scholarly journals S57 Short-term clinically important deterioration predicts long-term clinical outcome in COPD patients: A post-hoc analysis of the TORCH trial

Thorax ◽  
2015 ◽  
Vol 70 (Suppl 3) ◽  
pp. A34.3-A35 ◽  
Author(s):  
I Naya ◽  
L Tombs ◽  
P Jones
Keyword(s):  
Clinical Outcome ◽  
Short Term ◽  
Post Hoc Analysis ◽  
Copd Patients ◽  
Clinically Important Deterioration ◽  
Post Hoc

scholarly journals 14 Long-term Efficacy of Brexpiprazole in Patients with Schizophrenia with Clinically Relevant Levels of Negative Symptoms

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 180-180
Author(s):  
Catherine Weiss ◽  
Peter Zhang ◽  
Ross A Baker ◽  
Mary Hobart ◽  
Nanco Hefting ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Extension Study ◽  
Short Term ◽  
Open Label ◽  
Term Study ◽  
Post Hoc Analysis ◽  
Long Term Study ◽  
Open Label Extension ◽  
Post Hoc

AbstractBackgroundEffective treatments for patients with high levels of negative symptoms of schizophrenia are lacking. Brexpiprazole is a serotonin–dopamine activity modulator that is a partial agonist at 5-HT1A and dopamine D2 receptors, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors, all with subnanomolar potency. Long-term treatment with brexpiprazole demonstrated broad efficacy across all five Marder factor groupings, including positive, negative, disorganized thoughts, uncontrolled hostility/excitement, and anxiety/depression. This post-hoc analysis of long-term effects of brexpiprazole in patients with clinically relevant levels of negative symptoms of schizophrenia is based on data from two similarly designed short-term, placebo-controlled studies (Vector; NCT01396421 or Beacon; NCT01393613) for the brexpiprazole-treated patients who continued into an open-label extension study (Zenith; NCT01397786).MethodsIn the short-term studies, patients with acute schizophrenia were randomly assigned to fixed once-daily doses of brexpiprazole 0.25mg (Vector), 1mg (Beacon), 2mg , 4mg or placebo for 6weeks. The long-term study was an open-label, 52-week (amended to 26weeks), safety extension study with flexible-dose (1–4mg/day) brexpiprazole. The post-hoc analyses were performed on brexpiprazole-treated patients from the short-term studies who continued into the long-term study, and who had clinically relevant negative symptoms, defined as PANSS Factor Score for Negative Symptoms (PANSS-FSNS; N1, N2, N3, N4, G7, G16) of ≥24, and score of ≥4 on at least two of three core negative symptom PANSS items at randomization in the parent study. The outcome of the analysis included change from baseline to up to 58weeks in PANSS-FSNS, PANSS Total, and PSP. Safety was also assessed.ResultsA total of 187 patients with clinically relevant levels of negative symptoms in the parent study rolled-over into the open-label extension study and were available for analysis. Eighty-three of these patients remained in the studies for 58weeks. Due to the study amendment, not all patients had the opportunity of complete 52weeks of open-label treatment. Baseline PANSS Total score was 104.4, while baseline PANSS-FSNS was 27.6 and baseline PSP Total score was 41.3. Mean change (SD) from baseline in PANSS-FSNS was –10.9 (5.0), and –44.2 (17.5) for PANSS Total score at Week 58. Change from baseline (SD) to Week 58 for PSP Total score was 24.8 (12.9) with improvement in all domains (socially useful activities, personal and social relationship, self-care, and disturbing and aggressive behaviors). The TEAEs reported ≥5% were schizophrenia (18.9%), insomnia (8.6%), weight increased (5.9%) and akathisia (5.9%).ConclusionThis post-hoc analysis suggests that brexpiprazole has long-term effectiveness on negative symptoms and functioning in patients with schizophrenia and clinically relevant levels of negative symptoms.Funding Acknowledgements: The study was funded by Otsuka Pharmaceutical Development & Commercialization Inc. and H. Lundbeck A/S

scholarly journals 160 Lurasidone and Metabolic Syndrome: Results from Short- and Long-Term Clinical Studies in Patients with Bipolar Depression

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 302-303
Author(s):  
Michael Tocco ◽  
John W. Newcomer ◽  
Yongcai Mao ◽  
Andrei Pikalov
Keyword(s):  
Metabolic Syndrome ◽  
Adjunctive Therapy ◽  
Bipolar Depression ◽  
Prevention Study ◽  
Short Term ◽  
Post Hoc Analysis ◽  
Short And Long Term ◽  
Post Hoc ◽  
Therapy Studies

Abstract:Background:Among patients with depressive disorders, the prevalence of metabolic syndrome (MetS) is estimated to range from 35-40% and has been associated with increased mortality rates. The aim of this post-hoc analysis was to assess the effect of treatment with lurasidone on the prevalence of MetS in patients with bipolar depression.Method:Lurasidone data (dose range, 20-120 mg/d) used in the current analyses consisted of 3 double-blind (DB), placebo-controlled, 6-week studies in adults with bipolar I depression (total N=1,192), consisting of 1 monotherapy, and 2 adjunctive therapy trials with lithium or valproate. Patients who completed the short-term trials continued into a 6-month open-label (OL) extension study, with 6-month (LOCF-endpoint) data available on 274 patients treated with lurasidone monotherapy, and 436 patients treated with lurasidone adjunctive therapy. Also analyzed was a recurrence prevention study in stabilized bipolar patients who completed up to 20 weeks of OL adjunctive treatment with lurasidone, and then were randomized to 28 weeks of DB adjunctive therapy with lurasidone or placebo (N=497). MetS was defined based on NCEP ATP III criteria (2005 revision).Results:In the short-term monotherapy and adjunctive therapy studies, the proportion of patients at baseline meeting NCEP III criteria for MetS were 27.6% and 23.6%, respectively, for lurasidone, and 23.8% and 25.1%, respectively, for placebo; and at week 6 (LOCF) the proportion with MetS was 27.5% and 26.6%, respectively, for lurasidone and 29.9% and 20.2%, respectively, for placebo. The proportion of patients who did not meet MetS criteria at baseline but developed MetS at week 6 (LOCF) was similar for lurasidone vs. placebo in the monotherapy study (9.9% vs. 11.6%); and in the two adjunctive therapy studies (10.3% vs. 8.3%). During the 6-month OL extension study, the proportion of patients treated with lurasidone monotherapy and adjunctive therapy who did not meet MetS criteria at OL baseline but developed MetS at month 6 (LOCF) was 11.7% and 11.9%, respectively. Conversely, the proportion of patients who met MetS criteria at OL baseline, but no longer met criteria at month 6 (LOCF) was 9.5% and 7.7%, respectively. In the 20-week, OL phase of the recurrence prevention study, the proportion of patients treated with adjunctive lurasidone who did not meet MetS criteria at OL baseline but developed MetS at endpoint was 11.5% (LOCF). After up to 28 weeks of DB treatment, the proportion of patients who did not meet MetS criteria at DB baseline but developed MetS at endpoint was 9.0% in the adjunctive lurasidone group, and 10.5% in the adjunctive placebo group (LOCF).Conclusion:This post-hoc analysis found that short- and long-term treatment with lurasidone was associated with a relatively low risk for the development of metabolic syndrome in patients with bipolar I disorder. These findings are consistent with similar analyses in patients with schizophrenia.Funding Acknowledgements:Supported by funding from Sunovion Pharmaceuticals Inc.

scholarly journals Cardiometabolic Safety of Lumateperone (ITI−007): Post Hoc Analyses of Short-Term Randomized Trials and an Open-Label Long-Term Study in Schizophrenia

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 152-152
Author(s):  
John B. Edwards ◽  
Andrew Satlin ◽  
Suresh Durgam ◽  
Robert E. Davis ◽  
Richard Chen ◽  
...  
Keyword(s):  
Metabolic Effects ◽  
Short Term ◽  
Open Label ◽  
Term Study ◽  
Study Objective ◽  
Post Hoc Analysis ◽  
Long Term Study ◽  
Conversion Rates ◽  
Post Hoc

AbstractStudy ObjectiveCurrent treatments for schizophrenia are often associated with increased rates of metabolic syndrome (MetSy). MetSy is defined as meeting 3 of the following 5 criteria: waist circumference >40in (men) or >35in (women), triglycerides =150mg/dL, high density lipoprotein cholesterol (HDL) <40mg/dL (men) or <50mg/dL (women), systolic blood pressure (BP) =130mmHg or diastolic BP =85mmHg, fasting glucose =100mg/dL. Patients with MetSy have an elevated risk of developing type II diabetes and increased mortality due to cardiovascular disease. Lumateperone (lumateperone tosylate, ITI−007), a mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, is FDA approved for the treatment of schizophrenia. This distinct pharmacological profile has been associated with favorable tolerability and a low risk of adverse metabolic effects in clinical trials. This post hoc analysis of 2 randomized, double-blind, placebo-controlled studies of patients with an acute exacerbation of schizophrenia compared rates of MetSy with lumateperone and risperidone. Data from an open-label long-term trial of lumateperone were also evaluated.MethodThe incidence and shift in MetSy were analyzed in data pooled from 2 short-term (4 or 6 week) placebo- and active-controlled (risperidone 4mg) studies of lumateperone 42mg (Studies 005 and 302). The pooled lumateperone data were compared with data for risperidone. Data from an open-label 1-year trial (Study 303) evaluated MetSy in patients with stable schizophrenia switched from prior antipsychotic (PA) treatment to lumateperone 42mg.ResultsIn the acute studies (n=256 lumateperone 42mg, n=255 risperidone 4mg), rates of MetSy were similar between groups at baseline (16% lumateperone, 19% risperidone). At the end of treatment (EOT), MetSy was less common with lumateperone than with risperidone (13% vs 25%). More lumateperone patients (46%) compared with risperidone (25%) patients improved from having MetSy at baseline to no longer meeting MetSy criteria at EOT. Conversely, more patients on risperidone than on lumateperone developed MetSy during treatment (13% vs 5%). Differences in MetSy conversion rates were driven by changes in triglycerides and glucose. In the long-term study (n=602 lumateperone 42mg), 33% of patients had MetSy at PA baseline. Thirty-six percent of patients (36%) with MetSy at PA baseline improved to no longer meeting criteria at EOT. Fewer than half that percentage shifted from not meeting MetSy criteria to having MetSy (15%).ConclusionsIn this post hoc analysis, lumateperone 42mg patients had reduced rates of MetSy compared with risperidone patients. In the long-term study, patients with MetSy on PA switched to lumateperone 42mg had a reduction in the risk of MetSy. These results suggest that lumateperone 42mg is a promising new treatment for schizophrenia with a favorable metabolic profile.FundingIntra-Cellular Therapies, Inc.

Relative Timing of Clinically Important Deterioration and Related Long-Term Outcomes in COPD: A Post Hoc Analysis of the UPLIFT Study

Pneumologie ◽  
2018 ◽  
Vol 72 (S 01) ◽  
pp. S86-S87 ◽  
Author(s):  
KF Rabe ◽  
D Halpin ◽  
F Martinez ◽  
D Singh ◽  
MK Han ◽  
...  
Keyword(s):  
Relative Timing ◽  
Long Term Outcomes ◽  
Post Hoc Analysis ◽  
Clinically Important Deterioration ◽  
Post Hoc

Clinical Outcomes, Structure, and Function Improve With Both Heavy and Moderate Loads in the Treatment of Patellar Tendinopathy: A Randomized Clinical Trial

2021 ◽  
Vol 49 (4) ◽  
pp. 982-993
Author(s):  
Anne-Sofie Agergaard ◽  
Rene B. Svensson ◽  
Nikolaj M. Malmgaard-Clausen ◽  
Christian Couppé ◽  
Mikkel H. Hjortshoej ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Outcome ◽  
Randomized Clinical Trial ◽  
Clinical Outcomes ◽  
Rating Scale ◽  
Power Doppler ◽  
Patellar Tendinopathy ◽  
Short Term ◽  
Level Of Evidence

Background: Loading interventions have become a predominant treatment strategy for tendinopathy, and positive clinical outcomes and tendon tissue responses may depend on the exercise dose and load magnitude. Purpose/Hypothesis: The purpose was to investigate if the load magnitude influenced the effect of a 12-week loading intervention for patellar tendinopathy in the short term (12 weeks) and long term (52 weeks). We hypothesized that a greater load magnitude of 90% of 1 repetition maximum (RM) would yield a more positive clinical outcome, tendon structure, and tendon function compared with a lower load magnitude of 55% of 1 RM when the total exercise volume was kept equal in both groups. Study Design: Randomized clinical trial; Level of evidence, 1. Methods: A total of 44 adult participants with chronic patellar tendinopathy were included and randomized to undergo moderate slow resistance (MSR group; 55% of 1 RM) or heavy slow resistance (HSR group; 90% of 1 RM). Function and symptoms (Victorian Institute of Sport Assessment–Patella questionnaire [VISA-P]), tendon pain during activity (numeric rating scale [NRS]), and ultrasound findings (tendon vascularization and swelling) were assessed before the intervention, at 6 and 12 weeks during the intervention, and at 52 weeks from baseline. Tendon function (functional tests) and tendon structure (ultrasound and magnetic resonance imaging) were investigated before and after the intervention period. Results: The HSR and MSR interventions both yielded significant clinical improvements in the VISA-P score (mean ± SEM) (HSR: 0 weeks, 58.8 ± 4.3; 12 weeks, 70.5 ± 4.4; 52 weeks, 79.7 ± 4.6) (MSR: 0 weeks, 59.9 ± 2.5; 12 weeks, 72.5 ± 2.9; 52 weeks, 82.6 ± 2.5), NRS score for running, NRS score for squats, NRS score for preferred sport, single-leg decline squat, and patient satisfaction after 12 weeks, and these were maintained after 52 weeks. HSR loading was not superior to MSR loading for any of the measured clinical outcomes. Similarly, there were no differences in functional (strength and jumping ability) or structural (tendon thickness, power Doppler area, and cross-sectional area) improvements between the groups undergoing HSR and MSR loading. Conclusion: There was no superior effect of exercising with a high load magnitude (HSR) compared with a moderate load magnitude (MSR) for the clinical outcome, tendon structure, or tendon function in the treatment of patellar tendinopathy in the short term. Both HSR and MSR showed equally good, continued improvements in outcomes in the long term but did not reach normal values for healthy tendons. Registration: NCT03096067 (ClinicalTrials.gov identifier)

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