Patients with Fontan failure are high-risk candidates for heart transplantation and other advanced therapies. Understanding the outcomes following initial heart failure consultation can help define appropriate timing of referral for advanced heart failure care.

This is a survey study of heart failure providers seeing any Fontan patient for initial heart failure care. Part 1 of the survey captured data on clinical characteristics at the time of heart failure consultation, and Part 2, completed 30 days later, captured outcomes (death, transplant evaluation outcome, and other interventions). Patients were classified as “too late” (death or declined for transplant due to being too sick) and/or “care escalation” (ventricular assist device implanted, inotrope initiated, and/or listed for transplant), within 30 days. “Late referral” was defined as those referred too late and/or had care escalation.

Between 7/2020 and 7/2022, 77 Fontan patients (52% inpatient) had an initial heart failure consultation. Ten per cent were referred too late (6 were too sick for heart transplantation with one subsequent death, and two others died without heart transplantation evaluation, within 30 days), and 36% had care escalation (21 listed ± 5 ventricular assist device implanted ± 6 inotrope initiated). Overall, 42% were late referrals. Heart failure consultation < 1 year after Fontan surgery was strongly associated with late referral (OR 6.2, 95% CI 1.8–21.5, p=0.004).

Over 40% of Fontan patients seen for an initial heart failure consultation were late referrals, with 10% dying or being declined for transplant within a month of consultation. Earlier referral, particularly for those with heart failure soon after Fontan surgery, should be encouraged.

Sleep disturbance is an important factor in the pathophysiology and progression of psychiatric disorders, but whether it is a cause, or a downstream effect is still not clear.

To investigate causal relationships between three sleep-associated traits and seven psychiatric diseases, we used genetic variants related to insomnia, chronotype and sleep duration to perform a two-sample bidirectional Mendelian randomisation analysis. Summary-level data on psychiatric disorders were extracted from the Psychiatric Genomics Consortium. Effect estimates were obtained by using the inverse-variance-weighted (IVW), weights modified IVW, weighted-median methods, MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO) test and Robust Adjusted Profile Score (RAPS).

The causal odds ratio (OR) estimate of genetically determined insomnia was 1.33 (95% confidence interval (CI) 1.22–1.45; p = 5.03 × 10−11) for attention-deficit/hyperactivity disorder (ADHD), 1.31 (95% CI 1.25–1.37; p = 6.88 × 10−31) for major depressive disorder (MDD) and 1.32 (95% CI 1.23–1.40; p = 1.42 × 10−16) for post-traumatic stress disorder (PTSD). There were suggestive inverse associations of morningness chronotype with risk of MDD and schizophrenia (SCZ). Genetically predicted sleep duration was also nominally associated with the risk of bipolar disorder (BD). Conversely, PTSD and MDD were associated with an increased risk of insomnia (OR = 1.06, 95% CI 1.03–1.10, p = 7.85 × 10−4 for PTSD; OR = 1.37, 95% CI 1.14–1.64; p = 0.001 for MDD). A suggestive inverse association of ADHD and MDD with sleep duration was also observed.

Our findings provide evidence of potential causal relationships between sleep disturbance and psychiatric disorders. This suggests that abnormal sleep patterns may serve as markers for psychiatric disorders and offer opportunities for prevention and management in psychiatric disorders.

Insomnia is a common, distressing, and impairing psychological outcome experienced by informal caregivers (ICs) of patients with cancer. Cognitive behavioral therapy for insomnia (CBT-I) and acupuncture both have known benefits for patients with cancer, but such benefits have yet to be evaluated among ICs. The purpose of the present study was to evaluate the feasibility, acceptability and preliminary effects of CBT-I and acupuncture among ICs with moderate or greater levels of insomnia.

Participants were randomized to eight sessions of CBT-I or ten sessions of acupuncture.

Results highlighted challenges of identifying interested and eligible ICs and the impact of perception of intervention on retention and likely ultimately outcome.

Findings suggest preliminary support for non-pharmacological interventions to treat insomnia in ICs and emphasize the importance of matching treatment modality to the preferences and needs of ICs.

Health system preparedness for coronavirus disease (COVID-19) includes projecting the number and timing of cases requiring various types of treatment. Several tools were developed to assist in this planning process. This review highlights models that project both caseload and hospital capacity requirements over time.

We systematically reviewed the medical and engineering literature according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We completed searches using PubMed, EMBASE, ISI Web of Science, Google Scholar, and the Google search engine.

The search strategy identified 690 articles. For a detailed review, we selected 6 models that met our predefined criteria. Half of the models did not include age-stratified parameters, and only 1 included the option to represent a second wave. Hospital patient flow was simplified in all models; however, some considered more complex patient pathways. One model included fatality ratios with length of stay (LOS) adjustments for survivors versus those who die, and accommodated different LOS for critical care patients with or without a ventilator.

The results of our study provide information to physicians, hospital administrators, emergency response personnel, and governmental agencies on available models for preparing scenario-based plans for responding to the COVID-19 or similar type of outbreak.

The risk factors of criminal behavior in patients with schizophrenia are not well explored. This study is to explore the risk factors for criminal behavior in patients with schizophrenia in rural China.

We used data from a 14-year prospective follow-up study (1994-2008) of criminal behavior among a cohort (n=510) of patients with schizophrenia in Xinjin County, Chengdu, China.

There were 489 patients (95.9%) who were followed up from 1994 to 2008. The rate of criminal behavior was 13.5% among these patients with schizophrenia during the follow-up period. Compared with female subjects (6 cases, 20.0%), male patients had significantly higher rate of violent criminal behavior (e.g., arson, sexual assault, physical assault, and murder) (24 cases, 80.0%) (p< 0.001). Bivariate analyses showed that the risk of criminal behavior was significantly associated with being unmarried, of younger age, previous violent behavior, homelessness, lower family economic status, no family caregivers, and higher scores on measures (PANSS) of positive, negative, and total symptoms of illness. In multiple logistic regression analyses being unmarried and previous violent behavior were identified as independent predictors of increased criminal behavior in persons with schizophrenia.

The risk factors for criminal behavior among patients with schizophrenia should be understood within a particular social context. Criminal behavior may be predicted by specific characteristics of patients with schizophrenia in rural community. The findings of risk factors for criminal behavior should be considered in planning community mental health care and interventions for high-risk patients and their families.

Schizophrenia is a chronic disease; consequently, long-term maintenance of efficacy is an important clinical goal.

To evaluate lurasidone as maintenance treatment for schizophrenia.

To demonstrate maintenance of efficacy with lurasidone.

Adult patients experiencing an acute exacerbation of schizophrenia received 12–24 weeks of open-label treatment with lurasidone (40–80 mg/d, flexibly dosed). Those who maintained clinical stability for ≥12 weeks were randomized to placebo or lurasidone (40–80 mg/d, flexibly dosed) and entered the 28-week, double-blind withdrawal phase.

Of 676 enrolled patients, 285 met protocol-specified stabilization criteria and were randomized to lurasidone (N=144) or placebo (N=141). Relapse occurred in a greater proportion of patients receiving placebo (41.1%) than lurasidone (29.9%). Time to relapse based on Kaplan-Meier survival analysis was significantly longer for lurasidone compared with placebo (log-rank test, p=0.039). Lurasidone was associated with a 33.7% reduction in risk of relapse versus placebo (Cox hazard ratio [95% confidence interval], 0.663 [0.447, 0.983]; p=0.041). Patients receiving placebo demonstrated significantly greater worsening on PANSS and CGI-S scores compared to lurasidone-treated patients (PANSS mean change, +12.4 vs +8.3, p=0.029; CGI-S mean change, +0.7 vs +0.4, p=0.015; ANCOVA-LOCF). The discontinuation rate due to adverse events was 13.9% for lurasidone and 15.6% for placebo. Minimal changes in weight, prolactin, lipid, and glucose parameters were observed.

This study demonstrated the efficacy of lurasidone for the maintenance treatment of patients with schizophrenia. Lurasidone was generally well tolerated, with minimal effects on weight and other metabolic parameters.

Study sponsored by Sunovion Pharmaceuticals Inc.

ClinicalTrials.gov identifier: NCT01435928

To evaluate the efficacy of lurasidone for schizophrenia using an established five-factor model of the Positive and Negative Syndrome Scale (PANSS).

Patient-level data were pooled from five randomized, double-blind, placebo-controlled, 6-week studies of lurasidone (fixed doses, 40–160 mg/d) for patients with an acute exacerbation of schizophrenia. Changes in five established PANSS factors were assessed using mixed-model repeated measures analysis.

Compared with placebo (n = 496), lurasidone (n = 1029, dose groups pooled) significantly improved the PANSS total score at Week 6 (−22.6 vs. −12.8; P < 0.001; effect size, 0.45), as well as all factor scores (P < 0.001 for each): positive symptoms (−8.4 vs. −6.0; effect size, 0.43), negative symptoms (−5.2 vs. −3.3; effect size, 0.33), disorganized thought (−4.9 vs. −2.8; effect size, 0.42), hostility/excitement (−2.7 vs. −1.6; effect size, 0.31), and depression/anxiety (−3.2 vs. −2.3; effect size, 0.31). Separation from placebo occurred at Week 1 for the positive symptoms, disorganized thought, and hostility/excitement factors and at Week 2 for the other factors.

In this pooled analysis of short-term studies in patients with acute schizophrenia, lurasidone demonstrated significant improvement for each of the five PANSS factor scores, indicating effectiveness across the spectrum of schizophrenia symptoms.

This post-hoc analysis evaluated whether the efficacy of lurasidone in major depressive disorder (MDD) with mixed features is moderated by the number and characteristics of manic symptoms present at study baseline.

Patients meeting DSM-IV-TR criteria for MDD who presented with two or three manic symptoms (consistent with the DSM–5 mixed features specifier) were randomly assigned to 6 weeks of double-blind treatment with either lurasidone 20–60 mg/d (n = 109) or placebo (n = 100). Finite mixture models were applied to identify latent class patterns of the 10 baseline manic symptoms.

Three latent class profiles were identified: 105 (50.5%) patients had manic symptom profile 1 (MIX 1) with mean MADRS 33.0, mean YMRS 9.2, mean number of manic symptoms 3.8; 63 (30.3%) patients had manic symptom profile 2 (MIX 2) with similar baseline mean MADRS (32.4) and YMRS (9.3) and lower number of manic symptoms 3.5; 40 patients had manic symptom profile 3 (MIX 3) with significantly higher severity scores in MADRS (35) and YMRS (14.9) and mean number of manic symptoms 4.6. A significant moderating effect on change in YMRS score was observed for the “decreased need for sleep” symptom, with greater lurasidone effect size (vs. Placebo) found in patients without vs. With this symptom (P < 0.05).

In this post-hoc analysis of a placebo-controlled trial involving MDD patients with mixed features, absence of “decreased need for sleep” was found to be significantly associated with improvement in manic and depressive symptoms and to moderate the treatment effect on manic symptoms.

I am full time employee of Sunovion pharmaceuticals Inc.

Evidence indicates that manic symptoms, below the threshold for hypomania (mixed features), are common in individuals with major depressive disorder (MDD).

To evaluate the effect of lurasidone on specific depressive and manic symptoms, based on Montgomery Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) items, in patients with MDD with mixed features.

Patients meeting DSM-IV-TR criteria for MDD, who presented with 2–3 protocol-specified manic symptoms, were randomized to 6 weeks of double-blind treatment with lurasidone monotherapy 20–60 mg/d (n = 109) or placebo (n = 100). Change from baseline in the MADRS total, MADRS-6 core depression subscale, individual MADRS items, and total and individual items of the YMRS were analyzed by MMRM, and Cohen's d effect sizes (d) were calculated for week 6 change scores.

Lurasidone improved depressive symptoms at week 6 in the MADRS total score (–20.5 vs. –13.0; P < 0.0001; d = 0.8) and MADRS-6 core depression score (–13.0 vs. –8.5; P < 0.0001; d = 0.7). Significant improvement on lurasidone was observed at week 6 on all ten MADRS items (d = 0.36–0.78). Effect sizes for the MADRS-6 core depression subscale items ranged from 0.36 to 0.78 at week 6. Treatment with lurasidone was associated with significantly greater week 6 improvement on the YMRS (–7.0 vs. –4.9; P < 0.0001). Effect sizes for the 5 YMRS items with baseline item severity ≥ 2 ranged from 0.32 to 0.48.

In this study of MDD with mixed features, lurasidone was effective in treating the range of depressive and manic symptoms that patients presented with.

Sponsored by Sunovion Pharmaceuticals Inc.

The authors have not supplied their declaration of competing interest.

Information is not available on the maintenance efficacy of lurasidone in bipolar disorder.

To evaluate the recurrence prevention efficacy of lurasidone plus lithium (Li) or valproate (VPA) for the maintenance treatment of bipolar disorder.

Patients with bipolar I disorder received up to 20 weeks of open-label lurasidone (20–80 mg/d) plus Li or VPA. Patients who achieved consistent clinical stability were randomized to 28 weeks of double-blind treatment with lurasidone (20–80 mg/d) or placebo, plus Li or VPA.

A total of 496 patients met stabilization criteria and were randomized to adjunctive lurasidone vs. placebo. Fewer patients in the lurasidone group had recurrence of any mood episode compared with the placebo group, with a hazard ratio of 0.71 (P = 0.078). In pre-planned secondary analyses, recurrence rates were significantly lower for the lurasidone group treated with a modal open-label dose of 80 mg/d (hazard ratio [HR], 0.35; P = 0.020); when patients presented with an index episode of depression (HR = 0.57; P = 0.039); and when outcome was time-to-all-cause discontinuation (HR = 0.72; P = 0.034), or time-to-recurrence based on symptom severity criteria (HR = 0.53; P = 0.025).

In patients stabilized on lurasidone plus Li or VPA, continued treatment was associated with non-significant reduction in risk of recurrence of any mood disorder (primary). Consistent with dose-response effects observed during acute treatment of bipolar depression, risk of recurrence on lurasidone was significantly reduced after open-label treatment with the 80 mg/d dose, and in the 20–80 mg/d dose in patients presenting with an index episode of depression.

Clinicaltrials.gov: NCT01358357.

Sponsored by Sunovion Pharmaceuticals Inc.

Drs. Pikalov, Cucchiaro, Mao, and Loebel are employees of Sunovion Pharmaceuticals IncDr. Calabrese has received research support from Abbott, AstraZeneca, Bristol-Myers Squibb, Cephalon, Cleveland Foundation, Eli Lilly, GlaxoSmithKline, Janssen, Lundbeck, NARSAD, Repligen, Stanley Medical Research Institute, Takeda, and Wyeth. Dr. Calabrese consulted to or served on advisory boards of Abbott, AstraZeneca, Bristol-Myers Squibb, Cephalon, Dainippon Sumitomo, Elan, EPI-Q, Inc., Forest, France Foundation, GlaxoSmithKline, Hoffman LaRoche, Janssen, Johnson and Johnson, Lundbeck, Merck, Neurosearch, OrthoMcNeil, Otsuka, Pfizer, Repligen, Servier, Solvay, Sunovion, Supernus, Synosia, Takeda, Teva, and Wyeth. Dr. Calabrese has provided CME lectures supported by AstraZeneca, Bristol-Myers Squibb, France Foundation, GlaxoSmithKline, Janssen, Johnson and Johnson, Merck, Sanofi-Aventis, Schering-Plough, Pfizer, Solvay, Sunovion, and Wyeth.