An investigation of the flow field within patient-specific models of an abdominal aortic aneurysm under steady inflow conditions.

The flow fields within three patient-specific models of an abdominal aortic aneurysm (AAA) were investigated under steady laminar inflow conditions over a range of Reynolds numbers. Each model extended from the renal arteries to downstream of the iliac bifurcation. The aneurysms (referred to as models A, B, and C) are mature, with D/d ratios of 1.83, 1.57, and 1.95 respectively. The mass flowrates in each of the iliac arteries were equal. Using flow visualization it was observed that the flow proximally in the aneurysm was characterized by a primary jet that separated from either the posterior wall or the lateral wall or both, producing large recirculating zones. The primary jet impinged either normally or obliquely upon the anterior or right lateral wall in the distal half of the aneurysm, the flow distally in the aneurysm having been greatly disturbed. Measurements of the turbulence intensity along the median lumen centre-line showed that in each model the onset of transition and full turbulence occurred at Reynolds numbers much lower than those previously measured in idealized models. Computational fluid dynamics showed substantial differences in the velocity and stress fields when using the shear stress transport turbulence model as opposed to a laminar viscous model. It was also observed that turbulence was largely produced along the shear layers surrounding the primary jet and, in particular, at interfaces between the jet and the recirculating zones. In conclusion, turbulence may be expected to exist at Reynolds numbers typically encountered within an AAA, and it must be taken account of in an analysis of the flow field.

A comparison of the measured and predicted flowfield in a patient-specific model of an abdominal aortic aneurysm.

Numerical simulation is increasingly being used to predict the flowfield within patient-specific geometries of abdominal aortic aneurysms under physiologically realistic flow conditions. This paper reports on a comparison between the flowfield measured in vitro within a patient-specific model of a mature abdominal aortic aneurysm and that predicted using computational fluid dynamics (CFD). Visualization and traverses of axial velocity were obtained at a number of locations in the aneurysm region under both steady and physiologically realistic pulsatile flow conditions. Comparisons between the measured and predicted flowfield show good agreement throughout the aneurysm. Although turbulence was observed distal in the aneurysm during late diastole, best agreement was achieved using a simple laminar flow model.

Patient's therapeutic skill acquisition and response to psychotherapy, alone or in combination with medication.

BACKGROUND: We tested the hypotheses that the addition of medication to psychotherapy enhances participation in the latter by: (1) speeding the acquisition of the psychotherapy's targeted skill; and (2) facilitating higher skill level acquisition. METHOD: Participants were 431 chronically depressed patients who received Cognitive Behavioral Analysis System of Psychotherapy (CBASP), alone (N=214) or in combination with nefazodone (N=217), as part of a randomized chronic depression study (Keller et al. 2000). CBASP, developed specifically to treat chronic depression, uses a specific procedure, 'situational analysis' to help patients engage in more effective goal-oriented interpersonal behaviours. At the end of each session, therapists rated patients on their performance of situational analysis. Outcome on depressive symptoms was assessed with the 24-item Hamilton Rating Scale for Depression. RESULTS: Although reductions in depression were significantly greater in combined treatment compared to CBASP alone, there were no between-group differences in either the rate of skill acquisition or overall skill level at the end of treatment. Proficiency in the use of the main skill taught in psychotherapy at treatment midpoint predicted outcome independently of medication status and of baseline depressive severity. CONCLUSIONS: Effective participation in CBASP, as reflected by proficiency in the compensatory skill taught in psychotherapy, is not enhanced by the addition of medication and does not mediate the between-group difference in depression outcome.

Comparison of DSM-III-R chronic major depression and major depression superimposed on dysthymia (double depression): validity of the distinction.

The nosology of chronic depression has become increasingly complex since the publication of the revised third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R; American Psychiatric Association, 1987), but there are few data available to evaluate the validity of the distinctions between the subtypes of chronic depression. The validity of the distinction between DSM-III-R chronic major depression (CMD) and major depression superimposed on dysthymia (double depression, DD) was examined. Participants were 635 patients with chronic depression in a 12-week trial of antidepressant medications. Patients with CMD, DD, and a 3rd group with a chronic major depressive episode superimposed on dysthymia (DD/CMD) were compared on demographic and clinical characteristics, family history, and response to treatment. Few differences were evident, although the depression of patients with DD/CMD tended to be more severe.

Gender differences in treatment response to sertraline versus imipramine in chronic depression.

OBJECTIVE: The authors examined gender differences in treatment response to sertraline, a selective serotonin reuptake inhibitor (SSRI), and to imipramine, a tricyclic antidepressant, in chronic depression. METHOD: A total of 235 male and 400 female outpatients with DSM-III-R chronic major depression or double depression (i.e., major depression superimposed on dysthymia) were randomly assigned to 12 weeks of double-blind treatment with sertraline or with imipramine after placebo washout. RESULTS: Women were significantly more likely to show a favorable response to sertraline than to imipramine, and men were significantly more likely to show a favorable response to imipramine than to sertraline. Gender and type of medication were also significantly related to dropout rates; women who were taking imipramine and men who were taking sertraline were more likely to withdraw from the study. Gender differences in time to response were seen with imipramine, with women responding significantly more slowly than men. Comparison of treatment response rates by menopausal status showed that premenopausal women responded significantly better to sertraline than to imipramine and that postmenopausal women had similar rates of response to the two medications. CONCLUSIONS: Men and women with chronic depression show differential responsivity to and tolerability of SSRIs and tricyclic antidepressants. The differing response rates between the drug classes in women was observed primarily in premenopausal women. Thus, female sex hormones may enhance response to SSRIs or inhibit response to tricyclics. Both gender and menopausal status should be considered when choosing an appropriate antidepressant for a depressed patient.

Gender differences in chronic major and double depression.

BACKGROUND: While the sex difference in prevalence rates of unipolar depression is well established, few studies have examined gender differences in clinical features of depression. Even less is known about gender differences in chronic forms of depression. METHODS: 235 male and 400 female outpatients with DSM-III-R chronic major depression or double depression (i.e., major depression superimposed on dysthymia) were administered an extensive battery of clinician-rated and self-report measures. RESULTS: Women were less likely to be married and had a younger age at onset and greater family history of affective disorder compared to men. Symptom profile was similar in men and women, with the exception of more sleep changes, psychomotor retardation and anxiety/somatization in women. Women reported greater severity of illness and were more likely to have received previous treatment for depression with medications and/or psychotherapy. Greater functional impairment was noted by women in the area of marital adjustment, while men showed more work impairment. LIMITATIONS: Since our population consisted of patients enrolling in a clinical trial, study exclusion criteria may have affected gender-related differences found. CONCLUSIONS: Chronicity of depression appears to affect women more seriously than men, as manifested by an earlier age of onset, greater family history of affective disorders, greater symptom reporting, poorer social adjustment and poorer quality of life. These findings represent the largest study to date of gender differences in a population with chronic depressive conditions.

A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression.

BACKGROUND: Patients with chronic forms of major depression are difficult to treat, and the relative efficacy of medications and psychotherapy is uncertain. METHODS: We randomly assigned 681 adults with a chronic nonpsychotic major depressive disorder to 12 weeks of outpatient treatment with nefazodone (maximal dose, 600 mg per day), the cognitive behavioral-analysis system of psychotherapy (16 to 20 sessions), or both. At base line, all patients had scores of at least 20 on the 24-item Hamilton Rating Scale for Depression (indicating clinically significant depression). Remission was defined as a score of 8 or less at weeks 10 and 12. For patients who did not have remission, a satisfactory response was defined as a reduction in the score by at least 50 percent from base line and a score of 15 or less. Raters were unaware of the patients' treatment assignments. RESULTS: Of the 681 patients, 662 attended at least one treatment session and were included in the analysis of response. The overall rate of response (both remission and satisfactory response) was 48 percent in both the nefazodone group and in the psychotherapy group, as compared with 73 percent in the combined-treatment group. (P<0.001 for both comparisons). Among the 519 subjects who completed the study, the rates of response were 55 percent in the nefazodone group and 52 percent in the psychotherapy group, as compared with 85 percent in the combined-treatment group (P<0.001 for both comparisons). The rates of withdrawal were similar in the three groups. Adverse events in the nefazodone group were consistent with the known side effects of the drug (e.g., headache, somnolence, dry mouth, nausea, and dizziness). CONCLUSIONS: Although about half of patients with chronic forms of major depression have a response to short-term treatment with either nefazodone or a cognitive behavioral-analysis system of psychotherapy, the combination of the two is significantly more efficacious than either treatment alone.

Early- versus late-onset dythymic disorder: comparison in out-patients with superimposed major depressive episodes.

BACKGROUND: This study examined the validity of the early-late onset subtyping distinction in dysthymic disorder. METHODS: Participants were 340 out-patients meeting DSM-III-R criteria for dysthymia and a concurrent major depressive episode (MDE). The sample was drawn from a 12-site double-blind randomized parallel group trial comparing the efficacy of sertraline and imipramine in the treatment of chronic depression. All patients received comprehensive evaluations using semi-structured interviews and rating scales. RESULTS: 73% of the sample met criteria for the early-onset, and 27% for the late-onset, subtype. The early-onset patients had a significantly longer index MDE, significantly higher rates of personality disorders and lifetime substance use disorders, and a significantly greater proportion had a family history of mood disorder. The subgroups did not differ in symptom severity or functional impairment at baseline, nor in response to a 12-week trial of antidepressants. LIMITATIONS: Further work is needed to extend these findings to dysthymic disorder without superimposed MDEs. CONCLUSIONS: These results support the distinction between early-onset and late-onset dysthymic disorder.

Age of onset in chronic major depression: relation to demographic and clinical variables, family history, and treatment response.

BACKGROUND: The clinical and etiological significance of the early-late onset distinction in chronic major depressive disorder was explored. METHOD: Subjects were 289 outpatients with DSM-III-R chronic major depression drawn from a multi-site study comparing the efficacy of sertraline and imipramine in the acute and long-term treatment of chronic depression. Patients received comprehensive evaluations using semi-structured interviews and rating scales. RESULTS: Early-onset chronic major depression was associated with a longer index major depressive episode and higher rates of recurrent major depressive episodes, comorbid personality disorders, lifetime substance use disorders, depressive personality traits, and a history of psychiatric hospitalization. In addition, more early-onset patients tended to have a family history of mood disorders. The early-late onset distinction was not associated with differences in symptom severity, functional impairment, or treatment response. LIMITATIONS: Family members were not interviewed directly; there were a large number of statistical comparisons; and interrater reliability of the assessments was not evaluated. CONCLUSIONS: Early-onset chronic major depression has a more malignant course and is associated with greater comorbidity than late-onset chronic major depression.

Maintenance phase efficacy of sertraline for chronic depression: a randomized controlled trial.

CONTEXT: The chronic form of major depression is associated with a high rate of prevalence and disability, but no controlled research has examined the impact of long-term treatment on the course and burden of illness. OBJECTIVE: To determine if maintenance therapy with sertraline hydrochloride can effectively prevent recurrence of depression in the high-risk group of patients experiencing chronic major depression or major depression with antecedent dysthymic disorder ("double depression"). DESIGN: A 76-week randomized, double-blind, parallel-group study, conducted from September 1993 to November 1996. SETTING: Outpatient psychiatric clinics at 10 academic medical centers and 2 clinical research centers. INTERVENTION: Maintenance treatment with either sertraline hydrochloride (n = 77) in flexible doses up to 200 mg or placebo (n = 84). PATIENTS: A total of 161 outpatients with chronic major or double depression who responded to sertraline in a 12-week, double-blind, acute-phase treatment trial and continued to have a satisfactory therapeutic response during a subsequent 4-month continuation phase. MAIN OUTCOME MEASURE: Time to recurrence of major depression. RESULTS: Sertraline afforded significantly greater prophylaxis against recurrence than did placebo (5 [6%] of 77 in the sertraline group vs 19 [23%] of 84 in the placebo group; P = .002 for the log-rank test of time-to-recurrence distributions). Clinically significant depressive symptoms reemerged in 20 (26%) of 77 patients treated with sertraline vs 42 (50%) of 84 patients who received placebo (P = .001). With use of a Cox proportional hazards model, patients receiving placebo were 4.07 times more likely (95% CI, 1.51-10.95; P = .005) to experience a depression recurrence, after adjustment for study site, type of depression, and randomization strata. CONCLUSIONS: Maintenance therapy with sertraline is well tolerated and has significant efficacy in preventing recurrence or reemergence of depression in chronically depressed patients.

The treatment of chronic depression, part 1: study design and rationale for evaluating the comparative efficacy of sertraline and imipramine as acute, crossover, continuation, and maintenance phase therapies.

BACKGROUND: Chronic depressions are common, disabling, and undertreated, and prior chronicity predicts future chronicity. However, few studies directly inform the acute or maintenance phase treatments of chronic depressions and even less is known about the effects of treatment on psychosocial functioning. METHOD: We describe the design and rationale for 2 parallel double-blind, randomized, multicenter acute and maintenance phase treatment trials. One focused on DSM-III-R major depression currently in a chronic (> or = 2 years) major depressive episode, the other on DSM-III-R major depression with concurrent DSM-III-R dysthymia ("double depression"). RESULTS: Considering the critical knowledge deficits, we designed a 12-week acute phase safety and efficacy trial of sertraline versus imipramine, followed by a 16-week continuation treatment phase for subjects with a satisfactory therapeutic response. Patients receiving sertraline who successfully completed the continuation phase entered a 76-week maintenance trial to compare sertraline with placebo; those taking imipramine continued without a placebo substitution. As part of the acute trial, subjects completing but failing to respond to the initial 12-week acute phase medication were crossed over (double-blind) to the alternative medication for a 12-week acute phase trial. We obtained naturalistic follow-up data (up to 18 months) for subjects exiting the protocol at any time. CONCLUSION: Multiphase protocols for chronic depression can test efficacy by randomized contrasts as well as shed light on key clinical issues such as the degree of response or attrition expected at particular times in a trial or the preferred medication sequence in a potential multistep treatment program.

The treatment of chronic depression, part 2: a double-blind, randomized trial of sertraline and imipramine.

BACKGROUND: Chronic depression appears to be a common, frequently disabling illness that is often inadequately treated. Unlike episodic depressions with shorter illness duration, neither acute nor long-term treatment approaches for chronic depression have been well studied. METHOD: 635 outpatients at 12 sites who met DSM-III-R criteria for chronic major depression or double depression were randomly assigned to 12 weeks of double-blind treatment with either sertraline (in daily doses of 50-200 mg) or imipramine (in daily doses of 50-300 mg). Efficacy and safety were assessed either weekly or every 2 weeks during the 12 weeks of acute treatment. RESULTS: Despite high rates of chronicity (mean duration of major depression = 8.9+/-9.1 years; mean duration of dysthymia = 23+/-13 years) and high rates of comorbidity, 52% of patients achieved a satisfactory therapeutic response to sertraline or imipramine (by a conservative, intent-to-treat analysis). Approximately 21% of the patients who had achieved a therapeutic response at week 12 had not done so at week 8, confirming the longer time to response in depressions with high chronicity. Patients treated with sertraline reported significantly fewer adverse events and were significantly less likely to discontinue treatment due to side effects than imipramine-treated patients (6.3% vs. 12.0%). CONCLUSION: These results indicate that patients suffering from depression with high chronicity can achieve a good therapeutic response to acute treatment with either sertraline or imipramine, although sertraline is better tolerated.

Symptomatology in dysthymic and major depressive disorder.

The lists of associated symptoms included in the DSM-III, DSM-III-R, and DSM-IV criteria for dysthymic disorder have been criticized for lacking content and discriminant validity. The literature on the content and discriminant validity of dysthymic symptoms was reviewed and relevant data from the DSM-IV Mood Disorders Field Trial were presented. These data indicate that cognitive and social-motivational symptoms are much more characteristic of dysthymic disorder than are vegetative and psychomotor symptoms. In addition, subjects with major depressive disorder exhibit higher rates of most depressive symptoms than do subjects with dysthymic disorder, but there is little evidence of qualitative distinctions in symptomatology between these conditions. Finally, after taking course and exclusion criteria into account, variations in the symptom criteria do not have a major effect on case definition.

Differential diagnosis of chronic depressive disorders.

This article has traced the development of the diagnostic nomenclature for the chronic affective disorders during the past four decades. Much has been accomplished. In fact, our current differential diagnostic capabilities have surpassed our knowledge of how to treat the chronic depressions. It is hoped that in the next decade there will be notable increases in the treatment efficacy literature of the chronic mild depressions. Next, we suggest that practitioners assist academic investigators in determining the best way to treat the chronic depressions. To realize this goal, clinicians must begin to view themselves as part-time researchers. Several technological procedures have been described to facilitate this undertaking. We suggest that the assumption of such a research practitioner role will, in the long run, improve the quality of patient care.

Results of the DSM-IV mood disorders field trial.

OBJECTIVE: The DSM-IV mood disorders field trial, a multisite collaborative study, was designed to explore the reliability of a course-based diagnostic classification system for major depression, evaluate the symptom criteria for dysthymia, and explore the need for additional diagnostic categories for milder forms of mood disorder (e.g., minor and recurrent brief depression). METHOD: Five hundred twenty-four depressed subjects were recruited from inpatient, outpatient, and community settings at five sites and evaluated with structured interviews according to DSM-III and DSM-III-R criteria, with careful attention to longitudinal course. Within- and across-site interrater reliability studies and 6-month test-retest reliability studies were also conducted on subsets of the sample. RESULTS: For evaluations of major depression and dysthymia, intrasite reliability was good to excellent and intersite reliability was fair to good; 6-month test-retest reliability was fair for dysthymia and poor to fair for major depression. Interrater reliability for six course of illness specifiers was fair to good, and almost all subjects could be assigned to a specific type of course. CONCLUSIONS: The results supported the use of a course-based classification system for major depression. They also suggested that the content validity of the DSM-III-R symptom criteria for dysthymia could be improved by emphasizing cognitive and social/motivational symptoms, although such changes are unlikely to sharpen the distinction between dysthymia and major depression. Finally, 91% of the subjects met the criteria for current or lifetime major depression or dysthymia, suggesting that additional categories for milder forms of depression are not needed.

Treatment of chronic depression with sertraline or imipramine: preliminary blinded response rates and high rates of undertreatment in the community.

Despite the prevalence of chronic depression and its associated morbidity, there has been little systematic study of pharmacotherapy for this disorder. In this article, we report a preliminary analysis of the first 12-week phase of a multicenter clinical trial that will eventually include approximately 635 patients in acute, continuation, crossover, and maintenance studies of sertraline, a selective serotonin reuptake inhibitor (SSRI), and imipramine, a tricyclic antidepressant, for the treatment of chronic depression. Of the first 212 patients to enter the study, 168 completed all 12 weeks; of these, 61.3 percent were responders, including 58.9 percent of the 73 patients with chronic major depression and 63.2 percent of the 95 patients with double depression. Only 26.8 percent of the 198 patients for whom such data were available had ever had an adequate trial of an antidepressant medication, defined as 150 mg/day of imipramine or its equivalent taken for at least 4 consecutive weeks. In general, demographic and diagnostic characteristics were more similar than different for patients with chronic major and double depression. However, comorbid generalized anxiety disorder was significantly more common in patients with chronic major depression (11.2% threshold for chronic versus 4.9% threshold for double depression, p = .02). The results of this study provide preliminary evidence of the responsiveness of patients with chronic major or double depression to an SSRI or a tricyclic antidepressant.

One-year prospective replication study of an untreated sample of community dysthymia subjects.

This study replicates an earlier naturalistic-prospective investigation of nontreatment, community DSM-III-R dysthymia subjects. Major goals were to determine spontaneous remission rates and monitor the stability of psychosocial functioning levels over time. Twenty-four dysthymia subjects were followed for 1 year. Three remissions (13%) were diagnosed at the final interview. At a 4-year diagnostic follow-up contact with the remitters only, one remitter had relapsed and two remained in remission. Subjects were monitored for depressive symptom intensity, personality functioning, general medical distress, cognitive functioning, coping stylistics, interpersonal functioning, quality of their social support resources, and general family functioning. Stable levels of psychosocial functioning were maintained across all measures over the 1-year period. Current psychometric findings confirm the conclusions of the earlier nontreatment prospective study that dysthymia is a chronic mood disorder with stable psychosocial features and is unlikely to remit spontaneously over time.

Comparison of a community dysthymia sample at screening with a matched group of nondepressed community controls.

The primary goal of the study was to compare the psychosocial functioning of an untreated, community sample of DSM-III-R dysthymia subjects (N = 24) at screening to that of a matched sample of community nondepressed volunteers (N = 18) with no lifetime or current history of axis I disorders. Subjects were compared across a number of psychosocial indices. The dysthymics were found to be less sociable (introversion) and clinically high on neuroticism-instability, external in regard to their causal attributions, less stable for positive uncontrollable events and more stable and global for negative uncontrollable events, relying more on coping strategies such as wishful thinking and self-blame, more interpersonally submissive and hostile, and to have a poorer social support-resource network. In addition, the dysthymics reported more family dysfunction and a higher rate of negative major life events.

Psychotherapy for dysthymia. A naturalistic study of ten patients.

Ten early and late onset dysthymia cases, diagnosed by DSM-III criteria, were treated with the Cognitive-Behavioral Analysis System of Psychotherapy, a standardized, three-stage therapy system developed specifically for the treatment of dysthymia. The cases are presented as naturalistic, direct-replication studies. Reliability of data trends within and across stages of treatment and generalization of effects across patients were demonstrated. The out-of-control depressive state at treatment outset is challenged by demonstrating to each patient that their depressive predicament is self-produced and maintained by maladaptive living strategies. The essential goals of therapy are teaching the patient a) to accept total responsibility for their depression and b) to achieve and maintain mood control by enacting adaptive daily living strategies. The progressive assumption of personal responsibility for the debilitative mood state is accompanied by a corresponding shift in a locus of control set from externality to internality. Patients were then taught situational coping strategies, and treatment ended when mood control was evinced. All cases were treated by J.P.M. The 10 cases met therapy termination criteria, and nine (one exception) were found in remission for dysthymia at follow-up of 2 years or more. Cognitive behavior psychotherapy, which directly attacks the helplessness and hopelessness plight of the dysthymic and teaches adaptive coping skills, appears to be an effective therapeutic strategy for the disorder.