Antipsychotic utilisation and persistence in Australia: A nationwide 5-year study

Objectives: To evaluate the utilisation and persistence of antipsychotics for the treatment of schizophrenia in Australia. Methods: A retrospective study using the Australian Pharmaceutical Benefits Scheme database of a representative 10% sample. All adults with schizophrenia who were dispensed three or more supplies of oral (including clozapine) or long-acting injectable antipsychotics between 1 June 2015 and 31 May 2020 were included. Persistence time in treatment was evaluated using survival analysis and Cox hazard ratios. Results: In all, 26,847 adults with schizophrenia were studied. Oral second-generation antipsychotics were more frequently dispensed than the other antipsychotic groups studied. Median treatment persistence times were 18.3 months for second-generation antipsychotic long-acting injectables, 10.7 months for oral second-generation antipsychotics and were significantly lower for both formulations of first-generation antipsychotics at 5.2 months (long-acting injectables) and 3.7 months (oral). The median persistence time for clozapine was significantly longer than all other antipsychotics groups. Conclusions: Oral second-generation antipsychotics and second-generation antipsychotic long-acting injectables accounted for over 75% and 13% of all antipsychotics in Australia, respectively. Concerns over medication adherence and subsequent relapse have not translated into increased long-acting injectable usage despite their significantly longer persistence. Clozapine, the single most ‘persistent’ antipsychotic, was only used in 9% of people, although up to a third of all cases are likely to be treatment-resistant. Our data suggest clinicians should give consideration to the earlier use of second-generation antipsychotic long-acting injectables and clozapine, to ameliorate prognosis in schizophrenia.

Pre-treatment clinical and gene expression patterns predict developmental change in early intervention in autism

Early detection and intervention are believed to be key to facilitating better outcomes in children with autism, yet the impact of age at treatment start on the outcome is poorly understood. While clinical traits such as language ability have been shown to predict treatment outcome, whether or not and how information at the genomic level can predict treatment outcome is unknown. Leveraging a cohort of toddlers with autism who all received the same standardized intervention at a very young age and provided a blood sample, here we find that very early treatment engagement (i.e., <24 months) leads to greater gains while controlling for time in treatment. Pre-treatment clinical behavioral measures predict 21% of the variance in the rate of skill growth during early intervention. Pre-treatment blood leukocyte gene expression patterns also predict the rate of skill growth, accounting for 13% of the variance in treatment slopes. Results indicated that 295 genes can be prioritized as driving this effect. These treatment-relevant genes highly interact at the protein level, are enriched for differentially histone acetylated genes in autism postmortem cortical tissue, and are normatively highly expressed in a variety of subcortical and cortical areas important for social communication and language development. This work suggests that pre-treatment biological and clinical behavioral characteristics are important for predicting developmental change in the context of early intervention and that individualized pre-treatment biology related to histone acetylation may be key.

A - 18 Parent-Ratings of Patient Depressive Symptoms Are Predictive of Concussion Care Outcomes in a Pediatric Sample

Objective The present study aims to examine how parental perception and child self-perception of depressive symptoms influence key clinical outcomes post-concussion, including symptom burden, treatment time, and treatment retention. Methods Participants 10–18 years (14.3 ± 2.2, 44.3% female, 3.8% history of depression) were recruited from a specialty clinic within 30 days of concussion (n = 106). The Mood and Feelings Questionnaire-Short (MFQ) Parent and Child versions and the Post-concussion Symptom Scale (PCSS) were completed at initial (Time 1) and second (Time 2) visits. Scores ≥8 indicate clinically significant depression on the MFQ, producing child-rated depression (CRD) and parent-rated depression (PRD) scores. Time in treatment was calculated as days between initial and clearance visits. Results Results of linear regression demonstrated higher PRD predicted longer treatment, B = 0.21, t(103) = 2.07, p &lt; 0.05. CRD was not predictive of treatment time, B = -0.0, t(103) = −0.1, p = 0.99. Another regression using Time 2 PCSS score as the outcome demonstrated that CRD at Time 1 predicted PCSS score at Time 2, B = 0.29, t(94) = 2.85, p &lt; 0.01, while PRD did not, B = 0.14, t(94) = 1.41, p = 0.16. Results of a logistic regression predicting return for formal clearance indicated that higher PRD predicted increased likelihood of being lost to follow-up, B = 0.21, p &lt; 0.05, 95% CI = 1.05–1.44. Conclusions Patients whose parents perceived them as being more depressed were in treatment longer and were less likely to be formally cleared after concussion. However, child rated depression at initial visit was more useful in predicting concussion symptom burden at follow up. Future research should further investigate how parental perceptions may influence pediatric concussion recovery.

The current state of the problem of predicting spontaneous combustion and explosiveness of sulfide ores and host rocks at a depth of more than 1500 m.

The mining factors of ore fire hazard during mining of the lower horizons of the Oktyabrskiy and Talnakhskiy northern deposits are considered. It is noted that the probability of self-heating of sulfide ores and the sulfide dust’s tendency to spontaneous combustion and explosiveness in certain sections of rich sulfide copper-nickel ores are quite high. The oxidation of sulfide ores occurs continuously due to the absorption of oxygen from the mine atmosphere and is accompanied by the release of heat. The oxidation can be accompanied by intense heating of the ore in mining conditions, with the accumulation of large volumes of broken rock mass for a long time in treatment and preparation workings and with free access of air to the bulk of the ore mass. The processes of ore and rock oxidation are especially intense when their moisture content is 1–4%. When the ore is heated above 35 °C, sulfurous gas (SO2) may be released. The main signs of the above-mentioned oxidative processes’ development and signs of the initial phase of a possible underground endogenous fire are indicated along with a constant increase in the temperature of the air coming from the bottom of the face. It is noted that in case of detecting at least one of the signs of a possible underground endogenous fire’s initial phase, urgent measures are taken to improve the ventilation of this working face, to ensure maximum intensity of shipped ore from the fresh stream and the content of sulfurous gas and hydrogen sulfide and mine air temperature are determined every 4 hours. If after two days on the outgoing stream there is no decrease in the content of sulfur dioxide and air temperature, then it should be considered that an endogenous fire has occurred. Measures for the prevention, localization and elimination of foci of spontaneous combustion are given. As an additional safety measure, it is recommended to moisten the dust, since sulfide dust becomes non-explosive at a moisture content of 9–9,5%, and at a humidity of 10% the dust does not transmit an explosive impulse.

Investigating the effect of hydrogen peroxide as an electron acceptor in increasing the capability of slurry photocatalytic process in dye removal

The hydrogen peroxide role in photocatalytic degradation of an anionic azo dye, Acid Orange 7 (AO7), was investigated in a slurry reactor. Commercial ZnO nanoparticles with an average size between 10 to 30 nm were used as catalysts. Optimum conditions for different parameters, including dye concentration (10–100 mg/L), catalyst concentration (0.1–0.5 g/L), and pH (5–10), were determined first in the absence of H2O2. Changes in the COD were measured for the optimum condition. The impact of adding hydrogen peroxide at different concentrations to the system operating at optimum conditions was investigated. It was observed that 0.416 mM hydrogen peroxide increased the system's efficiency and decreased reaction time by 40 min. The reaction followed first-order kinetic. Hydrogen peroxide alone did not contribute to oxidizing the contaminant, and its positive impact was attributed to decreasing electron-hole recombination in the photocatalytic process. Not only can the hydrogen peroxide-assisted photocatalytic process decrease retention time in treatment units, but it can also result in more contaminant degradation. Therefore, it can reduce the treatment cost.

Treatment use patterns in a large extended-treatment tobacco cessation program: predictors and cost implications

BackgroundTobacco dependence follows a chronic and relapsing course, but most treatment programmes are short. Extended care has been shown to improve outcomes. Examining use patterns for longer term programmes can quantify resource requirements and identify opportunities for improving retention.MethodsWe analyse 38 094 primary care treatment episodes from a multisite smoking cessation programme in Ontario, Canada that provides free nicotine replacement therapy (NRT) and counselling. We calculate distributional measures of weeks of NRT used, clinical visits attended and total length of care. We then divide treatment courses into four exclusive categories and fit a multinomial logistic regression model to measure associations with participant characteristics, using multiple imputation to address missing data.ResultsTime in treatment (median=50 days), visits (median=3) and weeks NRT used (median=8) were well below the maximum available. Of all programme enrolments, 28.8% (95% CI=28.3% to 29.3%) were single contacts, 31.3% (30.8% to 31.8%) lasted <12 weeks, 19.2% (18.8% to 19.6%) were ≥12 weeks with an 8-week interruption and 20.7% (20.3%–21.1%) were ≥12 weeks without interruptions. Care use was most strongly associated with participant age and whether the nicotine patch was dispensed at the first visit.ConclusionTreatment use results imply that the marginal costs of extending treatment programmes are relatively low. The prevalence of single contacts supports additional engagement efforts at the initial visit, while interruptions in care highlight the ability of longer term care to address relapse. Results show that use of the nicotine patch is associated with retention in care, and that improving engagement of younger patients should be a priority.

Safety and Tolerability of Manual Push Administration of Subcutaneous IgPro20 at High Infusion Rates in Patients with Primary Immunodeficiency: Findings from the Manual Push Administration Cohort of the HILO Study

Purpose To evaluate the safety and tolerability of IgPro20 manual push (also known as rapid push) infusions at flow rates of 0.5–2.0 mL/min. Methods Patients with primary immunodeficiency (PID) with previous experience administering IgPro20 (Hizentra®, CSL Behring, King of Prussia, PA, USA) were enrolled in the Hizentra® Label Optimization (HILO) study (NCT03033745) and assigned to Pump-assisted Volume Cohort, Pump-assisted Flow Rate Cohort, or Manual Push Flow Rate Cohort; this report describes the latter. Patients administered IgPro20 via manual push at 0.5, 1.0, and 2.0 mL/min/site for 4 weeks each. Responder rates (percentage of patients who completed a predefined minimum number of infusions), safety outcomes, and serum immunoglobulin G (IgG) trough levels were evaluated. Results Sixteen patients were treated; 2 patients (12.5%) discontinued at the 1.0-mL/min level (unrelated to treatment). Responder rates were 100%, 100%, and 87.5% at 0.5-, 1.0-, and 2.0-mL/min flow rates, respectively. Mean weekly infusion duration decreased from 103–108 to 23–28 min at the 0.5- and 2.0-mL/min flow rates, respectively. Rates of treatment-related treatment-emergent adverse events (TEAEs) per infusion were 0.023, 0.082, and 0.025 for the 0.5-, 1.0-, and 2.0-mL/min flow rates, respectively. Most TEAEs were mild local reactions and tolerability (infusions without severe local reactions/total infusions) was 100% across flow rate levels. Serum IgG levels (mean [SD]) were similar at study start (9.36 [2.53] g/L) and end (9.58 [2.12] g/L). Conclusions Subcutaneous IgPro20 manual push infusions at flow rates up to 2.0 mL/min were well tolerated and reduced infusion time in treatment-experienced patients with PID. Trial Registration NCT03033745

AB0318 CHARACTERISTICS OF PATIENTS WITH RHEUMATOID ARTHRITIS WHO HAVE WITHDRAWN THE LAST BIOLOGICAL DRUG: REAL-LIFE RESULTS FROM A LOCAL REGISTRY

Objectives:To assess the characteristics of patients with rheumatoid arthritis (RA), who have withdrawn the last biological drug (bDMARD), and to know the reasons for withdrawal of treatment.Methods:Retrospective and cross-sectional study on December 31, 2019, of patients with RA, treated with any of the bDMARDs, including JAK (JAKi) inhibitor drugs, commonly used, from 1/1/2000 to 12/31/2019. General data were collected from patients, and RA: time of evolution, presence of rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA), type of bDMARD, time in bDMARD, and cause of withdrawal.Results:Of 252 patients, who have received some bDMARD, 81 (32%) patients had withdrawn on 12/31/2019. 62 (77%) patients were women, with a mean age at diagnosis of RA of 48 years (SD: 16.5 years) and 59.5 (15) years at the beginning of the first bDMARD (F1), with an average evolution of RA 10.2 (2.5) years. 68% and 74% of patients were positive for RF and ACPA, respectively.In 64 (79%) patients, bDMARD was withdrawn as second to fifth bDMARD received (F2 to F5): as F2: 37/81 (46%) patients, F3: 14 (18%), F4: 8 (10%) and as F5: (6%) patients.When comparing the last bDMARD received, before the suspension as F1 vs F2-F5, 95% vs. 61% of patients (p <0.0001), the drug was an anti-TNF (TNFi); Abatacept: 1 (1%) vs 9 (14%); Tocilizumab: 0% vs 8 (12%); Rituximab: 1 (1%) vs 5 (8%) and JAKi: 4 (5%) vs 3 (5%). The mean time in treatment with some bDMARD was 2.6 (SD: 3) years in the F1 group vs 1.7 (2) years in the F2-F5 group (p = 0.034). Among the F3-F5 patients, 9 (14%) patients had failed at 2 different previous therapeutic targets and 6 (9%) at 3 targets.No differences were detected between the F1 group vs F2-F5, regarding the causes of withdrawal of bDMARD: whether it had occurred due to 1) loss of efficacy (25/31% patients vs 19/30%); 2) adverse events (31/38% vs. 29/45%): infection: 18/81 (22%) patients, malignancy: 5 (6%), malaise/pain: 11 (14%), laboratory parameters alteration: 7 (9%), death: 5 (6%), others: 14 (17%); 3) change of address/loss of follow-up (20/25% vs. 7/11%) or by 4) voluntary abandonment of treatment by the patient (5/6% vs. 9/14%).Conclusion:1. 32% of patients with RA withdraw the bDMARD. 2. The group treated with TNFi withdraws it significantly higher among the F1 group. 3. Survival of bDMARD is significantly higher in group F1 compared to F2-F5. 4. No differences were detected between the groups regarding the cause of withdrawal of bDMARD. 25% -30% of patients withdraw it due to loss of follow-up or voluntary abandonment of bDMARD.Acknowledgments:The study was supported by a research grant from the Association for Research in Rheumatology of the Marina Baixa (AIRE-MB).Disclosure of Interests:None declared

Testing an Interactionist Theory of Treatment Engagement in a Pennsylvania Prison-Based Therapeutic Community

The prison-based Therapeutic Community (TC) is a promising substance use treatment program that emphasizes peer influence. Although program evaluations demonstrate positive results, the cognitive, behavioral, and social processes that define the prison-based TC are largely unknown. The TC model presumes that residents increase their treatment engagement and willingness to change through peer interactions and role modeling, but this process has received virtually no research attention. This study explores these peer-driven mechanisms by examining self, reflected, and peer appraisals of willingness to change of 177 male TC residents, predicting within-person changes in treatment engagement by changes in appraisal measures. Results suggest that self, peer, and reflected appraisals converge over time in treatment. In addition, fixed effects models demonstrate that changes in reflected appraisals are most predictive of changes in treatment engagement. Such results, consistent with symbolic interactionist perspectives, inform prison-based programming and contribute to research on individual-level trajectories of desistance and recovery.