Trend in and predictors for cardiovascular mortality in patients with rheumatoid arthritis over a period of 15 years: a prospective cohort study.

OBJECTIVES: To investigate a) the cardiovascular (CV) mortality in a clinical cohort of patients with established rheumatoid arthritis (RA) in comparison with the general population over 15 years, b) the trend in this CV mortality during the study period, and c) for a broad range of predictors, which baseline variables predict CV mortality. METHODS: In 1997, a sample of 1222 patients was randomly selected from the register of a rheumatology outpatient clinic in Amsterdam. Their CV mortality between 1997 and 2012 was obtained from Statistics Netherlands. The standardised mortality ratio (SMR) for CV mortality was calculated. A linear poisson regression analysis was performed to investigate if there was a trend in SMR over time. A Cox regression analysis was performed to determine which baseline variables predicted CV mortality. RESULTS: Mean age of the population at baseline was 60.4 (SD 15.4) years and 72.6% of the patients were women. Estimated SMR (95% confidence interval) for CV mortality was 1.24 (1.05, 1.43). The SMR decreased with 3% annually (p=0.16). Higher age, higher erythrocyte sedimentation rate, having CV comorbidity and diabetes mellitus (DM) were predictors for CV mortality. CONCLUSIONS: CV mortality among patients with RA in the past 15 years was still higher than in the general population. CV mortality decrease was not statistically significant. As CV mortality in RA is still higher than in the general population, continued attention for CV diseases in RA is important. Both tight control of disease activity and good care for comorbid conditions (CV diseases and DM) are advocated.

Caregiver burden and emotional problems in partners of stroke patients at two months and one year post-stroke: Determinants and prediction.

OBJECTIVES: (a) To determine levels of and factors explaining partners' burden, anxiety and depressive symptoms at two months post-stroke, (b) to predict partners' burden, anxiety and depressive symptoms at one year post-stroke based on patient and partner characteristics available at two months post-stroke. METHODS: Prospective cohort study. Partners of stroke patients (N=183) were included. Main outcome measures were the Caregiver Strain Index and the Hospital Anxiety and Depression Scale. RESULTS: Many partners experienced high burden, anxiety and depressive symptoms. At two months post-stroke, these outcomes were associated with the partner variables: age, relationship satisfaction, pro-active coping, self-efficacy, everyday social support, burden, anxiety and depressive symptoms; and the patient variables: stroke severity and depressive symptoms. Partner outcomes at one year post-stroke were mainly predicted by the level of these outcomes at two months post-stroke. CONCLUSIONS: Partner outcomes at two months post-stroke predict to a large degree partner outcomes at one year post-stroke. PRACTICE IMPLICATIONS: Measuring partners' burden and anxiety and depressive symptoms in the post-acute phase is recommended to trace partners at risk of long-term burden and emotional problems.

Physical and Mental Functioning in Patients with Established Rheumatoid Arthritis over an 11-year Followup Period: The Role of Specific Comorbidities.

OBJECTIVE: To investigate the longterm association of a wide range of comorbidities with physical and mental functioning in patients with rheumatoid arthritis (RA). METHODS: Longitudinal data over a period of 11 years were collected from 882 patients with RA. Somatic comorbidity and comorbid depression were measured at baseline, with a questionnaire including 20 chronic diseases and with the Center for Epidemiologic Depression Scale, respectively. Physical functioning was measured at 5 timepoints with a disease-specific measure [Health Assessment Questionnaire (HAQ)] and a generic measure [physical scales of the Medical Outcomes Study Short Form-36 (SF-36)]. Mental functioning was measured with the mental scales of the SF-36. To determine the association of baseline-specific comorbidities with functioning over time, we performed longitudinal analyses. RESULTS: At baseline, 72% percent of the patients were women, mean age ± SD was 59.3 ± 14.8 years, median RA disease duration was 5.0 years, and 68% had ≥ 1 comorbid condition. The effect of comorbid conditions was more apparent when physical functioning was measured with SF-36, a disease-generic measure, compared with the HAQ, a disease-specific measure. Circulatory conditions and depression were associated (p < 0.05) with worse physical functioning according to the HAQ. Respiratory conditions, musculoskeletal conditions, cancer, and depression were associated (p < 0.05) with worse physical functioning according to the SF-36. Respiratory conditions and depression were associated with worse mental functioning. CONCLUSION: Patients with specific comorbid conditions have an increased risk of low functioning in the long term. Targeted attention for these specific comorbid conditions by clinicians is recommended.

Course of social support and relationships between social support and patients' depressive symptoms in the first 3 years post-stroke.

OBJECTIVE: To describe the course of social support (everyday support, support in problem situations and esteem support) from initial inpatient rehabilitation until 3 years post-stroke and to examine the cross-sectional and longitudinal relationships of social support with depressive symptoms. DESIGN: Prospective cohort study. SUBJECTS: A total of 249 stroke patients. METHODS: Depressive symptoms were measured with the Center of Epidemiologic Studies Depression Scale. Perceived social support was assessed with the Social Support List-Interaction. Pearson correlations and multilevel analysis were performed. RESULTS: More than one-third of participants had depressive symptoms. Social support and its 3 subtypes declined significantly over time. Divergent relationships were found between subtypes of social support and depressive symptoms. Everyday support and esteem support had negative associations with depressive symptoms, whereas support in problem situations had a positive association. Social support in problem situations was a predictor of depressive symptoms over time. No effect-modification by participants with physical or cognitive limitations was found. CONCLUSION: Stroke survivors experience a decline in social support over time. Various subtypes of support show distinct relationships with depressive symptoms. Healthcare professionals should focus on the various subtypes of support when supporting patients to improve and maintain an adequate social support network.

Prevalence of fatigue, pain, and affective disorders in adults with duchenne muscular dystrophy and their associations with quality of life.

OBJECTIVES: To assess the prevalence of fatigue, pain, anxiety, and depression in adults with Duchenne muscular dystrophy (DMD), and to analyze their relationship with health-related quality of life. DESIGN: Cross-sectional study. SETTING: Home of participants. PARTICIPANTS: Adults (N=80) with DMD. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Fatigue was assessed with the Fatigue Severity Scale; pain with 1 item of the Medical Outcomes Study 36-Item Short-Form Health Survey and by interview; and anxiety and depression by using the Hospital Anxiety and Depression Scale. Health-related quality of life was assessed using the World Health Organization Quality of Life Scale-Brief Version. Associations between these conditions and quality of life were assessed by means of univariate and multivariate logistic regression analyses. RESULTS: Symptoms of fatigue (40.5%), pain (73.4%), anxiety (24%), and depression (19%) were frequently found. Individuals often had multiple conditions. Fatigue was related to overall quality of life and to the quality-of-life domains of physical health and environment; anxiety was related to the psychological domain. CONCLUSIONS: Fatigue, pain, anxiety, and depression, potentially treatable symptoms, occur frequently in adults with DMD and significantly influence health-related quality of life.

Quality of life of adult men with Duchenne muscular dystrophy in the Netherlands: implications for care.

OBJECTIVE: To assess quality of life of adults with Duchenne muscular dystrophy in the Netherlands and to identify domains and major problems influencing quality of life. DESIGN: Cross-sectional. SUBJECTS: Seventy-nine men aged ≥ 20 years with Duchenne muscular dystrophy. METHODS: The Medical Outcome Study Short Form-36 (SF-36), World Health Organization Quality of Life - BREF (WHOQOL-BREF) and an interview were used to assess quality of life and problems. RESULTS: Compared with Dutch general population reference values, the SF-36 domains scores were lower on all domains except mental health and role limitations due to emotional problems. On the WHOQOL-BREF the social relationships domain score was lower. Main problems were intimate relationships, work, leisure, transport and meaningfulness of life. Seventy-three percent stated overall quality of life as "(very) good". The SF-36 domains mental health (rs 0.53, p < 0.001) and vitality (rs 0.49, p < 0.001) had the strongest associations with overall quality of life. CONCLUSION: Adult men with Duchenne muscular dystrophy assess their health status as low in the physical, but not in the mental, domains. Experienced problems are mainly in the area of participation. They are generally satisfied with their overall quality of life.

Subjective caregiver burden of parents of adults with Duchenne muscular dystrophy.

PURPOSE: To describe subjective caregiver burden of parents of adults with Duchenne muscular dystrophy (DMD) and to identify factors associated with the level of subjective burden. METHODS: In a cross-sectional study in 80 parents of 57 adult, severely disabled DMD patients' level of subjective caregiver burden was measured with the Caregiver Strain Index (CSI) and the Self Rated Burden Scale. A visual analogue scale was used to measure happiness. The expanded CSI version, the CarerQoL and open questions were used to analyse caregiving in more depth. In uni and multivariate analyses, associations of objective care characteristics, patient characteristics and caregiver characteristics with burden were explored. RESULTS: Parents indicated substantial burden, but valued giving care as being important and rewarding. Subjective burden was associated with received support, tracheotomy, active coping by the patient and anxiety in patient and parents, together explaining 34%-36% of variance. Living situation was not associated with experienced burden. CONCLUSIONS: Caring for an adult son with DMD is burdensome, but rewarding. Subjective caregiver burden of parents may be alleviated by adequate support and respite care, by avoiding tracheotomy and by intervention programs targeting anxiety and promoting active coping by the patient from childhood.

Course of social support and relationships between social support and life satisfaction in spouses of patients with stroke in the chronic phase.

OBJECTIVE: To describe the course of social support in spouses of patients with stroke, and to examine direct and indirect relationships between social support and life satisfaction over time. METHODS: Prospective cohort study (N=180) with measurements at 2 months after discharge from inpatient rehabilitation, 1 year, and 3 years after stroke. Social support was assessed using the Social Support List-12, Life satisfaction with the Life Satisfaction Questionnaire (LiSat-9) and Caregiver strain with the Caregiver Strain Index. Random coefficient analyses was used. RESULTS: Total social support and the 3 subtypes of social support decreased significantly over time. In all models, caregiver strain was associated with lower life satisfaction and social support was associated with higher life satisfaction, but there were no interaction effects between caregiver strain and social support on life satisfaction. CONCLUSION: Spouses of patients with stroke experienced a decline of social support over time. Social support was positively associated with life satisfaction, regardless of the amount of caregiver strain experienced by the spouses. PRACTICE IMPLICATIONS: It is important to discuss with caregivers of stroke patients the importance of maintaining their own social contacts and to facilitate this by arranging support if appropriate.

Is there equity in long-term healthcare utilization after traumatic brain injury?

OBJECTIVE: To quantify the long-term use of various types of healthcare services in patients with traumatic brain injury and to estimate the relative contribution of predisposing characteristics, enabling factors and health-related needs to determine whether there is equity in healthcare utilization. DESIGN: Cross-sectional study. PATIENTS: Seventy-nine non-institutionalized moderate to severe patients with traumatic brain injury (age range 16-67 years). METHODS: Healthcare use was measured at 3-5 years post-injury. The relative contribution of predisposing characteristics, enabling factors, and health-related needs to the utilization of various types of care was analysed using logistic regression to determine whether there was equity in healthcare utilization. RESULTS: At least one healthcare service was used by 68% of the patients. Health-related needs explained most of the utilization. However, predisposing characteristics were also related to the use of other medical care and supportive care. Patients with a high internal locus of control were more likely to be users of supportive care, and patients with a high locus of control with the physician were more likely to visit medical specialists. CONCLUSION: The results suggest that most of our patients who needed care, received care. However, inequity could not be ruled out completely as predisposing characteristics also contributed to some types of healthcare utilization.

Impact of preexisting depression on length of stay and discharge destination among patients hospitalized for acute stroke: linked register-based study.

BACKGROUND AND PURPOSE: There exists limited knowledge regarding the relation between depression and healthcare utilization in stroke patients. The objective of this register-based study was to examine the impact of having preexisting depression at the time of hospital admission for acute stroke on length of hospital stay and discharge destination. METHODS: Data from a general-practice database were linked to those of a hospital database to identify patients hospitalized for stroke and were used to categorize these patients into 3 groups based on preexisting mental health (MH) status at admission, ie, those with preexisting depression, those with another preexisting MH condition, and those without any preexisting MH condition. Multilevel analyses controlling for several potentially important covariates were performed to estimate the associations under study. RESULTS: Both patients with preexisting depression (n=41) and those with another preexisting MH condition (n=62) did not differ significantly from patients without any preexisting MH condition (n=211) regarding length of hospital stay for acute stroke. Among patients who survived hospitalization, those with preexisting depression had significantly higher odds of being discharged to an institution instead of their home than did patients without any preexisting MH condition. Having another preexisting MH condition had no significant effect on discharge destination. CONCLUSIONS: Having preexisting depression at admission seems to be a relevant factor in determining discharge to institutional care after acute stroke hospitalization. Further research is needed to determine the mechanism(s) through which preexisting depression decreases the chances of being discharged to home.

Cerebrovascular risk factors and subsequent depression in older general practice patients.

BACKGROUND: This general practice-based case-control study tested the association between cerebrovascular risk factors (CVRFs) and the development of later-life depression by focusing on the impact of exposure duration to CVRFs and the modifying influence of age at depression onset. METHODS: Cases were 286 patients aged > or = 50 years with a first diagnosis of depression at age > or = 50 years. Nondepressed controls (N=832) were individually matched for age, gender and practice. CVRF diagnoses (hypertension, diabetes mellitus, cardiovascular conditions) prior to depression were determined. Analyses controlled for education, somatic and nondepressive psychiatric disease. RESULTS: No CVRF variable examined was significantly associated with subsequent depression in the total sample. An unexpected impact of age at onset of depression was observed: the odds ratio associated with having any CVRF was smaller for patients with age at onset > or = 70 years than for patients with onset between ages 50-59 years (p=.002) and 60-69 years (p=.067). Subsequent analyses excluding patients with onset at age > or = 70 years revealed that CVRF variables, including long-term exposure to CVRFs, significantly increased the odds of subsequent depression with onset between ages 50 and 69 years. LIMITATIONS: Reliance on GPs' records of morbidity may have resulted in bias towards underestimation in patients with depression onset at age > or = 70 years. CONCLUSIONS: Our findings suggest that CVRFs play a relevant role in the development of depression with onset between ages 50 and 69 years, but no evidence was found that they contribute to the occurrence of depression with onset at age > or = 70 years. Replication is warranted to exclude the possibility of bias.

Comorbidity was associated with neurologic and psychiatric diseases: a general practice-based controlled study.

BACKGROUND AND OBJECTIVE: To comprehensively examine comorbidity in unselected cohorts of patients with depression, stroke, multiple sclerosis (MS), Parkinson's disease/parkinsonism (PD/PKM), dementia, migraine, and epilepsy. METHODS: This cross-sectional study used morbidity data recorded by Dutch general practitioners. Index disease cohort sizes ranged from 241 patients with MS to 6,641 patients with lifetime depression. Thirty somatic and seven psychiatric disease categories were examined to determine whether they were comorbid with the index diseases by performing comparisons with age- and gender-matched control cohorts. Identified comorbidities were classified as either "possible" or "highly probable" comorbidity. RESULTS: An extensive range of 26 disease categories was found to be comorbid with lifetime depression. The comorbidity profile of stroke was also wide, including 21 disease categories. The comorbidity patterns of migraine and epilepsy comprised each 11 disease categories. Those concerning MS, PD/PKM, and dementia included a small number of disease categories. CONCLUSION: This study provides comprehensive knowledge of the occurrence of somatic and psychiatric comorbidity in general populations of patients with depression, stroke, MS, PD/PKM, dementia, migraine, and epilepsy. The implications of the findings for clinical practice and research are discussed.

Future costs of stroke in the Netherlands: the impact of stroke services.

OBJECTIVES: In the next decades, the number of stroke patients is expected to increase. Furthermore, organizational changes, such as stroke services, are expected to be implemented on a large scale. The purpose of this study is to estimate the future healthcare costs by taking into account the expected increase of stroke patients and a nationwide implementation of stroke services. METHODS: By means of a dynamic multistate life table, the total number of stroke patients can be projected. The model calculates the annual number of patients by age and gender. The total healthcare costs are calculated by multiplying the average healthcare costs specified by age, gender, and healthcare sector with the total number of stroke patients specified by age and gender. RESULTS: In the year 2000, the healthcare costs for stroke amounted to euro 1.62 billion. This amount is approximately 4.4 percent of the total national healthcare budget. Projections of the total costs of stroke based on current practice result in an increase of 28 percent (euro 2.08 billion) in the year 2020. A nationwide implementation of stroke services in 2020 would result in a substantial reduction of the costs of stroke (euro 1.81 billion: 13 percent cost reduction) compared with the regular care scenario. CONCLUSIONS: A nationwide implementation of stroke services is a strong policy tool for cost containment of health care in an aging population like that in the Netherlands. Policy makers should optimize the organization of stroke care.

Comorbidity in patients with diabetes mellitus: impact on medical health care utilization.

BACKGROUND: Comorbidity has been shown to intensify health care utilization and to increase medical care costs for patients with diabetes. However, most studies have been focused on one health care service, mainly hospital care, or limited their analyses to one additional comorbid disease, or the data were based on self-reported questionnaires instead of health care registration data. The purpose of this study is to estimate the effects a broad spectrum of of comorbidities on the type and volume of medical health care utilization of patients with diabetes. METHODS: By linking general practice and hospital based registrations in the Netherlands, data on comorbidity and health care utilization of patients with diabetes (n = 7,499) were obtained. Comorbidity was defined as diabetes-related comorbiiabetes-related comorbidity. Multilevel regression analyses were applied to estimate the effects of comorbidity on health care utilization. RESULTS: Our results show that both diabetes-related and non diabetes-related comorbidity increase the use of medical care substantially in patients with diabetes. Having both diabeterelated and non diabetes-related comorbidity incrases the demand for health care even more. Differences in health care utilization patterns were observed between the comorbidities. CONCLUSION: Non diabetes-related comorbidity increases the health care demand as much as diabetes-related comorbidity. Current single-disease approach of integrated diabetes care should be extended with additional care modules, which must be generic and include multiple diseases in order to meet the complex health care demands of patients with diabetes in the future.

Poor and good health outcomes in rheumatoid arthritis: the role of comorbidity.

OBJECTIVE: To assess the predictive value of selected sociodemographic characteristics, rheumatoid arthritis (RA)-specific clinical factors, and comorbidity with respect to patient-reported health outcomes, i.e., pain, disability, and health-related quality of life, among patients with RA. METHODS: Data were collected between 1997 and 2002 among 882 patients with RA of varying disease duration using questionnaires and clinical examinations. Health outcomes were evaluated over 5 years as a function of disease duration by means of random intercept linear regression. Then we selected the 10% of patients with the poorest and best health outcomes during the 5 years of followup compared to others with equal disease duration. Separate multivariate logistic regression analyses were conducted to identify factors associated with poor and good outcomes. RESULTS: Sociodemographic characteristics seemed to be less important in the prediction of health outcomes. After RA-specific clinical factors, comorbidity appeared to be a major predictive factor for health outcomes. In particular, psychological comorbidity, i.e., depressive symptomatology, was a consistent predictive factor with respect to all health outcomes. CONCLUSION: Assessment of comorbidity needs to be incorporated into the management of RA in order to prevent poor outcomes and to adapt therapies to the specific situation of individual patients. Periodic routine screening for and monitoring of somatic and psychological comorbidity should be included in clinical practice.

Course of patient-reported health outcomes in rheumatoid arthritis: comparison of longitudinal and cross-sectional approaches.

OBJECTIVE: To describe health outcomes reported by patients with rheumatoid arthritis (RA), i.e., pain, disability and health-related quality of life, as a function of disease duration in a longitudinal approach, and to compare the course of patient-reported health outcomes by a longitudinal versus a cross-sectional approach. METHODS: Data were collected with 4 series of questionnaires between 1997 and 2002 among patients with RA (maximum number = 882) of varying disease duration. The course of patient-reported health outcomes as a function of disease duration was evaluated using both longitudinal data and cross-sectional data of the first series. RESULTS: The course of RA shows a different pattern for various health outcomes. We observed similar trends in health outcomes in this large patient sample using the longitudinal and the cross-sectional approach. CONCLUSION: Although longterm consequences of RA are preferably assessed in longer duration followup studies, cross-sectional studies, including patients with a broad range of disease durations, seem to provide fairly reliable estimates of the course of health outcomes.

Hierarchy levels, sum score, and worsening of disability are related to depressive symptoms in elderly men from three European countries.

OBJECTIVES: The objectives were to investigate the predictive value of hierarchy levels and sum score of disability and change in disability on depressive symptoms. METHOD: Longitudinal data of 723 men age 70 and older from the Finland, Italy, and the Netherlands Elderly Study were collected in 1990 and 1995. Self-reported disability was based on three disability domains (instrumental activities, mobility, and basic activities) and depressive symptoms on the Zung questionnaire. RESULTS: Severity levels of disability were positively associated with depressive symptoms. Men with no disability scored 5 to 17 points lower (p < .01) on depressive symptoms than did those with disability in all domains. Among men with mild disability, those who had worsening of disability status in the preceding 5 years scored 5 points higher (p = .004) on depressive symptoms than did men who improved. DISCUSSION: Hierarchic severity levels, sum score of disability, and preceding changes in disability status are risk factors for depressive symptoms.

Economic valuation of informal care: lessons from the application of the opportunity costs and proxy good methods.

This paper reports the results of the application of the opportunity costs and proxy good methods to determine a monetary value of informal care. We developed a survey in which we asked informal caregivers in The Netherlands to indicate the different types of time forgone (paid work, unpaid work and leisure) in order to be able to provide care. Moreover, we asked informal caregivers how much time they spent on a list of 16 informal care tasks during the week before the interview. Data were obtained from surveys in two different populations: informal caregivers and their care recipients with stroke and with rheumatoid arthritis (RA). A total of 218 care recipients with stroke and their primary informal caregivers completed a survey as well as 147 caregivers and their care recipients with RA. The measurement of care according to both methods is more problematic compared to the valuation. This is especially the case for the opportunity costs method and for the housework part in the proxy good method. More precise guidelines are necessary for the consistent application of both methods in order to ensure comparability of results and of economic evaluations of health care.

The contribution of self-rated health and depressive symptoms to disability severity as a predictor of 10-year mortality in European elderly men.

OBJECTIVES: To investigate the effect of disability severity and the contribution of self-rated health and depressive symptoms to 10-year mortality. METHODS: Longitudinal data were collected from 1141 men aged 70 to 89 years from the Finland, Italy, and the Netherlands Elderly Study from 1990 to 2000. Disability severity was classified into 4 categories: no disability, instrumental activities, mobility, and basic activities of daily living. Self-rated health and depressive symptoms were classified into 2 and 3 categories, respectively. Multivariate Cox proportional hazard models were used to calculate mortality risks. RESULTS: Men with severe disability had a risk of mortality that was more than 2-fold higher (hazard ratio [HR]=2.41; 95% confidence interval [CI]=1.84, 3.16) than that of men without disability. Men who had severe disability and did not feel healthy had the highest mortality risk (HR = 3.30; 95% CI = 2.52, 4.33). This risk was lower at lower levels of disability and higher levels of self-rated health. The same trend was observed for depressive symptoms. CONCLUSIONS: For adequate prognoses on mortality or for developing intervention strategies, not only physical aspects of health but also other health outcomes should be taken into account.

Accuracy of diagnosing depression in primary care: the impact of chronic somatic and psychiatric co-morbidity.

BACKGROUND: Depression is highly co-morbid with both psychiatric and chronic somatic disease. These types of co-morbidity have been shown to exert opposite effects on underdiagnosis of depression by general practitioners (GPs). However, past research has not addressed their combined effect on underdiagnosis of depression. METHOD: Co-morbidity data on 191 depressed primary-care patients selected by a two-stage sampling procedure were analysed. Diagnoses of major depression and/or dysthymia in the last 12 months were assessed using a standardized psychiatric interview (CIDI) and compared with depression diagnoses registered by GPs in patient contacts during the same period. Presence of psychiatric and chronic somatic co-morbidity was determined using the CIDI and contact registration, respectively. RESULTS: Regression analysis showed a significant interaction effect between psychiatric and chronic somatic co-morbidity on GPs' diagnosis of depression, while taking into account the effects of sociodemographic variables, depression severity and number of GP contacts. Subsequent stratified analysis revealed that in patients without chronic somatic co-morbidity, a lower educational level, a less severe depression, and fewer GP contacts all significantly increased the likelihood of not being diagnosed as depressed. In contrast, in patients with chronic somatic co-morbidity, only having no psychiatric co-morbidity significantly decreased the likelihood of receiving a depression diagnosis. CONCLUSIONS: Our results indicate that the effects of psychiatric co-morbidity and other factors on underdiagnosis of depression by GPs differ between depressed patients with and without chronic somatic co-morbidity. Efforts to improve depression diagnosis by GPs seem to require different strategies for depressed patients with and without chronic somatic co-morbidity.