[Prognostic modelling and proactive intervention in psychosis: efficacy and cost-effectiveness]. / Prognostisch modelleren en proactieve interventie bij psychose: effectiviteit en kosteneffectiviteit.

BACKGROUND: Diagnoses have heterogeneous outcomes, varying from good to extremely poor. There is a need to single out an ultra-high-risk group of individuals who have illnesses that might well end unfavourably or who might later develop serious psychopathology.
AIM: To devise a screening instrument that can identify a group of individuals who run a very high risk of developing a first-episode psychosis, and to create a type of intervention that can modify the course of the illness.
METHOD: We developed a short screening instrument (PQ-16) and were able to ascertain its predictive value. We also tested an intervention that could influence risk factors and deal with emerging symptoms thereby achieving a better outcome for the patient.
RESULTS: We developed a two-step detection instrument with a positive predictive value of 44%. The intervention, involving cognitive behavioural therapy for ultra-high-risk patients, was effective and led to a risk reduction of about 50%. Using the ultra-high-risk group of patients, we were able to model three prognostic profiles, each carrying a 4%, 13%, and 70% risk of subsequently developing psychosis. The intervention was cost-effective, reducing the financial burden on the health care services and on society as a whole.
CONCLUSION: Prognostic modelling and proactive intervention can achieve improvements in health at lower costs.

Development of a stage-dependent prognostic model to predict psychosis in ultra-high-risk patients seeking treatment for co-morbid psychiatric disorders.

BACKGROUND: Current ultra-high-risk (UHR) criteria appear insufficient to predict imminent onset of first-episode psychosis, as a meta-analysis showed that about 20% of patients have a psychotic outcome after 2 years. Therefore, we aimed to develop a stage-dependent predictive model in UHR individuals who were seeking help for co-morbid disorders. METHOD: Baseline data on symptomatology, and environmental and psychological factors of 185 UHR patients (aged 14-35 years) participating in the Dutch Early Detection and Intervention Evaluation study were analysed with Cox proportional hazard analyses. RESULTS: At 18 months, the overall transition rate was 17.3%. The final predictor model included five variables: observed blunted affect [hazard ratio (HR) 3.39, 95% confidence interval (CI) 1.56-7.35, p < 0.001], subjective complaints of impaired motor function (HR 5.88, 95% CI 1.21-6.10, p = 0.02), beliefs about social marginalization (HR 2.76, 95% CI 1.14-6.72, p = 0.03), decline in social functioning (HR 1.10, 95% CI 1.01-1.17, p = 0.03), and distress associated with suspiciousness (HR 1.02, 95% CI 1.00-1.03, p = 0.01). The positive predictive value of the model was 80.0%. The resulting prognostic index stratified the general risk into three risk classes with significantly different survival curves. In the highest risk class, transition to psychosis emerged on average ⩾8 months earlier than in the lowest risk class. CONCLUSIONS: Predicting a first-episode psychosis in help-seeking UHR patients was improved using a stage-dependent prognostic model including negative psychotic symptoms (observed flattened affect, subjective impaired motor functioning), impaired social functioning and distress associated with suspiciousness. Treatment intensity may be stratified and personalized using the risk stratification.

Cannabis use and transition to psychosis in individuals at ultra-high risk: review and meta-analysis.

BACKGROUND: Previous research has established the relationship between cannabis use and psychotic disorders. Whether cannabis use is related to transition to psychosis in patients at ultra-high risk (UHR) for psychosis remains unclear. The present study aimed to review the existing evidence on the association between cannabis use and transition to psychosis in UHR samples. METHOD: A search of PsychInfo, Embase and Medline was conducted from 1996 to August 2015. The search yielded 5559 potentially relevant articles that were selected on title and abstract. Subsequently 36 articles were screened on full text for eligibility. Two random-effects meta-analyses were performed. First, we compared transition rates to psychosis of UHR individuals with lifetime cannabis use with non-cannabis-using UHR individuals. Second, we compared transition rates of UHR individuals with a current DSM-IV cannabis abuse or dependence diagnosis with lifetime users and non-using UHR individuals. RESULTS: We found seven prospective studies reporting on lifetime cannabis use in UHR subjects (n = 1171). Of these studies, five also examined current cannabis abuse or dependence. Lifetime cannabis use was not significantly associated with transition to psychosis [odds ratio (OR) 1.14, 95% confidence interval (CI) 0.856-1.524, p = 0.37]. A second meta-analysis yielded an OR of 1.75 (95% CI 1.135-2.710, p = 0.01), indicating a significant association between current cannabis abuse or dependence and transition to psychosis. CONCLUSIONS: Our results show that cannabis use was only predictive of transition to psychosis in those who met criteria for cannabis abuse or dependence, tentatively suggesting a dose-response relationship between current cannabis use and transition to psychosis.

Cost-effectiveness of preventing first-episode psychosis in ultra-high-risk subjects: multi-centre randomized controlled trial.

BACKGROUND: Although there is evidence for the effectiveness of interventions for psychosis among ultra-high-risk (UHR) groups, health economic evaluations are lacking. This study aimed to determine the cost effectiveness and cost-utility of cognitive-behavioural therapy (CBT) to prevent first-episode psychosis. METHOD: The Dutch Early Detection and Intervention Evaluation study was a randomized controlled trial of 196 UHR patients with an 18-month follow-up. All participants were treated with routine care (RC) for non-psychotic disorders. The experimental group (n = 95) received add-on CBT to prevent first-episode psychosis. We report the intervention, medical and travel costs, as well as costs arising from loss of productivity. Treatment response was defined as psychosis-free survival and quality-adjusted life years (QALYs) gained. RESULTS: In the cost-effectiveness analysis, the proportion of averted psychoses was significantly higher in the CBT condition (89.5% v. 76.2%). CBT showed a 63.7% probability of being more cost effective, because it was less costly than RC by US$844 (£551) per prevented psychosis. In the cost-utility analysis, QALY health gains were slightly higher for CBT than for RC (0.60 v. 0.57) and the CBT intervention had a 52.3% probability of being the superior treatment because, for equal or better QALY gains, the costs of CBT were lower than those of RC. CONCLUSIONS: Add-on preventive CBT for UHR resulted in a significant reduction in the incidence of first psychosis. QALY gains show little difference between the two conditions. The CBT intervention proved to be cost saving.

Detection of people at risk of developing a first psychosis: comparison of two recruitment strategies.

OBJECTIVE: Better recruitment strategies are needed to improve the identification of people at ultra-high risk of developing psychosis. This study explores the effectiveness of two recruitment strategies: a screening method in a consecutive help-seeking population entering secondary mental health services for non-psychotic problems vs. a population referred to the diagnostic center of an early-psychosis clinic. METHOD: From February 2008 to February 2010, all general practitioner and self-referrals (aged 18-35 years) to the secondary mental healthcare service in The Hague and Zoetermeer were screened with the Prodromal Questionnaire; patients who scored above the cutoff of 18 and had a decline in social functioning were assessed using the Comprehensive Assessment of At-Risk Mental States (CAARMS). All referrals (aged 14-35 years) to the diagnostic center in Amsterdam were also assessed with the CAARMS. RESULTS: The screening detected a three-fold higher prevalence of at-risk mental states: these subjects were older and more often female. manova showed significantly higher scores for the screened population on depression, social anxiety, distress with positive symptoms, and a higher rate of transition to psychosis within 12 months. CONCLUSION: The screening method detects more patients with at-risk mental states than the referral method. The latter method is biased to young male patients in an earlier prodromal stage and a lower transition rate.

Ethnicity and baseline symptomatology in patients with an At Risk Mental State for psychosis.

BACKGROUND: Ethnicity has been associated with different incidence rates and different symptom profiles in young patients with psychotic-like disorders. No studies so far have examined the effect of ethnicity on symptoms in people with an At Risk Mental State (ARMS). METHOD: In this cross-sectional study, we analysed the relationship between ethnicity and baseline data on the severity of psychopathology scores in 201 help-seeking patients who met the ARMS criteria and agreed to participate in the Dutch Early Detection and Intervention (EDIE-NL) trial. Eighty-seven of these patients had a non-Dutch ethnicity. We explored the possible mediating role of ethnic identity. RESULTS: Higher rates of negative symptoms, and of anhedonia in particular, were found in the ethnic minority group. This result could be attributed mainly to the Moroccan-Dutch and Turkish-Dutch subgroups, who also presented with more depression symptoms when the groups were examined separately. The ethnic minority group displayed a lower level of ethnic group identity compared to the immigrants of the International Comparative Study of Ethnocultural Youth (ICSEY). Ethnic identity was inversely related to symptoms in the Moroccan-Dutch patient group. CONCLUSIONS: The prevalence of more severe negative symptoms and depression symptoms in ethnic minority groups deserves more attention, as the experience of attenuated positive symptoms when accompanied by negative symptoms or distress has proven to be predictive for transition to a first psychotic episode.

Reduction in noise-induced temporary threshold shift in humans following oral magnesium intake.

A previous study demonstrated the prophylactic effects of magnesium on noise-induced permanent threshold shift in humans. For the first time, this study explores the effects of magnesium on temporary threshold shift in 20 human subjects, all men (16-37 years, mean age 21 years). The study was conducted in a double-blind manner on the same subjects tested in three different phases (placebo, magnesium, no-drug). The cochlear changes were assessed using both behavioural (audiograms) and objective (otoacoustic emission) measures. Blood samples were collected at the beginning and end of each phase. Amongst subjects and phases, magnesium intake was associated with significantly lower temporary threshold shift, compared with the other two phases, which were reflected both by the behavioural and cochlear measures. A correlation was found between the blood magnesium levels and temporary threshold shift reduction. No side-effects were associated with the oral ingestion of the magnesium. Magnesium provides significant protection against temporary threshold shift, complementing the previous permanent threshold shift human study. Both human noise-induced hearing loss studies introduced a novel, biological, natural agent for prevention and possible treatment of noise-induced cochlear damage in humans.

Low frequency noise and stress: bronchitis and cortisol in children exposed chronically to traffic noise and exhaust fumes.

A correlation of respiratory diseases to traffic related air pollution and noise was observed in an interview study. Since in that study the exposure was subjectively assessed, in the present field study nitrogen dioxide as indicator for vehicle exhausts and the mean night-time noise level were measured outside the children's windows in representative locations. Based on these measurements each child was placed in one of the following categories: low, medium or high traffic immission (ambient emissions). The physician contacts due to bronchitis of 68 children were assessed retrospectively from the files of the participating paediatricians. Saliva samples were collected from all children and the cortisol concentration was estimated. Children under high noise exposure (L(night, 8h) = 54-70dB(A)) had in comparison to all other children significantly increased morning saliva cortisol concentrations, indicating an activation of the hypothalamus-pituitary-adrenal (HPA) axis. Analysing a subgroup of children without high noise exposure showed, that children with frequent physician contacts due to bronchitis did not have increased morning saliva cortisol. However, multiple regression analysis with stepwise exclusion of variables showed that bronchitis was correlated more closely to morning salvia cortisol than to traffic immissions. On the other hand, the rate of physician contacts due to bronchitis increased in a dose dependent manner and significantly with increasing traffic immissions. From these results it can be concluded that high exposure to traffic noise, especially at nighttime, activates the HPA axis and this leads in the long term to an aggravation of bronchitis in children. This seems to be more important than the effect of exhaust fumes on bronchitis symptoms. The results of the present study should be subjected to further investigation using specially designed studies.

Health effects caused by noise: evidence in the literature from the past 25 years.

Traffic noise is the most important source of environmental annoyance. According to the Environmental Expert Council of Germany, severe annoyance persistent over prolonged periods of time is to be regarded as causing distress. Previously, extraaural noise effects were mostly assessed using a paradigm in which the sound level played the major role. On the basis of this paradigm the relatively low sound level of environmental noise was not considered to be a potential danger to health. In contrast to this numerous empirical results have shown long-term noise-induced health risks. Therefore a radical change of attitude - a change of paradigm - is necessary. For an immediate triggering of protective reactions (fight/flight or defeat reactions) the information conveyed by noise is very often more relevant than the sound level. It was shown recently that the first and fastest signal detection is mediated by a subcortical area - the amygdala. For this reason even during sleep the noise from aeroplanes or heavy goods vehicles may be categorised as danger signals and induce the release of stress hormones. In accordance with the noise stress hypothesis chronic stress hormone dysregulations as well as increases of established endogenous risk factors of ischaemic heart diseases have been observed under long-term environmental noise exposure. Therefore, an increased risk of myocardial infarction is to be expected. The results of individual studies on this subject in most cases do not reach statistical significance. However, according to the Environmental Expert Council, these studies show a consistent trend towards an increased cardiovascular risk if the daytime immission level exceeds 65 dB(A). Most of the previous studies on the extraaural effects of occupational noise have been invalidated by exposure misclassifications. In future studies on health effects of noise a correct exposure assessment is one of the most important preconditions.

Stress effects of noise in a field experiment in comparison to reactions to short term noise exposure in the laboratory.

Reactions to noise-induced communication disturbance of 42 men during a seminar were investigated. Stress reactions with or without road traffic noise (Lm = 60 dBA) were compared. Traffic noise was played back via loudspeakers during one day in the seminar room. The following parameters were measured: Fatigue and mental tension by questionnaire; blood pressure and heart rate; excretion of adrenaline, noradrenaline and cAMP from the collected urine. The same subjects participated in a laboratory test where the blood pressure was measured during 5 minutes of rest and after 5 minutes of exposure to intermittent white noise (Lm=97 dBA). It was found that the noise in the field experiment caused psychological and physiological stress effects in half of the subjects. Increased mental tension was correlated to increases as well as decreases of the blood pressure. Systolic blood pressure reactions were stronger than the reactions of diastolic blood pressure. Noise sensitive subjects reacted stronger than the others. In the short-term laboratory test, systolic blood pressure increases were smaller than the diastolic increases. At the end of the 5 minutes noise exposure only the diastolic blood pressure increases were significant. There was no correlation between the blood pressure reactions in the two different noise exposure experiments. There existed a positive correlation between noise sensitivity and the systolic blood pressure increases during the seminar, whilst the correlation, between noise sensitivity and systolic blood pressure increases in the laboratory exposure, was negative. From these results we conclude that short-term noise exposure experiments do not provide information about the effects of long-term real life exposure to environmental noise. Potential health effects of chronic noise-induced disturbances of activities are discussed.

Health status as a potential effect modifier of the relation between noise annoyance and incidence of ischaemic heart disease.

AIMS: Traffic noise is a psychosocial stressor. Epidemiological studies suggest chronic noise stress to be a risk factor for cardiovascular disorders. METHODS: In a prospective cohort study, the association between annoyance and disturbances due to road traffic noise and the incidence of ischaemic heart disease (IHD) was studied in 3950 middle aged men. RESULTS: Depending on the questionnaire item, non-significant odds ratios for IHD incidence ranging from 0.9 to 1.4 were found for the highly noise annoyed/disturbed subjects when compared with the less annoyed/disturbed subjects, over the six year follow up period. However, this relation was strongly modified by the prevalence of pre-existing chronic diseases. In subjects free of any chronic disease at the beginning of the follow up, significant odds ratios between 1.7 and 3.0 were seen. In the subgroup with chronic diseases no such noise effects were seen. This surprising result of no effect in the group of people with a potential risk, due to pre-existing health problems, may be because of the dilution of the true effect due to recall bias. CONCLUSIONS: Annoyance and disturbance due to road traffic noise is associated with a higher incidence of IHD. Prevalence of disease can be an important effect modifier of the relation between noise annoyance and health outcomes.

Respiratory and dermatological diseases in children with long-term exposure to road traffic immissions.

The pathogenesis of allergies can be stimulated by adjuvant effects--i.e. air pollutants such as NO(2) and particles from diesel exhausts as well as noise--the latter especially during night-time. During sleep, noise signals which are associated with danger (i.e. lorry noise) have the potential to trigger stress reactions even if the noise level is low. Increases of cortisol in the first half of the night seem to play an important role. In a blind interview study, the combined effects of chronic exposure to traffic related air pollution and noise, upon the risk of skin and respiratory diseases in children were studied. All children between 5-12 years, who had consulted one of two participating paediatricians were included in the study. The paediatricians diagnoses of 400 children were analysed together with their parents answers regarding the density of road traffic on their street and several confounding factors. Multiple regression analyses resulted in relative risks of asthma, chronic bronchitis and neurodermitis, which increased significantly with increasing traffic load. A comparison with the literature on such effects caused by air pollution alone, showed that traffic noise during the night might have an adjuvant effect on the pathogenesis of the mentioned diseases.

Increased catecholamine levels in urine in subjects exposed to road traffic noise: the role of stress hormones in noise research.

The nocturnal excretion of catecholamines in urine was studied in 30-45-year-old women whose bedroom and/or living room were facing streets of varying traffic volume. The traffic volume of the streets was used as an indicator of noise exposure; adrenaline and noradrenaline concentrations were assessed as indicators of the outcome of the physiological stress. Significant associations between traffic volume and noradrenaline concentrations in urine were found with regard to the exposure of the bedroom (not the living room), indicating a higher chronic physiological arousal in noise-exposed subjects as compared to less exposed. Subjective measures of disturbance due to traffic noise were positively correlated with the noradrenaline level. However, this was only found in subjects where closing the window could not reduce the perceived disturbance, which points to the effectiveness of individual coping mechanisms. Stress hormones are useful indicators to study associations, mechanisms, and interactions between noise, health outcomes, and effect modifiers in epidemiological noise research.

Community noise exposure and stress in children.

Although accumulating evidence over the past two decades points towards noise as an ambient stressor for children, all of the data emanate from studies in high-intensity, noise impact zones around airports or major roads. Extremely little is known about the nonauditory consequences of typical, day-to-day noise exposure among young children. The present study examined multimethodological indices of stress among children living under 50 dB or above 60 dB (A-weighted, day-night average sound levels) in small towns and villages in Austria. The major noise sources were local road and rail traffic. The two samples were comparable in parental education, housing characteristics, family size, marital status, and body mass index, and index of body fat. All of the children were prescreened for normal hearing acuity. Children in the noisier areas had elevated resting systolic blood pressure and 8-h, overnight urinary cortisol. The children from noisier neighborhoods also evidenced elevated heart rate reactivity to a discrete stressor (reading test) in the laboratory and rated themselves higher in perceived stress symptoms on a standardized index. Furthermore girls, but not boys, evidenced diminished motivation in a standardized behavioral protocol. All data except for the overnight urinary neuroendocrine indices were collected in the laboratory. The results are discussed in the context of prior airport noise and nonauditory health studies. More behavioral and health research is needed on children with typical, day-to-day noise exposure.

Ear damage caused by leisure noise.

Noise is a health risk. Recent findings suggest that leisure noise is a substantial danger especially to children, teenagers and young adults. Epidemiological studies of teenagers with no occupational noise exposure show an increasing number with a substantial and measurable irreversible inner ear damage. This is basically due to the wide spread exposition to very loud toys (pistols and squibs), crackers and exposure to electronically amplified music, e.g. from personal cassette players (PCP), at discos or concerts etc. Protection against irreversible ear damage by leisure noise has an important impact in preventive medical care. Therefore the general public must be informed that loud leisure activities may cause damage to the ear. In order to protect children, young people and adults, the legislature ought to set limits for sound levels in discos, concert halls and for music equipment and toys by establishing the necessary standards and regulations.

Preventive effect of magnesium supplement on noise-induced hearing loss in the guinea pig.

The effect of magnesium (Mg) on noise-induced hearing loss was investigated in two groups of adult pigmented guinea pigs maintained either on optimal or suboptimal (physiologically high or low) Mg produced by different diets. The total Mg concentrations of the perilymph (PL), cerebrospinal fluid, blood plasma and red blood cells were measured by atomic absorption spectrometry and were found to differ significantly between the two groups (P < 0.01). One ear of each animal was exposed to either a single shooting impulse at a peak pressure level of 187 dB or two impulse noise series at a rate of 1/s and peak pressure levels of 150 dB (1,000 impulses) and 167 dB (2,280 impulses), respectively. Temporary (TTS) and permanent (PTS) hearing threshold shifts in anesthetized animals were measured 2 h and 1 week after the noise exposure, using auditory brain stem response (ABR) audiometry at a frequency range from 3.75 to 30 kHz. Exposure to the single noise impulse resulted in a mean TTS that was significantly lower in the high Mg group than that in the low Mg group (P < 0.05), although no substantial PTS was observed in either group. In the animals exposed to 150 dB noise, the TTS showed a tendency towards an Mg-related reduction at the higher frequencies. A small difference in PTS was found between the low Mg and high Mg groups, but was not significant. Exposure to the 167-dB noise series caused a considerable TTS, which was significantly lower in the high Mg group at 7.5 and 15 kHz than in the low Mg group (P < 0.05). The mean PTS showed a significant difference between the two Mg groups over the whole frequency range (P < 0.05) and was found to correlate negatively with the total Mg concentrations of both PL and plasma (P < 0.05). Moreover, the high Mg group showed a faster recovery from the hearing threshold shift than the low Mg group. The present findings show that preventive oral Mg supplements can significantly reduce the rate of acoustic trauma caused by high-level impulse noise exposure in the guinea pig.

Acute and chronic endocrine effects of noise: Review of the research conducted at the Institute for Water, Soil and Air Hygiene.

This is a review of the research into endocrine effects of noise since the early 1980s at the Institute for Water, Soil and Air Hygiene. According to our knowledge, no other group has studied systematically the endocrine effects of acute and chronic noise exposure. Mechanisms of acute noise-induced stress reactions as well as long-term increase of stress hormones in animal and persons under chronic noise exposure were studied. Our theoretical background was Henry's psychophysiological stress model with the two reaction alternatives : (i) The fight-flight reaction, characterised by an increase in adrenalin and noradrenaline (ii) The defeat reaction with increased cortisol. Extremely intense acute noise exposure near the threshold of pain caused an increased release of cortisol from the suprarenal cortex but acute noise exposure with levels between 90 and 100 dB(A) caused an increase of catecholamines. Non-habituated noise increased primarily the release of adrenalin from the suprarenal medulla, whereas habituated noise caused a chronic increase of noradrenaline from the sympathetic synapses under longterm noise exposure at work. Environmental noise exposure (Leq >/= 60 dB(A)) caused catecholamine increase if activities such as conversation, concentration, recreation etc were disturbed through noise. In sleeping persons, traffic noise with only Leq >/= 30 dB (A) and Lmax >/= 55 dB(A) caused significant acute increase of cortisol, which developed into chronic increase if the noise exposure was repeated consistently. Parallel to cortisol, chronic noradrenaline increase was also observed. Based upon the empirical results, a noise stress model was developed which is a first step forward in the theoretical understanding of endocrine noise effects.