There are few data on the profile of those with serious mental illness (SMI) admitted to hospital for physical health reasons.

To compare outcomes for patients with and without an SMI admitted to hospital in England where the primary reason for admission was chronic obstructive pulmonary disease (COPD).

This was a retrospective, observational analysis of the English Hospital Episodes Statistics data-set for the period from 1 April 2018 to 31 March 2019, for patients aged 18–74 years with COPD as the dominant reason for admission. Patient with an SMI (psychosis spectrum disorder, bipolar disorder) were identified.

Data were available for 54 578 patients, of whom 2096 (3.8%) had an SMI. Patients with an SMI were younger, more likely to be female and more likely to live in deprived areas than those without an SMI. The burden of comorbidity was similar between the two groups. After adjusting for covariates, SMI was associated with significantly greater risk of length of stay than the median (odds ratio 1.24, 95% CI 1.12–1.37, P ≤ 0.001) and with 30-day emergency readmission (odds ratio 1.51, 95% confidence interval 1.34–1.69, P ≤ 0.001) but not with in-hospital mortality.

Clinicians should be aware of the potential for poorer outcomes in patients with an SMI even when the SMI is not the primary reason for admission. Collaborative working across mental and physical healthcare provision may facilitate improved outcomes for people with SMI.

The study is aimed to identify brain functional connectomes predictive of depressed and elevated mood symptomatology in individuals with bipolar disorder (BD) using the machine learning approach Connectome-based Predictive Modeling (CPM).

Functional magnetic resonance imaging data were obtained from 81 adults with BD while they performed an emotion processing task. CPM with 5000 permutations of leave-one-out cross-validation was applied to identify functional connectomes predictive of depressed and elevated mood symptom scores on the Hamilton Depression and Young Mania rating scales. The predictive ability of the identified connectomes was tested in an independent sample of 43 adults with BD.

CPM predicted the severity of depressed [concordance between actual and predicted values (r = 0.23, pperm (permutation test) = 0.031) and elevated (r = 0.27, pperm = 0.01) mood. Functional connectivity of left dorsolateral prefrontal cortex and supplementary motor area nodes, with inter- and intra-hemispheric connections to other anterior and posterior cortical, limbic, motor, and cerebellar regions, predicted depressed mood severity. Connectivity of left fusiform and right visual association area nodes with inter- and intra-hemispheric connections to the motor, insular, limbic, and posterior cortices predicted elevated mood severity. These networks were predictive of mood symptomatology in the independent sample (r ⩾ 0.45, p = 0.002).

This study identified distributed functional connectomes predictive of depressed and elevated mood severity in BD. Connectomes subserving emotional, cognitive, and psychomotor control predicted depressed mood severity, while those subserving emotional and social perceptual functions predicted elevated mood severity. Identification of these connectome networks may help inform the development of targeted treatments for mood symptoms.

To evaluate efficiency and impact of a novel antimicrobial stewardship program (ASP) prospective-audit-with-feedback (PAF) review process using the Cerner Multi-Patient Task List (MPTL).

Retrospective cohort study.

A 367-bed free-standing, pediatric academic medical center.

The ASP PAF review process expanded to monitor all systemic and inhaled antibiotics through use of the MPTL on July 23, 2020. Average number of daily ASP reviews, absolute number of monthly interventions, and time to conduct ASP reviews were compared between the preimplementation period and the postimplementation period following expansion. Antibiotic days of therapy (DOT) per 1,000 patient days for overall and select antibiotics were compared between periods. ASP intervention characteristics were assessed.

Average daily ASP reviews significantly increased following program expansion (9 vs 14 reviews; P < .0001), and the absolute number of ASP interventions each month also increased (34 vs 52 interventions; P ≤ .0001). Time to conduct daily ASP reviews increased in the postimplementation period (1.03 vs 1.32 hours). Overall antibiotic DOT per 1,000 patient days significantly decreased in the postimplementation period (457.9 vs 427.9; P < .0001) as well as utilization of select, narrow-spectrum antibiotics such as ampicillin and clindamycin. Intervention type and antibiotics were similar between periods. The ASP documented 128 “nonantibiotic interventions” in the postimplementation period, including culture and/or susceptibility testing (32.8%), immunizations (25.8%), and additional diagnostic testing (22.7%).

Implementation of an ASP PAF review process using the MPTL allowed for efficient expansion of a pre-existing ASP and a decrease in overall antibiotic utilization. ASP documentation was enhanced to fully track the impact of the program.

Onset of schizophrenia commonly occurs during late adolescence or early adulthood and is often characterized by greater symptom severity and impairment.

To evaluate the efficacy and safety of lurasidone in the treatment of acute schizophrenia in adolescents and young adults.

The 4 studies in this pooled analysis used similar study designs. Patients (ages 13-25 years) were randomized to 6 weeks of double-blind, placebo-controlled treatment with once-daily lurasidone (37 mg, 74 mg, 111 mg, 148 mg). The primary outcome was endpoint change in the Positive and Negative Syndrome Scale (PANSS) total score; secondary measures included the Clinical Global Impression, Severity scale (CGI-S).

The safety population consisted of 537 patients; 79.1% completed the studies. Treatment with lurasidone was significant (P<0.001) at Week 6 endpoint for change in the PANSS total score, with higher effect sizes (ES) at higher doses (37 mg, 0.53; 74 mg, 0.57; 111 mg, 0.67; 148 mg, 1.35); significance was also observed for change in the CGI-S (37 mg, 0.51; 74 mg, 0.49; 111 mg, 0.57; 148 mg, 1.75). For lurasidone (combined doses), 3 adverse events occurred with a frequency ≥5% (nausea, 13.5%; somnolence, 12.1%; akathisia, 10.1%); 4.8% of patients discontinued due to an adverse event. At LOCF-endpoint, 3.6% of patients had weight gain ≥7%, and 1.5% had weight loss ≥7%. Minimal median changes were observed at endpoint in metabolic lab values.

In adolescents and young adults with schizophrenia, treatment with lurasidone in doses of 37-148 mg/d was a safe, well-tolerated, and effective treatment.

Presenter is an employee of Sunovion Pharmaceuticals Inc. The study summarized in this Abstract was supported by Funding from Sunovion Pharmaceuticals Inc.

Compared with adult onset, early onset schizophrenia is typically characterized by greater illness severity and less favorable prognosis.

To evaluate the proportion of adolescent patients with schizophrenia who achieved sustained remission and recovery during 2 years of treatment with lurasidone.

Patients aged 13-17 years with a DSM-IV-TR diagnosis of schizophrenia, and a Positive and Negative Symptom Scale (PANSS) total score ≥70 and <120, were randomized to 6 weeks of double-blind (DB), fixed-dose treatment with lurasidone (37 or 74 mg/d) or placebo. Patients who completed 6 weeks of DB treatment were eligible to enroll in a 2-year, open-label (OL), flexible dose extension study of lurasidone (18.5-74 mg/d). Criteria for sustained remission, were the 6-month consensus criteria summarized by Andreasen (Am J Psych 2005;162:441-9). Criteria for sustained recovery consisted of meeting sustained remission criteria with a Children’s Global Assessment Scale (CGAS) score ≥70 for at least 6-months indicating no clinically significant functional impairment.

A total of 271 patients completed the 6-week DB study and entered the extension study, and 186 (68.6%) and 156 (57.6%) completed 52 weeks and 104 weeks of treatment, respectively. During OL treatment with lurasidone, 52.8% met sustained remission criteria, with a Kaplan-Meier (KM) estimate of 64.1 weeks for median time to sustained remission; and 28.8% met sustained recovery criteria, KM estimate of 104.6 weeks for median time to sustained recovery.

For adolescents with schizophrenia, treatment with lurasidone was associated with high rates of sustained remission and sustained recovery over a two-year period.

Employee of Sunovion Pharmaceuticals Inc. The study summarized in this Abstract was supported by funding from Sunovion Pharmaceuticals Inc

Lurasidone has demonstrated efficacy for schizophrenia and bipolar depression in adults.

To identify a tolerated dose range of lurasidone for pediatric studies.

To characterize PK and tolerability profiles of lurasidone in a pediatric population.

Patients aged 6 to 17 years diagnosed with ADHD and conduct disorder/disruptive behavior disorder, bipolar disorder, schizophrenia, Tourette syndrome, or autism spectrum disorder were assigned to 1 of 5 open-label lurasidone dosing cohorts (20, 40, 80, 120, or 160 mg/d). If a dose level was tolerated, the next dose cohort was initiated. In the single-dose phase, blood was collected predose and for 48 hours postdose. In the multiple-dose phase, patients received once-daily lurasidone for 7 to 9 days; blood was collected before and for 24 hours after the final dose. Lurasidone PK parameters, including maximum serum concentration and area under the concentration-time curve, were calculated.

In 105 patients, the observed lurasidone PK were consistent with a PK model of adult exposure at steady state. The most common AEs were somnolence (42%), sedation (18%), and nausea (17%); incidence of AEs was generally dose-dependent across the 20-160 mg/d dose range. All 6- to 9-year-old patients experienced somnolence at 120 mg/d. Two serious AEs (parkinsonism, dystonia) were reported, both at 80 mg/d.

The PK and AE profiles of lurasidone in this heterogeneous pediatric population were consistent with data observed in adult populations. Based on this study, doses of lurasidone 20-80 mg/d are selected for evaluation in pediatric clinical trials.

Sunovion Pharmaceuticals Inc.

Controlled data on optimization of dosing regimen for antipsychotics in schizophrenia is an unmet medical need.

To evaluate the efficacy of low dose lurasidone in schizophrenia; and to determine optimal dosing for patients not achieving improvement in Positive and Negative Syndrome Scale (PANSS) total score by week 2 of standard dosing.

Patients with schizophrenia were randomized to double-blind treatment with fixed daily doses of lurasidone 18.5 mg (for 6 wks; N=101), 74 mg (for 2 wks; N=198), or placebo (for 6 wks; N=112). After 2 weeks of treatment, patients in the 74 mg group with <20% PANSS improvement were re-randomized to continue on the 74 mg dose, or increase to a dose of 148 mg, for the next 4 wks.

Lurasidone 18.5 mg did not demonstrate significant improvement vs. placebo at Week 6 (−17.6 vs −14.5; P=0.25). In the group with <20% PANSS improvement after 2 weeks (N=95), titration to lurasidone 148 mg resulted in significantly greater improvement in PANSS total score at Week 6 compared with 4 additional weeks of treatment at the 74 mg dose (−16.6 vs. −8.9; p=0.023).

This trial supports the 37 mg/d dose of lurasidone as minimally effective dose in patients with acute schizophrenia consistent with evidence from previous studies. Increasing the dose of lurasidone to 148 mg/d after 2 weeks of nonresponse at 74 mg/d resulted in a significant efficacy advantage with important potential implications for clinical practice.

NCT01821378.

Sponsored by Sunovion Pharmaceuticals Inc.

Lurasidone is an atypical antipsychotic that demonstrated efficacy in the treatment of adults with schizophrenia in the dose range of 37–148 mg/day.

The objective of this analysis was to evaluate the efficacy of lurasidone in adolescent patients with schizophrenia.

Adolescents (13–17 years old) diagnosed with schizophrenia were randomly assigned to six weeks of double-blind treatment with lurasidone 37 mg/day, 74 mg/day or placebo. Changes from baseline to week 6 in PANSS total and subscale (positive, negative, general psychopathology, excitability) scores were evaluated using mixed-model repeated-measures analysis.

A total of 326 patients (mean age, 15.4 years) were randomized and received lurasidone 37 mg/day (n = 108), 74 mg/day (n = 106), or placebo (n = 112). The PANSS total score at week 6 demonstrated a placebo-adjusted, least-squares (LS) mean improvement of –8.0 (P < 0.001; effect size [ES], 0.51) for the 37 mg/day group and –7.7 (P < 0.001; ES = 0.48) for the 74 mg/day group. Placebo-adjusted LS mean change for lurasidone 37 mg/day and 74 mg/day, respectively, was –3.2 (P < 0.001; ES = 0.62) and –3.2 (P < 0.001; ES = 0.60) on the PANSS positive subscale, –1.7 (P = 0.011; ES = 0.41) and –1.6 (P = 0.022; ES = 0.35) on the PANSS negative subscale, –2.8 (P = 0.012; ES = 0.38) and –2.8 (P = 0.011; ES = 0.37) on the PANSS general psychopathology subscale, and –1.1 (P = 0.016; ES = 0.36) and –1.8 (P < 0.001; ES = 0.53) on the PANSS excitability subscale.

In adolescent patients with schizophrenia, lurasidone (37 mg/day and 74 mg/day) demonstrated statistically significant efficacy and clinically meaningful improvement across a wide spectrum of symptoms associated with schizophrenia. Sponsored by Sunovion Pharmaceuticals Inc. ClinicalTrials.gov identifier: NCT01911429.

Dr Correll reports being a consultant and/or advisor for Alkermes, Forum Pharmaceuticals Inc., Gerson Lehrman Group, IntraCellular Therapies, Janssen/J&J, Lundbeck, Medavante, Medscape, Otsuka, Pfizer Inc, ProPhase, Sunovion Pharmaceuticals Inc., Supernus, Takeda, and Teva providing expert testimony for Bristol-Myers Squibb Company, Janssen, and Otsuka serving on a Data Safety Monitoring Board for Lundbeck and Pfizer Inc and receiving grant support from Takeda. Drs Goldman, Cucchiaro, Deng and Loebel are employees of Sunovion Pharmaceuticals Inc.

Lurasidone, an atypical antipsychotic, demonstrated efficacy and safety in adults with schizophrenia.

To evaluate the efficacy and safety of lurasidone in adolescent patients with schizophrenia.

Adolescents (13–17 years old) with schizophrenia were randomly assigned to six weeks of double-blind treatment with lurasidone 37 mg/day, 74 mg/day or placebo. An ANCOVA using an LOCF approach was performed to assess change from baseline on secondary study endpoints: Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) and Children's Global Assessment Scale (CGAS).

Patients were randomized to lurasidone 37 mg/d (n = 108), 74 mg/day (n = 106), or placebo (n = 112). Placebo-adjusted LS mean improvement at week 6 on the PQ-LES-Q was 5.3 (P = 0.001) and 5.8 (P < 0.001) for the 37 mg/day and 74 mg/day groups, respectively; and, on the CGAS was 4.6 (P = 0.002) and 4.9 (P < 0.001) for the 37 mg/day and 74 mg/d groups, respectively. The most common adverse events occurring at ≥ 5% in either lurasidone group and at least twice the rate of placebo were: nausea, somnolence, akathisia, vomiting and sedation. Mean change in weight at week 6 for placebo, 37 mg/day, and 74 mg/day groups was 0.05 kg, 0.17 kg, and 0.49 kg, respectively. Lurasidone treated patients did not show clinically meaningful differences from placebo on laboratory measures of cholesterol, triglycerides, glucose, and prolactin.

Adolescent patients with schizophrenia treated with lurasidone demonstrated significant improvement in quality of life and function. Lurasidone was generally well-tolerated and associated with minimal changes in weight and metabolic parameters. Sponsored by Sunovion Pharmaceuticals Inc. ClinicalTrials.gov identifier: NCT01911429.

Dr. Findling receives or has received research support, acted as a consultant and/or served on a speaker's bureau for Alcobra, American Academy of Child & Adolescent Psychiatry, American Physician Institute, American Psychiatric Press, Bracket, CogCubed, Cognition Group, Coronado Biosciences, Dana Foundation, Elsevier, Forest, Guilford Press, Ironshore, Johns Hopkins University Press, Jubilant Clinsys, KemPharm, Lundbeck, Merck, NIH, Neurim, Novartis, Otsuka, Oxford University Press, Pfizer, Physicians Postgraduate Press, Purdue, Rhodes Pharmaceuticals, Roche, Sage, Shire, Sunovion, Supernus Pharmaceuticals, Transcept Pharmaceuticals, Tris, Validus, and WebMD. Drs. Goldman, Cucchiaro, Deng, and Loebel are employees of Sunovion Pharmaceuticals Inc.

To evaluate the clinical impact of an antimicrobial stewardship program (ASP) on high-risk pediatric patients.

Retrospective cohort study.

Free-standing pediatric hospital.

This study included patients who received an ASP review between March 3, 2008, and March 2, 2017, and were considered high-risk, including patients receiving care by the neonatal intensive care (NICU), hematology/oncology (H/O), or pediatric intensive care (PICU) medical teams.

The ASP recommendations included stopping antibiotics; modifying antibiotic type, dose, or duration; or obtaining an infectious diseases consultation. The outcomes evaluated in all high-risk patients with ASP recommendations were (1) hospital-acquired Clostridium difficile infection, (2) mortality, and (3) 30-day readmission. Subanalyses were conducted to evaluate hospital length of stay (LOS) and tracheitis treatment failure. Multivariable generalized linear models were performed to examine the relationship between ASP recommendations and each outcome after adjusting for clinical service and indication for treatment.

The ASP made 2,088 recommendations, and 50% of these recommendations were to stop antibiotics. Recommendation agreement occurred in 70% of these cases. Agreement with an ASP recommendation was not associated with higher odds of mortality or hospital readmission. Patients with a single ASP review and agreed upon recommendation had a shorter median LOS (10.2 days vs 13.2 days; P < .05). The ASP recommendations were not associated with high rates of tracheitis treatment failure.

ASP recommendations do not result in worse clinical outcomes among high-risk pediatric patients. Most ASP recommendations are to stop or to narrow antimicrobial therapy. Further work is needed to enhance stewardship efforts in high-risk pediatric patients.