Triglyceride-rich lipoprotein, remnant cholesterol, and apolipoproteins CII, CIII and E in patients with schizophrenia.

Patients with schizophrenia show a disproportionally increased risk of cardiovascular disease. Hypertriglyceridemia is prevalent in this population, however how this relates to levels of remnant cholesterol, triglyceride (TG)-rich lipoprotein (TRL) particle size and composition, TG turnover, and apolipoprotein (apo) and angiopoietin-like protein (ANGPTL) concentrations is unknown. Fasting levels of cholesterol (total [TC], LDL-C, HDL-C, non-HDL-C and remnant cholesterol) and TG were determined in 110 patients diagnosed with schizophrenia, and 46 healthy controls. TRL particle size, concentration and composition, and ß-hydroxybutyrate (TG turnover marker) were assessed by NMR. ApoCII, apoCIII, apoE, ANGPTL3, ANGPTL4 and ANGPTL8 levels were measured by ELISA, and apoCII, apoCIII and apoE were further evaluated in HDL and non-HDL fractions. Patients with schizophrenia had significantly elevated TG, TG:apoB ratio, non-HDL-C, remnant cholesterol, non-HDL-apoCII and non-HDL-apoCIII, and HDL-apoE (all p<0.05), lower HDL-C and apoA-I (all p<0.001), and comparable apoB, TC, TC:apoB ratio, LDL-C, ß-hydroxybutyrate, ANGPTL3, ANGPTL4 and ANGPTL8 to healthy controls. Patients had a 12.0- and 2.5-fold increase in the concentration of large and medium TRL particles respectively, but similar cholesterol:TG ratio within each particle. Plasma TG, remnant cholesterol, and large and medium TRL particle concentrations correlated strongly with apoCII, apoCIII, and apoE in the non-HDL fraction, and with apoCIII and apoE in the HDL fraction in patients with schizophrenia. Differences in TG, HDL-C, TRL particle concentrations, apoCIII and apoE between patients and controls persisted after adjustment for conventional risk factors. Patients with schizophrenia have a marked increase in large and medium TRL species associated with elevated remnant cholesterol, apoCII, apoCIII and apoE. These results are consistent with impaired TRL lipolysis and clearance which may be responsive to targeting apoCIII.

Prevalence of, and factors associated with, diabetes mellitus in people with severe mental illness attending a multidisciplinary, outpatient cardiometabolic health assessment service.

INTRODUCTION: Evaluate the prevalence of, and factors associated with, diabetes in people with severe mental illness (SMI) attending the Collaborative Centre for Cardiometabolic Health in Psychosis (ccCHiP) tertiary referral clinics. RESEARCH DESIGN AND METHODS: Adult patients attending an initial ccCHiP clinic consultation (2014-2019) were studied. Diabetes was defined by an hemoglobin A1c of ≥6.5%, fasting blood glucose of ≥7.0 mmol/L, or a self-reported diagnosis of diabetes and prescription of antihyperglycemic medication. RESULTS: Over 5 years, 1402 individuals attended a baseline consultation. Mean age of 43.9±12.8 years, 63.1% male and 63.5% had a diagnosis of schizophrenia. Prevalence of diabetes was 23.0% (n=322); an additional 19.5% fulfilled criteria for pre-diabetes. Of those with diabetes, 15.8% were newly diagnosed. Of those with pre-existing diabetes, 84.5% were receiving treatment with antihyperglycemic medication. Over 94% of individuals with diabetes had dyslipidemia; half were current smokers; and 46.4% reported sedentary behavior. On multivariate analysis, diabetes was associated with older age, Aboriginal, Indian or Middle Eastern maternal ethnicity, elevated waist-to-height ratio, family history of diabetes and use of antipsychotic medication. CONCLUSION: Prevalence of diabetes mellitus in this multiethnic cohort with SMI is significantly higher than the Australian population. Targeted interventions via an assertive integrated approach are required to optimize cardiometabolic health in this population.

Hospitalisation for mental health disorders in Australians with type 1 or type 2 diabetes.

AIMS: To determine the burden and leading reasons for mental health hospitalisation among Australians with diabetes. METHODS: We determined the incidence of hospitalisation for all mental health disorders in people with type 1 or type 2 diabetes of all ages by linking the National Diabetes Services Scheme to hospital admission datasets from 2010 to 2017. We compared those with type 2 diabetes aged 15 and above to the general population using excess hospitalisations per 100,000 person-years associated with diabetes. RESULTS: Depressive disorders were the leading reason for mental health admission in Australians with diabetes, responsible for 6.09 (95% CI 5.78-6.42) and 7.05 (6.95-7.14) admissions per 1,000 person-years in those with type 1 and type 2 diabetes, respectively. When considering only one admission per person, mental health admission rates were up to 90% lower. Among males with type 2 diabetes, stress and adjustment disorders were the leading cause of excess admissions compared to the general population, while depressive disorders were the leading cause in females. CONCLUSIONS: We found a substantial burden of psychiatric hospitalisations among Australians with diabetes, reinforcing the importance of mental health awareness among diabetes clinicians, and support by psychiatric teams for those with diabetes to prevent readmission.

Pharmacokinetics and Effects on Saliva Flow of Sublingual and Oral Atropine in Clozapine-Treated and Healthy Adults: An Interventional Cross-Over Study.

Background: Sublingual atropine is an effective treatment of clozapine-induced hypersalivation. This study aims to investigate the pharmacokinetics of atropine after sublingual and oral administration and study the dose effect of atropine on saliva secretion. Methods: An interventional cross-over clinical trial where participants received 0.6 mg and 1.2 mg atropine sulfate sublingual solution and 0.6 mg oral tablet. Atropine plasma concentration was measured over 9 hours with validated LC-MS/MS method. Atropine effects on saliva secretion rate, visual acuity and accommodation, and vital signs were assessed. Results: Four clozapine-treated and three healthy participants were enrolled in the study. The area under the atropine plasma concentration-time curve (AUC0-∞) was highest after the 1.2 mg sublingual solution administration in comparison with 0.6 mg tablet or sublingual solution (8.58±1.66 µg.L-1.h vs. 4.65±1.29 vs. 2.98±0.73 µg.L-1.h, respectively). The Cmax for the 0.6 mg and 1.2 mg sublingual solutions was 1.11±0.99 and 1.76±0.62 µg.L-1, and tmax was 2.18±0.59 and 1.9±0.71 h, respectively. In comparison with the 0.6 mg sublingual solution dose, the saliva secretion reduction was larger after the oral tablet administration (-40% (-59, -22%) vs. -69% (-80, -57)) and largest after the 1.2 mg sublingual solution administration (-79% (-93,-64)). Conclusion: Both the sublingual and oral atropine are effective in reducing the saliva secretion however at a lower plasma concentration after sublingual administration, with a dose-dependent effect. Both have significantly reduced the blood pressure and pulse rate over 3 hours without significant changes in vision. No major safety concerns were reported.

Acceptability and face validity of two mental health screening tools for use in the routine surgical setting.

BACKGROUND: Preoperative assessment of mental health rarely occurs within routine surgery. Any screening tool selected to form part of this process must be deemed practical, acceptable and valid by clinicians and consumers alike. This study aims to assess the acceptability and face validity of two existing mental health screening tools to select one for further development and use in the routine surgical setting. METHODS: A survey of clinicians and consumers was conducted from October 2020 to March 2021 at a tertiary hospital in Sydney, Australia. Using a Likert scale (1-5, lowest to highest rating), the clinicians evaluated four domains for acceptability and two for validity (six overall) and the consumers four domains for acceptability and one for validity (five overall) on the preoperative use of the amended Kessler Psychological Distress Scale (K10) and the Somatic and Psychological Health Report-12 (SPHERE-12). Consensus was achieved through a rating of 4 or 5 being given by 70% or more of participants with domains able to remain unchanged. Free text responses were analysed into themes. RESULTS: A total of 73 participants (51 clinicians; 22 consumers) were included. The K10 received consensus scores (≥ 70%) in four out of six domains for clinicians (4/4 acceptability; 0/2 validity), and all five domains for consumers (4/4 acceptability; 1/1 validity). The SPHERE-12 received consensus scores (≥ 70%) in three domains for clinicians (3/4 acceptability; 0/2 validity), and three domains for consumers (3/4 acceptability; 0/1 validity). Six qualitative themes were described including (1) amendments to tool structure and language; (2) scale response options; (3) difficulty with somatic questions; (4) practicality and familiarity with K10; (5) challenges for specific patient cohorts and (6) timing considerations for patients. CONCLUSION: Adequate acceptability was established for the K10. However further development is required to strengthen its validity for this specific surgical cohort and purpose. Future research to determine the feasibility and acceptability of implementing and using the K10 in the routine surgical setting is now needed.

Surgical experience for patients with serious mental illness: a qualitative study.

BACKGROUND: People with serious mental illness (SMI) have significantly worse surgical outcomes compared to the general population. There are many contributing factors to this complex issue, however consideration of the surgical experience from the patient's own perspective has never been undertaken. This lack of understanding prevents the provision of truly patient centred care and may limit the impact of potential improvement initiatives. Therefore this study aims to describe and better understand the surgical experience from the perspective of patients with SMI. METHODS: Within this qualitative study, semi-structured, audio-recorded interviews were conducted between August 2019 - June 2020, with 10 consenting participants with SMI who had surgery in the previous 2 years. A thematic analysis approach was used to explore both the positive and negative aspects of the participant's surgical experience commencing from pre-operative consultation to hospital discharge and follow-up. RESULTS: Four main themes and related subthemes emerged including i) the perceived lack of mental ill health recognition, ii) highly variable patient and clinician interactions, iii) the impact of healthcare services, and iv) strategies for improvement. CONCLUSION: Surgical patients with SMI want to be treated like everyone else whilst still having their mental ill health acknowledged and proactively managed despite this rarely occurring, which is valuable information for all surgical teams to consider and learn from. Participants were able to describe several readily implementable strategies to potentially improve their care and overall surgical experience, and as such highlight considerable opportunities for these to be tested and evaluated for this underserved patient group.

The effect of sublingual atropine sulfate on clozapine-induced hypersalivation: a multicentre, randomised placebo-controlled trial.

BACKGROUND: Hypersalivation and drooling are commonly reported in clozapine-treated patients. Current management strategies have been evaluated using subjective measures. Many case reports describe the successful use of atropine in the treatment of the condition. AIMS: To measure the effect and safety of sublingual atropine on nocturnal unstimulated saliva secretion. Secondary aims were to evaluate the patient's satisfaction with the atropine effect on hypersalivation (or sialorrhea), drooling, and sleep. METHOD: Twenty-one clozapine-treated patients with hypersalivation, or drooling, were randomised to take a single 600-µg dose of sublingual atropine drops or a matching placebo. The saliva secretion was measured over 5 min at baseline and 2 h after the administration of the study medication. RESULTS: Sublingual atropine reduced the saliva secretion significantly more than the placebo (mean difference = - 57.21%, 95% CI: - 104.30, - 10.11, P = 0.02). A significant decrease in standing pulse rate was recorded in the participants in the atropine group (- 5.8 (- 9.54, - 2.15), P = 0.002). Subjectively, more patients in the atropine group found their pillow to have less saliva the following morning and found their sleep to be better. CONCLUSIONS: Sublingual atropine drops significantly reduces nocturnal unstimulated clozapine-induced saliva secretion. More research is required to compare the effect of sublingual atropine with other anticholinergic medications and different dosage forms. TRIAL REGISTRATION: ACTRN12618000051246.

The evaluation of e-learning resources as an adjunct to otolaryngology teaching: a pilot study.

BACKGROUND: The concept of e-Learning has been rapidly accepted as an important component of medical education and is especially adept at teaching clinical skills. However, their impact on learning, particularly in Otolaryngology Head and Neck Surgery (OHNS) medical school curriculum, has yet to be adequately explored. The aim of this pilot study is to develop interactive e-Learning resources and evaluate their impact in enhancing OHNS teaching in medical school. METHODS: This pilot study is a randomized controlled trial assessing the effectiveness of e-Learning resources in enhancing the current traditional lecture and tutorial-based teaching of OHNS in medical school. Nineteen final-year medical students from the University of Sydney were recruited for this study, who were randomly allocated into intervention group with additional e-Learning resources (Group A) and control group (Group B). Student knowledge was assessed through objective structured clinical examinations (OSCE) with use of standardized forms for objective scoring. Assessors were blinded to student randomization status. A post-study questionnaire was distributed to assess student feedback on the e-Learning resources. RESULTS: Eight students were allocated to Group A and 11 students to Group B. Group A performed significantly better than Group B in the overall examination scores (78.50 ± 13.88 v. 55.82 ± 8.23; P = < 0.01). With the minimum pass mark of 65%, the majority of students in Group A was able to pass the OSCE assessments, while the majority of students in Group B failed (87.50% v. 9.10%; P = 0.01). The post-test questionnaire on the e-Learning resources showed very favorable feedback from the students' perspective. CONCLUSION: Results from our pilot study suggests that the use of interactive online e-Learning resources can be a valuable adjunct in supplementing OHNS teaching in medical school, as they are readily accessible and allow flexible on-demand learning. Future studies involving large numbers of medical students are needed to validate these results.

Impact of serious mental illness on surgical patient outcomes.

BACKGROUND: People with comorbid mental illness have poorer health status and disparate access to healthcare. Several studies internationally have reported mixed findings regarding the association between mental illness and surgical patient outcomes. This study examines the surgical outcomes in people with decompensated serious mental illness (SMI) within the setting of the Australian universal healthcare system. METHODS: Retrospective cohort study involving elective overnight surgical patients aged 18 years and above who attended a large public tertiary referral hospital in Sydney, Australia, between 2010 and 2014. Patients were identified using ICD-10-AM diagnosis codes. Outcomes measure including in-hospital mortality, post-operative complications, morbidity, admission and time in intensive care, length and cost of hospitalization, discharge destination and 28-day re-admission rates were examined. RESULTS: Of 23 343 surgical patient admissions, 451 (2%) patients had decompensated comorbid SMI with a subset of 47 (0.2%) having a specific psychotic illness. Patients with SMI comorbidity had significantly higher in-hospital mortality (2% versus 0%), post-operative complications (22% versus 8%), total comorbidity (7.6 versus 3.4 secondary codes), admissions (29% versus 9%) and time in intensive care (34.6 h versus 5.0 h), stay in hospital (12.2 days versus 4.6 days), admission costs ($24 162 versus $12 336), re-admission within 28 days (14% versus 10%) and discharges to another facility (11% versus 3%). CONCLUSION: Patients with comorbid SMI had significantly worse surgical outcomes and incur much higher costs compared with the general surgical population. These results strongly highlight that specific perioperative interventions are needed to proactively improve the identification, management and outcomes for these disadvantaged patients.

Cardiovascular disease in patients with schizophrenia.

Patients with schizophrenia die on average 25 years earlier than the general population, and this gap appears to be increasing. Most of the excess mortality is due to premature cardiovascular deaths rather than suicide. Many psychotropic agents are orexigenic and can increase weight and promote dyslipidaemia. Traditional cardiac risk factors are undertreated among patients with schizophrenia, and they are less likely to receive cardiac revascularisation than those without a mental illness. Clozapine is an atypical antipsychotic medication effective for treatment of refractory schizophrenia, but is associated with the risk of myocarditis and cardiomyopathy. Established protocols in Australia screen for myocarditis for patients who are initiating clozapine therapy and for long term monitoring for cardiomyopathy with echocardiography. Coordinated care between tertiary providers, general practitioners and primary health care professionals should monitor the physical health of people with psychosis or schizophrenia at least annually and treatment should be offered accordingly.

The Sydney Mental Health Client Mortality Audit: what does it tell us and what are we to do?

OBJECTIVES: To examine the characteristics of those mental health clients of an Australian metropolitan health service who died during a 6 year period, 2005 - 2010. METHODS: The medical records, and where available, coronial post-mortem examinations were audited for 109 people with schizophrenia who died while they were clients of the mental health service. RESULTS: The mean age of death for men was 45 years and for women, 47 years, compared to the general population's male and female life expectancy of 79 and 84 years, respectively. About one-half of the deaths were due to suicide (n = 55), followed by natural causes (n = 42; 39%), undetermined causes (n = 7), and accidents or acts of violence (n = 5). Smoking rates, diagnosed diabetes and hypertension were higher in the group that died from natural causes. Morbid obesity (body mass index (BMI) > 35 kg/m(2)) rates were higher in the group that died of natural causes (38%), compared with the suicide group (5%). CONCLUSIONS: While suicide accounts for the majority of those dying prematurely in this study cohort, it appears that for those who survive the risk of suicide in the earlier period of a chronic psychotic illness, there is yet another threat to life expectancy: death from preventable cardiorespiratory disorders, due to a poor lifestyle and social deprivation.

A randomized controlled pilot trial comparing the impact of access to clinical endocrinology video demonstrations with access to usual revision resources on medical student performance of clinical endocrinology skills.

BACKGROUND: Demonstrating competence in clinical skills is key to course completion for medical students. Methods of providing clinical instruction that foster immediate learning and potentially serve as longer-term repositories for on-demand revision, such as online videos demonstrating competent performance of clinical skills, are increasingly being used. However, their impact on learning has been little studied. The aim of this study was to determine the value of adjunctive on-demand video-based training for clinical skills acquisition by medical students in endocrinology. METHODS: Following an endocrinology clinical tutorial program, 2nd year medical students in the pre-assessment revision period were recruited and randomized to either a set of bespoke on-line clinical skills training videos (TV), or to revision as usual (RAU). The skills demonstrated on video were history taking in diabetes mellitus (DMH), examination for diabetes lower limb complications (LLE), and examination for signs of thyroid disease (TE). Students were assessed on these clinical skills in an observed structured clinical examination two weeks after randomization. Assessors were blinded to student randomization status. RESULTS: For both diabetes related clinical skills assessment tasks, students in the TV group performed significantly better than those in the RAU group. There were no between group differences in thyroid examination performance. For the LLE, 91.7% (n = 11/12) of students randomized to the video were rated globally as competent at the skill compared with 40% (n = 4/10) of students not randomized to the video (p = 0.024). For the DMH, 83.3% (n = 10/12) of students randomized to the video were rated globally as competent at the skill compared with 20% (n = 2/10) of students not randomized to the video (p = 0.007). CONCLUSION: Exposure to high quality videos demonstrating clinical skills can significantly improve medical student skill performance in an observed structured clinical examination of these skills, when used as an adjunct to clinical skills face-to-face tutorials and deliberate practice of skills in a blended learning format. Video demonstrations can provide an enduring, on-demand, portable resource for revision, which can even be used at the bedside by learners. Such resources are cost-effectively scalable for large numbers of learners.

An Acute Recovery Unit: the first 18 months.

OBJECTIVES: To describe a new type of acute inpatient unit, the Acute Recovery Unit, at the Concord Centre for Mental Health, Sydney and to report patient characteristics and outcome data for the first 18 months of operation. METHODS: The mission, values, principles of care and operation of the Acute Recovery Unit are presented, including the lessons from a review of the first 18 months of operation. The specialist assessment procedure, academic detailing and range of specialist interventions are described. RESULTS: Clinical outcome measures including the Health of the Nation Outcome Scale, Multidimensional Incomplete Recovery - Clinical Global Index and community tenure time post-discharge are presented. CONCLUSIONS: The Acute Recovery Unit is an important component of the range of services required at a regional level to respond to those who will develop treatment refractory mental illness.

Long acting risperidone in Australian patients with chronic schizophrenia: 24-month data from the e-STAR database.

BACKGROUND: This observational study was designed to collect treatment outcomes data in patients using the electronic Schizophrenia Treatment Adherence Registry (e-STAR). METHODS: Patients with schizophrenia or schizoaffective disorder in Australia who were prescribed risperidone long-acting injection (RLAI) between 2003 and 2007 were assessed 12-months retrospectively, at baseline and 24-months prospectively at 3-monthly intervals. The intent-to-treat population, defined as all patients who received at least one dose of RLAI at baseline, was used for the efficacy and safety analyses. RESULTS: At total of 784 patients (74% with schizophrenia, 69.8% male) with a mean age of 37.1 ± 12.5 years and 10.6 ± 9.5 years since diagnosis were included in this Australian cohort. A significant improvement in mean Clinical Global Impression - severity score was observed at 24-months (4.52 ± 1.04 at baseline, 3.56 ± 1.10 at 24-months). Most of this improvement was seen by 3-months and was also reflected in mean Global Assessment of Functioning score, which improved significantly at 24-months (42.9 ± 14.5 at baseline, 59 ± 15.4 at 24-months). For patients still receiving RLAI at 24-months there was an increase from a mean baseline RLAI dose of 26.4 ± 5 mg to 43.4 ± 15.7 mg. Sixty-six percent of patients discontinued RLAI before the 24-month period--this decreased to 46% once patients lost to follow-up were excluded. CONCLUSION: Over the 24-month period, initiation of RLAI was associated with improved patient functioning and illness severity in patients with schizophrenia or schizoaffective disorder. Improved outcomes were observed early and sustained throughout the study. TRIAL REGISTRATION: Clinical Trials Registration Number, NCT00283517.

Are cardiometabolic and endocrine abnormalities linked to sleep difficulties in schizophrenia? A hypothesis driven review.

Schizophrenia is a psychiatric disorder that includes symptoms such as hallucinations, disordered thoughts, disorganized or catatonic behaviour, cognitive dysfunction and sleep-wake disturbance. In addition to these symptoms, cardiometabolic dysfunction is common in patients with schizophrenia. While previously it has been thought that cardiometabolic symptoms in patients with schizophrenia were associated with medications used to manage this disorder, more recently it has been demonstrated that these symptoms are present in drug naive and unmedicated patients. Sleep-wake disturbance, resulting in chronic sleep loss has also been demonstrated to induce changes in cardiometabolic function. Chronic sleep loss has been associated with an increased risk for weight gain, obesity and cardiac and metabolic disorders, independent of other potentially contributing factors, such as smoking and body mass index. We hypothesise that the sleep-wake disturbance comorbid with schizophrenia may play a significant role in the high prevalence of cardiometabolic dysfunction observed in this patient population. Here we present a critical review of the evidence that supports this hypothesis.

The cost associated with administering risperidone long-acting injections in the Australian community.

BACKGROUND: Risperidone long-acting injection (LAI) is mostly administered twice weekly to people with schizophrenia by nurses at community mental health centres (CMHC) or through mobile outreach visits. This study estimates the cost of resource utilisation associated with the administration of risperidone LAI and the potential savings from substituting two-weekly injections with a longer interval product of therapeutic equivalence. METHODS: A survey of mental health staff overseeing the administration of risperidone LAI at 253 distinct Australian CMHCs was undertaken in November 2009. For the two-week period prior to the survey, respondents were asked questions on injection time (and related tasks) and, for mobile outreach visits, distance and time travelled as well as reduction in visits. Results were stratified by Australian Standard Geographical Classification (ASGC) region. Resource use was quantified and valued in Australian dollars. RESULTS: Results are derived from 74 CMHCs, representing approximately 26% of the national average risperidone LAI unit two-week sales. Stratified average injection time (including related tasks) for risperidone LAI ranged from 18-29 minutes, with a national average of 20.12 minutes. For mobile outreach visits, average distance per patient ranged from 19.4 to 55.5 km for One Staff Visits and 15.2 to 218.1 km for More Than One Staff Visits, and average time travelled ranged from 34.1 to 54.5 minutes for One Staff Visits and 29.2 to 136.3 minutes for More Than One Staff visits. The upper range consistently reflected greater resource utilisation in rural areas compared to urban areas. If administration of risperidone LAI had not been required, 20% fewer mobile outreach visits would have occurred. CONCLUSIONS: The national average saving per two-weekly risperidone long-acting injection avoided is $75.14. In 2009 in Australia, this would have saved ~$11 million for injection administration costs alone if all patients taking two-weekly risperidone LAI had instead been treated with a therapeutically equivalent long-acting injectable antipsychotic requiring one less injection per month.

Effectiveness of injectable risperidone long-acting therapy for schizophrenia: data from the US, Spain, Australia, and Belgium.

BACKGROUND: Because wide variations in mental health care utilization exist throughout the world, determining long-term effectiveness of psychotropic medications in a real-world setting would be beneficial to physicians and patients. The purpose of this analysis was to describe the effectiveness of injectable risperidone long-acting therapy (RLAT) for schizophrenia across countries. METHODS: This was a pragmatic analysis of data from two prospective observational studies conducted in the US (Schizophrenia Outcomes Utilization Relapse and Clinical Evaluation [SOURCE]; ClinicalTrials.gov registration number for the SOURCE study: NCT00246194) and Spain, Australia, and Belgium (electronic Schizophrenia Treatment Adherence Registry [eSTAR]). Two separate analyses were performed to assess clinical improvement during the study and estimate psychiatric hospitalization rates before and after RLAT initiation. Clinical improvement was evaluated using the Clinical Global Impressions-Severity (CGI-S) and Global Assessment of Functioning (GAF) scales, and change from baseline was evaluated using paired t tests. Psychiatric hospitalization rates were analyzed using incidence densities, and the bootstrap resampling method was used to examine differences between the pre-baseline and post-baseline periods. RESULTS: The initial sample comprised 3,069 patients (US, n = 532; Spain, n = 1,345; Australia, n = 784; and Belgium, n = 408). In all, 24 months of study participation, completed by 39.3% (n = 209), 62.7% (n = 843), 45.8% (n = 359), and 64.2% (n = 262) of patients from the US, Spain, Australia, and Belgium, respectively, were included in the clinical analysis. Improvements compared with baseline were observed on both clinical assessments across countries (P < 0.001 at all post-baseline visits). The mean improvement was approximately 1 point on the CGI-S and 15 points on the GAF. A total of 435 (81.8%), 1,339 (99.6%), 734 (93.6%), and 393 (96.3%) patients from the US, Spain, Australia, and Belgium, respectively, had ≥1 post-baseline visit and were included in the analysis of psychiatric hospitalization rates. Hospitalization rates decreased significantly in all countries regardless of hospitalization status at RLAT initiation (P < 0.0001) and decreased significantly in the US and Spain (P < 0.0001) when the analysis was limited to outpatients only. CONCLUSIONS: RLAT in patients with schizophrenia was associated with improvements in clinical and functional outcomes and decreased hospitalization rates in the US, Spain, Australia, and Belgium, despite differences in health care delivery systems.