Efficacy of individual and group hypnotherapy in irritable bowel syndrome (IMAGINE): a multicentre randomised controlled trial.

BACKGROUND: Hypnotherapy for irritable bowel syndrome (IBS) has been used primarily in patients with refractory symptoms in specialised departments and delivered on an individual basis. We aimed to test the hypothesis that hypnotherapy would be more effective than educational supportive therapy, and that group hypnotherapy would be non-inferior to individual hypnotherapy for patients with IBS referred from primary and secondary care. METHODS: We did a multicentre randomised controlled trial (IMAGINE) in 11 hospitals in the Netherlands. Patients with IBS, aged 18-65 years, who were referred from primary or secondary care were randomly allocated (3:3:1) in blocks of six using a computer-based random number table procedure by staff not involved in the treatment to receive six sessions of individual or group hypnotherapy or group educational supportive therapy (control group). The primary outcome was adequate relief of IBS symptoms, with responders defined as patients who reported adequate relief when asked once weekly on three or four occasions in 4 consecutive weeks. We compared hypnotherapy (both groups) with control in the intention-to-treat population (excluding individuals subsequently found to be ineligible for enrolment), and assessed non-inferiority of group hypnotherapy versus individual hypnotherapy in the per-protocol population (with a non-inferiority margin of 15%) at 3 months and 12 months. This trial is registered with ISRCTN, number ISRCTN22888906, and is completed. FINDINGS: Between May 31, 2011, and April 6, 2016, 494 patients referred for psychological treatment for IBS were assessed for eligibility, of whom 354 were randomly allocated to the three groups: 150 to individual hypnotherapy, 150 to group hypnotherapy, and 54 to educational supportive therapy. After exclusion of individuals subsequently found to be ineligible for enrolment, 142 patients in the individual hypnotherapy group, 146 in the group hypnotherapy group, and 54 in the control group were included in the intention-to-treat population. Of these, 22 (15%) patients in the individual hypnotherapy group, 22 (15%) in the group hypnotherapy group, and 11 (20%) in the control group dropped out before or during therapy. In the intention-to-treat analysis, the adequate response rate was 40·8% (95% CI 31·7-50·5) in the individual hypnotherapy group, 33·2% (24·3-43·5) in the group hypnotherapy group, and 16·7% (7·6-32·6) in the control group at 3 months. At 12 months, 40·8% (31·3-51·1) of patients in the individual hypnotherapy group, 49·5% (38·8-60·0) of patients in the group hypnotherapy group, and 22.6% (11·5-39·5) of patients in the control group reported adequate relief. Hypnotherapy was more effective than control at 3 months (odds ratio 2·9, 95% CI 1·2-7·4, p=0·0240) and 12 months (2·8, 1·2-6·7, p=0·0185). In the per-protocol analysis, 49·9% (39·2-60·6) in the individual hypnotherapy group and 42·7% (32·3-53·8) in the group hypnotherapy group had adequate relief at 3 months, and 55·5% (43·4-67·1) of individual and 51·7% (40·2-63·0) of group hypnotherapy patients reported adequate relief at 12 months. Group hypnotherapy was therefore non-inferior to individual hypnotherapy. Eight unexpected serious adverse reactions (six in the individual hypnotherapy group and two in the group hypnotherapy group) were reported, most of which were cancer or inflammatory bowel disease, and were judged by the medical ethics committee as not being related to the therapy. INTERPRETATION: Hypnotherapy should be considered as a possible treatment for patients with IBS in primary and secondary care. Furthermore, group therapy could allow many more patients to be treated for the same cost. FUNDING: None.

Systematic review: The placebo effect of psychological interventions in the treatment of irritable bowel syndrome.

AIM: To determine the placebo response rate associated with different types of placebo interventions used in psychological intervention studies for irritable bowel syndrome. METHODS: Randomized controlled trials comparing psychological interventions (stress management/relaxation therapy (cognitive) behavioral therapy, short-term psychodynamic therapy, and hypnotherapy) for the treatment of adult patients with irritable bowel syndrome (IBS) diagnosed with the Manning or Rome criteria with an adequate placebo control treatment and reporting data on IBS symptom severity were identified by searching PubMed, Embase, the Cochrane Library, CINAHL and PsycINFO databases. Full-text articles that were written in English and published between 1966 and February 2016 in peer-reviewed journals were selected for the present review. Placebo interventions were considered to be adequate if the number of sessions and the amount of time spent with the therapist were the same as in the active treatment. The placebo response rate (PRR) was computed for IBS symptom severity (primary outcome measure) as well as for anxiety, depression and quality of life (secondary outcome measures). RESULTS: Six studies, with a total of 555 patients met the inclusion criteria. Four studies used an educational intervention, whereas two studies used a form of supportive therapy as the placebo intervention. The PRR for IBS symptom severity ranged from 25% to 59%, with a pooled mean of 41.4%. The relative PRR for the secondary outcome measures ranged from 0% to 267% for anxiety, 6% to 52% for depression 20% to 125% for quality of life. The PRR associated with pharmacological treatments, treatment with dietary bran and complementary medicine ranged from 37.5% to 47%. Contrary to our expectations, the PRR in studies on psychological interventions was comparable to that in studies on pharmacological, dietary and alternative medical interventions. CONCLUSION: The PRR is probably determined to a larger extent by patient-related factors, such as expectations and desire for the treatment to be effective, than the content of the placebo intervention.

Local Geographical Distribution of Acute Involuntary Psychiatric Admissions in Subdistricts In and Around Utrecht, the Netherlands.

BACKGROUND: Acute involuntary psychiatric admissions (AIPA) tend to be applied more often in urban areas. OBJECTIVE: The current study aims to describe AIPA prevalence differences between the subdistricts in an urban area, and to identify which district characteristics are associated with a higher AIPA district density. METHODS: Information was collected on consecutive AIPAs over a 64-month period (2005-2010) in 49 subdistricts in and around the city of Utrecht, the Netherlands, including 1098 AIPAs. District characteristics included several demographic and economical factors and health care characteristics such as number of sheltered living facilities. RESULTS: The AIPA density (mean 4.4/10,000 inhabitants/y) was four to five times higher in the most urbanized subdistrict (around 12) compared to the suburban subdistricts (2.5-3). On the district level, the main correlates with AIPA density per district were unemployment rate and small household size. Other correlates were percentage of non-Western immigrants and number of facilities of sheltered living. CONCLUSIONS: The considerable AIPA density variation between subdistricts in this urban environment reflects that people who are prone to psychiatric admissions live in economically less prosperous environments. Impaired social networks and economic concerns may also contribute to an environment representing social defeat, increased demoralization, or social fragmentation.

Effects of a culturally sensitive assessment on symptom profiles in native Dutch and Moroccan patients with a first psychosis referral.

Previous studies have reported a higher incidence of psychosis in Moroccan immigrants in the Netherlands than among native-born residents. However, this disparity was substantially attenuated when cultural differences in symptom presentation were taken into account. To better understand the impact of different diagnostic procedures on incidence rates, we examined the effects of the use of a culturally sensitive diagnostic interview, compared to a standard semi-structured diagnostic interview, on symptom profiles among Moroccan immigrant and native Dutch patients in the Netherlands. A total of 26 Dutch and 26 Moroccan patients referred with a possible first psychosis diagnosis were interviewed twice: once with the standard version and once with a culturally adapted version of the Comprehensive Assessment of Symptoms and History questionnaire (CASH and CASH-CS, respectively). Among native Dutch patients, symptoms profiles based on CASH and CASH-CS interviews were very similar. By contrast, among Moroccan immigrant patients, symptom profiles based on CASH and CASH-CS interviews differed substantially, with more mania symptoms (+30%; p < .05) and fewer delusions (-31%; p < .05) reported when using the CASH-CS. These results suggest that the over-diagnosis of schizophrenia in Moroccan immigrants with a first psychosis referral may be related to a tendency to under-detect mood symptoms and over-detect positive psychotic symptoms when a standard diagnostic procedure is used. This bias may be corrected, at least in part, by the use of a culturally sensitive interview instrument such as the CASH- CS.

Comparison of medical costs generated by IBS patients in primary and secondary care in the Netherlands.

BACKGROUND: Irritable Bowel Syndrome (IBS) is a functional somatic syndrome characterized by patterns of persistent bodily complaints for which a thorough diagnostic workup does not reveal adequate explanatory structural pathology. Detailed insight into disease-specific health-care costs is critical because it co-determines the societal impact of the disease, enables the assessment of cost-effectiveness of existing and new treatments, and facilitates choices in treatment policy. In the present study the aim was, to compare the costs and magnitude of healthcare consumption for patients diagnosed with Irritable Bowel Syndrome (IBS) in primary and secondary care, compare these costs with the average health care expenditure for patients without IBS and describe these costs in further detail. METHODS: Reimbursement data for patients diagnosed with IBS by a general practitioner (GP) or specialist between 2006 and 2009 were extracted from a healthcare insurance company and compared to an age and gender matched control group of patients without IBS. Using a case-control design, direct medical costs for GP consultations, specialist care and medication prescriptions were calculated. RESULTS: Data of 326 primary care and 9274 secondary care IBS patients were included in the analysis. For primary care patients, the mean total annual health care costs for the three years after diagnosis compared to the three years before diagnosis, increased with 486 Euro after IBS was diagnosed, whereas for secondary care patients, these costs increased with 2328 Euro. Total health care costs remained higher in the three years after the initial diagnosis when the patient is treated in secondary care, compared to primary care. This increase was significant for hospital specialist costs and medications, but not for GP contacts. For controls, there was no significant difference in mean total annual health costs in the three years before and the three years after the diagnosis and also no significant difference in cost increases between both primary- and secondary-care control patients. CONCLUSION: Total healthcare costs per patient substantially increase after a diagnosis of IBS and IBS related costs are significantly higher when patients are treated in secondary-care compared to primary-care. IBS patients should be treated in primary-care where possible, not only because guidelines recommend this from a quality of care viewpoint, but also to optimize use of health care resources. Referral should be restricted to those patients with alarm symptoms, with ill-matching symptoms, or other cases of diagnostic uncertainty.

Differences in health care utilisation between elderly from ethnic minorities and ethnic Dutch elderly.

INTRODUCTION: In the Netherlands, as in other Western countries, ethnic minority elderly are more often in poorer health than the indigenous population. The expectation is that this health disadvantage results in more frequent use of health care services. METHODS: We studied registered data on the proportion of health care receivers, frequency of use, and health care costs collected by a major Dutch health insurance company in 2010. Data from 10,316 Turkish, 14,490 Moroccan, 8,619 Surinamese, and 1,064 Moluccan adults aged 55 years and older were compared with data from a sample of 33,725 ethnic Dutch older adults. RESULTS: Unadjusted and adjusted (for age and gender) analyses showed the following. Moluccans had lower usage levels for all types of health care services. Use of primary health care facilities was higher for Turks, Moroccans, and Surinamese compared with the ethnic Dutch, with the exception that physical therapy was less frequently used among the Turks and Moroccans. Use of hospital care was lower, except for the Surinamese, who had a similar level of usage to that of the ethnic Dutch. CONCLUSIONS: The health disadvantage previously observed within most ethnic minority elderly populations does not result in an overall more frequent use of health care services. Further research is needed for the interpretation of the ethnic variations in health care use as potentially inequitable, by taking medical need, patient treatment preferences, and treatment adherence into account.

Can assertive community treatment remedy patients dropping out of treatment due to fragmented services?

Previously, many patients with severe mental illness had difficulties to engage with fragmented mental health services, thus not receiving care. In a Dutch city, Assertive Community Treatment (ACT) was introduced to cater specifically for this group of patients. In a pre-post comparison, changes in mental health care consumption were examined. All mental health care contacts, ACT and non-ACT, of patients in the newly started ACT-teams were extracted from the regional Psychiatric Case Register. Analyses of mental health care usage were performed comparing the period before ACT introduction with the period thereafter. After the introduction of ACT, mental health care use increased in this group of patients, although not all patients remained under the care of ACT teams. ACT may succeed in delivering more mental health care to patients with severe mental illness and treatment needs who previously had difficulties engaging with fragmented mental health care services.

Factors associated with increasing functional decline in multimorbid independently living older people.

OBJECTIVES: With increasing age the levels of activities of daily living (ADL) deteriorate. In this study we aimed to investigate which demographic characteristics and disorders are associated with ADL disabilities in multi-morbid older people. STUDY DESIGN: We performed a cross-sectional study with baseline patient data from a large Dutch trial in independently living multi-morbid older people combined with the reimbursed healthcare data for the same subjects. MAIN OUTCOME MEASURES: The primary outcome of our study was the level of independence of activities of daily living (ADL) as assessed with the Modified Katz Activities of Daily Living (KATZ-15) scale. RESULTS: In our study we were able to include 1187 persons (63.0% female) for whom both questionnaire data and reimbursed healthcare data was available. In total, 59% had a Katz-15 score of 1 or higher. The strongest associations with ADL disabilities in women were psychiatric disorders, with prevalence rate (PR) estimates of 1.37 (95% confidence interval (CI): 1.17-1.60) and transient ischaemic attacks and cerebrovasculair accidents in men, with PR estimates of 1.94 (95% CI: 1.41-2.66). Although univariate analysis seemed to also reveal associations with socio-demographic factors such as living together with a partner or the socio-economic status, these factors were not independently associated with ADL disabilities. CONCLUSIONS: In this cross-sectional study we found that 71% of the multi-morbid female elderly had a sub-optimal level of activities of daily living, as assessed with the Katz-15 scale. The results of our study show that multiple disorders are associated with ADL disabilities in multi-morbid older men and women. We found socio-demographic characteristics not to be independently associated ADL disabilities.

Cancer mortality in patients with psychiatric diagnoses: a higher hazard of cancer death does not lead to a higher cumulative risk of dying from cancer.

PURPOSE: Both increased as well as decreased cancer mortality among psychiatric patients has been reported, but competing death causes were not included in the analyses. This study aims to investigate whether observed cancer mortality in patients with psychiatric disorders might be biased by competing death causes. METHOD: In this retrospective cohort study on data from the Psychiatric Case Register Middle Netherlands linked to the death register of Statistics Netherlands, the risk of cancer death among patients with schizophrenia (N = 4,590), bipolar disorder (N = 2,077), depression (N = 15,130) and their matched controls (N = 87,405) was analyzed using a competing risk model. RESULTS: Compared to controls, higher hazards of cancer death were found in patients with schizophrenia (HR = 1.61, 95 % CI 1.26-2.06), bipolar disorder (HR = 1.20, 95 % CI 0.81-1.79) and depression (HR = 1.26, 95 % CI 1.10-1.44). However, the HRs of death due to suicide and other death causes were more elevated. Consequently, among those who died, the 12-year cumulative risk of cancer death was significantly lower. CONCLUSIONS: Our analysis shows that, compared to the general population, psychiatric patients are at higher risk of dying from cancer, provided that they survive the much more elevated risks of suicide and other death causes.

Psychosis and suicide risk by ethnic origin and history of migration in the Netherlands.

BACKGROUND: There is an increased incidence of non-affective psychotic disorders (NAPD) among first- and second-generation migrants in Europe. The purpose of this population-based study was to compare the risk of suicide in Dutch natives and immigrants with or without NAPD. METHODS: Cases of NAPD (n=12 580) from three Dutch psychiatric registers were linked to the cause of death register of Statistics Netherlands and were compared to matched controls (n=244 792) from the population register, who had no such diagnosis. Hazard ratios (HRs) of suicide were estimated and adjusted for age and gender by Cox regression analysis. RESULTS: The presence of NAPD was strongly associated with suicide risk in each ethnic group. However, for all ethnic minority groups the HRs were somewhat lower than among Dutch natives, for whom the HR was 23.4 (95%-CI; 18.5-29.7). A closer examination revealed that suicide risk was influenced by the history of migration. While the risk for immigrants of the first generation, diagnosed with NAPD, was significantly lower than that for native Dutch patients (HR=0.45; 95%-CI: 0.28-0.73), the risk for those of the second generation was more similar to that for the Dutch (HR=0.85; 95%-CI: 0.51-1.40) (P value of history of migration=0.005). CONCLUSION: Immigrants diagnosed with NAPD of the first generation appear to be protected against suicide, whereas this protection is waning among those of the second generation. This is the first study worldwide on suicide in migrants with NAPD and the first study of suicide in patients with NAPD in the Netherlands.

Familial clustering of schizophrenia, bipolar disorder, and major depressive disorder.

PURPOSE: To investigate familial clustering of schizophrenia, bipolar disorder, and major depressive disorder. METHODS: Combining data from a psychiatric case registry and Statistics Netherlands provided information on 4,673 affected probands and 18,692 matched population controls. RESULTS: Probands with schizophrenia had relative risks (RRs) for having a sibling with schizophrenia of 3.77 (95% confidence interval (CI): 2.60-5.46) and with bipolar disorder of 1.79 (95% CI: 0.64-4.96) as compared with a reference proband. Probands affected with bipolar disorder have an RR of 6.51 (95% CI: 2.60-16.29) for having a sibling with bipolar disorder and of 1.71 (95% CI: 0.71-4.14) for having a sibling with schizophrenia as compared with a reference proband. Probands affected with major depressive disorder also have increased risk for having a sibling with schizophrenia (RR: 2.04, 95% CI: 1.54-2.72) as compared with a reference proband, which was similar to the risk for having a sibling with major depressive disorder (RR: 1.91, 95% CI: 1.63-2.24) or bipolar disorder (RR: 2.06, 95% CI: 1.18-3.60). CONCLUSION: Our findings suggest, as previous studies have, that risk across schizophrenia and bipolar disorder is considerably lower (twofold) than within diagnostic entities, whereas for major depressive disorder risk is similar within and across diagnostic entities.

A randomised controlled trial on hypnotherapy for irritable bowel syndrome: design and methodological challenges (the IMAGINE study).

BACKGROUND: Irritable Bowel Syndrome (IBS) is a common gastro-intestinal disorder in primary and secondary care, characterised by abdominal pain, discomfort, altered bowel habits and/or symptoms of bloating and distension. In general the efficacy of drug therapies is poor. Hypnotherapy as well as Cognitive Behaviour Therapy and short Psychodynamic Therapy appear to be useful options for patients with refractory IBS in secondary care and are cost-effective, but the evidence is still limited. The IMAGINE-study is therefore designed to assess the overall benefit of hypnotherapy in IBS as well as comparing the efficacy of individual versus group hypnotherapy in treating this condition. METHODS/DESIGN: The design is a randomised placebo-controlled trial. The study group consists of 354 primary care and secondary care patients (aged 18-65) with IBS (Rome-III criteria). Patients will be randomly allocated to either 6 sessions of individual hypnotherapy, 6 sessions of group hypnotherapy or 6 sessions of educational supportive therapy in a group (placebo), with a follow up of 9 months post treatment for all patients. Ten hospitals and four primary care psychological practices in different parts of The Netherlands will collaborate in this study. The primary efficacy parameter is the responder rate for adequate relief of IBS symptoms. Secondary efficacy parameters are changes in the IBS symptom severity, quality of life, cognitions, psychological complaints, self-efficacy as well as direct and indirect costs of the condition. Hypnotherapy is expected to be more effective than the control therapy, and group hypnotherapy is expected not to be inferior to individual hypnotherapy. DISCUSSION: If hypnotherapy is effective and if there is no difference in efficacy between individual and group hypnotherapy, this group form of treatment could be offered to more IBS patients, at lower costs. TRIAL REGISTRATION NUMBER: ISRCTN: ISRCTN22888906.

Predictive validity of a culturally informed diagnosis of schizophrenia: a 30 month follow-up study with first episode psychosis.

UNLABELLED: Previous research has shown discrepancies between a standard diagnostic interview for schizophrenia (CASH) and a culture sensitive version of this instrument (CASH-CS) in Moroccan patients. More specifically we showed that among Moroccan immigrants the CASH-CS resulted in fewer patients with a diagnosis of schizophrenia compared with diagnoses based on the CASH, whereas for Native Dutch patients there was no difference between the CASH and the CASH-CS. The aim of the current study was to compare the predictive validity of a diagnosis of schizophrenia according to the CASH and CASH-CS. METHOD: Thirty months after referral, 26 Moroccan and 26 native Dutch patients with a suspected first psychotic episode were compared with regard to 30-month diagnostic stability, symptom development, psychosocial functioning, medication use and hospitalization using baseline diagnoses based on the two versions of the CASH. RESULTS: Moroccan patients who were diagnosed with schizophrenia using the standard CASH at baseline had a significantly better 30-month prognosis than native Dutch patients with the same CASH diagnosis. Prognosis of schizophrenia according to the CASH-CS was similar for Moroccans and native Dutch patients. Diagnostic stability according to the CASH was high for native Dutch (92%), but low for Moroccan patients (27%), whereas diagnostic stability according to the CASH-CS was high for both groups (85% and 81%, respectively). CONCLUSION: These data raise questions regarding the validity of the standard CASH in Moroccan immigrants in The Netherlands and support the validity of the CASH-CS. As a consequence, there are serious doubts about the validity of previous studies showing an increased incidence of schizophrenia in immigrants using standard diagnostic procedures.

A comorbid anxiety disorder does not result in an excess risk of death among patients with a depressive disorder.

BACKGROUND: Several studies have demonstrated increased mortality associated with depression and with anxiety. Mortality due to comorbidity of two mental disorders may be even more increased. Therefore, we investigated the mortality among patients with depression, with anxiety and with both diagnoses. METHODS: By linking the longitudinal Psychiatric Case Register Middle-Netherlands, which contains all patients of psychiatric services in the Utrecht region, to the death register of Statistics Netherlands, hazard ratio's of death were estimated overall and for different categories of death causes separately. RESULTS: We found an increased risk of death among patients with an anxiety disorder (N=6919): HR=1.45 (95%CI: 1.25-1.69), and among patients with a depression (N=14,778): HR=1.83, (95%CI: 1.72-1.95), compared to controls (N=103,824). The hazard ratios among both disorders combined (N=4260) were similar to those with only a depression: HR=1.91, (95% CI: 1.64-2.23). Among patients with a depression, mortality across all important disease-related categories of death causes (neoplasms, cardiovascular, respiratory, and other diseases) and due to suicide was increased, without an excess mortality in case of comorbid anxiety. LIMITATIONS: The presented data are restricted to broad categories of patients in specialist services. No data on behavioral or intermediate factors were available. CONCLUSIONS: Although anxiety is associated with an increased risk of death, the presence of anxiety as comorbid disorder does not give an additional increase in the risk of death among patients with a depressive disorder. The increased mortality among patients with depression is not restricted to suicide and cardiovascular diseases, but associated with a broad range of death causes.

The psychiatric case register middle Netherlands.

BACKGROUND: The Psychiatric Case Register Middle Netherlands (PCR-MN) registers the mental healthcare consumption of over Dutch 760,000 inhabitants in the centre of the Netherlands. In 2010 the follow-up period was over ten years. In this paper we describe the content, aims and research potential of this case register. DESCRIPTION: All mental healthcare institutions in the middle-western part of the province of Utrecht participate in the PCR-MN case register. All in- and out-patients treated in these institutions have been included in the database from the period 2000 to 2010. Diagnosis according to DSM-IV on axis I to IV, visits to in- and out-patient clinics and basic demographics are recorded. A major advantage of this register is the possibility to link patients anonymously from the PCR-MN cohort to other databases to analyze relationships with determinants and outcomes, such as somatic healthcare consumption, mortality, and demographics, which further increases the research potential CONCLUSIONS: The PCR-MN database has a large potential for scientific research because of its size, duration of follow-up and ability to link with additional databases, and is accessible for academic researchers.

Paternal age and psychiatric disorders: findings from a Dutch population registry.

BACKGROUND: We measured the association between paternal age and schizophrenia (SCZ), autism spectrum disorders (ASD), major depressive disorder (MDD), and bipolar disorder (BPD) in the Dutch population. METHODS: In total, 14231 patients and 56924 matched controls were collected and analyzed for an association with paternal age by logistic regression. RESULTS: ASD is significantly associated with increased paternal age: Older fathers >40 years of age have a 3.3 times increased odds of having a child with ASD compared to young fathers <20 years of age. SCZ has significant associations for fathers aged >35 years (OR=1.27, 95% Confidence Interval: 1.05 and 1.53). For MDD, both younger and older fathers have increased odds. No association was found for BPD. CONCLUSIONS: The effects of paternal age as a risk factor are different for ASD and SCZ on one hand, and the affective disorders on the other hand. Different types of association might indicate different biological or psychosocial mechanisms. Late paternity (associated with predispositions to psychiatric disorders) seems the most probable explanation for the association with paternal age.

Adjuvant aspirin therapy reduces symptoms of schizophrenia spectrum disorders: results from a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Inflammatory processes may play a role in the pathophysiology of schizophrenia. The aim of this study was to determine the efficacy of adjuvant treatment with aspirin (acetylsalicylic acid) in schizophrenia spectrum disorders. METHOD: This randomized, double-blind, placebo-controlled study was conducted between May 2004 and August 2007. Seventy antipsychotic-treated inpatients and outpatients from 10 psychiatric hospitals in The Netherlands with a DSM-IV-diagnosed schizophrenia spectrum disorder were included. Patients were randomized to adjuvant treatment with aspirin 1000 mg/d or placebo. During a 3-month follow-up, psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS). Other assessments included cognitive tests and immune function. The primary efficacy outcome was the change in total PANSS score. Secondary outcomes were changes in the PANSS subscales and cognitive test results. RESULTS: Mixed-effect models showed a 4.86-point (95% CI, 0.91 to 8.80) and 1.57-point (95% CI, 0.06 to 3.07) larger decrease in the aspirin group compared to the placebo group on the total and positive PANSS score, respectively. Similar but not statistically significant results were observed for the other PANSS subscale scores. Treatment efficacy on total PANSS score was substantially larger in patients with the more altered immune function (P = .018). Aspirin did not significantly affect cognitive function. No substantial side effects were recorded. CONCLUSION: Aspirin given as adjuvant therapy to regular antipsychotic treatment reduces the symptoms of schizophrenia spectrum disorders. The reduction is more pronounced in those with the more altered immune function. Inflammation may constitute a potential new target for antipsychotic drug development. TRIAL REGISTRATION: controlled-trials.com Identifier: ISRCTN27745631.

Effect of treatment of subclinical neonatal seizures detected with aEEG: randomized, controlled trial.

OBJECTIVES: The goals were to investigate how many subclinical seizures in full-term neonates with hypoxic-ischemic encephalopathy (HIE) would be missed without continuous amplitude-integrated electroencephalography (aEEG) and whether immediate treatment of both clinical and subclinical seizures would result in a reduction in the total duration of seizures and a decrease in brain injury, as seen on MRI scans. METHODS: In this multicenter, randomized, controlled trial, term infants with moderate to severe HIE and subclinical seizures were assigned randomly to either treatment of both clinical seizures and subclinical seizure patterns (group A) or blinding of the aEEG registration and treatment of clinical seizures only (group B). All recordings were reviewed with respect to the duration of seizure patterns and the use of antiepileptic drugs (AEDs). MRI scans were scored for the severity of brain injury. RESULTS: Nineteen infants in group A and 14 infants in group B were available for comparison. The median duration of seizure patterns in group A was 196 minutes, compared with 503 minutes in group B (not statistically significant). No significant differences in the number of AEDs were seen. Five infants in group B received AEDs when no seizure discharges were seen on aEEG traces. Six of 19 infants in group A and 7 of 14 infants in group B died during the neonatal period. A significant correlation between the duration of seizure patterns and the severity of brain injury in the blinded group, as well as in the whole group, was found. CONCLUSIONS: In this small group of infants with neonatal HIE and seizures, there was a trend for a reduction in seizure duration when clinical and subclinical seizures were treated. The severity of brain injury seen on MRI scans was associated with a longer duration of seizure patterns.

Glucocorticosteroids associated with a decreased risk of psychosis.

The hypothesis that chronic inflammation may play a role in psychosis receives increasing attention. In this study, we aim to investigate whether the use of steroidal anti-inflammatory drugs is associated with a decreased risk of psychosis.A longitudinal nested case-control study was performed investigating the association of glucocorticosteroid (GCS) consumption with a new diagnosis of a psychotic disorder. Significantly reduced odds ratios of 0.52 (95% confidence interval, 0.36-0.75) were found for GCS in men only (odds ratio in women, 0.84 [95% confidence interval, 0.590-1.20]). Similar risk reductions were present for the inhaled and systemic GCSs. A dose-response relationship was present. Our finding of an inverse relation between GCS consumption and new psychotic episodes may promote further research into inflammation in schizophrenia.

NQO1 and NFE2L2 polymorphisms, fruit and vegetable intake and smoking and the risk of colorectal adenomas in an endoscopy-based population.

Both environment and genetics contribute to the pathogenesis and prevention of colorectal neoplasia. NAD(P)H: quinone oxidoreductase (NQO1) is a detoxification enzyme that is polymorphic and inducible. We investigated interactions between lifestyle factors and polymorphisms in NQO1 and its key regulatory transcription factor NFE2L2 in colorectal adenoma risk. The NQO1 c.609C>T and g.-718A>G and NFE2L2 g.-650C>A, g.-684G>A and g.-686A>G polymorphisms were determined among 740 Dutch adenoma cases and 698 endoscopy-based controls. Dietary intake was assessed by food frequency questionnaire, other lifestyle information by questionnaire. The NQO1 609CT genotype was associated with a higher adenoma risk (OR 1.27, 95% CI 1.00-1.62) compared with the 609CC genotype, whereas the 609TT genotype was not (OR 1.03, 95% CI 0.56-1.88). The higher risk with the NQO1 609CT-genotype was seen among smokers (OR 1.96, 95% CI 1.40-2.76), but not among nonsmokers (OR 0.91, 95% CI 0.62-1.35; interaction p = 0.030). Fruit and vegetable consumption did not protect smokers from adenomas and did not interact with the NQO1 609C>T polymorphism or the NFE2L2 polymorphisms. A higher adenoma risk seen with high fruit and vegetable consumption among NQO1 -718GG genotypes was absent among -718GA genotypes (interaction p = 0.071). Gene-gene interactions were observed between the NQO1 609C>T and NFE2L2 -686A>G polymorphisms (interaction p = 0.056) and between the NQO1 -718 G>A and NFE2L2 -650C>A polymorphisms (interaction p = 0.013). IN CONCLUSION: the NQO1 609CT genotype is associated with increased adenoma risk among smokers, which is not diminished by high fruit and vegetable consumption. The observed gene-gene interactions may point to a role for NFE2L2 polymorphisms in NQO1-related adenoma formation.