Exercise therapy and cognitive behavioural therapy to improve fatigue,daily activity performance and quality of life in Postpoliomyelitis Syndrome: the protocol of the FACTS-2-PPS trial

Background  

Postpoliomyelitis Syndrome (PPS) is a complex of late onset neuromuscular symptoms with new or increased muscle weakness and muscle fatigability as key symptoms. Main clinical complaints are severe fatigue, deterioration in functional abilities and health related quality of life. Rehabilitation management is the mainstay of treatment. Two different therapeutic interventions may be prescribed (1) exercise therapy or (2) cognitive behavioural therapy (CBT). However, the evidence on the effectiveness of both interventions is limited. The primary aim of the FACTS-2-PPS trial is to study the efficacy of exercise therapy and CBT for reducing fatigue and improving activities and quality of life in patients with PPS. Additionally, the working mechanisms, patients' and therapists' expectations of and experiences with both interventions and cost-effectiveness will be evaluated.     

Fatigue In Teenagers on the interNET - The FITNET Trial. A randomized clinical trial of web-based cognitive behavioural therapy for adolescents with chronic fatigue syndrome: study protocol. [ISRCTN59878666]

Background  

Chronic Fatigue Syndrome (CFS) is increasingly recognized as a cause of disability and inactivity in adolescents in the Netherlands. CFS is characterized by unexplained fatigue lasting more than 6 months. Cognitive Behavioural Therapy (CBT) has proven to be effective. However, CBT availability for adolescents with CFS is limited and requires special therapeutic skills not always readily available. An alternative to the face-to-face CBT is FITNET, a web-based therapeutic program designed specifically for adolescents diagnosed with CFS, and their parents. This new CBT approach appeals to the modern youth, who grow up with internet as their main source of information. A web-based program offers the opportunity to lower thresholds for the acceptance and realization of healthcare. This treatment can be activated at any chosen time. The communication between patient and therapist can elapse asynchronously. If effective, this web-based program would greatly increase the therapeutic accessibility.     

Protocol for the PACE trial: A randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy

Background

Chronic fatigue syndrome (CFS, also called myalgic encephalomyelitis/encephalopathy or ME) is a debilitating condition with no known cause or cure. Improvement may occur with medical care and additional therapies of pacing, cognitive behavioural therapy and graded exercise therapy. The latter two therapies have been found to be efficacious in small trials, but patient organisations' surveys have reported adverse effects. Although pacing has been advocated by patient organisations, it lacks empirical support. Specialist medical care is commonly provided but its efficacy when given alone is not established. This trial compares the efficacy of the additional therapies when added to specialist medical care against specialist medical care alone.

Methods/Design

600 patients, who meet operationalised diagnostic criteria for CFS, will be recruited from secondary care into a randomised trial of four treatments, stratified by current comorbid depressive episode and different CFS/ME criteria. The four treatments are standardised specialist medical care either given alone, or with adaptive pacing therapy or cognitive behaviour therapy or graded exercise therapy. Supplementary therapies will involve fourteen sessions over 23 weeks and a 'booster session' at 36 weeks. Outcome will be assessed at 12, 24, and 52 weeks after randomisation. Two primary outcomes of self-rated fatigue and physical function will assess differential effects of each treatment on these measures. Secondary outcomes include adverse events and reactions, subjective measures of symptoms, mood, sleep and function and objective measures of physical activity, fitness, cost-effectiveness and cost-utility. The primary analysis will be based on intention to treat and will use logistic regression models to compare treatments. Secondary outcomes will be analysed by repeated measures analysis of variance with a linear mixed model. All analyses will allow for stratification factors. Mediators and moderators will be explored using multiple linear and logistic regression techniques with interactive terms, with the sample split into two to allow validation of the initial models. Economic analyses will incorporate sensitivity measures.

Discussion

The results of the trial will provide information about the benefits and adverse effects of these treatments, their cost-effectiveness and cost-utility, the process of clinical improvement and the predictors of efficacy.     

Transfer of manualized CBT for social phobia into clinical practice (SOPHO-PRAX): a study protocol for a cluster-randomized controlled trial

ABSTRACT: BACKGROUND: Cognitive-behavioral therapy (CBT) is generally known to be efficacious in the treatment of social phobia when applied in RCT's, namely when the treatment manual is based on the Clark-Wells approach. However, little is known about the efficacy of manualized treatments in routine clinical practice (Phase IV of psychotherapy research). The present study (SOPHO-PRAX) is a continuation of a large multi-centre randomized clinical trial (SOPHO-NET) and analyses the extent to which additional training practitioners in manualized procedures enhances treatment effect. METHODS: N = 36 private practitioners will be included in three treatment centres and randomly designated to either training in manualized CBT or no specific training. The treatment effects of the therapies conducted by both groups of therapists will be compared. A total of 162 patients (N = 116 completers; N = 58 per condition) will be enrolled. Liebowitz Social Anxiety Scale (LSAS) will serve as primary outcome measure. Remission from social phobia is defined as LSAS total [less than or equal to] 30 points. Data will be collected at treatment begin, after 8, 15, and 25 sessions (50 mins. each), at treatment completion, as well at 6 and 12 months post-treatment. DISCUSSION: The present CBT trial combines elements of randomized-controlled trials and naturalistic studies in an innovative way. It will directly inform about the incremental effects of procedures established in a controlled trial into clinical practice. Study results are relevant to health care decisions and policy. They may serve to improve quality of treatment, and shorten the timeframe between the development and widespread dissemination of effective methods, thereby reducing health cost expenditures. The results of this study will not only inform about the degree to which the new methods lead to an improvement of treatment course and outcome, but also about whether the effects of routine psychotherapeutic treatment are comparable to those of the controlled, strictly manualized treatments of the SOPHO-NET study. Trial Registration: ClinicalTrials.gov identifier: NCT01388231. This study was funded by the German Federal Ministry of Education and Research (SOPHO-NET: BMBF 01GV0607; SOPHO-PRAX: BMBF 01GV1001).     

Effect of aerobic exercise training and cognitive behavioural therapy on reduction of chronic fatigue in patients with facioscapulohumeral dystrophy: protocol of the FACTS-2-FSHD trial

Background

In facioscapulohumeral dystrophy (FSHD) muscle function is impaired and declines over time. Currently there is no effective treatment available to slow down this decline. We have previously reported that loss of muscle strength contributes to chronic fatigue through a decreased level of physical activity, while fatigue and physical inactivity both determine loss of societal participation. To decrease chronic fatigue, two distinctly different therapeutic approaches can be proposed: aerobic exercise training (AET) to improve physical capacity and cognitive behavioural therapy (CBT) to stimulate an active life-style yet avoiding excessive physical strain. The primary aim of the FACTS-2-FSHD (acronym for Fitness And Cognitive behavioural TherapieS/for Fatigue and ACTivitieS in FSHD) trial is to study the effect of AET and CBT on the reduction of chronic fatigue as assessed with the Checklist Individual Strength subscale fatigue (CIS-fatigue) in patients with FSHD. Additionally, possible working mechanisms and the effects on various secondary outcome measures at all levels of the International Classification of Functioning, Disability and Health (ICF) are evaluated.

Methods/Design

A multi-centre, assessor-blinded, randomized controlled trial is conducted. A sample of 75 FSHD patients with severe chronic fatigue (CIS-fatigue ≥ 35) will be recruited and randomized to one of three groups: (1) AET + usual care, (2) CBT + usual care or (3) usual care alone, which consists of no therapy at all or occasional (conventional) physical therapy. After an intervention period of 16 weeks and a follow-up of 3 months, the third (control) group will as yet be randomized to either AET or CBT (approximately 7 months after inclusion). Outcomes will be assessed at baseline, immediately post intervention and at 3 and 6 months follow up.

Discussion

The FACTS-2-FSHD study is the first theory-based randomized clinical trial which evaluates the effect and the maintenance of effects of AET and CBT on the reduction of chronic fatigue in patients with FSHD. The interventions are based on a theoretical model of chronic fatigue in patients with FSHD. The study will provide a unique set of data with which the relationships between outcome measures at all levels of the ICF could be assessed.

Trial registration

Dutch Trial Register, NTR1447.

     

Therapist Effects and the Impact of Early Therapeutic Alliance on Symptomatic Outcome in Chronic Fatigue Syndrome

Few studies have examined therapist effects and therapeutic alliance (TA) in treatments for chronic fatigue syndrome (CFS). Therapist effects are the differences in outcomes achieved by different therapists. TA is the quality of the bond and level of agreement regarding the goals and tasks of therapy. Prior research suffers the methodological problem that the allocation of therapist was not randomized, meaning therapist effects may be confounded with selection effects. We used data from a randomized controlled treatment trial of 296 people with CFS. The trial compared pragmatic rehabilitation (PR), a nurse led, home based self-help treatment, a counselling-based treatment called supportive listening (SL), with general practitioner treatment as usual. Therapist allocation was randomized. Primary outcome measures, fatigue and physical functioning were assessed blind to treatment allocation. TA was measured in the PR and SL arms. Regression models allowing for interactions were used to examine relationships between (i) therapist and therapeutic alliance, and (ii) therapist and average treatment effect (the difference in mean outcomes between different treatment conditions). We found no therapist effects. We found no relationship between TA and the average treatment effect of a therapist. One therapist formed stronger alliances when delivering PR compared to when delivering SL (effect size 0.76, SE 0.33, 95% CI 0.11 to 1.41). In these therapies for CFS, TA does not influence symptomatic outcome. The lack of significant therapist effects on outcome may result from the trial’s rigorous quality control, or random therapist allocation, eliminating selection effects. Further research is needed.Trial Registration: ISRCTN74156610     

Increased daily physical activity and fatigue symptoms in chronic fatigue syndrome

Individuals with chronic fatigue syndrome (CFS) have been shown to have reduced activity levels associated with heightened feelings of fatigue. Previous research has demonstrated that exercise training has beneficial effects on fatigue-related symptoms in individuals with CFS. PURPOSE: The aim of this study was to sustain an increase in daily physical activity in CFS patients for 4 weeks and assess the effects on fatigue, muscle pain and overall mood. METHODS: Six CFS and seven sedentary controls were studied. Daily activity was assessed by a CSA accelerometer. Following a two week baseline period, CFS subjects were asked to increase their daily physical activity by 30% over baseline by walking a prescribed amount each day for a period of four weeks. Fatigue, muscle pain and overall mood were reported daily using a 0 to 100 visual analog scale and weekly using the Profile of Mood States (Bipolar) questionnaire. RESULTS: CFS patients had significantly lower daily activity counts than controls (162.5 +/- 51.7 x 103 counts/day vs. 267.2 +/- 79.5 x 103 counts/day) during a 2-week baseline period. At baseline, the CFS patients reported significantly (P < 0.01) higher fatigue and muscle pain intensity compared to controls but the groups did not differ in overall mood. CFS subjects increased their daily activity by 28 +/- 19.7% over a 4 week period. Overall mood and muscle pain worsened in the CFS patients with increased activity. CONCLUSION: CFS patients were able to increase their daily physical activity for a period of four weeks. In contrast to previous studies fatigue, muscle pain, and overall mood did not improve with increased activity. Increased activity was not presented as a treatment which may account for the differential findings between this and previous studies. The results suggest that a daily "activity limit" may exist in this population. Future studies on the impact of physical activity on the symptoms of CFS patients are needed.     

Effectiveness of smoking-cessation interventions for urban hospital patients: study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: Hospitalization may be a particularly important time to promote smoking cessation, especially in the immediate post-discharge period. However, there are few studies to date that shed light on the most effective or cost-effective methods to provide post-discharge cessation treatment, especially among low-income populations and those with a heavy burden of mental illness and substance use disorders. METHODS: This randomized trial will compare the effectiveness and cost-effectiveness of two approaches to smoking cessation treatment among patients discharged from two urban public hospitals in New York City. During hospitalization, staff will be prompted to ask about smoking and to offer nicotine replacement therapy (NRT) on admission and at discharge. Subjects will be randomized on discharge to one of two arms: One arm will be proactive multi-session telephone counseling with motivational enhancement delivered by study staff, and the other will be a faxed or online referral to the New York State Quitline. The primary outcome is 30-day point-prevalence abstinence from smoking at 6-month follow-up post-discharge. We will also examine cost-effectiveness from a societal and a payer perspective, as well as explore subgroup analyses related to patients' location of hospitalization, race/ethnicity, immigrant status, and inpatient diagnosis. DISCUSSION: This study will explore issues of implementation feasibility in a post-hospitalization patient population, as well as add information about the effectiveness and cost-effectiveness of different strategies for designing smoking cessation programs for hospitalized patients.     

Collaborative Interventions for Circulation and Depression (COINCIDE): study protocol for a cluster randomized controlled trial of collaborative care for depression in people with diabetes and/or coronary heart disease

ABSTRACT: BACKGROUND: Depression is up to two to three times as common in people with long-term conditions. It negatively affects medical management of disease and self-care behaviors, and leads to poorer quality of life and high costs in primary care. Screening and treatment of depression is increasingly prioritized, but despite initiatives to improve access and quality of care, depression remains under-detected and under-treated, especially in people with long-term conditions. Collaborative care is known to positively affect the process and outcome of care for people with depression and long-term conditions, but its effectiveness outside the USA is still relatively unknown. Furthermore, collaborative care has yet to be tested in settings that resemble more naturalistic settings that include patient choice and the usual care providers. The aim of this study was to test the effectiveness of a collaborative-care intervention, for people with depression and diabetes/coronary heart disease in National Health Service (NHS) primary care, in which low-intensity psychological treatment services are delivered by the usual care provider - Increasing Access to Psychological Therapies (IAPT) services.s. The study also aimed to evaluate the cost-effectiveness of the intervention over 6 months of collaborative care, and to assess qualitatively the extent to which collaborative care was implemented in the intervention general practices. METHODS: This is a cluster randomized controlled trial of 30 general practices allocated to either collaborative care or usual care. Fifteen patients per practice will be recruited after a screening exercise to detect patients with recognized depression (greater than or equal to 10 on the nine-symptom Patient Health Questionnaire; PHQ-9). Patients in the collaborative-care arm with recognized depression will be offered a choice of evidence-based low-intensity psychological treatments based on cognitive and behavioral approaches. Patients will be case managed by psychological well-being practitioners employed by IAPT in partnership with a practice nurse and/or general practitioner. The primary outcome will be change in depressive symptoms at 6 months on the 90-item Symptoms Checklist (SCL-90). Secondary outcomes include change in health status, self-care behaviors, and self-efficacy. A qualitative process evaluation will be undertaken with patients and health practitioners to gauge the extent to which the collaborative-care model is implemented, and to explore sustainability beyond the clinical trial. DISCUSSION: COINCIDE will assess whether collaborative care can improve patient-centered outcomes, and evaluate access to and quality of care of co-morbid depression of varying intensity in people with diabetes/coronary heart disease. Additionally, by working with usual care providers such as IAPT, and by identifying and evaluating interventions that are effective and appropriate for routine use in the NHS, the COINCIDE trial offers opportunities to address translational gaps between research and implementation.Trial Registration NumberISRCTN80309252Trial StatusOpen.     

Psychoanalytic and cognitive-behavior therapy of chronic depression: study protocol for a randomized controlled trial

ABSTRACT: BACKGROUND: Despite limited effectiveness of short-term psychotherapy for chronic depression, there is a lack of trials of long-term psychotherapy. Our study is the first to determine the effectiveness of controlled long-term psychodynamic and cognitive-behavioral (CBT) treatments and to assess the effects of preferential vs. randomized assessment. Methods / Design: Patients are assigned to treatment according to their preference or randomized (if they have no clear preference). Up to 80 sessions of psychodynamic or psychoanalytically oriented treatments (PAT) or up to 45 sessions of CBT are offered during the first year in the study. After the first year, PAT can be continued according to the "naturalistic", usual way of treating such patients within the system of German health care system (normally 240 up to 300 sessions), CBT therapists may extend their treatment up to 80 sessions, but focus mainly on maintenance and relapse prevention. We plan to recruit a total of 240 patients (60 per arm). A total of 11 assessments are conducted throughout treatment and up to 3 years after initiation of treatment. The primary outcome measures are the QIDS (independent clinician rating) and the BDI after year 1, 2 and 3. DISCUSSION: We combine an RCT and a naturalistic approach in order to investigate, how effectively chronic depression can be treated on an outpatient basis by the two forms of treatment reimbursed in the German health care system and we will determine the effects of treatment preference vs. randomization.     

Adaptive pacing, cognitive behaviour therapy, graded exercise, and specialist medical care for chronic fatigue syndrome: a cost-effectiveness analysis

Background

The PACE trial compared the effectiveness of adding adaptive pacing therapy (APT), cognitive behaviour therapy (CBT), or graded exercise therapy (GET), to specialist medical care (SMC) for patients with chronic fatigue syndrome. This paper reports the relative cost-effectiveness of these treatments in terms of quality adjusted life years (QALYs) and improvements in fatigue and physical function.

Methods

Resource use was measured and costs calculated. Healthcare and societal costs (healthcare plus lost production and unpaid informal care) were combined with QALYs gained, and changes in fatigue and disability; incremental cost-effectiveness ratios (ICERs) were computed.

Results

SMC patients had significantly lower healthcare costs than those receiving APT, CBT and GET. If society is willing to value a QALY at £30,000 there is a 62.7% likelihood that CBT is the most cost-effective therapy, a 26.8% likelihood that GET is most cost effective, 2.6% that APT is most cost-effective and 7.9% that SMC alone is most cost-effective. Compared to SMC alone, the incremental healthcare cost per QALY was £18,374 for CBT, £23,615 for GET and £55,235 for APT. From a societal perspective CBT has a 59.5% likelihood of being the most cost-effective, GET 34.8%, APT 0.2% and SMC alone 5.5%. CBT and GET dominated SMC, while APT had a cost per QALY of £127,047. ICERs using reductions in fatigue and disability as outcomes largely mirrored these findings.

Conclusions

Comparing the four treatments using a health care perspective, CBT had the greatest probability of being the most cost-effective followed by GET. APT had a lower probability of being the most cost-effective option than SMC alone. The relative cost-effectiveness was even greater from a societal perspective as additional cost savings due to reduced need for informal care were likely.     

Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT): Study Protocol for a Randomized Controlled Trial

ABSTRACT: BACKGROUND: Limited controlled data exist to guide treatment choices for clinicians caring for patients with major depressive disorder (MDD). Although many putative predictors of treatment response have been reported, most were identified through retrospective analyses of existing datasets and very few have been replicated in a manner that can impact clinical practice. One major confound in previous studies examining predictors of treatment response is the patient's treatment history, which may affect both the predictor of interest and treatment outcomes. Moreover, prior treatment history provides an important source of selection bias, thereby limiting generalizability. Consequently, we initiated a randomized clinical trial designed to identify factors that moderate response to three treatments for MDD among patients never treated previously for the condition. METHODS: Treatment-naive adults aged 18-65 years with moderate-to-severe, non-psychotic MDD are randomized equally to one of three 12-week treatment arms: 1) cognitive behavior therapy (CBT, 16 sessions), 2) duloxetine (30-60 mg/d), or 3) escitalopram (10-20 mg/d). Prior to randomization, patients undergo multiple assessments, including resting state functional magnetic resonance imaging (fMRI), immune markers, DNA and gene expression products, and dexamethasone-corticotropin releasing hormone (Dex/CRH) testing. Prior to or shortly after randomization, patients also complete a comprehensive personality assessment. Repeat assessment of the biological measures (fMRI, immune markers, and gene expression products) occur at an early time-point in treatment, and upon completion of 12-week treatment, when a a second Dex/CRH test is also conducted, Patients remitting by the end of this acute treatment phase are then eligible to enter a 21-month follow-up phase, with quarterly visits to monitor for recurrence. Non-remitters are offered augmentation treatment for a second 12-week course of treatment, during which they receive a combination of CBT and antidepressant medication. Predictors of the primary outcome, remission, will be identified for overall and treatment-specific effects, and a statistical model incorporating multiple predictors will be developed to predict outcomes. DISCUSSION: The PReDICT study's evaluation of biological, psychological, and clinical factors that may differentially impact treatment outcomes represents a sizeable step toward developing personalized treatments for MDD. Identified predictors should help guide the selection of initial treatments, and identify those patients most vulnerable to recurrence, who thus warrant maintenance or combination treatments to achieve and maintain wellness.     

PISA. The effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute stroke: Protocol for a phase II double-blind randomised placebo-controlled trial [ISRCTN98608690]

Background

During the first days after stroke, one to two fifths of the patients develop fever or subfebrile temperatures. Body temperature is a strong prognostic factor after stroke. Pharmacological reduction of temperature in patients with acute ischaemic stroke may improve their functional outcome. Previously, we studied the effect of high dose (6 g daily) and low dose (3 g daily) paracetamol (acetaminophen) in a randomised placebo-controlled trial of 75 patients with acute ischemic stroke. In the high-dose paracetamol group, mean body temperature at 12 and 24 hours after start of treatment was 0.4°C lower than in the placebo group. The effect of ibuprofen, another potent antipyretic drug, on body-core temperature in normothermic patients has not been studied.

Aim

The aim of the present trial is to study the effects of high-dose paracetamol and ibuprofen on body temperature in patients with acute ischaemic stroke, and to study the safety of these treatments.

Design

Seventy-five (3 × 25) patients with acute ischaemic stroke confined to the anterior circulation will be randomised to treatment with either: 400 mg ibuprofen, 1000 mg acetaminophen, or with placebo 6 times daily during 5 days. Body-temperatures will be measured with a rectal electronic thermometer at the start of treatment and after 24 hours. An infrared tympanic thermometer will be used to monitor body temperature at 2-hour intervals during the first 24 hours and at 12-hour intervals thereafter. The primary outcome measure will be rectal temperature at 24 hours after the start of treatment. The study results will be analysed on an intent-to-treat basis, but an on-treatment analysis will also be performed. No formal interim analysis will be carried out.     

Lessons from a pilot study of transfer factor in chronic fatigue syndrome

Transfer Factor (TF) was used in a placebo controlled pilot study of 20 patients with chronic fatigue syndrome (CFS). Efficacy of the treatment was evaluated by clinical monitoring and testing for antibodies to Epstein-Barr virus (EBV) and human herpes virus-6 (HHV-6). Of the 20 patients in the placebo-controlled trial, improvement was observed in 12 patients, generally within 3-6 weeks of beginning treatment. Herpes virus serology seldom correlated with clinical response. This study provided experience with oral TF, useful in designing a larger placebo-controlled clinical trial.     

Cognitive behavioral therapy and fluoxetine for binge eating disorder: two-year follow-up

Objective: This study assessed the long‐term effects of group behavioral treatment plus individual cognitive behavioral therapy (CBT) and/or fluoxetine in binge eating disorder (BED) patients. Research Methods and Procedures: A total of 116 individuals were randomized to an initial five‐month trial and were followed up over two years. Assessments, including binge frequency, weight, and self‐report measures, were administered at pre‐treatment, post‐treatment, and ～6, 12, 18, and 24 months after initial treatment. Results: Across treatment groups, there was overall improvement over 29 months in binge frequency and in binge abstinence. The odds of binge abstinence 2 years post‐treatment were 1.373 times the odds of binge abstinence immediately post‐treatment. There was no significant change in weight over the two‐year period. Subjects who received individual CBT evidenced lower binge frequency over the two‐year follow‐up period than patients who had not received individual CBT. Similarly, CBT was associated with increased rates of binge abstinence. There were no main effects of treatment assignment on weight over the two‐year follow‐up period. There was a significant advantage for fluoxetine assignment over the two‐year follow‐up period on depressive symptoms. Discussion: The major significance of the study rests in its examination of the long‐term effects of standardized interventions for BED. Our findings provide support for the ideas that short‐term treatment may confer long‐term benefit and that not all treatments are equivalent in the benefits they confer.     

Cognitive behavioural therapy versus supportive therapy for persistent positive symptoms in psychotic disorders: The POSITIVE Study, a multicenter, prospective, single-blind, randomised controlled clinical trial

Background

It has been demonstrated that cognitive behavioural therapy (CBT) has a moderate effect on symptom reduction and on general well being of patients suffering from psychosis. However, questions regarding the specific efficacy of CBT, the treatment safety, the cost-effectiveness, and the moderators and mediators of treatment effects are still a major issue. The major objective of this trial is to investigate whether CBT is specifically efficacious in reducing positive symptoms when compared with non-specific supportive therapy (ST) which does not implement CBT-techniques but provides comparable therapeutic attention.

Methods/Design

The POSITIVE study is a multicenter, prospective, single-blind, parallel group, randomised clinical trial, comparing CBT and ST with respect to the efficacy in reducing positive symptoms in psychotic disorders. CBT as well as ST consist of 20 sessions altogether, 165 participants receiving CBT and 165 participants receiving ST. Major methodological aspects of the study are systematic recruitment, explicit inclusion criteria, reliability checks of assessments with control for rater shift, analysis by intention to treat, data management using remote data entry, measures of quality assurance (e.g. on-site monitoring with source data verification, regular query process), advanced statistical analysis, manualized treatment, checks of adherence and competence of therapists. Research relating the psychotherapy process with outcome, neurobiological research addressing basic questions of delusion formation using fMRI and neuropsychological assessment and treatment research investigating adaptations of CBT for adolescents is combined in this network. Problems of transfer into routine clinical care will be identified and addressed by a project focusing on cost efficiency.

Discussion

This clinical trial is part of efforts to intensify psychotherapy research in the field of psychosis in Germany, to contribute to the international discussion on psychotherapy in psychotic disorders, and to help implement psychotherapy in routine care. Furthermore, the study will allow drawing conclusions about the mediators of treatment effects of CBT of psychotic disorders.

Trial Registration

Current Controlled Trials ISRCTN29242879     

Adherence to Internet-Based and Face-to-Face Cognitive Behavioural Therapy for Depression: A Meta-Analysis

Background

Internet-based cognitive behavioural therapy (iCBT) is an effective and acceptable treatment for depression, especially when it includes guidance, but its treatment adherence has not yet been systematically studied. We conducted a meta-analysis, comparing the adherence to guided iCBT with the adherence to individual face-to-face CBT.

Methods

Studies were selected from a database of trials that investigate treatment for adult depression (see www.evidencebasedpsychotherapies.org), updated to January 2013. We identified 24 studies describing 26 treatment conditions (14 face-to-face CBT, 12 guided iCBT), by means of these inclusion criteria: targeting depressed adults, no comorbid somatic disorder or substance abuse, community recruitment, published in the year 2000 or later. The main outcome measure was the percentage of completed sessions. We also coded the percentage of treatment completers (separately coding for 100% or at least 80% of treatment completed).

Results

We did not find studies that compared guided iCBT and face-to-face CBT in a single trial that met our inclusion criteria. Face-to-face CBT treatments ranged from 12 to 28 sessions, guided iCBT interventions consisted of 5 to 9 sessions. Participants in face-to-face CBT completed on average 83.9% of their treatment, which did not differ significantly from participants in guided iCBT (80.8%, P  =  .59). The percentage of completers (total intervention) was significantly higher in face-to-face CBT (84.7%) than in guided iCBT (65.1%, P < .001), as was the percentage of completers of 80% or more of the intervention (face-to-face CBT: 85.2%, guided iCBT: 67.5%, P  =  .003). Non-completers of face-to-face CBT completed on average 24.5% of their treatment, while non-completers of guided iCBT completed on average 42.1% of their treatment.

Conclusion

We did not find studies that compared guided iCBT and face-to-face CBT in a single trial. Adherence to guided iCBT appears to be adequate and could be equal to adherence to face-to-face CBT.     

A functional polymorphism in the disrupted-in schizophrenia 1 gene is associated with chronic fatigue syndrome

AimsDisrupted-in schizophrenia 1 (DISC1), identified in a pedigree with a familial psychosis with the chromosome translocation (1:11), is a putative susceptibility gene for psychoses such as schizophrenia and major depressive disorder (MDD). Patients with chronic fatigue syndrome (CFS) report having continuous severe fatigue and many overlapping symptoms with MDD; however, the mechanism and effective treatment of CFS are still unclear. We focused on the overlapping symptoms between CFS and MDD and performed an association study of the functional single-nucleotide polymorphism (SNP) in the DISC1 gene with CFS.Main methodsVenous blood was drawn from CFS patients and controls and genomic DNA was extracted from the whole blood according to standard procedures. Ser704Cys DISC1 SNP was genotyped using the TaqMan 5′-exonuclease allelic discrimination assay.Key findingsWe found that the Cys704 allele of Ser704Cys SNP was associated with an increased risk of CFS development compared with the Ser704 allele.SignificanceDISC1 Ser704Cys might be a functional variant that affects one of the mechanisms implicated in the biology of CFS. Some patients with CFS showed a phenotype similar to that of patients with MDD, but further studies are needed to clarify the biological mechanism, because this study is of a rather preliminary nature. Despite the variety of patients with CFS, DISC1 Ser704Cys has an association with CFS, which may also suggest that DISC1 plays a central role in the induction of various psychiatric diseases.     

Bayesian Two-Stage Biomarker-Based Adaptive Design for Targeted Therapy Development

We propose a Bayesian two-stage biomarker-based adaptive randomization (AR) design for the development of targeted agents. The design has three main goals: (1) to test the treatment efficacy, (2) to identify prognostic and predictive markers for the targeted agents, and (3) to provide better treatment for patients enrolled in the trial. To treat patients better, both stages are guided by the Bayesian AR based on the individual patient’s biomarker profiles. The AR in the first stage is based on a known marker. A Go/No-Go decision can be made in the first stage by testing the overall treatment effects. If a Go decision is made at the end of the first stage, a two-step Bayesian lasso strategy will be implemented to select additional prognostic or predictive biomarkers to refine the AR in the second stage. We use simulations to demonstrate the good operating characteristics of the design, including the control of per-comparison type I and type II errors, high probability in selecting important markers, and treating more patients with more effective treatments. Bayesian adaptive designs allow for continuous learning. The designs are particularly suitable for the development of multiple targeted agents in the quest of personalized medicine. By estimating treatment effects and identifying relevant biomarkers, the information acquired from the interim data can be used to guide the choice of treatment for each individual patient enrolled in the trial in real time to achieve a better outcome. The design is being implemented in the BATTLE-2 trial in lung cancer at the MD Anderson Cancer Center.