Facilitating Recovery of Daily Functioning in People With a Severe Mental Illness Who Need Longer-Term Intensive Psychiatric Services: Results From a Cluster Randomized Controlled Trial on Cognitive Adaptation Training Delivered by Nurses.

BACKGROUND: Feasible and effective interventions to improve daily functioning in people with a severe mental illness (SMI), such as schizophrenia, in need of longer-term rehabilitation are scarce. AIMS: We assessed the effectiveness of Cognitive Adaptation Training (CAT), a compensatory intervention to improve daily functioning, modified into a nursing intervention. METHOD: In this cluster randomized controlled trial, 12 nursing teams were randomized to CAT in addition to treatment as usual (CAT; n = 42) or TAU (n = 47). Daily functioning (primary outcome) was assessed every 3 months for 1 year. Additional follow-up assessments were performed for the CAT group in the second year. Secondary outcomes were assessed every 6 months. Data were analyzed using multilevel modeling. RESULTS: CAT participants improved significantly on daily functioning, executive functioning, and visual attention after 12 months compared to TAU. Improvements were maintained after 24 months. Improved executive functioning was related to improved daily functioning. Other secondary outcomes (quality of life, empowerment, negative symptoms) showed no significant effects. CONCLUSIONS: As a nursing intervention, CAT leads to maintained improvements in daily functioning, and may improve executive functioning and visual attention in people with SMI in need of longer-term intensive psychiatric care. Given the paucity of evidence-based interventions in this population, CAT can become a valuable addition to recovery-oriented care.

Chronic solvent-induced encephalopathy: course and prognostic factors of neuropsychological functioning.

PURPOSE: Working in conditions with daily exposure to organic solvents for many years can result in a disease known as chronic solvent-induced encephalopathy (CSE). The aims for this study were to describe the neuropsychological course of CSE after first diagnosis and to detect prognostic factors for neuropsychological impairment after diagnosis. METHODS: This prospective study follows a Dutch cohort of CSE patients who were first diagnosed between 2001 and 2011 and underwent a second neuropsychological assessment 1.5-2 years later. Cognitive subdomains were assessed and an overall cognitive impairment score was calculated. Paired t tests and multivariate linear regression analyses were performed to describe the neuropsychological course and to obtain prognostic factors for the neuropsychological functioning at follow-up. RESULTS: There was a significant improvement on neuropsychological subdomains at follow-up, with effect sizes between small and medium (Cohen's d 0.27-0.54) and a significant overall improvement of neuropsychological impairment with a medium effect size (Cohen's d 0.56). Prognostic variables for more neuropsychological impairment at follow-up were a higher level of neuropsychological impairment at diagnosis and having a comorbid diagnosis of a psychiatric disorder at diagnosis. CONCLUSIONS: Results are in line with previous research on the course of CSE, stating that CSE is a non-progressive disease after cessation of exposure. However, during follow-up the percentage patients with permanent work disability pension increased from 14 to 37%. Preventive action is needed in countries where exposure to organic solvents is still high to prevent new cases of CSE.

[Brain damage caused by exposure to organic solvents; diagnostics and disease course of chronic solvent-induced encephalopathy]. / Hersenschade door blootstelling aan oplosmiddelen; diagnostiek en beloop van chronische toxische encefalopathie.

Since 1997 more than 3,000 patients have been referred to one of the two Dutch Solvent Teams with health problems that may have been caused by long-term occupational exposure to organic solvents. A diagnosis of 'chronic solvent-induced encephalopathy' was made in approximately 500 patients. The diagnostics of this disease is based on five elements: (a) symptoms in line with the diagnosis; (b) relevant exposure to an organic solvent with neurotoxic effects; (c) a clear temporal relationship between the onset of symptoms and exposure to a solvent with neurotoxic effects; (d) exclusion of other causes for the symptoms; and (e) impairment on neuropsychological assessment. Exposure to organic solvents can cause chronic health effects, which may even persist years after exposure has ceased. In general, no more serious deterioration of health is observed after exposure has ceased.

Decision rules for assessment of chronic solvent-induced encephalopathy: Results in 2370 patients.

For the diagnosis of patients suspected of chronic solvent-induced encephalopathy (CSE), it would be helpful if the applied cognitive tests show a characteristic profile of impairment in this disease. We investigated the existence of such a profile. In 1997-2006 two expert teams in The Netherlands systematically examined 2370 patients referred for evaluation of suspected CSE. The procedure included two selection steps: (1) intake interview, using criteria of exposure, development of symptoms and absence of non-solvent causes, and (2) seven tests of the computerized Neurobehavioural Evaluation System (NES). Patients showing negligible impairments were considered free from CSE and were not further examined. The third step comprised a neuropsychological, neurological and exposure evaluation. Explicit decision rules for the diagnosis of CSE were developed, including a minimum score for cognitive impairment summarizing 25 cognitive tests. These rules were retroactively applied to 563 patients, comprising 513 patients who had regularly completed all diagnostic steps and a sample of 50 out of the approximately 450 patients with negligible impairments on the NES, who were fully examined. The data from this sample were extrapolated to the original number of 450. In the combined population of 963 patients, a calculated 301 patients were given the diagnosis 'Solely CSE', 242 'CSE and other disease', 158 'Other Disease' and 262 'No (known) disease'. In the Solely CSE patients, the most impaired tests regarded Verbal Fluency & -Similarities, Motor Speed and Simple Attention. A profile of test results that might support the identification of patients with CSE amongst the other referred patients, was not found. The diverging results of related cognitive tests indicate that the use of a core test battery is needed to improve comparability. We consider the decision rules as a step towards a more objective assessment of CSE.

Cognitive functioning in euthymic recurrently depressed patients: relationship with future relapses and prior course of disease.

BACKGROUND: Cognitive impairment seems to persist during the euthymic phase of recurrent depression but its relationship with future relapses as with prior course of the disease has to be elucidated. The purpose of this study is to investigate the presence and prognostic value of cognitive dysfunctions for relapse in high risk euthymic patients and to identify relevant associations between cognitive functioning and prior course of illness. METHODS: Standardized neuropsychological tests of mental speed, memory and executive functioning were assessed in 137 remitted patients and compared with clinically used published normative data. Previous episodes and relapses within 24 months were measured using the Structured Clinical Interview for DSM-IV. RESULTS: Cognitive performance was significantly impaired on 12 of the 14 variables indicating deficits in the domain of speed of information processing and memory. With Cox regression no significant neuropsychological predictors for relapse or recurrence were identified. Furthermore, Pearson correlations between neuropsychological test scores and number of previous episodes, residual depressive symptoms and duration of remission were non-significant. Later age of onset was correlated with a slower speed of information processing and lower verbal memory performance. LIMITATIONS: Published test reference data were used but no healthy control group. CONCLUSION: Presence of mild cognitive impairment in remitted patients was demonstrated but did not predict future relapses nor was it related with prior course of disease except for age of onset. Though, mild cognitive impairment after remission might have an impact on the quality of life, adding techniques from cognitive rehabilitation might prove to be a treatment option.

Chronic solvent-induced encephalopathy: European consensus of neuropsychological characteristics, assessment, and guidelines for diagnostics.

INTRODUCTION: The presence of neuropsychological impairment is a hallmark of chronic solvent-induced encephalopathy (CSE), and using clinical neuropsychological procedures to generate a valid assessment of the condition is crucial for its diagnosis. The goals of this consensus document are to provide updated knowledge of the neuropsychological characteristics of CSE and to provide internationally acceptable guidelines for using neuropsychological assessments in the process of diagnosing patients who are suspected of having CSE. MATERIALS AND METHODS: A European working group that was composed of experts in the field of the clinical diagnosis of CSE met at several round-table meetings and prepared this report. The first section of the consensus paper addresses a review of the relevant literature that was published between 1985 and March 2012. The second section addresses recommendations for the clinical neuropsychological assessment of patients who are suspected of having CSE. RESULTS: The literature review indicates that the most common neuropsychological impairments in CSE patients are within the domains of attention, particularly the speed of information processing, memory, and motor performance. It appears that the influence of CSE on memory processes mainly involves immediate recall and generally involves verbal, visual and visuospatial material. In the second section, six recommendations are presented regarding important functional domains for the neuropsychological diagnostic process of CSE that relate to the evaluation of neuropsychological impairment, the assessment and evaluation of symptoms, differential diagnostic considerations, the reliability and validity of neuropsychological test results, and the retesting of patients. DISCUSSION AND CONCLUSIONS: These recommendations will contribute to the improvement of the process for accurately diagnosing CSE, better counselling for CSE patients, the comparability of epidemiological data between countries, and finally, by raising awareness, these recommendations will contribute to combating the adverse health effects of occupational exposure to solvents.

The course of chronic solvent induced encephalopathy: a systematic review.

BACKGROUND: Worldwide millions of workers are exposed to organic solvents. Long term exposure leads in some workers to the development of Chronic Solvent induced Encephalopathy (CSE). The first reports about CSE came from the European Nordic countries in the 1970s. In spite of decades of experience with this disease, little is known about the course and prognostic factors of CSE. OBJECTIVE: To provide an overview of the evidence about the course and prognostic factors of CSE. METHODS: A systematic review was conducted. Databases PubMed, PsycINFO (1970-2008) and EMBASE (1980-2008) were searched with the search strategy: solvent AND follow up AND (encephalopathy OR chronic intoxication). Inclusion criteria were: written in English, study population of CSE patients, follow-up time of at least 1 year. Included articles were assessed on methodological quality. RESULTS: Sixty unique articles were retrieved of which sixteen met the inclusion criteria. Data extraction provided information about domains of neurology, neuropsychology, physical and mental health perceptions, and social consequences. In a number of studies no significant changes, and in other studies improvement of functioning could be measured. Prognostic factors resulting from included studies were summarized for each domain indicating a potential positive influence of younger age and lower exposure variables. DISCUSSION: Due to the large heterogeneity of methodology no levels of evidence could be obtained. This review shows that there is a need for future research that addresses a variety of domains of functioning, hopefully resulting in an overall prognostic model for CSE. CONCLUSION: Studies in this review are in agreement about CSE being a non-progressive disease in which no severe deterioration of functioning occurs after diagnosis. In a number of studies no significant changes, and in other studies improvement of functioning could be measured. Presumably cessation of exposure might be one of the causal factors for the non-progressive character of the disease as has been found. Future studies are needed to clarify the role of various prognostic factors on the course of CSE.

Psychosocial and cognitive rehabilitation of patients with solvent-induced chronic toxic encephalopathy: a randomised controlled study.

BACKGROUND: There is little experience with the (neuro) psychological treatment of patients with solvent-induced chronic toxic encephalopathy (CSE). In this randomised controlled trial (RCT), a treatment programme was evaluated based on previous outcome studies of patients with chronic fatigue, whiplash and traumatic brain damage. METHODS: The treatment consisted of 8 group sessions based on cognitive behavioural principles focusing on inadequate illness behaviours, and 8 sessions of cognitive strategy training to compensate memory problems. The research design was an RCT with follow-up, comparing the cumulative effect of the 2 interventions allocated in random order with a waiting-list control group. Outcome measures were treatment satisfaction, self-ratings of psychosocial and cognitive changes, psychosocial and memory questionnaires and neuropsychological tests. Multiple linear regression analyses were performed with baseline scores, treatment versus control condition, effort status, and litigation or financial compensation status as predictors. RESULTS: Ninety-five patients started treatment, 84 patients had complete data. Treatment satisfaction was high. After the treatment, only the treatment group had improved on objective memory tests and on complaints related to CSE, but not on other questionnaires. Treatment effects diminished at follow-up. Insufficient effort and litigation were negatively associated with treatment outcome. CONCLUSIONS: The positive treatment effects on the cognitive tests were only temporary. It might be important to study the effect of booster sessions to update practiced cognitive strategies. Effort was an important predictor of success, more important than involvement in a litigation procedure. This finding should have implications for the selection of patients.

Polymorphisms in the brain-specific thyroid hormone transporter OATP1C1 are associated with fatigue and depression in hypothyroid patients.

INTRODUCTION: Some hypothyroid patients continue to have significant impairments in psychological well-being, despite adequate treatment with levothyroxine (LT4). T4 transport across the blood-brain barrier is one of the crucial processes for thyroid hormone action in the brain. OATP1C1, a thyroid hormone transporter expressed at the blood-brain barrier, is considered to play a key role in delivering serum T4 to the brain. OBJECTIVE: To examine whether polymorphisms in OATP1C1 are determinants of well-being, neurocognitive functioning and preference for replacement therapy with a combination of LT4 and liothyronine (LT3). DESIGN AND PARTICIPANTS: We studied 141 patients with primary autoimmune hypothyroidism, adequately treated with LT4 monotherapy and participating in a randomized clinical trial comparing LT4 therapy with LT4-LT3 combination therapy. OUTCOME MEASUREMENTS: Different questionnaires on well-being and neurocognitive tests were performed at baseline. Serum thyroid parameters, OATP1C1-intron3C > T, OATP1C1-Pro143Thr and OATP1C1-C3035T polymorphisms were determined. RESULTS: Allele frequencies of the OATP1C1 polymorphisms in patients with primary hypothyroidism were similar to those of healthy controls. Both the OATP1C1-intron3C > T and the OATP1C1-C3035T polymorphism, but not the OATP1C1-Pro143Thr polymorphism, were associated with symptoms of fatigue and depression. OATP1C1 polymorphisms were not associated with measures of neurocognitive functioning or preference for combined LT4-LT3 therapy. CONCLUSIONS: OATP1C1 polymorphisms are associated with fatigue and depression, but do not explain differences in neurocognitive functioning or appreciation of LT4-LT3 combination therapy. Future studies are needed to confirm these findings.

Cognitive functioning and well-being in euthyroid patients on thyroxine replacement therapy for primary hypothyroidism.

OBJECTIVE: Hypothyroidism is associated with neurocognitive impairment. Sparse data suggest that treatment of hypothyroidism, resulting in a return to euthyroidism, may be associated with only partial recovery of overall neurocognitive functioning. The aim of this study was to assess neurocognitive functioning and well-being in euthyroid patients with primary hypothyroidism on adequate thyroxine (T4) treatment. We also investigated whether serum TSH and thyroid antibodies are determinants of neurocognitive functioning and well-being. DESIGN: We assessed neurocognitive functioning and well-being in 141 patients with primary hypothyroidism. METHODS: Neurocognitive test results and scores on questionnaires measuring well-being of 141 patients were compared with the reference values for these tests as published and used in Dutch clinical neuropsychological practice. Assessment of neurocognitive functioning included tests for cognitive or psychomotor speed, attention, working memory as well as learning and memory. Well-being was measured with the Symptom Check List-90 total score and the Rand 36-item Health Survey subscales for 'mental health' and 'vitality'. RESULTS: Patients showed poor performance on various domains of neurocognitive functioning compared with mean standard reference values, especially on a complex attention task and on verbal memory tests. Levels of well-being were significantly lower for patients compared with those of the general population. Neither serum TSH nor thyroid antibodies were determinants of neurocognitive functioning and well-being. CONCLUSION: The results of this study suggest that neurocognitive functioning as well as psychological well-being may not be completely restored in patients with hypothyroidism, despite T4 treatment.

Polymorphisms in type 2 deiodinase are not associated with well-being, neurocognitive functioning, and preference for combined thyroxine/3,5,3'-triiodothyronine therapy.

INTRODUCTION: Some patients on levothyroxine replacement display significant impairment in psychological well-being, compared with sex- and age-matched controls. Levothyroxine-treated patients can be assumed to derive T3 exclusively from deiodination of T4, which, in the central nervous system, is regulated by type II deiodinase (DII). OBJECTIVE: We investigated whether two recently identified polymorphisms in the DII gene (DII-ORFa-Gly3Asp and DII-Thr92Ala) are determinants of well-being and neurocognitive functioning and associated with a preference for replacement with a combination of T3 and T4. METHODS: Genotypes for both polymorphisms were determined in 141 patients with primary autoimmune hypothyroidism, adequately treated with levothyroxine monotherapy and participating in a randomized clinical trial comparing T4 therapy with T4/T3 combination therapy. Questionnaires on well-being and neurocognitive tests were performed at baseline. RESULTS: Allele frequencies in patients with primary hypothyroidism were similar to those of healthy blood bank donors (32.0 vs. 33.9% for DII-ORFa-Gly3Asp and 40.4 vs. 38.8% for DII-Thr92Ala). DII polymorphisms were not associated with measures of well-being, neurocognitive functioning, or preference for combined T4/T3 therapy. CONCLUSION: The DII-ORFa-Gly3Asp and DII-Thr92Ala polymorphisms do not explain differences in well-being, neurocognitive functioning, or appreciation of T4/T3 combination therapy in patients treated for hypothyroidism.

Combined therapy with levothyroxine and liothyronine in two ratios, compared with levothyroxine monotherapy in primary hypothyroidism: a double-blind, randomized, controlled clinical trial.

Controversy remains about the value of combined treatment with levothyroxine (LT4) and liothyronine (LT3), compared with LT4 alone in primary hypothyroidism. We compared combined treatment with LT4 and LT3 in a ratio of 5:1 or 10:1 with LT4 monotherapy. We conducted a double-blind, randomized, controlled trial in 141 patients (18-70 yr old) with primary autoimmune hypothyroidism, recruited via general practitioners. Inclusion criteria included: LT4 treatment for 6 months or more, a stable dose for 6 wk or more, and serum TSH levels between 0.11 and 4.0 microU/ml (mU/liter). Randomization groups were: 1) continuation of LT4 (n = 48); 2) LT4/LT3, ratio 10:1 (n = 46); and 3) LT4/LT3, ratio 5:1 (n = 47). Subjective preference of study medication after 15 wk, compared with usual LT4, was the primary outcome measure. Secondary outcomes included scores on questionnaires on mood, fatigue, psychological symptoms, and a substantial set of neurocognitive tests. Study medication was preferred to usual treatment by 29.2, 41.3, and 52.2% in the LT4, 10:1 ratio, and 5:1 ratio groups, respectively (chi2 test for trend, P = 0.024). This linear trend was not substantiated by results on any of the secondary outcome measures: scores on questionnaires and neurocognitive tests consistently ameliorated, but the amelioration was not different among the treatment groups. Median end point serum TSH was 0.64 microU/ml (mU/liter), 0.35 microU/ml (mU/liter), and 0.07 microU/ml (mU/liter), respectively [ANOVA on ln(TSH) for linear trend, P < 0.01]. Mean body weight change was +0.1, -0.5, and -1.7 kg, respectively (ANOVA for trend, P = 0.01). Decrease in weight, but not decrease in serum TSH was correlated with increased satisfaction with study medication. Of the patients who preferred combined LT4/LT3 therapy, 44% had serum TSH less than 0.11 microU/ml (mU/liter). Patients preferred combined LT4/LT3 therapy to usual LT4 therapy, but changes in mood, fatigue, well-being, and neurocognitive functions could not satisfactorily explain why the primary outcome was in favor of LT4/LT3 combination therapy. Decrease in body weight was associated with satisfaction with study medication.

Psychological treatment of patients with chronic toxic encephalopathy: lessons from studies of chronic fatigue and whiplash.

BACKGROUND: Chronic toxic encephalopathy (CTE), which can result from long-term exposure to organic solvents, is characterized by problems of attention and memory, fatigue and affective symptoms. There is little experience with (neuro)psychological treatment in this patient group. We reviewed treatment outcome studies of CTE and comparable syndromes, namely, chronic whiplash-associated disorder (WAD) and chronic fatigue syndrome (CFS), with a view to providing recommendations for the psychological treatment of patients with CTE. METHODS: PubMed and PsychLIT were systematically searched and reference lists of retrieved articles were studied. The articles were classified according to study design and level of evidence. RESULTS: The studies of CFS provided high-level evidence for the effectiveness of cognitive-behavior therapy (CBT) in challenging dysfunctional cognitions regarding the effectiveness of rest and in stimulating graded activity. The studies of WAD were methodologically weaker, and most evaluated a combination of CBT and graded activity training. There was some evidence that changing fatigue- or pain-related behaviors may result in cognitive improvement. Two uncontrolled studies of CTE evaluated cognitive rehabilitation techniques but yielded inconsistent findings. CONCLUSIONS: CBT techniques focusing on changing illness attributions and on stimulating graded activity might be useful for patients with CTE, diminishing fatigue-related problems of concentration and memory. Future studies should evaluate whether cognitive deficits of CTE patients as a result of neurotoxic effects of exposure should be treated by cognitive rehabilitation.

Suboptimal performance on neuropsychological tests in patients with suspected chronic toxic encephalopathy.

Suboptimal performance during neuropsychological testing can seriously complicate assessment in behavioral neurotoxicology. We present data on the prevalence of suboptimal performance in a group of Dutch patients with suspected chronic toxic encephalopathy (CTE) after long-term occupational exposure to solvents. One hundred and forty-five subjects referred to one of two Dutch national assessment centers for CTE were administered the Amsterdam Short-Term Memory Test (ASTM) and the Test of Memory Malingering (TOMM), two tests specifically developed for the detection of suboptimal performance. For both tests, very cautious cut-off scores were chosen with a specificity of 99%. Results indicated that suboptimal performance appears to be a substantial problem in this group of patients with suspected CTE after long-term exposure to organic solvents. Only 54% of our subjects obtained normal scores on both tests of malingering, i.e. at or above cut-off score. The two tests seemed to measure the same concept in that nearly all the subjects with low TOMM scores also had low ASTM scores. However, a higher proportion of subjects scored below the cut-off on the ASTM than on the TOMM.