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A randomized controlled trial of the use of self-help materials in addition to standard general practice treatment of depression compared to standard treatment alone.

BACKGROUND: The purpose of the study was to examine whether the addition of a brief individual self-help package to standard primary-care treatment of depression with antidepressants is associated with any additional improvements in clinical outcome. METHOD: Individuals with major depressive disorder who were prescribed an antidepressant were recruited through their general practitioner (GP) and allocated randomly to standard treatment alone or standard treatment plus self-help. Assessments of symptoms, social adjustment, global functioning, satisfaction with treatment and knowledge about the management of the disorder were completed at three time points over 26 weeks. RESULTS: One hundred and twelve individuals agreed to participate and 96 met criteria for inclusion in the randomized controlled trial. Subjects in both treatment conditions improved substantially over the study period; the mean Beck Depression Inventory (BDI) score fell from 27.3 to 13.9 in the intention-to-treat analysis. There were no between group differences in outcome on any of the primary outcome measures, nor did these approach even marginal significance. Patients and GPs were highly satisfied with the self-help programme, and the intervention as compared to the control group reported significantly greater improvements in knowledge about depression and satisfaction with information received about depression. CONCLUSIONS: An individualized self-help package improved perceived knowledge about depression but did not have identifiable effects on outcome when offered to patients treated in primary care. The study was sufficiently well powered to detect relatively small effects.

Adolescent↗

The role of exposure with response prevention in the cognitive-behavioural therapy for bulimia nervosa.

BACKGROUND: One hundred and thirty-five women with bulimia nervosa participated in a randomized clinical trial designed to determine whether the addition of exposure with response prevention to a core of cognitive-behavioural therapy (CBT) leads to greater clinical improvement and lower risk of relapse. We present results from the end of treatment and 6- and 12-month follow-up. METHODS: Participants received eight sessions of CBT and were then randomized to either exposure to pre-binge cues (B-ERP), exposure to pre-purge cues (P-ERP), or a relaxation training control condition (RELAX). RESULTS: CBT produced significant clinical change. At the end of the behavioural treatments, there were no significant differences across the three groups on abstinence (66% in B-ERP, 45% in P-ERP and 47% in RELAX), or frequency of bingeing and purging. B-ERP, but not P-ERP, significantly reduced anxiety on the cue reactivity assessment, food restriction, body dissatisfaction and depression. These differences were not maintained at 6-month follow-up. At 12-months, B-ERP was independently associated with lower food restriction and better global functioning. CONCLUSIONS: CBT is a highly effective treatment for bulimia nervosa. B-ERP was modestly superior to P-ERP at post-treatment; however, the advantage did not remain throughout the follow-up interval. ERP for bulimia nervosa is an expensive and logistically complicated treatment that does not appear to offer any significant additive benefits that are proportional to the amount of effort required to implement the treatment.

Adolescent↗

Butyrylcholinesterase: an important new target in Alzheimer's disease therapy.

Acetylcholinesterase (AChE) predominates in the healthy brain, with butyrylcholinesterase (BuChE) considered to play a minor role in regulating brain acetylcholine (ACh) levels. However, BuChE activity progressively increases in patients with Alzheimer's disease (AD), while AChE activity remains unchanged or declines. Both enzymes therefore represent legitimate therapeutic targets for ameliorating the cholinergic deficit considered to be responsible for the declines in cognitive, behavioral and global functioning characteristic of AD. The two enzymes differ in substrate specificity, kinetics and activity in different brain regions. Experimental evidence from the use of agents with enhanced selectivity for BuChE (cymserine analogues, MF-8622) and the dual inhibitor of both AChE and BuChE, rivastigmine, indicates potential therapeutic benefits of inhibiting both AChE and BuChE in AD and related dementias. Recent evidence suggests that both AChE and BuChE may have roles in the aetiology and progression of AD beyond regulation of synaptic ACh levels. The development of specific BuChE inhibitors and further experience with the dual enzyme inhibitor rivastigmine will improve understanding of the aetiology of AD and should lead to a wider variety of potent treatment options.

Acetylcholine↗

Impact of rivastigmine on costs and on time spent in caregiving for families of patients with Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) places a significant burden on health care systems worldwide. As new treatments are developed, their cost-effectiveness is often assessed to help health care professionals make informed decisions. In addition to the more common practice of assessing direct medical costs, indirect costs, including time spent in caregiving, should be evaluated. METHODS: This study examined the potential effects of the dual cholinesterase inhibitor rivastigmine (Exelon) on caregivers of patients with AD. Results from two 26-week, placebo-controlled trials have demonstrated the clinically relevant and statistically significant efficacy of rivastigmine (6-12 mg/day) compared to placebo, on cognition, activities of daily living, and global functioning. By delaying progression of AD, significant savings in caregiver burden are anticipated, as measured by time spent caregiving and its related costs. Data collected in a prospective, observational study of AD patients and their caregivers were used to establish the relationship between disease severity (based on Mini-Mental State Examination [MMSE] score) and time spent caregiving (according to the 5-item Caregivers Activity Survey score). A significant correlation was observed between the two scores (N = 43, r = -.56, p < .0001), demonstrating that more time for supervision from caregivers is required as the disease progresses. This finding was used to estimate the reduced caregiver burden resulting from the delay in disease progression that was demonstrated with use of rivastigmine. RESULTS: Over a 2-year period, the reduction in time spent in caregiving reached 691 hours for caregivers of patients with mild AD (MMSE score 21-30), resulting in a total savings of approximately 11,253 dollars. Treatment of patients with moderately severe AD was also evaluated. The trend was similar but the impact was less, suggesting an economic benefit to early therapy. CONCLUSION: Early diagnosis and a pharmacologic intervention that allows the patients to remain at home longer by delaying disease progression would have a beneficial impact on patients, caregivers, and payers, and should therefore be encouraged through initiatives designed to identify and treat patients early in the course of disease.

Activities of Daily Living↗

The differing prognostic utility of exercise radionuclide ventriculography in coronary artery disease patients with and without prior myocardial infarction.

UNLABELLED: Previous studies have documented the prognostic utility of left ventricular ejection fraction response to exercise primarily in populations without prior myocardial infarction. We undertook a study to assess the prognostic utility of exercise left ventricular ejection fraction and segmental wall motion response during exercise radionuclide ventriculography in coronary artery disease patients with and without prior myocardial infarction. METHODS: We examined the comparative prognostic utility of left ventricular ejection fraction and segmental wall motion response during upright bicycle exercise radionuclide ventriculography in 419 coronary artery disease patients with (n = 217) and without (n = 202) prior myocardial infarction using univariate and multivariate hierarchical regression analyses. RESULTS: During an average followup period of 61 months, 96 patients (23%) suffered cardiac events, including 55/217 (25%) of the patients with prior myocardial infarction and 41/200 (21%) of the patients without prior myocardial infarction (p = ns). Both cumulative Kaplan-Meier survival analyses and stepwise hierarchical Cox survival analyses demonstrated that peak left ventricular ejection fraction < 55% was a significant predictor of cardiac events in patients without prior myocardial infarction (p = 0.04), whereas an exercise wall motion worsening score > or = 2 was a significant predictor in patients with a prior myocardial infarction (p = 0.0001). CONCLUSIONS: The prognostic utility of exercise radionuclide ventriculography variables differ according to the presence or absence of prior myocardial infarction. Global function, assessed by peak left ventricular ejection fraction, adds the greatest prognostic information in patients without prior myocardial infarction, whereas regional function, assessed by exercise wall motion worsening, is the best predictor among patients with prior myocardial infarction.

Adult↗

Health-related quality of life and sequelae in patients treated with brachytherapy and external beam irradiation for localized prostate cancer.

PURPOSE: To evaluate late physical and psychosocial sequelae in patients treated with an association of external beam irradiation (EBI) and brachytherapy (BT) for localized prostate cancer. PATIENTS AND METHODS: Seventy-one patients free of disease, treated at the Centre François Baclesse from 1988 to 1992, were enrolled in a case-control study. Seventy-one healthy controls, matched on age and residence, were selected at random from electoral rolls. Two self-administered questionnaires were mailed in January 1996. The French translation of the Nottingham Health Profile questionnaire and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 core questionnaire were used to evaluate physical, role, emotional, cognitive and social functioning, global health status as well as energy and sleep disturbance. Specific problems related to prostate cancer were explored using the prostate specific module developed by the EORTC Genito-Urinary Tract Cancer Cooperative Group. Concordance between clinical complications reported by patients and those reported by physicians was also analyzed. RESULTS: General health quality of life scale scores did not significantly differ between patients and controls, nor did general symptom scale scores. Furthermore, no more late psychosocial sequelae were reported by patients than by controls. No major digestive complications were observed among patients. However, statistical differences were observed concerning interest in sex (P = 0.016) and sexual activity (P < 0.001), urinary incontinence (P < 0.001) and cystitis (P = 0.01). Late subjective morbidity (dysuria, nocturia, urinary incontinence, pelvic pain) appraisal differed slightly between patients and physicians who generally underestimate its severity. While nocturia was reported more often by physicians than by patients (P = 0.0016), patients reported urinary incontinence and pelvic pain more often than physicians (P < 0.001 and P < 0.001, respectively). CONCLUSIONS: The study demonstrates that survivors from localized prostate cancer treated with an association of BT and EBI have good global health status. Major problems that persist are sexual disorders, urinary incontinence and cystitis while digestive disorders were rare. This association could be an alternative to standard EBI in patients with localized prostate cancer. Whatever the treatment choice, patients should be involved in the therapeutic decision which should consider not only expected survival rate but also quality of life.

Aged↗

Recovery as a psychological construct.

Mental health advocates have proposed recovery as a vision for severe mental illness. The purpose of this study is to examine psychometric characteristics of a measure of the psychological construct. Thirty-five participants in a partial hospitalization program were administered the Recovery Scale and measures of quality of life, social support, self-esteem, consumer empowerment, psychiatric symptoms, needs and resources, global functioning, and verbal intelligence. Results showed the scale to have satisfactory test-retest reliability and internal consistency. Analysis of the concurrent validity of the Recovery Scale showed recovery to be positively associated with self-esteem, empowerment, social support, and quality of life. It was inversely associated with psychiatric symptoms and age. Implications of these findings for a psychological model of recovery are discussed.

Adult↗

Continuity and intensity of care among women receiving outpatient care for PTSD.

Continuity of care (COC) is often used as an indicator of treatment quality for patients with severe psychiatric or addictive disorders. However, few studies have examined the relationship between measures of COC and treatment outcomes. This study used standard regression models to examine the strength of the association between continuity of care measures and health outcomes for a sample of female veterans newly entering outpatient treatment for PTSD. There were few consistently significant associations between COC and outcome measures. Four months following program entry only one measure of treatment process, commitment to treatment, was positively associated with one or more continuity of care measures and several COC measures were associated with poor outcomes. Eight months following program entry patients with greater COC during the first four months of treatment had greater declines in violent behavior and PTSD measurements and larger increases in global functioning. However, when a Bonferonni corrected alpha of P < .001 was used to adjust for multiple comparisons, none of the relationships remained statistically significant. Thus, this study provides only weak and inconsistent evidence of the clinical benefits of continuity of care.

Adult↗

The perception of needs for care in staff and patients in community-based mental health services. The South-Verona Outcome Project 3.

OBJECTIVE: The present study aims to assess needs for care rated by patients and staff and their agreement on needs assessment in a community-based mental health service by using the Camberwell Assessment of Need (CAN). METHOD: The Italian version of the CAN was used in a sample of 247 patient-staff pairs. RESULTS: Patients and staff showed poor agreement on both the presence of a need and on whether need had been met or not. Higher disability predicted a higher number of patient-rated needs, while higher disability, higher number of service contacts and patient unemployment predicted a higher number of staff-rated needs. Lower global functioning predicted higher disagreement in patients and staff ratings of needs. CONCLUSION: Patients and staff show different perceptions of needs for care and therefore multiple perspectives should be taken into account for planning and providing effective needs-led mental health care.

Adult↗

Duration of untreated psychosis and its correlates in first-episode psychosis in Finland and Spain.

OBJECTIVE: To examine the association of duration of untreated psychosis (DUP) with early course characteristics in first-episode psychosis in Finland and Spain. METHOD: Eighty-six patients from Finland (49) and Spain (37) were evaluated on various early course characteristics. RESULTS: The mean value of DUP was 4.0 months (median 2 months) for the Finnish patients and 9.9 months (median 2 months) for the Spanish ones. In both groups, long DUP was associated with insidious onset, poor global functioning, and laboral incapability. Among the Finnish patients exclusively, long DUP correlated with a weak earlier social network, instability of professional identity, long duration of prodromal symptoms, psychological dependency on the family, and criticism by the parents of the patient. Among the Spanish patients only, longer DUP was associated with more severe positive symptoms at admission. CONCLUSION: There are universal psychosocial factors influencing DUP, but also cultural differences may have an impact on the treatment delay.

Adolescent↗

Electrodermal activity and clinical status in chronic schizophrenia.

The present study investigated the association between electrodermal nonresponsiveness and clinical state in schizophrenia. Sixty-three patients with a DSM-III diagnosis of chronic schizophrenia served as subjects. Clinical status was assessed using multiple measures, including age of onset, symptom severity, illness duration, hospitalization history, global functioning, and occupational functioning. Electrodermal hypoactivity was found to be associated with poorer functioning and a more severe form of illness. In addition, hyporesponsive patients displayed more conceptual disorganization and alogia.

Adolescent↗

Effectiveness of targeting the vulnerability factors of depression in cognitive therapy.

I. H. Gotlib and C.L. Hammen's (1992) psychopathology model of depression was used as a conceptual framework for studying the process of change in an effective course of cognitive therapy (CT) for depression. Archived CT transcripts from 30 depressed outpatients in the Cognitive-Pharmaco-therapy Treatment project (S. D. Hollon et al., 1992) were studied. An observational coding system was used to assess whether therapists focused on the cognitive, interpersonal, and developmental vulnerabilities of depression and whether these interventions were associated with symptom reduction. Therapists maintained a primarily cognitive focus, but it was interventions that addressed the interpersonal and developmental domains that were associated with improvement. A developmental focus also predicted a longer time of recovery and better global functioning over the 24-month followup period. These findings are consistent with recent theoretical developments in cognitive therapy and with the psychopathology research on depression.

Adaptation, Psychological↗

Predictors of homicidal ideation and intent in schizophrenia: an empirical study.

Correlations of age, gender, and psychosocial variables with ratings of current homicidal ideation and intent were investigated among psychiatric facility clients with schizophrenia. Multiple regression analyses revealed, irrespective of age or gender, significantly positive correlations of three psychosocial variables--manic symptoms, psychotic symptoms, and impaired global functioning--with homicidal ideation and intent. Implications for research are discussed.

Adolescent↗

Mental health in adolescence: is America's youth flourishing?

A continuous assessment and a categorical diagnosis of the presence of mental health, described as flourishing, and the absence of mental health, characterized as languishing, are proposed and applied to data from the second wave of the Child Development Supplement (CDS-II) of the Panel Study of Income Dynamics (PSID), in which a comprehensive set of subjective well-being items were administered to a sample of 1,234 youth ages 12-18. Flourishing was the most prevalent diagnosis among youth ages 12-14; moderate mental health was the most prevalent diagnosis among youth ages 15-18. Depressive symptoms decreased as mental health increased. Prevalence of conduct problems (arrested, skipped school, alcohol use, cigarette smoking, and marijuana use) also decreased and measures of psychosocial functioning (global self-concept, self-determination, closeness to others, and school integration) increased as mental health increased. Findings suggest the importance of positive mental health in future research on adolescent development.

Adolescent↗

Patients' versus informants' reports of personality disorders in predicting 7 1/2-year outcome in outpatients with depressive disorders.

Concordance between patients' and informants' reports of personality disorders (PDs) is low, raising the questions of which source provides more valid data and whether both contribute unique information. This study compared patients' and informants' reports of PDs in predicting outcome in a 7 1/2-year follow-up of 85 depressed outpatients. Patients and informants were independently evaluated using structured interviews; outcome was assessed using structured interviews with patients. Both patients' and informants' reports of PD diagnoses and dimensional scores independently predicted depression symptoms and global functioning at follow-up. However, only informants' reports made a unique contribution to predicting social adjustment. This finding indicates that both patients and informants provide unique information on Axis II psychopathology and argues for the use of both sources in the assessment of PDs.

Adult↗

Intensive day program for psychiatrically disturbed truant adolescents.

Results of a day treatment program tailored to psychiatrically disturbed truant adolescents were compared to those of traditional outpatient treatment for effects on truancy, psychiatric symptoms, global improvement, and global functioning. Significantly greater reductions of truancy were found in the day treatment program, along with significantly greater improvement in the other factors measured.

Absenteeism↗

A pilot study of MVP (mitomycin-C, vinblastine and cisplatin) chemotherapy in small-cell lung cancer.

MVP chemotherapy (mitomycin C 8 mg m(-2), courses 1, 2, 4 and 6, vinblastine 6 mg m(-2), cisplatin 50 mg m(-2)) is an active low-toxicity regimen in non-small-cell lung cancer (NSCLC). Based on the single-agent activity of these agents in SCLC, we have conducted a phase II trial of MVP in SCLC. Fifty chemo-naive patients with SCLC were entered in this trial. There were 33 men and 17 women with median age 66 years (range 46-83 years); 18 patients had limited disease (LD) and 32 extensive disease (ED). WHO performance status (PS) was: three patients PS 0, 33 patients PS 1, ten patients PS 2, four patients PS 3. A maximum of six cycles was given in responding patients. On completion of chemotherapy, patients with LD obtaining complete response (CR)/good partial response (PR) received thoracic irradiation and those obtaining CR were offered entry into the ongoing MRC Prophylactic Cranial Irradiation Trial. The overall response was 79% with 17% CR and 62% PR. For LD patients, 38% obtained CR but for ED only one patient achieved CR. Median response duration for LD patients was 8 months and for ED patients 5 months. Median survival was 10 months for LD patients and 6 months for ED patients. There was complete resolution of symptoms in 24%, partial improvement in 68%, no change in 2% and progressive symptoms in 6%. As regards toxicity, 24% developed WHO grade 3/4 neutropenia, 16% grade 3/4 thrombocytopenia and 6% significant hair loss. Two patients died during the first week of treatment with neutropenic infection. Quality of life using the EORTC questionnaire (QLC-C30) with lung cancer module demonstrated significant improvements from baseline levels in emotional and cognitive functioning, global QOL, of pain, dyspnoea and cough. MVP, an effective palliative regimen for NSCLC, is also active against SCLC with low toxicity and merits comparison with more toxic conventional schedules.

Aged↗

Global organization of metabolic fluxes in the bacterium Escherichia coli.

Cellular metabolism, the integrated interconversion of thousands of metabolic substrates through enzyme-catalysed biochemical reactions, is the most investigated complex intracellular web of molecular interactions. Although the topological organization of individual reactions into metabolic networks is well understood, the principles that govern their global functional use under different growth conditions raise many unanswered questions. By implementing a flux balance analysis of the metabolism of Escherichia coli strain MG1655, here we show that network use is highly uneven. Whereas most metabolic reactions have low fluxes, the overall activity of the metabolism is dominated by several reactions with very high fluxes. E. coli responds to changes in growth conditions by reorganizing the rates of selected fluxes predominantly within this high-flux backbone. This behaviour probably represents a universal feature of metabolic activity in all cells, with potential implications for metabolic engineering.

Escherichia coli↗