Computer-aided neurocognitive remediation in schizophrenia: Durability of rehabilitation outcomes in a follow-up study

Cognitive deficits in patients with schizophrenia constitute a limiting factor to the chances of rehabilitation of daily living abilities, like personal and relational autonomy and working ability. Cognitive Remediation Therapy (CRT) is a rehabilitative technique that aims at the recovery of single cognitive functions through the execution of massive exercises of impaired cognitive domains. This study aims to establish if the results achieved through an intensive deficit-specific neurocognitive treatment of three months duration, were maintained over time. The sample consists in 100 patients diagnosed with schizophrenia according to the criteria of DSM IV. Patients were assessed on cognitive and daily functioning at baseline, after 3 months of either CRT or placebo training added to their standard rehabilitation treatment, at 6 month and 12-month follow-up. Results showed significant changes that were maintained at follow-up for executive function, attention and psychomotor coordination. Moreover the significant improvement in daily functioning was maintained at 6 and 12-month follow-up. In conclusion improvements in cognitive functions and daily functioning achieved through the association of CRT and standard rehabilitation treatment persist over time after the conclusion of the training period.     

A randomized single-blind pilot study of compensatory strategies in schizophrenia outpatients

In a previous study, we found that cognitive adaptation training (CAT)--a manual-driven program of environmental supports designed to bypass cognitive deficits--improved multiple domains of outcome in schizophrenia patients recently discharged from a State psychiatric facility. The present study examined the efficacy of CAT in a sample of patients who had been in the community at least 3 months. Forty-five medicated schizophrenia patients were randomly assigned for 9 months to one of three conditions: (1) CAT, (2) a condition that controlled for therapist time and provided environmental changes unrelated to cognitive deficits, or (3) follow-up only. Comprehensive assessments were conducted every 3 months by blinded raters. Results of repeated measures analyses of covariance for mixed models indicated that patients participating in CAT had better adaptive function and quality of life, and fewer positive symptoms than those in the two non-CAT conditions. Results indicate that compensatory strategies may improve various outcomes in schizophrenia outpatients.     

Family-directed cognitive adaptation pilot: Teaching cognitive adaptation to families of individuals with schizophrenia

ABSTRACT

Cognitive deficits are a major determinant of functional outcome in schizophrenia. A promising treatment involves teaching individuals to use cognitive adaptation strategies to minimize the functional impact of cognitive difficulties. We developed Family-Directed Cognitive Adaptation (FCA) to train caregivers to help their relatives with schizophrenia use cognitive adaptations to improve living skills. The goal of this open pilot trial was to examine the feasibility of FCA. Ten adults with schizophrenia, each with at least one relative, participated in FCA and were evaluated at baseline, posttreatment, and 6-month follow-up. Domains assessed included adaptive functioning, psychiatric symptoms, school/work involvement, hospitalizations, family burden, and treatment satisfaction. Participants reported high levels of satisfaction with FCA, and all families completed the 16-session intervention. Relatives reported reduced burden at termination and follow-up. No participants were hospitalized during the treatment or follow-up period, and rates of work/school involvement increased from 30% at baseline to 50% at the end of treatment and follow-up. Individuals improved in negative symptoms and adaptive functioning over the course of treatment, but these gains were not maintained. This pilot provides preliminary support for the acceptability and feasibility of FCA and points to the need to address the maintenance of treatment gains after termination.     

Course of cognitive functioning during the stabilization phase of schizophrenia

The present study aimed at examining the longitudinal course of neuropsychological impairments in schizophrenia patients during the stabilization phase of the illness. Cognitive functioning of 151 schizophrenia patients was assessed at baseline, 9-month, and 15-month follow-up with a comprehensive battery of cognitive tests. Cognitive performance of 40 matched controls was also examined at baseline and follow-up in order to control for effects of repeated testing. We found significant improvements in memory, attention, and global cognitive functioning from baseline to 9-month follow-up. Abstraction was stable at a relatively normal level. Global cognitive functioning remained at 9-month follow-up one standard deviation below normative level. Improvements in patients' cognitive performance between the 9-month and the 15-month follow-up were fewer and less pronounced. The present study implies that schizophrenia is a static encephalopathy with trait and state dependent cognitive components particularly in the attention and memory domain. The statistically and clinically significant cognitive improvements should be ground for clinical optimism.     

Social Cognition Enhancement Training for Schizophrenia: A Preliminary Randomized Controlled Trial

The purpose of this study was to evaluate whether social cognition enhancement training (SCET) is effective in improving social context appraisal and perspective-taking abilities of patients with schizophrenia. A total of 34 patients were randomly assigned to receive SCET plus standard psychiatric rehabilitation training or standard psychiatric rehabilitation training only. SCET was conducted twice weekly on a group basis for 6 months. Some social cognitive abilities were improved rapidly after 2-month treatment whereas some improved only after 6-month treatment. These results show promise for the impact of SCET on the social cognitive functioning of individuals with chronic schizophrenia, and further investigation is merited.Kee-Hong Choi and Jung-Hye Kwon are affiliated with the Department of Psychology, Korea University, Seoul, Korea     

A controlled trial of cognitive remediation in schizophrenia

A randomized, controlled trial of a 3-month cognitive remediation program was examined for its efficacy at ameliorating deficits in social and emotion perception in 42 hospitalized patients with schizophrenia. Generalization of training effects to attention, memory, and executive functioning was also examined. The program included an eclectic mix of self-instruction, memory enhancement, inductive reasoning, and compensatory training procedures, while the control condition included participation in a leisure group that was matched to the experimental group for staff involvement time. Patient care management, including type and dose of antipsychotic medication, remained constant throughout the study period. The results indicated that the cognitive training program improved emotion perception, with some evidence of generalization to measures of executive functioning; other areas of neurocognitive functioning were largely unaffected. While cognitive training programs may improve targeted areas of neurocognitive processing, broad generalization effects to domains outside those targeted for intervention are not likely concomitants.     

Multimodal Cognitive Therapy: Combining Treatments That Bypass Cognitive Deficits and Deal With Reasoning and Appraisal Biases

The process of recovery in schizophrenia involves resolving persistent symptoms, addressing cognitive impairments, and improving functional outcomes. Our research group has demonstrated the efficacy of cognitive adaptation training (CAT)—a home-based psychosocial treatment utilizing environmental supports such as medication containers, signs, checklists, and the organization of belongings to bypass deficits in cognitive functioning and cue and sequence adaptive behavior) for improving adherence to medications and functional outcomes in schizophrenia. Early CAT pilot studies utilizing some therapists with training in cognitive behavior therapy (CBT) techniques for psychosis found significant improvements in positive symptoms. More recent larger scale randomized clinical trials failed to replicate this finding with CAT therapists not trained in CBT techniques. Persistent psychotic symptoms substantially impair patients’ ability to adapt to life in the community. Cognitive behavior therapy for psychosis (CBTp) is an evidence-based practice for addressing persistent positive symptoms and the distress associated with them. CBTp decreases symptomatology and minimizes the negative effect of persisting symptoms upon individuals with this disorder. We now describe a home-delivered, multimodal cognitive treatment targeting functional outcomes and persistent positive symptoms for individuals with schizophrenia by utilizing both CAT and CBT techniques. We discuss the advantages and challenges of combining these 2 interventions, present a small retrospective data analysis to support their combination into a multimodal treatment, and describe the design of an ongoing randomized trial to investigate efficacy.     

Durability of cognitive remediation training in schizophrenia: performance on two memory tasks at 6-month and 12-month follow-up

Patients with schizophrenia have consistently been found to exhibit cognitive deficits, particularly in memory, which have been suggested to mediate functional outcomes. Several recent reviews of cognitive retraining have concluded that these deficits respond to training, although the sustainability of cognitive improvement following completion of training has not been adequately evaluated. Most studies had small samples and very short follow-up periods. As part of a larger study, we examined performance on two memory tasks in two groups of participants: those who received computerized cognitive remediation training in addition to work therapy (n=45), vs. those who only received work therapy (n=49). Computerized cognitive remediation included hierarchical training on a computerized digit span task and a computerized words serial position task. Assessments using the same computerized tasks were made at three time points: baseline, end of active intervention, and 6-month follow-up. Compared to the active control condition (work therapy only), the group receiving computerized cognitive remediation in addition to work therapy showed significantly greater improvements on the trained digit span task following training. These improvements were maintained at the 6-month follow-up. There were no significant group differences on the word serial position task at any time point. Results indicate that computerized training can lead to sustained improvements on some, but not all, training tasks.     

Cognitive functioning in young people with first episode psychosis: relationship to diagnosis and clinical characteristics

OBJECTIVE: To examine the extent and nature of neuropsychological deficits in adolescents and young people with first episode psychosis (FEP), and to determine whether the pattern and extent of neuropsychological deficits varied according to diagnosis. METHOD: A total of 83 FEP subjects aged 13-25 years, and 31 healthy controls completed a comprehensive battery of neuropsychological tests, grouped into 10 cognitive domains. First episode psychosis subjects were stratified into three diagnostic groups (schizophrenia, affective disorders, substance-induced psychosis) and differences in cognitive profiles were examined. The contribution of demographic and clinical characteristics to cognitive performance was also explored. RESULTS: The schizophrenia group demonstrated significantly worse performance on tasks of verbal learning and memory than the affective disorders group. Compared to healthy controls, the schizophrenia group also demonstrated global impairment across the majority of cognitive domains. The substance-induced group's performance lay between that of the schizophrenia and affective disorders groups. Analyses of differential deficits revealed that verbal learning, verbal memory and current intellectual functioning were selectively impaired in the schizophrenia group, whereas the affective disorders group demonstrated a selective deficit in speeded processing. Premorbid intellectual functioning, negative symptomatology and medication levels were the strongest predictors of cognitive performance in FEP subjects. CONCLUSIONS: Verbal memory deficits differentiate individuals with schizophrenia from those with psychotic affective disorders. Although significant cognitive deficits are evident across all diagnostic FEP groups, individuals with schizophrenia appear to have more generalized impairment across a broad array of cognitive functions than other psychotic diagnoses. Lower premorbid intellectual functioning does not appear to contribute to greater cognitive deterioration following onset of psychosis, but severity of illness may be a more important factor than levels of mood disturbance.     

A randomized controlled trial of cognitive-behavioral therapy for persistent symptoms in schizophrenia resistant to medication

BACKGROUND: Research evidence supports the efficacy of cognitive-behavioral therapy in the treatment of drug-refractory positive symptoms of schizophrenia. Although the cumulative evidence is strong, early controlled trials showed methodological limitations. METHODS: A randomized controlled design was used to compare the efficacy of manualized cognitive-behavioral therapy developed particularly for schizophrenia with that of a nonspecific befriending control intervention. Both interventions were delivered by 2 experienced nurses who received regular supervision. Patients were assessed by blind raters at baseline, after treatment (lasting up to 9 months), and at a 9-month follow-up evaluation. Patients continued to receive routine care throughout the study. An assessor blind to the patients' treatment groups rated the technical quality of audiotaped sessions chosen at random. Analysis was by intention to treat. RESULTS: Ninety patients received a mean of 19 individual treatment sessions over 9 months, with no significant between-group differences in treatment duration. Both interventions resulted in significant reductions in positive and negative symptoms and depression. At the 9-month follow-up evaluation, patients who had received cognitive therapy continued to improve, while those in the befriending group did not. These results were not attributable to changes in prescribed medication. CONCLUSION: Cognitive-behavioral therapy is effective in treating negative as well as positive symptoms in schizophrenia resistant to standard antipsychotic drugs, with its efficacy sustained over 9 months of follow-up.     

慢性精神分裂症住院患者辅以认知矫正治疗的随机对照研究(英文)

背景 认知矫正治疗(Cognitive Remediation Therapy,CRT)是一种很有希望的、新的非药物治疗方法,能够减少精神分裂症患者的认知缺损。但未在国内得到充分的验证。目的 探讨认知矫正治疗对慢性精神分裂症患者认知功能、社会功能及自知力的疗效。方法 将126例病情相对稳定的慢性精神分裂症住院患者随机分成干预组和对照组。干预组接受行认知矫正治疗,对照组接受常规的工娱治疗,两组在治疗频度和治疗持续时间一致,均为每周5次,共3个月。于治疗前及治疗末分别采用威斯康星卡片分类测验(Wisconsin Card Sorting Test,WCST)评估认知功能,采用住院慢性精神分裂症患者社会功能评定量表(Scale of Social Skills of chronic schizophrenia Inpatients,SSSI)评估社会功能以及采用自知力与治疗态度问卷(Insight and Treatment Attitude Questionnaire,ITAQ)评估自知力。结果 研究过程中有4例患者脱落,干预组60例、对照组62例最终进入结果分析。治疗3个月后,两组的WCST测评结果均较治疗前显著改善,而干预组的WCST各指标的改善均比对照组明显。两组在3个月治疗后的SSSI总分均显著改善,但改善程度在两组间无显著性差异;两组的ITAQ总分也均有提高,但干预组的改善程度比对照组更明显。结论 在药物治疗的基础上,为期3个月的认知矫正治疗对改善慢性精神分裂症住院患者的认知功能及自知力比常规的工娱治疗更为有效。     

The use of individually tailored environmental supports to improve medication adherence and outcomes in schizophrenia

Cognitive adaptation training (CAT) is a psychosocial treatment that uses environmental supports such as signs, checklists, alarms, and the organization of belongings to cue and sequence adaptive behaviors in the home. Ninety-five outpatients with schizophrenia (structured clinical interview for diagnosis, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) were randomly assigned to (1) Full-CAT (CAT focused on many aspects of community adaptation including grooming, care of living quarters, leisure skills, social and role performance, and medication adherence), (2) Pharm-CAT (CAT focused only on medication and appointment adherence), or (3) treatment as usual (TAU). Treatment lasted for 9 months, and patients were followed for 6 months after the withdrawal of home visits. Medication adherence (assessed during unannounced, in-home pill counts) and functional outcomes were assessed at 3-month intervals. Results of mixed-effects regression models indicated that both CAT and Pharm-CAT treatments were superior to TAU for improving adherence to prescribed medication (P < .0001). Effects on medication adherence remained significant when home visits were withdrawn. Full-CAT treatment improved functional outcome relative to Pharm-CAT and TAU (P < .0001). However, differences for functional outcome across groups decreased following the withdrawal of home visits and were no longer statistically significant at the 6-month follow-up. Survival time to relapse or significant exacerbation was significantly longer in both CAT and Pharm-CAT in comparison to TAU (.004). Findings indicate that supports targeting medication adherence can improve and maintain this behavior. Comprehensive supports targeting multiple domains of functioning are necessary to improve functional outcomes. Maintenance of gains in functional outcome may require some form of continued intervention.     

Neuropsychological predictors of functional outcome in Cognitive Behavioral Social Skills Training for older people with schizophrenia

Cognitive Behavioral Social Skills Training (CBSST) is a 24-session weekly group therapy intervention to improve functioning in people with schizophrenia. In our prior randomized clinical trial comparing treatment as usual (TAU) with TAU plus group CBSST (Granholm, E., McQuaid, J.R., McClure, F.S., Auslander, L., Perivoliotis, D., Pedrelli, P., Patterson, T., Jeste, D.V., 2005. A randomized controlled trial of cognitive behavioral social skills training for middle-aged and older outpatients with chronic schizophrenia. Am. J. Psychiatry 162, 520–529.), participants with schizophrenia in CBSST showed significantly better functional outcome than participants in TAU. The present study was a secondary analysis of neuropsychological predictors of functional outcome in our prior CBSST trial. We examined (1) whether neuropsychological impairment at baseline moderated functional outcome in CBSST relative to TAU, and (2) whether improvement in neuropsychological abilities mediated improvement in functional outcome in CBSST. Attention, verbal learning/memory, speed of processing, and executive functions were assessed at baseline, end of treatment, and 12-month follow-up. Greater severity of neuropsychological impairment at baseline predicted poorer functional outcome for both treatment groups (nonspecific predictor), but the interaction between severity of neuropsychological impairment and treatment group was not significant (no moderation). Effect sizes for the difference between treatment groups on functional outcome measures at 12-month follow-up were similar for participants with relatively mild (d = .44–.64) and severe (d = .29–.60) neuropsychological impairment. Results also did not support the hypothesis that improvement in neuropsychological abilities mediated improvement in functioning in CBSST. Adding CBSST to standard pharmacologic care, therefore, improved functioning relative to standard care alone, even for participants with severe neuropsychological impairment, and this improvement in functioning was not related to improvement in neuropsychological abilities in CBSST.     

A randomized, controlled trial of cognitive behavioral social skills training for middle-aged and older outpatients with chronic schizophrenia

OBJECTIVE: The number of older patients with chronic schizophrenia is increasing. There is a need for empirically validated psychotherapy interventions for these patients. Cognitive behavioral social skills training teaches cognitive and behavioral coping techniques, social functioning skills, problem solving, and compensatory aids for neurocognitive impairments. The authors compared treatment as usual with the combination of treatment as usual plus cognitive behavioral social skills training. METHOD: The randomized, controlled trial included 76 middle-aged and older outpatients with chronic schizophrenia, who were assigned to either treatment as usual or combined treatment. Cognitive behavioral social skills training was administered over 24 weekly group sessions. Blind raters assessed social functioning, psychotic and depressive symptoms, cognitive insight, and skill mastery. RESULTS: After treatment, the patients receiving combined treatment performed social functioning activities significantly more frequently than the patients in treatment as usual, although general skill at social functioning activities did not differ significantly. Patients receiving cognitive behavioral social skills training achieved significantly greater cognitive insight, indicating more objectivity in reappraising psychotic symptoms, and demonstrated greater skill mastery. The overall group effect was not significant for symptoms, but the greater increase in cognitive insight with combined treatment was significantly correlated with greater reduction in positive symptoms. CONCLUSIONS: With cognitive behavioral social skills training, middle-aged and older outpatients with chronic schizophrenia learned coping skills, evaluated anomalous experiences with more objectivity (achieved greater cognitive insight), and improved social functioning. Additional research is needed to determine whether cognitive insight mediates psychotic symptom change in cognitive behavior therapy for psychosis.     

A Randomized Trial Comparing In Person and Electronic Interventions for Improving Adherence to Oral Medications in Schizophrenia

Poor adherence to medication leads to symptom exacerbation and interferes with the recovery process for patients with schizophrenia. Following baseline assessment, 142 patients in medication maintenance at a community mental health center were randomized to one of 3 treatments for 9 months: (1) PharmCAT, supports including pill containers, signs, alarms, checklists and the organization of belongings established in weekly home visits from a PharmCAT therapist; (2) Med-eMonitor (MM), an electronic medication monitor that prompts use of medication, cues the taking of medication, warns patients when they are taking the wrong medication or taking it at the wrong time, record complaints, and, through modem hookup, alerts treatment staff of failures to take medication as prescribed; (3) Treatment as Usual (TAU). All patients received the Med-eMonitor device to record medication adherence. The device was programmed for intervention only in the MM group. Data on symptoms, global functioning, and contact with emergency services and police were obtained every 3 months. Repeated measures analyses of variance for mixed models indicated that adherence to medication was significantly better in both active conditions than in TAU (both p<0.0001). Adherence in active treatments ranged from 90–92% compared to 73% in TAU based on electronic monitoring. In-person and electronic interventions significantly improved adherence to medication, but that did not translate to improved clinical outcomes. Implications for treatment and health care costs are discussed.Key words: medication adherence, medication compliance, cognitive adaptation, training, environmental supports, electronic adherence intervention, smart, pill containers     

Development of specific social skills training programmes for schizophrenia patients: results of a multicentre study

OBJECTIVE: The efficacy of three newly developed cognitive social skills training programmes for residential, vocational and recreational functioning (experimental groups) were compared with a traditional social skills training programme (control group) referring to cognitive and social abilities, psychopathology and generalisation effects. METHOD: One hundred and five patients with a diagnosis of schizophrenia or schizoaffective disorder according to ICD-10 criteria were selected and assigned to the different treatment groups, using a matching procedure. The treatment phase lasted 6 months. A follow-up assessment was carried out after 1 year. RESULTS: Higher global therapy effects were obtained on almost all dependent variables in the experimental groups. Analyses of variance and covariance indicated higher symptom reduction for the experimental groups, but significantly greater improvements in some cognitive variables for the control group. Correlation analysis suggested associations between improvement of social behaviour with symptom reduction and improvements of cognitive skills. CONCLUSION: In view of these favourable effects, the developed cognitive social skills training programmes might facilitate the abilities of schizophrenia patients for their integration in the community.     

Cognitive Deficits and Psychiatric Rehabilitation Outcomes in Schizophrenia

Many patients with schizophrenia are characterized by cognitive deficits that limit their ability to benefit from psychiatric rehabilitation interventions. While this suggests that cognitive rehabilitation is important, more needs to be known about which cognitive deficits interfere with which aspects of outcome and functioning before effective interventions are developed. We report data on cognitive predictors of three types of outcome: acquisition and performance of skills in a skills training group; aspects of daily ward functioning; and ability to be discharged from a state hospital. Our data indicate that poorer outcomes in each of these areas are associated with different, but somewhat overlapping, profiles of cognitive deficits. These data are relevant for designing both ward-based and individualized interventions. Integrating traditional psychiatric rehabilitation approaches with targeted cognitive interventions is necessary to maximize the impact of psychiatric rehabilitation services on individuals with chronic schizophrenia.     

Effects of new cognitive-behavioral therapy programs for improvement of specific social skills of schizophrenics--a controlled study

Based on the Integrated Psychological Therapy (IPT) for schizophrenia patients, the Berne group developed three specific cognitive behaviour therapy programmes for treating residential, vocational, and recreational functioning. We added new cognitive-emotional methods to these programmes that were devised especially for schizophrenia patients, taking into consideration the criticism of traditional social skill training methods. In the present multicentre study, these new programmes (experimental group) were compared with a traditional social skills training programme (control group, IPT "Social Skills" subprogramme). Both the therapy and aftercare phase each lasted 12 weeks and the follow-up phase 1 year. Assessment instruments covered psychopathology, cognitive functioning, and social adjustment. Higher ratings of global treatment effects and significant reductions in symptoms were obtained in the experimental group. In view of the favourable results, these newly designed social skill training programmes may replace more conventional therapy approaches in the future.     

Stability of adaptive behaviors in middle-school children with autism spectrum disorders

This 5-year follow-up study examined the stability of adaptive functioning in two cognitive ability groups of children with an autism spectrum disorder (ASD). Nonverbal intelligence (NVIQ) was assessed at the time of this study and no participant changed cognitive group membership from the previous study (High NVIQ ≥ 97; Low NVIQ ≤ 56). In each group, adaptive skills, as measured by the Vineland Adaptive Behavior Scales (VABS) composite standard score, were significantly below NVIQ. Both groups exhibited a significant decrease in the VABS composite standard scores over time, but analysis of VABS total raw scores showed a significant increase in adaptive functioning over time in the High NVIQ group with no change in the Low NVIQ group. Examining the profile of VABS age equivalent scores in each NVIQ group revealed potential suggestions for interventionists. Caregivers of the Low NVIQ group endorsed having significantly higher stress levels related to their child's level of adaptive functioning. Groups did not differ significantly in the quantity of treatment received within the 9 months preceding this study or caregiver satisfaction with intervention services. Caregivers from both groups identified a variety of school-based service needs to address their child's adaptive skill deficits.     

Are the effects of cognitive remediation therapy (CRT) durable? Results from an exploratory trial in schizophrenia

BACKGROUND: This paper investigates the durability of the effects of cognitive remediation therapy (CRT). In a randomised control trial, CRT was compared with a control therapy (intensive occupational therapy activities), matched for length of therapist contact. The main three cognitive outcomes, (i) number of categories achieved on the Wisconsin Card Sort Test, (ii) age-scaled score on the Digit Span subtest of the WAIS-R, and (iii) mean number of moves on the Tower of London test, were chosen because they are known to be problematic in schizophrenia. In addition, a wide variety of other outcomes (symptoms, social functioning, self-esteem and cognition) were assessed. At the end of treatment, CRT conferred a benefit to people with schizophrenia in cognition and self-esteem [Schizophr. Bull. 25 (1999) 291]. This study investigates these outcomes 6 months after the therapies were withdrawn. METHOD: Participants were assessed at baseline, posttreatment and 6-month follow-up (n=17 for the CRT group; n=16 for the control therapy group). In addition to the functioning measures, data on use of services and cost of therapy were collected. RESULTS: The effects of CRT on cognition were still apparent at follow-up, particularly in the memory domain. When these cognitive improvements reached a criterion threshold, there were also improvements in social behaviour and symptoms. The gains made in self-esteem disappeared following the withdrawal of therapy. The economic analysis showed overall reductions in the care packages of both patient groups but there was a significant increase in day-care costs for patients who have received CRT. This additional use of day care may confer further advantages to the CRT group, such as improved social functioning and quality of life. CONCLUSIONS: The overall results of this first trial of a novel CRT approach have produced encouraging results which merit further investigation.