At-risk Criteria Research Articles

A New Classification System for Forearm Deformities Caused by Hereditary Multiple Osteochondromas

The objective of this study was to evaluate the Masada and Jo classifications for clinical use in patients with forearm deformity caused by hereditary multiple osteochondroma and propose a new classification system that is all-inclusive and can guide clinical management. A retrospective review of 275 forearms was performed. A split-sample approach was used, where 138 forearms were analyzed to create a new classification, which was then validated on the remaining 137 forearms. Radiographs were reviewed to determine the number and location of osteochondromas and the presence of radial head dislocation (RHD) and to measure radiographic parameters. Multivariable logistic regression analysis was performed to identify radiological parameters associated with RHD. According to the Masada and Jo classifications, 95 of 275 forearms (34.5%) were unclassifiable. Analyses of the split group (n= 138) revealed 42 forearms with RHD. All these had distal ulna lesions, qualifying as the greatest associated factor for RHD. Further subgroup multivariable logistic regression analysis of forearms with distal ulna lesions identified radiological parameter proportional ulna length as a statistically significant association of RHD, qualifying as "at-risk" criteria. The area under the receiver operating characteristic curve for proportional ulna length was 0.89, with a receiver operating characteristic-derived ideal value of ≤ 0.95 (sensitivity 0.86 and specificity 0.86). We proposed a new classification system stratified into three groups-high, moderate, and low-risk of RHD-based on the identified factors associated with RHD. Type 1 comprises forearms with distal ulna osteochondromas-subdivided into type 1A (high-risk), where forearms meet the at-risk criteria for RHD and type 1B (moderate-risk), where forearms do not meet the at-risk criteria. Type 2 (low-risk) comprises forearms without distal ulna osteochondromas. Our classification system addresses the limitations of existing classifications by risk stratifying forearms into three groups-high, moderate, and low-risk of RHD.

Hypomania-Checklist-33: risk stratification and factor structure in a mixed psychiatric adolescent sample

BackgroundThe 33-item Hypomania Checklist (HCL-33) has been shown to distinguish between adolescent bipolar disorder (BD) and unipolar depression. To investigate the utility of the HCL-33 as a screening tool in routine diagnostics, the frequency and psychopathological characteristics of detected individuals in a mixed psychiatric sample necessitate more examination.MethodsThe HCL-33, Children’s Depression Inventory, Beck’s Anxiety Inventory, and Strengths and Difficulties Questionnaire were completed by 285 children and adolescents (12–18 years) in a mixed psychiatric sample. Applying the proposed HCL-33 cut-off score of ≥ 18, individuals with depressive symptoms were divided into at-risk or not at-risk for BD groups. The factorial structure, sum and factor score correlations with psychopathology, and impact on daily functioning were assessed.Results20.6% of the sample met at-risk criteria for BD. These individuals (n = 55) were older, more anxious, and showed more conduct problems vs the not at-risk group (n = 107). A two- and a three-factor model were pursued with the same Factor 1 (“active-elated”). Factor 2 (“risk-taking/irritable”) was separated into 2a (“irritable-erratic”) and 2b (“outgoing-disinhibited”) in the three-factor model. Whereas higher Factor 2 and 2a scores correlated with a broad range of more severe symptomatology (i.e., depression, anxiety, hyperactivity), higher Factor 1 and 2b scores correlated with more emotional and conduct problems, respectively. 51.7% of the sample reported a negative impact from hypomanic symptoms on daily functioning.LimitationsCross-sectional design and data collection in a single mental health service.ConclusionsThe HCL-33 may be a useful tool to improve diagnostics, especially in adolescents with depressive symptoms additionally presenting with anxious symptoms and conduct problems.

OA05 Potential impact of European Medicines Agency measures to minimise risk of serious side effects on those using JAK inhibitors in the UK

Abstract Background/Aims Janus kinase inhibitors (JAKi) are effective therapies for rheumatoid arthritis (RA). However, concerns about their safety in certain 'at-risk' populations have resulted in risk minimisation measures introduced by European Medicines Agency (EMA) in January 2023, which limits JAKi prescription to certain patient subgroups unless no suitable alternative is available. The potential impact on current and future JAKi use in the UK is unknown. Using a national cohort study of patients who have already started their first JAKi, this analysis aimed to describe the proportion meeting ≥1 of these criteria and therefore may be impacted by these changes. Methods RA patients starting their first-ever JAK inhibitor (tofacitinib, baricitinib, upadacitinib, or filgotinib) therapy in the British Society for Rheumatology RA Biologics Register (BSRBR-RA) before 31st May 2022 (pre-EMA warning) were included. Patients with missing data in any EMA criteria related variables were excluded. Descriptive statistics were used to present patients' characteristics at the start of JAKi. This analysis defined four at-risk criteria assessed at the treatment start: 1) aged ≥65; 2) increased risk of major cardiovascular issues (history of hypertension, hyperlipidaemia, diabetes, ischaemic heart disease, or stroke); 3) current or past smokers; 4) increased risk of cancer (defined as prior cancer). The previous number of distinct biological disease-modifying antirheumatic drugs (bDMARDs) classes was described among those who met the criteria. Results A total of 1,362 patients starting their first JAKi were included, most commonly baricitinib (76%), followed by tofacitinib (16%; see Table). The cohort was 78% female, with an average age of 60. Among them, 28% of patients had received ≥3 prior bDMARDs classes. 80% percent of patients (1,090) met ≥1 EMA risk criterion, with the most common individual criterion current/past smoker (54%). Of those who met ≥1 risk criteria, 645 (59%) met ≥1 EMA risk criterion and 29% had already received ≥3 prior bDMARDs classes. Conclusion A very high proportion of patients, four-in-five, initiating JAKi in UK before the EMA advisory would have fallen into the ‘high-risk' category for whom prescribing would only be advised if no suitable alternatives were available. Whilst almost a third of them had previously received ≥3 different bDMARDs classes, it’s likely that many of them would have suitable alternatives. These data highlight the enormous impact of the recent licensing updates for JAKi class. Disclosure Z. Tian: None. L. Kearsley-fleet: None. J. Galloway: Honoraria; Abbvie, Galapagos, Janssen, Lilly, Novartis, Pfizer, UCB, Vifor. Grants/research support; Abbvie, Galapagos, GSK, Janssen, Pfizer. K. Watson: None. M. Lunt: None. K.L. Hyrich: Honoraria; Abbvie. Grants/research support; Pfizer, BMS.

Bipolar At-Risk Criteria and Risk of Bipolar Disorder Over 10 or More Years

Predicting the onset of bipolar disorder (BD) could facilitate preventive treatments. Among risk measures, bipolar at-risk (BAR) criteria have shown promise in predicting onset of bipolar disorder in the first year in clinical cohorts; however, it is not known whether BAR criteria are associated with the onset of BD in the longer term. To assess the association of BAR criteria with onset of BD over 10 to 13 years follow-up. This prospective cohort study, completed between May 1, 2020, and November 7, 2022, included consenting people seeking help for nonpsychotic major mental health difficulties, including mood, personality, and substance use disorders, who were originally recruited at ages 15 to 25 years from a tertiary youth mental health setting in metropolitan Melbourne, Victoria, Australia, from May 1, 2008, to September 30, 2010. Meeting BAR criteria at baseline. Criteria included subthreshold mania, cyclothymic features, subthreshold depression, and family history of BD. A matched clinical comparison group was recruited from the same help-seeking population. The primary outcome was expert consensus diagnosis of BD I or II based on the Mini International Neuropsychiatric Interview, self-reported information collected through online assessments, and linked data on mental health service utilization in Victoria over 10 to 13 years of follow-up. Among 69 eligible participants, follow-up data were available for 60 (88.2%). The mean (SD) age at the end of follow-up was 32.9 (2.8) years, and 49 (81.7%) were women. A total of 28 participants met BAR criteria, and 32 were in the comparison group. In the BAR group, 8 patients (28.6%) developed BD over a mean (SD) of 11.1 (0.7) years of follow-up, and no patients in the comparison group developed BD. The risk of developing BD was higher in the BAR group than in the non-BAR group (χ21 = 70.0; P < .001). The proportions of transitions to BD were equal in the first and second halves of the follow-up period. In this cohort study of participants seeking care for mental health difficulties, patients meeting the BAR criteria were significantly more likely to transition to BD over a decade after ascertainment compared with patients not meeting the BAR criteria. The findings suggest that those meeting BAR criteria may benefit from longer-term monitoring and support. Evaluation of predictive properties in longer-term studies using a risk measure will help with implementation of BAR criteria in clinical settings.

Neurocognitive Functioning of Adolescents with Clinical High Risk for Psychosis, other Psychiatric Symptoms, and Psychosis

IntroductionClinical High Risk of Psychosis (CHR-P) condition and the clinical validity of at-risk criteria are still little studied in child and adolescent population.ObjectivesThis study aimed to discover neurocognitive profiles of adolescents with CHR-P, compared with adolescents with psychosis and youth with other psychiatric symptoms that do not meet CHR-P criteria.MethodsWe divided 116 adolescents (12-18 years old) in three groups according to the semi-structured interview Comprehensive Assessment of At-Risk Mental States (CAARMS): psychosis, attenuated psychosis syndrome (APS), non-APS. Moreover, we administered Wechsler scales to assess the IQ, Wisconsin Card Sorting Test to assess abstract reasoning and flexibility, Rey-Osterrieth complex figure to assess planning and attention, and Trail Making Test to assess psychomotor speed, visual attention and task switching. We administered BVN 12-18 subtests to assess lexical denomination, verbal and nonverbal working memory, selective auditory, visual attention, phonemic and categorial fluency, reasoning and problem solving.ResultsNineteen adolescents met criteria for psychosis, 47 for APS, and 50 did not meet criteria neither for psychosis nor for APS. APS group performed better than psychosis group and similar to non-APS group in processing speed, planning, visual attention, and categorial fluency. APS did not show a significant difference from the other groups in working memory and backward digit span, showing an intermediate profile; non-APS and psychosis groups still differed significantly in these functions.ConclusionsIdentifying typical neurocognitive profiles leads to more accurate diagnoses and early intervention that can lead to better patient outcomes.DisclosureThe authors declare that they do not have a significant financial interest, consultancy or other relationship with products, manufacturer(s) of products or providers of services related to this abstrac.

Alterations in blood proteins in the prodromal stage of bipolar II disorders

Although early intervention may help prevent the progression of bipolar disorder, there are some controversies over early pharmacological intervention. In this study, we recruited 40 subjects in the prodromal stage of BD-II (BP), according to bipolar at-risk state criteria. We compared the expression of their plasma proteins with that of 48 BD-II and 75 healthy control (HC) to identify markers that could be detected in a high-risk state. The multiple reaction monitoring method was used to measure target peptide levels with high accuracy. A total of 26 significant peptides were identified through analysis of variance with multiple comparisons, of which 19 were differentially expressed in the BP group when compared to the BD-II and HC groups. Two proteins were overexpressed in the BP group; and were related to pro-inflammation and impaired neurotransmission. The other under-expressed peptides in the BP group were related to blood coagulation, immune reactions, lipid metabolism, and the synaptic plasticity. In this study, significant markers observed in the BP group have been reported in patients with psychiatric disorders. Overall, the results suggest that the pathophysiological changes included in BD-II had already occurred with BP, thus justifying early pharmacological treatment to prevent disease progression.

Early detection of bipolar disorders and treatment recommendations for help-seeking adolescents and young adults: Findings of the Early Detection and Intervention Center Dresden

BackgroundEarly identification and intervention of individuals with risk factors for or subtle prodromal symptoms of bipolar disorders (BD) may improve the illness course and prevent adverse long-term consequences.MethodsWe examined sociodemographic, clinical and psychopathological characteristics of help-seeking adolescents and young adults who consulted the Early Detection and Intervention Center Dresden at the University of Dresden (Germany) and presented with or without pre-defined at-risk criteria for BD. The standardized diagnostic procedure for all help-seeking youth included a comprehensive psychiatric history and a structured clinical interview. When BD at-risk state was suspected, early detection instruments (EPIbipolar, BPSS-FP) were applied. Treatment recommendations were formulated in multi-professional case conferences.ResultsOut of 890 help-seeking persons between 05/2009 and 04/2018, 582 (65%) completed the diagnostic process. Of these, 24 (4%) had manifest BD and 125 (21%) fulfilled at-risk BD criteria (age = 23.9 ± 0.6 years, female = 62%). Of the pre-defined main risk factors, family history for BD was reported in 22% of the at-risk persons, (hypo-)mania risk state in 44%, and increasing cyclothymic mood swings with increased activity in 48%. The most common secondary risk factors were decreased psychosocial functioning (78%), lifetime diagnosis of depressive disorder (67%) and specific sleep/circadian rhythm disturbances (59%). Substance use was very common in subjects at-risk for BD (cannabis = 50%, alcohol = 33%) and highest in patients with BD (cannabis = 75%, alcohol = 40%). Psychiatric treatment history, including psychopharmacological therapy, was similar between the groups, while treatment recommendations differed, with more advice for psychotherapy and antidepressants in the at-risk group with a lifetime diagnosis of depression and more advice for specialized BD treatment including mood stabilizers in patients with BD.ConclusionThis analysis on the phenomenology of different BD at-risk stages suggests that early detection of individuals presenting with suggested risk factors for the development of BD is feasible in help-seeking young people. Future research should further develop/test stage-specific prevention and early targeted intervention approaches that were described in a naturalistic setting.

Efficacy of a centralized, blended electronic, and human intervention to improve direct oral anticoagulant adherence: Smartphones to improve rivaroxaban ADHEREnce in atrial fibrillation (SmartADHERE) a randomized clinical trial

Improving adherence to direct oral anticoagulants (DOAC) is challenging, and simple text messaging reminders have not been effective. SmartADHERE was a randomized trial that tested a personalized digital and human direct oral anticoagulant adherence intervention compared to usual care. Eligibility required age ≥18, newly-prescribed (≤90 days) rivaroxaban for atrial fibrillation (AF), 1 of 4 at-risk criteria for nonadherence, and a smartphone. The intervention consisted of combination of a medication management smartphone app, daily app-based reminders, adaptive text messaging, and phone-based counseling for severe nonadherence. The primary outcome was the proportion of days covered by rivaroxaban (PDC) at 6 months. There were 25 U.S. sites, all cardiology and electrophysiology outpatient practices, activated for a target sample size of 378, but the study was terminated by the sponsor prior to reaching target enrollment. There were 139 participants (age 65±9.6 years, 30% female, median CHA2DS2-VASc score 3 with IQR 2 to 4, mean total medication burden 7.7±4.4). DOAC adherence was high in both arms with no difference in the primary outcome (PDC 0.86±0.25 intervention vs 0.88±0.25 control, p=0.62) or in secondary outcomes including PDC ≥ 0.80 and medication persistence. Per protocol analyses had similar results. Because of the high overall PDC, the likelihood to answer the primary hypothesis was only 51% even if target enrollment were achieved. There were no study-related adverse events. The use of a centralized digital and human adherence intervention was feasible across multiple sites. Overall adherence was much higher than expected despite prescreening for at-risk individuals. SmartADHERE illustrates the challenges of trials of behavioral and technology interventions, where enrollment itself may lead to selection bias or treatment effects. Pragmatic study designs, such as cluster randomization or stepped-wedge implementation, should be considered to improve enrollment and generalizability.

O037 / #606: NON-INVASIVE VENTILATION PRACTICE FOR PRIMARY RESPIRATORY MANAGEMENT IN THE PEDIATRIC INTENSIVE CARE UNITS: AN INTERNATIONAL STUDY

Aims & Objectives: To describe current practices and outcomes of Non-Invasive Ventilation (NIV) in PICUs internationally. Methods: IRB approved point prevalence study over 10 study weeks at 52 PICUs in 12 countries. Children were included if NIV was newly initiated on screening days, including high flow nasal cannula [HFNC: > 3LPM (Term / <1 year), > 4LPM (1-3 years), or >5LPM (>3 years)], continuous (CPAP) or bilevel positive airway pressure (BiPAP), or other NIV mode. We excluded post-operative cardiac surgery, post-extubation, and home NIV. The risk factor analysis used mixed effects logistic regression with stepwise addition/deletion (retention cutoff: p=0.15) Results: Of 15,310 patients screened, 695 met inclusion criteria, including 472 (68%) HFNC, 158 (23%) BiPAP, 62 (9%) CPAP, and 3 other modes. Median age was 15.4 months (IQR: 5.1-63.3). Main NIV indications were acute hypoxemia (51%) and respiratory distress (27%). NIV interface was nasal cannula 399 (58%), nasal mask/prongs 111 (16%), bucco-nasal mask 18 (3%), full-face mask 154 (22%), or other 3 (0.4%). NIV duration was 2.1 days (1-4). NIV failure (endotracheal intubation) occurred in 18.6% cases, 69.8% of them before 48h of NIV (Figure). After adjustment for severity of illness, risk factors for NIV failure included meeting at-risk criteria for Pediatric Acute Respiratory Distress Syndrome (p=0.02) and exposure to parenteral nutrition (p=<0.001). Factors predictive of NIV success were respiratory admission category (p=0.001) and exposure to enteral nutrition (p=0.001).Conclusions: NIV is frequently used in PICUs, with heterogenous practice. NIV failure occurs in 18.6% cases, most frequently within the first 48hrs

Model for End-Stage Liver Disease With Additional Criteria to Predict Short-Term Mortality in Severe Flares of Chronic Hepatitis B.

The prognosis in severe acute flares of chronic hepatitis B (AFOCHB) is often unclear. The current study aimed to establish the predictive value using the Model for End-Stage Liver Disease (MELD) score for short-term mortality for severe AFOCHB. Patients with severe AFOCHB with bilirubin > 50 µmol/L, alanine aminotransferase > 10× upper limit of normal, and international normalized ratio > 1.5 were included. All patients were commenced on entecavir and/or tenofovir. Laboratory results and MELD scores were pooled to calculate mortality at four time points (days 7, 14, 21, and 28). A total of 240 patients were included. Median hepatitis B virus DNA was 7.77 log IU/mL (range, 4.11-10.06), and 49 (20.4%) were hepatitis B e antigen-positive. The 7, 14, 21, and 28-day survival was 96.7%, 88.5%, 79.5%, and 72.8%, respectively. Using pooled results derived from 4,201 blood samples, the area under the receiver operating curve for the MELD score to predict day 7, 14, 21, and 28 mortality was 0.909, 0.892, 0.883, and 0.871, respectively. For MELD ≤ 28, mortality at day 28 was low (<25%) compared with > 50% mortality for MELD ≥ 32. For MELD = 28-32, higher day-28 mortality was observed for four criteria: age ≥52 years, alanine aminotransferase > 217 U/L, platelets < 127, and abnormal baseline imaging (all P<0.001). In this MELD bracket, the 28-day mortality was 0%, 12.1%, 23.8%, 59.4%, and 78.8% for the presence of zero, one, two, three, and four criteria, respectively. MELD score at any time points can accurately predict the short-term mortality. Patients with MELD ≥ 28 should be worked up for liver transplantation, and those with MELD = 28-32 with three to four at-risk criteria, or MELD ≥ 32 should be listed.

Improving early recognition and intervention in people at increased risk for the development of bipolar disorder: study protocol of a prospective-longitudinal, naturalistic cohort study (Early-BipoLife)

BackgroundBipolar disorders (BD) belong to the most severe mental disorders, characterized by an early onset and recurrent, severe episodes or a chronic course with poor psychosocial functioning in a proportion of patients. Many patients with BD experience substantial symptomatology months or even years before full BD manifestation. Adequate diagnosis and treatment is often delayed, which is associated with a worse outcome. This study aims to prospectively evaluate and improve early recognition and intervention strategies for persons at-risk for BD.MethodsEarly-BipoLife is a prospective-longitudinal cohort study of 1419 participants (aged 15–35 years) with at least five waves of assessment over a period of at least 2 years (baseline, 6, 12, 18 and 24 months). A research consortium of ten university and teaching hospitals across Germany conducts this study. The following risk groups (RGs) were recruited: RG I: help-seeking youth and young adults consulting early recognition centres/facilities presenting ≥ 1 of the proposed risk factors for BD, RG II: in-/outpatients with unipolar depressive syndrome, and RG III: in-/outpatients with attention-deficit/hyperactivity disorder (ADHD). The reference cohort was selected from the German representative IMAGEN cohort. Over the study period, the natural course of risk and resilience factors, early symptoms of BD and changes of symptom severity (including conversion to manifest BD) are observed. Psychometric properties of recently developed, structured instruments on potential risk factors for conversion to BD and subsyndromal symptomatology (Bipolar Prodrome Symptom Scale, Bipolar at-risk criteria, EPIbipolar) and biomarkers that potentially improve prediction are investigated. Moreover, actual treatment recommendations are monitored in the participating specialized services and compared to recently postulated clinical categorization and treatment guidance in the field of early BD.DiscussionFindings from this study will contribute to an improved knowledge about the natural course of BD, from the onset of first noticeable symptoms (precursors) to fully developed BD, and about mechanisms of conversion from subthreshold to manifest BD. Moreover, these generated data will provide information for the development of evidence-based guidelines for early-targeted detection and preventive intervention for people at risk for BD.

M27. FUNCTIONAL OUTCOME OF CHILDREN AND ADOLESCENTS WITH ATTENUATED PSYCHOTIC SYMPTOMS: RESULTS FROM A LONGITUDINAL STUDY

BackgroundAssessing longitudinal functional outcomes, besides the risk of transition, seems important in underage population given the concerns about the use of at-risk criteria in this age range. Indeed, it has been highlighted that attenuated psychotic symptoms appear to be more common and transient than in adults and could, more often, represent normative experiences (Bartels-Velthuis et al. 2016; Schimmelmann et al. 2013). Thus, in this longitudinal cohort study, we aimed to evaluate socio-occupational functioning at follow-ups in children and adolescents with attenuated psychotic symptoms (APS) and to investigate potential clinical predictors of the functional outcome.MethodsHelp-seeking adolescents (aged 12–18 years) consecutively admitted to Child and Adolescent Neuropsychiatric inpatient and outpatient units of the IRCCS Mondino Foundation (Pavia, Italy) were recruited. The Comprehensive Assessment of At-Risk Mental State (CAARMS) was used in order to evaluate the presence of attenuated psychotic symptoms. The final sample consisted of 31adolescents suffering from early onset psychosis (EOP), 110 APS and 102 adolescents with psychiatric disorders other than APS and EOP (non-APS). At baseline patients underwent an extensive clinical and, in a subset, also neuropsychological assessment using standardized semi-structured interviews and instruments. All APS patients recruited until March 2019 were followed up for a median period of 33 months (range 4–81 months) and baseline measures were repeated (every 12 months). The level of functioning was defined through the Social and Occupational Functioning Assessment Scale (SOFAS).ResultsAt 12 months and last visit follow-ups APS patients overall continued to display a significant impairment in socio-occupational functioning that persisted over time (baseline SOFAS average score 47.3±9.6, average 12-months follow-up 51.7±13.7, average last-visit follow-up SOFAS 51.6±11.5). Also APS adolescents that did not develop psychosis continued to display a significant impairment in socio-occupational functioning that persisted over time. Besides conversion status (p=0.04), a higher SOFAS (p=0.0026) and better social functioning (p=0.016) and total IQ (p=0.02) at baseline and not having a baseline diagnosis of anxiety disorders (generalized anxiety disorder, p=0.005 and panic disorder, p=0.003) significantly predicted socio-occupational functioning at follow-up.DiscussionIn line with previous literature in adults, besides the risk of transitioning, at follow-ups APS adolescents overall continued to display a significant impairment in socio-occupational functioning that persisted over time. These data further show that APS adolescents are truly in need of care and underscore the need, also and especially in adolescents, not to focus only on transition risk, as APS adolescents appear to be both at risk of conversion to psychosis but also of functional disability persistent over time. Thus, preventive interventions should not only target emerging psychosis, but also improving APS social and global functional impairment that already at baseline seems to be linked with such a disabling outcome. In APS children and adolescents a multidimensional treatment plan including careful monitoring not only for a potential progression but also psychological interventions aiming at improving functioning is strongly recommended

Efficacy of cognitive-behavioral group therapy in patients at risk for serious mental illness presenting with subthreshold bipolar symptoms: Results from a prespecified interim analysis of a multicenter, randomized, controlled study.

Most patients with bipolar disorders (BD) exhibit prodromal symptoms before a first (hypo)manic episode. Patients with clinically significant symptoms fulfilling at-risk criteria for serious mental illness (SMI) require effective and safe treatment. Cognitive-behavioral psychotherapy (CBT) has shown promising results in early stages of BD and in patients at high risk for psychosis. We aimed to investigate whether group CBT can improve symptoms and functional deficits in young patients at risk for SMI presenting with subthreshold bipolar symptoms. In a multicenter, randomized, controlled trial, patients at clinical risk for SMI presenting with subthreshold bipolar symptoms aged 15-30years were randomized to 14weeks of at-risk for BD-specific group CBT or unstructured group meetings. Primary efficacy endpoints were differences in affective symptomatology and psychosocial functioning at 14weeks. At-risk status was defined as a combination of subthreshold bipolar symptomatology, reduction of psychosocial functioning and a family history for (schizo)affective disorders. A prespecified interim analysis was conducted at 75% of the targeted sample. Of 128 screened participants, 75 were randomized to group CBT (n=38, completers=65.8%) vs unstructured group meetings (n=37, completers=78.4%). Affective symptomatology and psychosocial functioning improved significantly at week 14 (P<.001) and during 6months (P<.001) in both groups, without significant between-group differences. Findings are limited by the interim character of the analysis, the use of not fully validated early detection interviews, a newly adapted intervention manual, and the substantial drop-outs. Results suggest that young patients at-risk for SMI presenting with subthreshold bipolar symptoms benefit from early group sessions. The degree of specificity and psychotherapeutic interaction needed requires clarification.

Predictors of Outcomes in Adolescents With Clinical High Risk for Psychosis, Other Psychiatric Symptoms, and Psychosis: A Longitudinal Protocol Study.

In children and adolescents, schizophrenia is one of the ten main causes of disability-adjusted life years. The identification of people at Clinical High Risk of developing Psychosis (CHR-P) is one of the most promising strategies to improve outcomes. However, in children and adolescents research on the CHR-P state is still in its infancy and the clinical validity of at-risk criteria appears understudied in this population. Furthermore, only few studies have evaluated the psychopathological, neuropsychological, neuroimaging characteristics and, especially, long-term outcomes of adolescents at high risk. We present here the protocol of an innovative longitudinal cohort study of adolescents aged 12-17. The sample will consist of patients admitted to a third level neuropsychiatric unit, belonging to one of the following three subgroups: 1) adolescents with established Diagnostic and Statistical Manual of Mental Disorder–Fifth Edition psychosis, 2) adolescents with CHR-P, and 3) adolescents with psychiatric symptoms other than established psychosis or CHR-P. The primary aim of our study is to evaluate the 2-year prognosis across the three groups. We will measure transition to psychosis (or the stability of the diagnosis of psychosis in the psychotic group), the risk of development of other psychiatric disorders, as well as socio-occupational functioning at outcome. The secondary aim will be to explore the effect of specific predictors (clinical, neuropsychological and neuroimaging factors) on the prognosis. At baseline, 1-year and 2-year follow-up participants will be assessed using standardized semi-structured interviews and instruments. Psychopathological and functioning variables, as well as neuropsychological domains will be compared across the three subgroups. Moreover, at baseline and 2-year follow-up all recruited patients will undergo a 3-Tesla magnetic resonance imaging examination and diffusion tensor imaging parameters will be analyzed. We believe that this study will advance our ability to predict outcomes in underage CHR-P samples. In particular, our data will enable a better understanding of the clinical significance of CHR-P in adolescents, and shed new light on prognostic factors that can be used to refine the prediction of clinical outcomes and the implementation of preventive interventions.

An At-Risk Population Screening Program for Mucopolysaccharidoses by Measuring Urinary Glycosaminoglycans in Taiwan.

Background: The mucopolysaccharidoses (MPSs) are a group of rare lysosomal storage disorders characterized by the accumulation of glycosaminoglycans (GAGs) and which eventually cause progressive damage to various tissues and organs. We developed a feasible MPS screening algorithm and established a cross-specialty collaboration platform between medical geneticists and other medical specialists based on at-risk criteria to allow for an earlier confirmative diagnosis of MPS. Methods: Children (<19 years of age) with clinical signs and symptoms compatible with MPS were prospectively enrolled from pediatric clinics between July 2013 and June 2018. Urine samples were collected for a non-specific total GAG analysis using the dimethylmethylene blue (DMB) spectrophotometric method, and the quantitation of three urinary GAGs (dermatan sulfate (DS), heparan sulfate (HS), and keratan sulfate (KS)) was performed by liquid chromatography/tandem mass spectrometry (LC-MS/MS). The subjects with elevated urinary GAG levels were recalled for leukocyte enzyme activity assay and genetic testing for confirmation. Results: Among 153 subjects enrolled in this study, 13 had a confirmative diagnosis of MPS (age range, 0.6 to 10.9 years—three with MPS I, four with MPS II, five with MPS IIIB, and one with MPS IVA). The major signs and symptoms with regards to different systems recorded by pediatricians at the time of the decision to test for MPS were the musculoskeletal system (55%), followed by the neurological system (45%) and coarse facial features (39%). For these 13 patients, the median age at the diagnosis of MPS was 2.9 years. The false negative rate of urinary DMB ratio using the dye-based method for these 13 patients was 31%, including one MPS I, two MPS IIIB, and one MPS IVA. However, there were no false negative results with urinary DS, HS and KS using the MS/MS-based method. Conclusions: We established an at-risk population screening program for MPS by measuring urinary GAG fractionation biomarkers using the LC-MS/MS method. The program included medical geneticists and other medical specialists to increase awareness and enable an early diagnosis by detecting MPS at the initial onset of clinical symptoms.

S164. “AT-RISK MENTAL STATES” PROGRAM IN LAUSANNE: INFLUENCE OF RECRUITMENT STRATEGIES ON THE RATE OF FALSE POSITIVES

BackgroundVarious strategies have been proposed to improve recruitment of “at risk mental state” patients; they may have an impact on the type of patients who reach such programs. We describe the clinical program for “at-risk” patients implemented in 2014 in Lausanne and the characteristics of referrals over the years.MethodsHelp seeking patients aged 14 to 35 were initially referred by health care providers for a specialized evaluation in case of suspicion of a potential “prodromal psychotic state” and more recently selected by PQ-16 (Ising et al. 2012) (cut-off: 6/16).At-Risk Mental State (ARMS) was defined according to the Basic Symptoms criterion (COPER-COGDIS criteria) from the Schizophrenia Proneness Instrument – Adult version (SPI-A) and to the Clinical High Risk criteria of the Structured Interview for Prodromal Syndromes (SIPS). ARMS patients underwent an extensive clinical evaluation (including Mini-SCID, SOFAS, MARDS, Yung Mania Scale, etc.) and were followed-up every 6 months over 3 years.ResultsWithin a catchment area of 260 000 inhabitants, 110 patients have been referred to our center since 2014 and 100 completed the investigation. 29 (29%) fulfilled ARMS criteria, 52 (52%) didn’t and 19 (19%) were already psychotic.The proportion of true ARMS patients decreased progressively over the years from 45% in 2014 and 2015, to only 22 and 13.9 % in 2016 and 2017.In our sample of help-seekers, the group of patients ARMS- negative received mostly a schizophrenia spectrum diagnosis (26/52 patients, 50%), associated with low psychosocial functioning, even when not in the precise range of at-risk criteria.DiscussionThe global prevalence (29%) of ARMS patients in our sample over the 4 years is marginally lower than previous reports on similar tertiary centers, which ranges from 33 to 51 % (Kline E., 2014). Our lower prevalence of ARMS patients within the sample may be linked to the limited resources we had to conduct an information strategy and our focus on psychologists and psychiatrists working at our department. The introduction in 2016 of more intense screening strategy based on the use of the PQ-16 lead to an increase in referral numbers but decreased the rate of ARMS among referred patients.Our results confirm the influence of the recruitment strategy and information campaigns on the prevalence of at-risk patients within a population of help-seekers. The prevalence of schizophrenia spectrum diagnosis in our group of patients ARMS-negative also suggests that a larger “vulnerability” model for psychosis, more sensitive to functioning and negative symptoms and not narrowed on the focus of the risk of imminent acute psychosis, may better fit patients’ needs.

Checking the predictive accuracy of basic symptoms against ultra high-risk criteria and testing of a multivariable prediction model: Evidence from a prospective three-year observational study of persons at clinical high-risk for psychosis

BackgroundThe aim of this study was to critically examine the prognostic validity of various clinical high-risk (CHR) criteria alone and in combination with additional clinical characteristics. MethodsA total of 188 CHR positive persons from the region of Zurich, Switzerland (mean age 20.5 years; 60.2% male), meeting ultra high-risk (UHR) and/or basic symptoms (BS) criteria, were followed over three years. The test battery included the Structured Interview for Prodromal Syndromes (SIPS), verbal IQ and many other screening tools. Conversion to psychosis was defined according to ICD-10 criteria for schizophrenia (F20) or brief psychotic disorder (F23). ResultsAltogether n=24 persons developed manifest psychosis within three years and according to Kaplan–Meier survival analysis, the projected conversion rate was 17.5%. The predictive accuracy of UHR was statistically significant but poor (area under the curve [AUC]=0.65, P<.05), whereas BS did not predict psychosis beyond mere chance (AUC=0.52, P=.730). Sensitivity and specificity were 0.83 and 0.47 for UHR, and 0.96 and 0.09 for BS. UHR plus BS achieved an AUC=0.66, with sensitivity and specificity of 0.75 and 0.56. In comparison, baseline antipsychotic medication yielded a predictive accuracy of AUC=0.62 (sensitivity=0.42; specificity=0.82). A multivariable prediction model comprising continuous measures of positive symptoms and verbal IQ achieved a substantially improved prognostic accuracy (AUC=0.85; sensitivity=0.86; specificity=0.85; positive predictive value=0.54; negative predictive value=0.97). ConclusionsWe showed that BS have no predictive accuracy beyond chance, while UHR criteria poorly predict conversion to psychosis. Combining BS with UHR criteria did not improve the predictive accuracy of UHR alone. In contrast, dimensional measures of both positive symptoms and verbal IQ showed excellent prognostic validity. A critical re-thinking of binary at-risk criteria is necessary in order to improve the prognosis of psychotic disorders.

Bipolar At-Risk Criteria: An Examination of Which Clinical Features Have Optimal Utility for Identifying Youth at Risk of Early Transition From Depression to Bipolar Disorders.

A clinical and research challenge is to identify which depressed youth are at risk of "early transition to bipolar disorders (ET-BD)." This 2-part study (1) examines the clinical utility of previously reported BD at-risk (BAR) criteria in differentiating ET-BD cases from unipolar depression (UP) controls; and (2) estimates the Number Needed to Screen (NNS) for research and general psychiatry settings. Fifty cases with reliably ascertained, ET-BD I and II cases were matched for gender and birth year with 50 UP controls who did not develop BD over 2 years. We estimated the clinical utility for finding true cases and screening out non-cases for selected risk factors and their NNS. Using a convenience sample (N = 80), we estimated the NNS when adjustments were made to account for data missing from clinical case notes. Sub-threshold mania, cyclothymia, family history of BD, atypical depression symptoms and probable antidepressant-emergent elation, occurred significantly more frequently in ET-BD youth. Each of these "BAR-Depression" criteria demonstrated clinical utility for screening out non-cases. Only cyclothymia demonstrated good utility for case finding in research settings; sub-threshold mania showed moderate utility. In the convenience sample, the NNS for each criterion ranged from ~4 to 7. Cyclothymia showed the optimum profile for case finding, screening and NNS in research settings. However, its presence or absence was only reported in 50% of case notes. Future studies of ET-BD instruments should distinguish which criteria have clinical utility for case finding vs screening.

Comparison of Bruch's Membrane Opening Minimum Rim Width Among Those With Normal Ocular Health by Race

To examine if racial differences in Bruch's membrane opening minimum rim width (BMO-MRW) in spectral-domain optical coherence tomography (SDOCT) exist, specifically between people of African descent (AD) and European descent (ED) in normal ocular health. Cross-sectional study. Patients presenting for a comprehensive eye examination at retail-based primary eye clinics were enrolled based on ≥1 of the following at-risk criteria for glaucoma: AD aged ≥40 years, ED aged ≥50 years, diabetes, family history of glaucoma, and/or pre-existing diagnosis of glaucoma. Participants with normal optic nerves on examination received SDOCT of the optic nerve head (24 radial scans). Global and regional (temporal, superotemporal, inferotemporal, nasal, superonasal, and inferonasal) BMO-MRW were measured and compared by race using generalized estimating equations. Models were adjusted for age, sex, and BMO area. SDOCT scans from 269 eyes (148 participants) were included in the analysis. Mean global BMO-MRW declined as age increased. After adjusting for age, sex, and BMO area, there was not a statistically significant difference in mean global BMO-MRW by race (P= .60). Regionally, the mean BMO-MRW was lower in the crude model among AD eyes in the temporal, superotemporal, and nasal regions and higher in the inferotemporal, superonasal, and inferonasal regions. However, in the adjusted model, these differences were not statistically significant. BMO-MRW was not statistically different between those of AD and ED. Race-specific normative data may not be necessary for the deployment of BMO-MRW in AD patients.

Eye Care Quality and Accessibility Improvement in the Community (EQUALITY): impact of an eye health education program on patient knowledge about glaucoma and attitudes about eye care.

PurposeTo assess the impact of the education program of the Eye Care Quality and Accessibility Improvement in the Community (EQUALITY) telemedicine program on at-risk patients’ knowledge about glaucoma and attitudes about eye care as well as to assess patient satisfaction with EQUALITY.Patients and methodsNew or existing patients presenting for a comprehensive eye exam (CEE) at one of two retail-based primary eye clinics were enrolled based on ≥1 of the following at-risk criteria for glaucoma: African Americans ≥40 years of age, Whites ≥50 years of age, diabetes, family history of glaucoma, and/or preexisting diagnosis of glaucoma. A total of 651 patients were enrolled. A questionnaire was administered prior to the patients’ CEE and prior to the patients receiving any of the evidence-based eye health education program; a follow-up questionnaire was administered 2–4 weeks later by phone. Baseline and follow-up patient responses regarding knowledge about glaucoma and attitudes about eye care were compared using McNemar’s test. Logistic regression models were used to assess the association of patient-level characteristics with improvement in knowledge and attitudes. Overall patient satisfaction was summarized.ResultsAt follow-up, all patient responses in the knowledge and attitude domains significantly improved from baseline (P≤0.01 for all questions). Those who were unemployed (odds ratio =0.63, 95% confidence interval =0.42–0.95, P=0.026) or had lower education (odds ratio =0.55, 95% confidence interval =0.29–1.02, P=0.058) were less likely to improve their knowledge after adjusting for age, sex, race, and prior glaucoma diagnosis. This association was attenuated after further adjustment for other patient-level characteristics. Ninety-eight percent (n=501) of patients reported being likely to have a CEE within the next 2 years, whereas 63% (n=326) had a CEE in the previous 2 years. Patient satisfaction with EQUALITY was high (99%).ConclusionImproved knowledge about glaucoma and a high intent to pursue eye care may lead to improved detection of early disease, thus lowering the risk of blindness.