Recent advances in reactive oxygen species measurement in biological systems.

Reactive oxygen species (ROS) play an essential role in facilitating signal transduction processes within the cell. However, the precise details of the redox dynamics involved are not well understood. The generation of ROS is tightly controlled both spatially and temporally within the cell, making the study of ROS dynamics particularly difficult. In order to measure these dynamics, precise tools that can specifically examine the relevant ROS are required. Recent advancements in methodologies for ROS measurement have allowed the study of ROS biology at a level of precision previously unachievable. Here, we discuss improvements to fluorescent ROS dye technologies, genetically encoded ROS reporters, nanoparticle delivery systems, and nanotube ROS probes. These technologies improve specificity, localization and sensitivity over previously available ROS probes.

Intranasal oxytocin increases facial expressivity, but not ratings of trustworthiness, in patients with schizophrenia and healthy controls.

BACKGROUND: Blunted facial affect is a common negative symptom of schizophrenia. Additionally, assessing the trustworthiness of faces is a social cognitive ability that is impaired in schizophrenia. Currently available pharmacological agents are ineffective at improving either of these symptoms, despite their clinical significance. The hypothalamic neuropeptide oxytocin has multiple prosocial effects when administered intranasally to healthy individuals and shows promise in decreasing negative symptoms and enhancing social cognition in schizophrenia. Although two small studies have investigated oxytocin's effects on ratings of facial trustworthiness in schizophrenia, its effects on facial expressivity have not been investigated in any population. METHOD: We investigated the effects of oxytocin on facial emotional expressivity while participants performed a facial trustworthiness rating task in 33 individuals with schizophrenia and 35 age-matched healthy controls using a double-blind, placebo-controlled, cross-over design. Participants rated the trustworthiness of presented faces interspersed with emotionally evocative photographs while being video-recorded. Participants' facial expressivity in these videos was quantified by blind raters using a well-validated manualized approach (i.e. the Facial Expression Coding System; FACES). RESULTS: While oxytocin administration did not affect ratings of facial trustworthiness, it significantly increased facial expressivity in individuals with schizophrenia (Z = -2.33, p = 0.02) and at trend level in healthy controls (Z = -1.87, p = 0.06). CONCLUSIONS: These results demonstrate that oxytocin administration can increase facial expressivity in response to emotional stimuli and suggest that oxytocin may have the potential to serve as a treatment for blunted facial affect in schizophrenia.

Migraine Prophylaxis and Acute Treatment Patterns Among Commercially Insured Patients in the United States.

OBJECTIVES: To describe prophylactic and acute medication treatment patterns, including timing, medication type, and duration of use in migraine patients initiating prophylaxis. BACKGROUND: Patients with migraine can be treated with acute and prophylactic therapies. Current treatment options for migraine prophylaxis are associated with poor tolerability and low adherence and persistence. METHODS: This retrospective cohort study used the Truven Health Analytics MarketScan® Research Databases to identify adults in the United States with a migraine diagnosis who initiated migraine prophylactic medication (index event) between January 1, 2008, and December 31, 2011. Prescribed prophylactic medications evaluated included topiramate, beta-blockers, and tricyclic antidepressants. Patients were required to have 12 months of pre- and post-index continuous enrollment. Patient characteristics, migraine-specific prescribed prophylactic treatment patterns (including gaps in therapy, treatment switches, and additions of index medications), and prescribed acute medication utilization were assessed. RESULTS: The study population comprised 107,122 patients, with 52,275 (49%) initiating topiramate, 22,658 (21%) initiating beta-blockers, and 32,189 (30%) initiating tricyclic antidepressants. Mean (SD) age was 41 (12) years and 83% were female. Persistence with migraine prophylactic medication was low; 81% of patients had gaps of >90 days in their migraine prophylaxis in the first year. The gap in therapy occurred early in treatment (mean, 95 days), and only 10% of patients restarted prophylactic therapy within that year. Switching from index medication to another prophylactic medication or adding prophylaxis was uncommon (13% and 5%, respectively). One year after initiating prophylaxis, 65% of patients were not receiving any prophylactic therapies. Most patients initiating migraine prophylaxis also utilized acute treatments (81%); opioid use was more frequent than triptan use (53% vs 48%) and was common (40%) among patients without other chronic pain conditions (eg, arthritis, fibromyalgia, and lower back pain). CONCLUSION: Patients with migraine who initiated prophylactic therapy had poor persistence with early gaps in therapy, were unlikely to switch prophylactic treatments, and most discontinued prophylaxis by the end of the first year.

Towards coherent data policy for biomedical research with ELSI 2.0: orchestrating ethical, legal and social strategies.

As the recent inaugural Ethical, Legal, and Social Issues (ELSI) 2.0 conference made clear, the effects of information communication technology (ICT) are pervasive in biomedical research. Data initiatives are arising in all corners of biomedicine. Data sharing efforts already promised to surpass even the ambitious goals of the National Human Genome Research Institute, only 5 years after publication of its 10-year vision. ELSI research was established, in part, to address challenges of open data access and data sharing. However, by and large, ELSI research projects address particular concerns of a given population, jurisdiction, type of research practice or type of data. This does not necessarily facilitate coherent data policy for sustainable data stewardship. Forward-looking, data friendly strategies need to be considered. Orchestration strategies are needed which overcome barriers to collective action. Here we present challenges policymakers face, and suggest three basics steps towards meeting them. First, policymakers must recognise the systematic change that occurs when ICT enables dataflow itself to become an organising principle of biomedical research. Second, methods for identifying and gathering types of metadata suitable for ELSI research ought to be developed and regulated. Third, policymakers need to organise in ways that mirror the new vision for data-enabled research that data technologies are making possible, as ELSI 2.0 encourages researchers to do. Taking these steps will help ensure research evolves in ways that warrants trust of the public while still supporting widespread ethical access to necessary data, research subjects, samples and findings.

Citizen science or scientific citizenship? Disentangling the uses of public engagement rhetoric in national research initiatives.

BACKGROUND: The language of "participant-driven research," "crowdsourcing" and "citizen science" is increasingly being used to encourage the public to become involved in research ventures as both subjects and scientists. Originally, these labels were invoked by volunteer research efforts propelled by amateurs outside of traditional research institutions and aimed at appealing to those looking for more "democratic," "patient-centric," or "lay" alternatives to the professional science establishment. As mainstream translational biomedical research requires increasingly larger participant pools, however, corporate, academic and governmental research programs are embracing this populist rhetoric to encourage wider public participation. DISCUSSION: We examine the ethical and social implications of this recruitment strategy. We begin by surveying examples of "citizen science" outside of biomedicine, as paradigmatic of the aspirations this democratizing rhetoric was originally meant to embody. Next, we discuss the ways these aspirations become articulated in the biomedical context, with a view to drawing out the multiple and potentially conflicting meanings of "public engagement" when citizens are also the subjects of the science. We then illustrate two uses of public engagement rhetoric to gain public support for national biomedical research efforts: its post-hoc use in the "care.data" project of the National Health Service in England, and its proactive uses in the "Precision Medicine Initiative" of the United States White House. These examples will serve as the basis for a normative analysis, discussing the potential ethical and social ramifications of this rhetoric. We pay particular attention to the implications of government strategies that cultivate the idea that members of the public have a civic duty to participate in government-sponsored research initiatives. We argue that such initiatives should draw from policy frameworks that support normative analysis of the role of citizenry. And, we conclude it is imperative to make visible and clear the full spectrum of meanings of "citizen science," the contexts in which it is used, and its demands with respect to participation, engagement, and governance.

Characterizing the severe asthma population in the United States: claims-based analysis of three treatment cohorts in the year prior to treatment escalation.

OBJECTIVES: Little is known about the disposition of severe patients prior to treatment escalation. To classify patients by treatment step using pharmacy data and describe their economic and healthcare utilization, insurance status, and sociodemographic characteristics in the year prior to escalation to Global Initiative for Asthma (GINA) steps 4 and 5. METHODS: This was a retrospective claims cohort study of asthma patients (age 12-75 years) newly initiated on "stable therapy" (three consecutive months of therapy) with omalizumab, high intensity corticosteroids (HICS; ≥1000 µg/d inhaled fluticasone equivalent or oral prednisone), or high-dose inhaled corticosteroid (HDICS; ≥500-<1000 µg/d fluticasone equivalent) from 2002 to 2011. Other asthma treatments were compared as a reference. RESULTS: Of 25,297 patients, 856 initiated omalizumab, 6926 initiated HICS, and 11,445 initiated HDICS. In the year prior to treatment escalation to omalizumab, HICS, and HDICS, respectively, individuals had high annual mean medical expenditures ($14,071, $12,030, and $7570), utilization (27 outpatient and 10 specialty care visits; 19 outpatient and three specialty; 15 outpatient and two specialty), asthma-related prescription drugs (11.74, 7.8, and 5.17) and chronic comorbidities (2.68, 2.67, and 2.19). Prior to omalizumab treatment, patients were more likely to be salaried, full-time employees with commercial PPO/POS insurance. CONCLUSIONS: Prior to escalating treatment to GINA steps 4 and 5, individuals experienced significant annual medical expenditures, healthcare resource utilization and polypharmacy burden, which may reflect poorly controlled asthma and the need to escalate treatment. Medical claims data and utilization-based measures may be helpful in classifying individuals by GINA treatment step.

Cannabis use and first-episode psychosis: relationship with manic and psychotic symptoms, and with age at presentation.

BACKGROUND: Cannabis use has been reported to be associated with an earlier onset of symptoms in patients with first-episode psychosis, and a worse outcome in those who continue to take cannabis. In general, studies have concentrated on symptoms of psychosis rather than mania. In this study, using a longitudinal design in a large naturalistic cohort of patients with first-episode psychosis, we investigated the relationship between cannabis use, age of presentation to services, daily functioning, and positive, negative and manic symptoms. METHOD: Clinical data on 502 patients with first-episode psychosis were collected using the MiData audit database from seven London-based Early Intervention in psychosis teams. Individuals were assessed at two time points--at entry to the service and after 1 year. On each occasion, the Positive and Negative Syndrome Scale, Young Mania Rating Scale and Global Assessment of Functioning Scale disability subscale were rated. At both time points, the use of cannabis and other drugs of abuse in the 6 months preceding each assessment was recorded. RESULTS: Level of cannabis use was associated with a younger age at presentation, and manic symptoms and conceptual disorganization, but not with delusions, hallucinations, negative symptoms or daily functioning. Cannabis users who reduced or stopped their use following contact with services had the greatest improvement in symptoms at 1 year compared with continued users and non-users. Continued users remained more symptomatic than non-users at follow-up. CONCLUSIONS: Effective interventions for reducing cannabis use may yield significant health benefits for patients with first-episode psychosis.

Are we really mapping psychosis risk? Neuroanatomical signature of affective disorders in subjects at ultra high risk.

BACKGROUND: The majority of people at ultra high risk (UHR) of psychosis also present with co-morbid affective disorders such as depression or anxiety. The neuroanatomical and clinical impact of UHR co-morbidity is unknown. METHOD: We investigated group differences in grey matter volume using baseline magnetic resonance images from 121 participants in four groups: UHR with depressive or anxiety co-morbidity; UHR alone; major depressive disorder; and healthy controls. The impact of grey matter volume on baseline and longitudinal clinical/functional data was assessed with regression analyses. RESULTS: The UHR-co-morbidity group had lower grey matter volume in the anterior cingulate cortex than the UHR-alone group, with an intermediate effect between controls and patients with major depressive disorder. In the UHR-co-morbidity group, baseline anterior cingulate volume was negatively correlated with baseline suicidality/self-harm and obsessive-compulsive disorder symptoms. CONCLUSIONS: Co-morbid depression and anxiety disorders contributed distinctive grey matter volume reductions of the anterior cingulate cortex in people at UHR of psychosis. These volumetric deficits were correlated with baseline measures of depression and anxiety, suggesting that co-morbid depressive and anxiety diagnoses should be carefully considered in future clinical and imaging studies of the psychosis high-risk state.

Reduced parahippocampal cortical thickness in subjects at ultra-high risk for psychosis.

BACKGROUND: Grey matter volume and cortical thickness represent two complementary aspects of brain structure. Several studies have described reductions in grey matter volume in people at ultra-high risk (UHR) of psychosis; however, little is known about cortical thickness in this group. The aim of the present study was to investigate cortical thickness alterations in UHR subjects and compare individuals who subsequently did and did not develop psychosis. METHOD: We examined magnetic resonance imaging data collected at four different scanning sites. The UHR subjects were followed up for at least 2 years. Subsequent to scanning, 50 UHR subjects developed psychosis and 117 did not. Cortical thickness was examined in regions previously identified as sites of neuroanatomical alterations in UHR subjects, using voxel-based cortical thickness. RESULTS: At baseline UHR subjects, compared with controls, showed reduced cortical thickness in the right parahippocampal gyrus (p < 0.05, familywise error corrected). There were no significant differences in cortical thickness between the UHR subjects who later developed psychosis and those who did not. CONCLUSIONS: These data suggest that UHR symptomatology is characterized by alterations in the thickness of the medial temporal cortex. We did not find evidence that the later progression to psychosis was linked to additional alterations in cortical thickness, although we cannot exclude the possibility that the study lacked sufficient power to detect such differences.

Changes in mental state associated with prison environments: a systematic review.

OBJECTIVE: To develop an understanding of the stability of mental health during imprisonment through review of existing research evidence relating physical prison environment to mental state changes in prisoners. METHOD: A systematic literature search was conducted looking at changes in mental state and how this related to various aspects of imprisonment and the prison environment. RESULTS: Fifteen longitudinal studies were found, and from these, three broad themes were delineated: being imprisoned and aspects of the prison regime; stage of imprisonment and duration of sentence; and social density. Reception into prison results in higher levels of psychiatric symptoms that seem to improve over time; otherwise, duration of imprisonment appears to have no significant impact on mental health. Regardless of social density, larger prisons are associated with poorer mental state, as are extremes of social density. CONCLUSION: There are large gaps in the literature relating prison environments to changes in mental state; in particular, high-quality longitudinal studies are needed. Existing research suggests that although entry to prison may be associated with deterioration in mental state, it tends to improve with time. Furthermore, overcrowding, ever more likely as prison populations rise, is likely to place a particular burden on mental health services.

Getting your DUCs in a row - standardising the representation of Digital Use Conditions.

Improving patient care and advancing scientific discovery requires responsible sharing of research data, healthcare records, biosamples, and biomedical resources that must also respect applicable use conditions. Defining a standard to structure and manage these use conditions is a complex and challenging task. This is exemplified by a near unlimited range of asset types, a high variability of applicable conditions, and differing applications at the individual or collective level. Furthermore, the specifics and granularity required are likely to vary depending on the ultimate contexts of use. All these factors confound alignment of institutional missions, funding objectives, regulatory and technical requirements to facilitate effective sharing. The presented work highlights the complexity and diversity of the problem, reviews the current state of the art, and emphasises the need for a flexible and adaptable approach. We propose Digital Use Conditions (DUC) as a framework that addresses these needs by leveraging existing standards, striking a balance between expressiveness versus ambiguity, and considering the breadth of applicable information with their context of use.

Neurogenesis in a young dog with epileptic seizures.

Epileptic seizures can lead to various reactions in the brain, ranging from neuronal necrosis and glial cell activation to focal structural disorganization. Furthermore, increased hippocampal neurogenesis has been documented in rodent models of acute convulsions. This is a report of hippocampal neurogenesis in a dog with spontaneous epileptic seizures. A 16-week-old epileptic German Shepherd Dog had marked neuronal cell proliferation (up to 5 mitotic figures per high-power field and increased immunohistochemical expression of proliferative cell nuclear antigen) in the dentate gyrus accompanied by microglial and astroglial activation. Some granule cells expressed doublecortin, a marker of immature neurons; mitotically active cells expressed neuronal nuclear antigen. No mitotic figures were found in the brain of age-matched control dogs. Whether increased neurogenesis represents a general reaction pattern of young epileptic dogs should be investigated.

Systematic review of medication related osteonecrosis of the jaw (MRONJ) in patients undergoing only antiangiogenic drug therapy: surgery or conservative therapy?

Osteonecrosis of the jaw is a severe adverse condition affecting patients exposed to specific types of medications. Previous studies have highlighted that osteonecrosis of the jaw is triggered by invasive dental procedures and can be very challenging to manage, especially in patients with cancer. The primary aim of this review was to analyse all available evidence on the management (surgical and/or conservative) of medication related osteonecrosis of the jaws (MRONJ) in patients with a history of antiangiogenic drugs therapy and who had not been previously exposed to any antiresorptive drug treatments. A multi-database search (PubMed, MEDLINE, EMBASE and CINAHL) was performed to identify related multi-language papers published from January 2003 until November 2020. Data were extracted from relevant papers and analysed according to the outcomes selected in this review. The search generated 28 studies eligible for the analysis. The total number of patients included in the analysis was 36. Sixteen patients were treated with anti-vascular endothelial growth factor drugs (anti-VEGF) while the remaining patients were administered a combination of antiangiogenic drugs. The most common MRONJ site was the mandible in 29 patients. MRONJ recurrence after treatment was only reported in six patients, the majority of which were treated conservatively. The data reviewed confirmed that an invasive procedure was the most common trigger of MRONJ with relatively high frequency of postoperative recurrence following treatment. However, due to the low quality of available research in the literature, it is difficult to draw a definitive conclusion on the validity of the presented treatment to manage patients affected by MRONJ associated with angiogenic therapy.

Impaired verbal self-monitoring in individuals at high risk of psychosis.

BACKGROUND: Cognitive models suggest that auditory verbal hallucinations arise through defective self-monitoring and the external attribution of inner speech. We used a paradigm that engages verbal self-monitoring (VSM) to examine whether this process is impaired in people experiencing prodromal symptoms, who have a very high risk of developing psychosis. METHOD: We tested 31 individuals with an At-Risk Mental State (ARMS) and 31 healthy volunteers. Participants read single adjectives aloud while the source and pitch of the online auditory verbal feedback was manipulated, then immediately identified the source of the speech they heard (Self/Other/Unsure). Response choice and reaction time were recorded. RESULTS: When reading aloud with distorted feedback of their own voice, ARMS participants made more errors than controls (misidentifications and unsure responses). ARMS participants misidentified the source of their speech as 'Other' when the level of acoustic distortion was severe, and misidentification errors were inversely related to reaction times. CONCLUSIONS: Impaired VSM is evident in people with an ARMS, although the deficit seems to be less marked than in patients with schizophrenia. Follow-up of these participants may clarify the extent to which the severity of this impairment predicts the subsequent onset of psychosis and development of positive symptoms.

Neural correlates of visuospatial working memory in the 'at-risk mental state'.

BACKGROUND: Impaired spatial working memory (SWM) is a robust feature of schizophrenia and has been linked to the risk of developing psychosis in people with an at-risk mental state (ARMS). We used functional magnetic resonance imaging (fMRI) to examine the neural substrate of SWM in the ARMS and in patients who had just developed schizophrenia. METHOD: fMRI was used to study 17 patients with an ARMS, 10 patients with a first episode of psychosis and 15 age-matched healthy comparison subjects. The blood oxygen level-dependent (BOLD) response was measured while subjects performed an object-location paired-associate memory task, with experimental manipulation of mnemonic load. RESULTS: In all groups, increasing mnemonic load was associated with activation in the medial frontal and medial posterior parietal cortex. Significant between-group differences in activation were evident in a cluster spanning the medial frontal cortex and right precuneus, with the ARMS groups showing less activation than controls but greater activation than first-episode psychosis (FEP) patients. These group differences were more evident at the most demanding levels of the task than at the easy level. In all groups, task performance improved with repetition of the conditions. However, there was a significant group difference in the response of the right precuneus across repeated trials, with an attenuation of activation in controls but increased activation in FEP and little change in the ARMS. CONCLUSIONS: Abnormal neural activity in the medial frontal cortex and posterior parietal cortex during an SWM task may be a neural correlate of increased vulnerability to psychosis.

Neural correlates of movement generation in the 'at-risk mental state'.

OBJECTIVE: People with 'prodromal' symptoms have a very high risk of developing psychosis. We examined the neurocognitive basis of this vulnerability by using functional MRI to study subjects with an at-risk mental state (ARMS) while they performed a random movement generation task. METHOD: Cross-sectional comparison of individuals with an ARMS (n = 17), patients with first episode schizophreniform psychosis (n = 10) and healthy volunteers (n = 15). Subjects were studied using functional MRI while they performed a random movement generation paradigm. RESULTS: During random movement generation, the ARMS group showed less activation in the left inferior parietal cortex than controls, but greater activation than in the first episode group. CONCLUSION: The ARMS is associated with abnormalities of regional brain function that are qualitatively similar to those in patients who have recently presented with psychosis but less severe.

Postdischarge Health Care Costs and Readmission in Patients With Hyperkalemia-Related Hospitalizations.

INTRODUCTION: Limited evidence is available regarding the postdischarge economic and readmission burdens of hyperkalemia. METHODS: Using the IBM MarketScan Commercial and Medicare-Supplemental Claims database (January 1, 2010-December 31, 2014), adult patients with a hospitalization with a hyperkalemia diagnosis (ICD-9-CM 276.7, hyperkalemia cohort) were 1:1 matched with patients with a hospitalization without evidence of hyperkalemia (nonhyperkalemia cohort) on age, chronic kidney disease stage, heart failure, dialysis, renin-angiotensin-aldosterone system inhibitor use, and major diagnostic categories of the hospitalization. All-cause health care costs and health care resource utilization measures were compared between cohorts during the 1-year postdischarge period. Postdischarge readmission and length of stay (LOS) were compared between hyperkalemia-related hospitalizations from the hyperkalemia cohort and matched hospitalizations unrelated to hyperkalemia from the nonhyperkalemia cohort. RESULTS: Patients with hyperkalemia-related hospitalizations (n = 4426) incurred $30,379 (95% confidence interval, $25,423-$35,335) higher 1-year total all-cause costs ($68,861 vs. $38,482) and had higher rates of inpatient admissions (1.0 vs. 0.4), emergency department visits (2.0 vs. 1.2), and outpatient visits (49.6 vs. 39.1) than the nonhyperkalemia cohort during the 1-year postdischarge study period (all P < 0.001). Hyperkalemia-related hospitalizations (n = 5377) were associated with significantly higher readmission rates (within 30 days: 0.15 vs. 0.09; 60 days: 0.25 vs. 0.16; 90 days: 0.36 vs. 0.23; all P < 0.001), longer LOS per readmission (8.1 vs. 7.1 days), and longer total inpatient days (10.5 vs. 5.8 days) compared with hospitalizations unrelated to hyperkalemia (all P < 0.001). Similar trends were observed across comorbidity subgroups. CONCLUSION: Hyperkalemia-related hospitalizations were associated with significant economic and readmission burdens during the 1-year postdischarge period.

Prevalence and economic burden of hyperkalemia in the United States Medicare population.

Objective: To estimate the prevalence and economic burden of hyperkalemia in the United States (US) Medicare population.Methods: Patients were selected from a 5% random sample of Medicare beneficiaries (01 January 2010-31 December 2014) to estimate the prevalence and economic burden of hyperkalemia. The prevalence for each calendar year was calculated as the number of patients with hyperkalemia divided by the total number of eligible patients per year. To estimate the economic burden of hyperkalemia, patients with hyperkalemia (cases) were matched 1:1 to patients without hyperkalemia (controls) on age group, chronic kidney disease [CKD] stage, dialysis treatment, and heart failure. The incremental 30-day and 1-year resource utilization and costs (2016 USD) associated with hyperkalemia were estimated.Results: The estimated prevalence of hyperkalemia was 2.6-2.7% in the overall population and 8.9-9.3% among patients with CKD and/or heart failure. Patients with hyperkalemia had higher 1-year rates of inpatient admissions (1.28 vs. 0.44), outpatient visits (30.48 vs. 23.88), emergency department visits (2.01 vs. 1.17), and skilled nursing facility admissions (0.36 vs. 0.11) than the matched controls (all p < .001). Patients with hyperkalemia incurred on average $7208 higher 30-day costs ($8894 vs. $1685) and $19,348 higher 1-year costs ($34,362 vs. $15,013) than controls (both p < .001). Among patients with CKD and/or heart failure, the 30-day and 1-year total cost differences between cohorts were $7726 ($9906 vs. $2180) and $21,577 ($41,416 vs. $19,839), respectively (both p < .001).Conclusions: Hyperkalemia had an estimated prevalence of 2.6-2.7% in the Medicare population and was associated with markedly high healthcare costs.

Economic impact of early intervention in people at high risk of psychosis.

BACKGROUND: Despite the increasing development of early intervention services for psychosis, little is known about their cost-effectiveness. We assessed the cost-effectiveness of Outreach and Support in South London (OASIS), a service for people with an at-risk mental state (ARMS) for psychosis. METHOD: The costs of OASIS compared to care as usual (CAU) were entered in a decision model and examined for 12- and 24-month periods, using the duration of untreated psychosis (DUP) and rate of transition to psychosis as key parameters. The costs were calculated on the basis of services used following referral and the impact on employment. Sensitivity analysis was used to test the robustness of all the assumptions made in the model. RESULTS: Over the initial 12 months from presentation, the costs of the OASIS intervention were pound1872 higher than CAU. However, after 24 months they were pound961 less than CAU. CONCLUSIONS: This model suggests that services that permit early detection of people at high risk of psychosis may be cost saving.