic characteristics but more so by their healthier lifestyle and positive attitude toward CAM. Further research is needed to explore the directionality of those associations and to assess the potential economic benefits of homeopathic management in primary care.

Adult attention-deficit/hyperactivity disorder in major depressed and bipolar subjects: role of personality traits and clinical implications.

A significant comorbidity between attention-deficit/hyperactivity disorder (ADHD) and affective disorders has been consistently reported in adults. Less data regarding the role of personality traits and the influence of ADHD co-occurrence on clinical characteristics and outcome of mood disorders are currently available. One hundred and six remitted major depressed, 102 euthymic bipolar subjects, and 120 healthy controls, homogeneous with respect to demographic characteristics, were included in the study. ADHD diagnosis was based on DSM-IV-TR criteria. Childhood and adult ADHD features were measured with the Wender Utah Rating Scale, the Adult ADHD Self-rating Scale, and the Brown Attention-Deficit Disorder Scale. The Revised NEO Personality Inventory was also administered to the clinical groups, in order to investigate personality dimensions. The occurrence of adult ADHD in subjects with bipolar disorders (BD) or major depressive disorder (MDD) was 15.7 and 7.5 %, respectively, compared to 3.3 % in healthy controls (HC). Significant associations (p < .001) between personality traits (neuroticism, conscientiousness, and extraversion) and ADHD features were observed. Logistic regression analysis of all clinical subjects (n = 208) showed that those with lower levels of neuroticism (OR = 1.031; p = .025) had a lower frequency of ADHD comorbidity. The present study emphasizes the close relationship between affective disorders, especially BD, and ADHD in adults. Our findings support the need to assess subjects with mood disorders in the clinical setting for possible coexisting ADHD and to further investigate personality traits to better understand the etiology of affective disorders and ADHD co-occurrence.

Ageing and trajectories of depressive symptoms in community-dwelling men and women.

OBJECTIVE: The aim of this study was to investigate age-related patterns of depressive symptoms in older men and women and to identify their determinants. METHODS: The Center for Epidemiological Studies Depression Scale was used to prospectively assess depressive symptoms in 1059 men and 1531 women, enrolled in a French representative population-based cohort (PAQUID study) and followed over a period of 20 years. Using a group-based trajectory method with an accelerated longitudinal design, we modelled the course of depressive symptoms between 65 and 104 years of age and examined associations between trajectory patterns and baseline socio-demographic and health variables. RESULTS: In men, we identified three rising trajectories: 'never depressed' including 65% of the sample, 'emerging depression' (28%) and 'increasing depression' (7%). Compared with the membership of the never-depressed trajectory, that of the two higher trajectories was significantly associated with a history of depression and dyspnoea. In women, we identified two slightly rising trajectories (never depressed, 56%, and 'rising subclinical', 33%) and one stable high trajectory ('persistent depression', 11%). Membership of the two higher trajectories was significantly associated with the use of benzodiazepine, polymedication and dyspnoea. A history of nondepressive psychiatric disorder was a risk factor for membership of the persistent-depression group, whereas being widowed seemed to be a protective factor for membership of this group. CONCLUSION: High-risk groups for later-life depression should be targeted differently in older men and women in order to implement appropriate interventions to prevent chronicity and disability.

Prescribing patterns of duloxetine in France: a prescription assessment study in real-world conditions.

Duloxetine is a serotonin and norepinephrine reuptake inhibitor approved in the European Union for the treatment of major depressive disorder, generalized anxiety disorder, and diabetic peripheral neuropathic pain in adults. This study aimed to assess the real-world conditions of duloxetine use in France. Between April 2009 and January 2010, 290 dispensing pharmacies, randomly selected from a nationally representative list, included 1,104 patients who presented a duloxetine prescription and consented to the study. Demographic, clinical, and prescription data were extracted from pharmacy records and requested from prescribing physicians. Of the 294 patients with full data available, the mean age (standard deviation) was 54.5 (13.5) years; 74.1% were female; and 86.7% presented with a renewal prescription. 73.5% of patients had major depressive disorder; 3.4% generalized anxiety disorder; and 3.4% diabetic peripheral neuropathic pain. Overall, 78.2% (95% CI: 73.1; 82.8) of patients received duloxetine for an EU-approved indication; 95.2% (95% CI: 92.1; 97.4) of patients had no contra-indication to duloxetine; and 99.0% (95% CI: 97.0; 99.8) received an approved dose. Combining these three criteria, the overall approved use of duloxetine was 73.7% (95% CI: 68.3; 78.7). The strengths and limitations of the study design are discussed.

Subjective motives for requesting in-patient treatment in female with anorexia nervosa: a qualitative study.

BACKGROUND: Anorexia nervosa is a severe psychiatric disorder mainly affecting women. Its treatment is long and accepted with much difficulty, in particular in-patient treatment. AIMS: To describe the subjective motives of women with anorexia nervosa for requesting in-patient admission, from a qualitative analysis of application letters. METHODS: Participants were adult women (18 years and older) with anorexia nervosa who were admitted as in-patients in a referral hospital unit in France from January 2008 to December 2010. The application letters, prerequisites to admission, were studied by the interpretative phenomenological method of content analysis. RESULTS: 63 letters have been analysed, allowing the identification of six themes related to requests for in-patient care: loss of control of behaviour, and of thoughts, mental exhaustion, isolation, inner struggle and fear of recovery. CONCLUSIONS: Requests for in-patient admission were motivated by very personal, subjective experiences, unrelated to medical reasons for admission. These results may help improve pre-admission motivational work with individuals, by basing it on their subjective experience.

The structure of the Montgomery-Åsberg depression rating scale over the course of treatment for depression.

The Montgomery-Åsberg Depression Rating Scale (MADRS) is a widely used clinician-rated measure of depressive severity. Empirical support for the factor structure of the MADRS is mixed; further, the comparison of MADRS scores within and between patients requires the demonstration of consistent instrument properties. The objective of the current investigation was to evaluate MADRS factor structure as well as MADRS factorial invariance across time and gender. The MADRS was administered to 821 depressed outpatients participating in a large-scale effectiveness study of combined pharmacotherapy and psychotherapy for depression. Treatment outcome did not differ across treatment groups. Factor structure and invariance was evaluated via confirmatory factor analysis. A four-factor model consisting of Sadness, Negative Thoughts, Detachment and Neurovegetative symptoms demonstrated a good fit to the data. This four-factor structure was invariant across time and gender. A hierarchical model, in which these four factors served as indicators of a general depression factor, was also supported. A limitation of the current study is the lack of comprehensive characterization of patient clinical features; results need to be replicated in more severely depressed or treatment refractory patients. Overall, evidence supported the use of the MADRS total score as well as subscales focused on affective, cognitive, social and somatic aspects of depression in male and female outpatients.

The role of CBT in explicit memory bias in bipolar I patients.

BACKGROUND AND OBJECTIVES: Cognitive and Behavioural Therapy (CBT) is widely used in bipolar disorder, but recent meta-analyses showed that its impact is either of limited effect or not significant for important aspects such as recurrence rate. A possible benefit of CBT could concern cognitive functions, known to be frequently impaired in patients with bipolar disorder. We analysed if the positive impact of 6 months group-CBT was associated with the improvement of a specific cognitive function, namely explicit memory, trying to disentangle if memory bias (i.e. different capacity according to the emotional valence of words to be recalled) was more improved than memory performance (i.e., total number of recalled words). METHODS: Depressive, manic, anxiety symptoms and explicit memory for emotional words were initially assessed in 68 remitted bipolar I patients. Six months later, with an attrition rate of 16.2%, patients were re-assessed after CBT (N = 42) or as control condition (waiting list, N = 15). The expected impact of CBT was assessed through the improvement in the Dysfunctional Attitudes Scale. RESULTS: After CBT, an increase was observed for the number of neutral, positive and total words recalled, whereas the number of negative words recalled decreased. This increase was still significant when the improvement of dysfunctional attitudes and mood symptoms are taken into account. LIMITATIONS: The small sample of control patients. CONCLUSIONS: CBT was effective, as it improved dysfunctional attitudes and reduced remaining symptoms, but also, and independently, it improved explicit memory performance while reducing memory bias in favour of negative words.

The great neurosis of Dr. Joseph Gerard.

The Great Neurosis, of Dr. Joseph Gerard, was published in 1889 in Paris. The book, intended for the general public, shows the different varieties of neuroses through picturesque and instructive examples. Its scientific and medical value is poor, but provides us with the various meanings of the word 'neurosis' in the late nineteenth century.

Propofol-interrupted tinnitus later suppressed by amantadine: a case-report.

Tinnitus is a frequent condition without consistently effective remediation. Mr V. was a 64 year old man with Behcet's disease, a generalized systemic relapsing vasculitis. Tinnitus appeared in 1998 and he had been both aware and distressed by his tinnitus 80% of his awake time. After his last colonoscopic examination, he mentioned a transient interruption of his tinnitus. Mr V. only received propofol, an anesthesic drug that selectively down-regulates glutamatergic synaptic transmission. Amantadine, another glutamate antagonist, was later prescribed and durably suppressed tinnitus. Systematically inquiry about post-anesthesia effects on tinnitus may help decide if amantadine may be tried on an individual basis.

Stressful life events as triggers of ischemic stroke: a case-crossover study.

BACKGROUND: Acute stressors, such as stressful life events, might trigger ischemic stroke. AIMS: Our objective was to investigate the association between life events exposure and ischemic stroke onset. METHODS: Consecutive patients were interviewed about life events exposure (e.g. bereavement) using the Interview for Recent Life Events. Using a case-crossover approach, life events exposure within one month of stroke onset (hazard period) was compared with exposure during five control periods of one month preceding the hazard period. Similarly, life events exposure within one week of stroke onset was compared with exposure during three control periods of one week. Odds ratios and 95% confidence intervals were calculated using conditional logistic regression. RESULTS: Two hundred forty-seven patients were interviewed within a median time of five days (interquartile range 3-7). Life events belonging to bereavement, health, and other categories accounted for half of life events. Over the six-month period, 187 patients were exposed to ≥1 life events. Patients were exposed to ≥1 life events more often during the first month preceding stroke onset than during the five control periods (odds ratio = 2·96; 95% confidence interval, 2·19-4·00). Over the four-week period, 97 patients were exposed to ≥1 life events. Patients were exposed to ≥1 life events more often during the first week preceding stroke onset than during the three control periods (odds ratio = 2·10; 1·40-3·17). CONCLUSIONS: Recent life events exposure is associated with an increased risk of ischemic stroke.