Sixfold Post-Fracture Mortality in 16- To 30-Year-Old Patients-Suicides, Homicides, and Intoxications Among Leading Causes of Death.

BACKGROUND AND AIMS:: The death of any young individual is associated with the loss of many potentially fulfilling years of life. It has been suggested that the relative mortality of fracture patients may be higher in younger age groups than in older cohorts. We determined the mortality and causes of death in a cohort of 16- to 30-year-old patients that had been hospitalized for fractures. MATERIAL AND METHODS:: We collected data using criteria based on the diagnosis code (International Statistical Classification of Diseases and Related Health Problems, 10th Revision), surgical procedure code (Nordic Medico-Statistical Committee), and seven additional characteristics of patients admitted to the trauma ward at the Central Finland Hospital between 2002 and 2008. Patients were then followed to ascertain their mortality status until the end of 2012. Standardized mortality ratios were calculated and causes of death were determined by combining our registry data with data provided by Statistics Finland. RESULTS:: During the study, 199 women and 525 men aged 16-30 years had sustained fractures. None of these patients died during the primary hospital stay. At the end of follow-up (mean duration 7.4 years), 6 women and 23 men had died. The standardized mortality ratio for all patients was 6.2 (95% Confidence Interval: 4.3-8.9). Suicides and intoxications comprised over half, and motor vehicle accidents and homicides comprised nearly a third of the post-fracture deaths. CONCLUSION:: We found a concerning increase in mortality among young adults that had been hospitalized due to a fracture compared to the general population that had been standardized by age, sex, and calendar-period. Leading causes of death were suicides and intoxications or motor vehicle accidents and homicides, which may be indicative of depressive disorders or impulse control disorders, respectively. Identification of the underlying psychosocial problems may provide an opportunity for preventive interventions.

Lifetime use of psychiatric medications and cognition at 43years of age in schizophrenia in the Northern Finland Birth Cohort 1966.

BACKGROUND: Higher lifetime antipsychotic exposure has been associated with poorer cognition in schizophrenia. The cognitive effects of adjunctive psychiatric medications and lifetime trends of antipsychotic use remain largely unclear. We aimed to study how lifetime and current benzodiazepine and antidepressant medications, lifetime trends of antipsychotic use and antipsychotic polypharmacy are associated with cognitive performance in midlife schizophrenia. METHODS: Sixty participants with DSM-IV schizophrenia from the Northern Finland Birth Cohort 1966 were examined at 43years of age with an extensive cognitive test battery. Cumulative lifetime and current use of psychiatric medications were collected from medical records and interviews. The associations between medication and principal component analysis-based cognitive composite score were analysed using linear regression. RESULTS: Lifetime cumulative DDD years of benzodiazepine and antidepressant medications were not significantly associated with global cognition. Being without antipsychotic medication (for minimum 11months) before the cognitive examination was associated with better cognitive performance (P=0.007) and higher lifetime cumulative DDD years of antipsychotics with poorer cognition (P=0.020), when adjusted for gender, onset age and lifetime hospital treatment days. Other lifetime trends of antipsychotic use, such as a long antipsychotic-free period earlier in the treatment history, and antipsychotic polypharmacy, were not significantly associated with cognition. CONCLUSIONS: Based on these naturalistic data, low exposure to adjunctive benzodiazepine and antidepressant medications does not seem to affect cognition nor explain the possible negative effects of high dose long-term antipsychotic medication on cognition in schizophrenia.

Long-term antipsychotic use and its association with outcomes in schizophrenia - the Northern Finland Birth Cohort 1966.

BACKGROUND: Due to the paucity of previous studies, we wanted to elucidate the pharmacoepidemiology of antipsychotics in schizophrenia in a general population sample, and the association between long-term antipsychotic use and outcomes. METHODS: The sample included 53 schizophrenia subjects from the Northern Finland Birth Cohort 1966 with at least ten years of follow-up (mean 18.6 years since illness onset). Data on lifetime medication and outcomes (remission, Clinical Global Impression [CGI], Social and Occupational Functioning Assessment Scale [SOFAS]) were collected from medical records, interviews, and national registers. RESULTS: During the first two years 22 (42%), between two to five years 17 (32%), and between five to ten years 14 (26%) subjects had used antipsychotics less than half of the time. Drug-free periods became rarer during the follow-up. The mean lifetime daily dose of antipsychotics was 319mg in chlorpromazine equivalents. A high lifetime average and cumulative dose and antipsychotic polypharmacy were associated with a poorer outcome in all measures, whereas having no drug-free periods was associated with a better SOFAS score and a low proportion of time on antipsychotics with a better CGI score. CONCLUSIONS: In our population-based sample, the use of antipsychotics increased during the first five years of illness and was relatively stable after that. Our results suggest that both low dose and proportion of use, and having no drug-free periods, are associated with better outcomes, which concords with current treatment recommendations and algorithms. High long-term doses and polypharmacy may relate to poor outcomes.

Use of antiepileptic or benzodiazepine medication and suicidal ideation--The Northern Finland Birth Cohort 1966.

Both antiepileptic drugs (AEDs) and benzodiazepines (BZDs) have previously been associated with an increased risk of suicidality. Our aim was to study the association between the use of conventional AEDs and BZDs and suicidal ideation in a large population-based cohort. Information on the medications used in the Northern Finland Birth Cohort 1966 was collected from the subjects at the age of 31 years, using a postal questionnaire (N=8211). The presence of suicidal ideation and other symptoms of depression and anxiety was assessed via the Hopkins Symptom Checklist - 25 questionnaire. The associations between medications and suicidal ideation were studied in different diagnostic groups and adjusted for symptoms of depression and anxiety. No difference was observed in suicidal ideation between AED users (n=54) and nonusers (n=8157). Subjects using BZDs (n=147) had greater suicidal ideation compared with nonusers (n=8064). Antiepileptic drug and benzodiazepine users more often exhibited other depression and anxiety symptoms. After adjustment for these symptoms, both AED and BZD users had less suicidal ideation compared with nonusers. In conclusion, in this population-based cohort, neither the use of AEDs nor that of BZDs was found to be associated with increased suicidal ideation when the symptoms of depression and anxiety were taken into account.

Brain morphometry of individuals with schizophrenia with and without antipsychotic medication ­ The Northern Finland Birth Cohort 1966 Study.

BACKGROUND: In schizophrenia, brain morphometric changes may be associated with antipsychotic medication. Only limited data is available concerning individuals with schizophrenia without antipsychotic medication. We aimed to study the associations of: use versus no use of antipsychotic medication; length of continuous time without antipsychotic medication; cumulative dose of lifetime antipsychotic medication; and type of antipsychotic medication; with brain morphometry in schizophrenia after an average of 10 years of illness. METHODS: Data of 63 individuals with schizophrenia (mean duration of illness 10.4 years) from the Northern Finland Birth Cohort 1966 were gathered by interview and from hospital and outpatient records. Structural MRI data at age 34 years were acquired and grey matter volume maps with voxel-based morphometry were analyzed using FSL tools. RESULTS: Of the individuals studied, 15 (24%) had taken no antipsychotic medication during the previous year. Individuals with antipsychotic medication had lower total grey matter (TGM) volume compared with non-medicated subjects, although this association was not statistically significant (Cohen's d=-0.51, P=0.078). Time without antipsychotic medication associated with increased TGM (P=0.028). Longer time without antipsychotic medication associated with increased regional volume in right precentral gyrus and right middle frontal gyrus. There were no associations between cumulative dose of lifetime antipsychotic medication or type of antipsychotic medication and brain morphometry. CONCLUSIONS: Unlike some previous investigators, we found no association between cumulative dose of lifetime antipsychotic medication and brain morphological changes in this population-based sample. However, longer continuous time without antipsychotic medication preceding the MRI scan associated with increased gray matter volume.

Antidepressant use among persons with recent-onset rheumatoid arthritis: a nationwide register-based study in Finland.

OBJECTIVES: The aim of this study was to investigate antidepressant use in a nationwide cohort of persons with incident rheumatoid arthritis (RA) in 2000-2007 in Finland. METHOD: Register data from the Social Insurance Institution of Finland were used to evaluate antidepressant use in ≥ 50-year-old incident RA patients (n = 10,356) and the same-age general population. RESULTS: Of the RA patients, 10.0% (n = 1034) had used antidepressants during the year preceding RA diagnosis. The cumulative incidence of antidepressant initiations after RA diagnosis was 11.4% [95% confidence interval (CI) 10.0-12.9] for men and 16.2% (95% CI 14.9-17.5) for women at the end of follow-up (mean 4.4 years). Female gender [age-adjusted hazard ratio (HR) 1.39, 95% CI 1.21-1.60] and increasing number of comorbidities (p for linearity < 0.001) predicted antidepressant initiations. In the last follow-up year, antidepressant use was at the same level among men with RA [prevalence rate ratio (PRR) 0.93, 95% CI 0.82-1.06] but lower among women (PRR 0.89, 95% CI 0.83-0.95) when compared to the general population. CONCLUSIONS: Antidepressant initiations in early RA were associated with female gender and comorbidity. Although depression is stated to be a sizeable problem in RA, the prevalence of antidepressant use did not exceed the population level.

Characteristics of subjects with schizophrenia spectrum disorder with and without antipsychotic medication - a 10-year follow-up of the Northern Finland 1966 Birth Cohort study.

OBJECTIVE: To estimate the prevalence of non-medicated subjects having schizophrenia spectrum disorder and to study how they differ from medicated subjects in terms of sociodemographic and illness-related variables. We also aim to find the predictors for successful antipsychotic withdrawal. METHODS: Data of 70 subjects with schizophrenic psychoses (mean duration of illness 10.4 years) from the Northern Finland 1966 Birth Cohort were gathered by interview at the age of 34 and from hospital records. The stability of remission was assessed by comparing hospitalization rates between non-medicated and medicated subjects over an 8.7-year additional follow-up period. RESULTS: Twenty-four (34%) subjects were currently not receiving medication. They were more often males, less often on a disability pension, more often in remission, and had better clinical outcomes. Relapses during the follow-up were equally frequent between non-medicated and medicated subjects (47% vs. 56%). Not having been hospitalised during previous 5 years before the interview predicted long-term successful antipsychotic withdrawal without relapse. CONCLUSIONS: Despite a lack of precise predictors, there might be subgroup of schizophrenia spectrum subjects who do not need permanent antipsychotic medication, and a fewer previous psychiatric treatments may indicate such a subgroup.

Prevalence of alcohol use disorders in schizophrenia--a systematic review and meta-analysis.

OBJECTIVE: Our aim was to present recent studies of alcohol use disorders (AUDs) in patients with schizophrenia, estimate overall prevalence and characteristics affecting the prevalence of AUDs. METHOD: We conducted a search using three literature databases and a manual search on articles published in 1996-2008. Meta-regression was used to study how prevalence is affected by different study characteristics. Articles that reported diagnoses according to DSM or ICD diagnostic systems were included. RESULTS: Altogether 60 studies met our criteria. The median of current AUD prevalence was 9.4% (inter-quartile range, IQR 4.6-19.0, 18 studies) and median of lifetime AUD prevalence 20.6% (IQR 12.0-34.5, 47 studies). In studies using DSM-III-R median prevalence was higher than that in studies using DSM-IV, ICD-9 or ICD-10 (32/17/11/6%). CONCLUSION: Approximately every fifth patient with schizophrenia had lifetime AUD diagnosis. When contrasted with the most recent review, there might be a descending trend in AUD prevalence in patients with schizophrenia.

Depressive symptoms predispose females to metabolic syndrome: a 7-year follow-up study.

OBJECTIVE: To evaluate the risk for developing metabolic syndrome when having depressive symptoms. METHOD: The prevalence of depressive symptoms and metabolic syndrome at baseline, and after a 7-year follow-up as measured with Beck depression inventory (BDI), and using the modified National Cholesterol Education Program--Adult Treatment Panel III criteria for metabolic syndrome (MetS) were studied in a middle-aged population-based sample (n = 1294). RESULTS: The logistic regression analysis showed a 2.5-fold risk (95% CI: 1.2-5.2) for the females with depressive symptoms (BDI >or=10) at baseline to have MetS at the end of the follow-up. The risk was highest in the subgroup with more melancholic symptoms evaluated with a summary score of the melancholic items in BDI (OR 6.81, 95% CI: 2.09-22.20). In men, there was no risk difference. CONCLUSION: The higher risks for MetS in females with depressive symptoms at baseline suggest that depression may be an important predisposing factor for the development of MetS.

Negative symptoms in schizophrenia: a review.

Negative symptoms refer to the weakening or lack of normal thoughts, emotions or behaviour in schizophrenia patients. Their prevalence in first-episode psychosis is high, 50-90%, and 20-40% of schizophrenia patients have persisting negative symptoms. Severe negative symptoms during the early stages of treatment predict poor prognosis. The aim of the study was to review the current literature on the negative symptoms of schizophrenia. In June 2007, the following databases were searched: Web of Science, PubMed, PsycINFO, Medline (Ovid) and Scopus. The search included articles written in English and no time limit was determined. The studies were manually screened by one of the authors according to the title and abstract. About one in three schizophrenia patients suffer from significant negative symptoms. In these patients, negative symptoms constitute a key element of overall symptoms, weakening their ability to cope with everyday activities, affecting their quality of life and their ability to manage without significant outside help. About one in three schizophrenia patients suffer from significant negative symptoms. Attention should be focused on negative symptoms during the early phase of treatment, because they cause significant impairment to patients' quality of life. So far, no treatment appears to substantially improve negative symptoms narrowly defined. However, according to clinical experience, when treating negative symptoms, the best effect is achieved by optimizing the dose of medication and by complementing it with psychosocial therapies.

No difference in insulin resistance and lipid levels between controls and adolescent subjects who later develop psychosis.

Type 2 diabetes and dyslipidemias co-occur frequently with psychoses, but it is not known how common they are in adolescents who later develop psychosis. We investigated waist circumference, blood glucose, lipid and insulin levels and insulin resistance in the Northern Finland 1986 Birth Cohort at the age of 15/16 (N=5410). The Social Insurance Institute register and the Finnish Hospital Discharge Register were used to find the participants who developed psychosis (N=21), and they were compared with other participants. There were no differences in the cardiometabolic variables, suggesting that psychotic episode is not preceded by glucose and lipid metabolism disturbances.

Insulin resistance and lipid levels in adolescents with familial risk for psychosis.

OBJECTIVE: Type 2 diabetes and dyslipidemias co-occur frequently with schizophrenia. It is not known how common they are in adolescents with a familial risk for psychosis. METHOD: The Northern Finland 1986 Birth Cohort consists of 9432 children born alive in the two Northernmost provinces in Finland. At the age of 15/16 they participated in clinical examination including measurements of glucose, lipids and IR, and a questionnaire including items about their diet and physical activity. The Finnish Hospital Discharge Register was used to find out non-organic psychoses in parents during 1972-2000. This familial risk was found out in 54 boys and 68 girls. Their results were compared with other cohort members. RESULTS: No differences were observed in the cardiometabolic risk factors between the study groups. CONCLUSION: Our results suggest that familial risk for psychosis is not directly associated with disturbances of glucose and lipid metabolism among adolescents.

Determination of soil adhesion to plastic surfaces using a radioactive tracer.

A quantitative radiochemical test procedure was developed for investigating soil adhesion on polyvinyl chloride (PVC) model materials containing different plasticizers (DOP and Hexamoll) and commercial flooring materials. A repeatable test procedure was developed, including soiling and cleaning with a Mini Cleanability Tester. Three soils all containing 51Cr emitting gamma radiation were used. The materials were subjected to successive soiling and cleaning cycles in order to generate soil accumulation. The type and amount of plasticizer appeared to affect soil adhesion on plastic model materials.

Serum lipids in schizophrenia and other functional psychoses: a general population northern Finland 1966 birth cohort survey.

OBJECTIVE: To compare fasting serum lipid concentrations of subjects with schizophrenia with a comparison group. METHOD: The study sample consists of 5654 members of the northern Finland 1966 birth cohort who participated in the field study with blood samples after overnight fasting and clinical examination in 1997-98. Total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides (TG) and glucose were analyzed. Analysis of variance were used for comparing differences in lipids means between diagnostic categories. RESULTS: Mean fasting TC in subjects with schizophrenia was 20 mg/dl higher than in the comparison group. TC and TG levels in the group of other psychoses resembled the schizophrenia group. CONCLUSION: Blood lipid levels in subjects with schizophrenia and other functional psychoses were high. As these persons are at special risk for hyperlipidemia their lipid levels should be regularly monitored, and cholesterol lowering diet, as well as medication, should be considered.

Psychotropics among the home-dwelling elderly--increasing trends.

OBJECTIVE: To assess the level of and changes in the use of psychotropics among the home-dwelling elderly in the 1990s. METHODS: A descriptive analysis based on data from two cross-sectional interview and health examination surveys of elderly persons aged 64 years or over conducted in Lieto, a typical semi-rural Finnish municipality, in 1990-91 and 1998-99. National prescription data were utilized to compare the use of psychotropics in the late 1990s by all Finnish home-dwelling elderly and the elderly in Lieto. In Lieto drug information was obtained from 1131 persons in 1990-91 and from 1197 in 1998-99, and the mean age of the informants was 73 years in both surveys. The brand names of the prescription drugs (both irregular and regular medication) taken by each interviewee during seven days prior to the interview were recorded and categorized by the Anatomical Therapeutic Chemical (ATC) classification system. RESULTS: Every fourth person was taking at least one psychotropic drug in both surveys. Most users were on regular psychotropic medication. The use of hypnotics and antidepressants increased most during the study period. Polypharmacy and the use of psychotropics were most prevalent among those aged 85 years or over, with women predominating. Concomitant use of two or more psychotropics increased statistically significantly from 7% to 10% between the surveys. The young elderly, aged 64-71 years, used cyclic antidepressants equally commonly in both surveys. None of the young elderly used new atypical antipsychotics in 1998-99. CONCLUSIONS: Psychotropics tend to be overprescribed and overused among the elderly, a group at the highest risk of adverse drug reactions. The tendency of prescribing for the elderly is not going in a better direction. New-generation psychotropics were not used. The need for long-standing use of psychotropics should be assessed regularly.

Prophylactic effect of citalopram in unipolar, recurrent depression: placebo-controlled study of maintenance therapy.

BACKGROUND: Major depression is highly recurrent. Antidepressant maintenance treatment has proven efficacy against recurrent depression. AIMS: Comparison of prophylactic efficacy of citalopram versus placebo in unipolar, recurrent depression. METHODS: Patients 18-65 years of age with recurrent unipolar major depression (DSM-IV), a Montgomery-Asberg Depression Rating Scale score of > or =22 and two or more previous depressive episodes, one within the past 5 years, were treated openly with citalopram (20-60 mg) for 6-9 weeks and, if responding, continued for 16 weeks before being randomised to double-blind maintenance treatment with citalopram or placebo for 48-77 weeks. RESULTS: A total of 427 patients entered acute treatment and 269 were randomised to double-blind treatment. Time to recurrence was longer in patients taking citalopram than in patients taking placebo (P:<0.001). Prophylactic treatment was well tolerated. CONCLUSIONS: Citalopram (20, 40 and 60 mg) is effective in the prevention of depressive recurrences. Patients at risk should continue maintenance treatment at the dose necessary to resolve symptoms in the acute treatment phase.

Citalopram controls phobic symptoms in patients with panic disorder: randomized controlled trial.

OBJECTIVE: To examine the effects of long-term treatment with citalopram or clomipramine on subjective phobic symptoms in patients with panic disorder. DESIGN: Double-blind, parallel-group, five-arm study. PATIENTS: Patients aged 18 to 65 years with panic disorder (DMS-III-R diagnosis) and with no major depressive symptoms. INTERVENTIONS: Four hundred and seventy-five patients were randomized to 8 weeks of treatment with either citalopram (10 to 15 mg per day; 20 to 30 mg per day; or 40 to 60 mg per day), clomipramine (60 to 90 mg per day) or placebo. Two hundred and seventy-nine patients continued treatment after the 8-week acute phase. OUTCOME MEASURES: Phobic symptoms were assessed using the Phobia Scale and the Symptom Checklist's (SCL-90) phobia-related factors. RESULTS: At all dosages, citalopram was more efficacious than placebo, with 20 to 30 mg generally being the most effective dosage. Citalopram (20 to 30 mg) generally decreased phobic symptoms significantly more than placebo after Month 3. Interpersonal sensitivity decreased when measured on the respective SCL-90 sub-scale. Alleviation of phobic symptoms generally continued to increase towards the end of the treatment. The effect of clomipramine was not as consistent. CONCLUSIONS: All active treatment groups, especially the group receiving 20 to 30 mg per day of citalopram, effectively controlled phobic symptoms in patients with panic disorder. Long-term treatment with citalopram further decreased phobic symptoms.