scholarly journals In the aftermath of clozapine discontinuation: comparative effectiveness and safety of antipsychotics in patients with schizophrenia who discontinue clozapine

2020 ◽  
Vol 217 (3) ◽  
pp. 498-505
Author(s):  
Jurjen J. Luykx ◽  
Noraly Stam ◽  
Antti Tanskanen ◽  
Jari Tiihonen ◽  
Heidi Taipale
Keyword(s):  
Treatment Failure ◽  
Comparative Effectiveness ◽  
Treatment Options ◽  
Psychiatric Ward ◽  
Treatment Cessation ◽  
Primary Analysis ◽  
Oral Olanzapine ◽  
Secondary Analyses ◽  
Long Acting ◽  
Risk Of Treatment

BackgroundAlthough clozapine is often discontinued, there is a paucity of guidelines and evidence on treatment options after clozapine discontinuation. Moreover, it is currently unknown whether reinstating clozapine in patients formerly using clozapine should be avoided.AimsTo compare the real-world effectiveness of antipsychotics after clozapine cessation.MethodFrom Finnish registry data (1995–2017), we identified 2250 patients with schizophrenia who had been using clozapine for ≥1 year before treatment cessation. The primary analysis consisted of adjusted within-individual analyses of psychiatric ward readmission owing to psychosis and treatment failure. Secondary analyses concerned between-individual mortality differences.ResultsCompared with no use of antipsychotics, risk of psychiatric ward readmission was lowest for reinitiation of clozapine (adjusted hazard ratio (aHR) 0.49; 95% CI 0.40–0.61; P < 0.0001), oral olanzapine (aHR 0.58; 95% CI 0.48–0.71; P < 0.0001) and antipsychotic polypharmacy (aHR 0.62; 95% CI 0.53–0.72; P < 0.0001). Risk of treatment failure was lowest for aripiprazole long acting injectable (aHR 0.42; 95% CI 0.27–0.65; P < 0.0001), reinitiation of clozapine (aHR 0.49; 95% CI 0.43–0.57; P < 0.0001) and oral olanzapine (aHR 0.69; 95% CI 0.61–0.77; P < 0.0001). Mortality risk was lowest for reinitiation of clozapine (aHR 0.18; 95% CI 0.09–0.36; P < 0.0001) and oral olanzapine (aHR 0.26; 95% CI 0.17–0.40; P < 0.0001).ConclusionsClozapine and olanzapine are the most effective and safest treatment options in those discontinuing clozapine for undefined reasons. Clozapine should therefore be reconsidered in patients with schizophrenia who previously discontinued this compound.

Risk of treatment failure after first-line sunitinib therapy in patients with metastatic renal cell carcinoma.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 438-438
Author(s):  
Chi-Chang Chen ◽  
Gregory P. Hess ◽  
Zhimei Liu ◽  
Dean H. Gesme ◽  
Sanjiv S. Agarwala ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Targeted Therapies ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Treatment Options ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Second Line ◽  
Sunitinib Treatment ◽  
Risk Of Treatment

438 Background: Treatment options for metastatic renal cell carcinoma (mRCC) are rapidly evolving. Current treatment options include surgery, immunotherapy, and several targeted therapies including kinase inhibitors, mTOR inhibitors and anti-VEGF agents. The aim of this study was to inform choices and outcomes on the sequential use of targeted therapies for mRCC through the evaluation of the comparative effectiveness of common second-line targeted therapies following 1st line sunitinib treatment. Methods: A retrospective observational study using claims data was conducted. Final study subjects were mRCC patients who received everolimus, sorafenib or temsirolimus from 4/1/2008 to 2/29/2011 following 1st line sunitinib treatment. Patients were followed from the start of second-line treatment until treatment failure or last observation in the database. Treatment failure was defined as advancement to a third-line of mRCC therapy, or mortality. Results were analyzed using Cox proportional hazards model controlling for baseline clinical and demographic factors. Results: The study sample consisted of 257 mRCC patients who received everolimus (n=117), temsirolimus (n=75) and sorafenib (n=65) following 1st line sunitinib treatment. Patients had a mean age of 63 years, and 72% were male. The mean observation period from the start of second-line treatment was ∼6.4 months. Treatment failure was observed in 38.5% (20.2% advanced from 2nd to 3rd line and 18.3% died) of the study sample and 61.5% of patients were censored at last observation without any treatment failure event. Results from the Cox proportional hazards model indicated that, compared to everolimus, both sorafenib and temsirolimus patients experienced a statistically significant higher adjusted risk of treatment failure (sorafenib: HR=1.77, p=0.043; temsirolimus: HR=2.05, p=0.004). Conclusions: Following systemic treatment for mRCC with first-line sunitinib, patients on second-line targeted therapies were observed with differential risks of treatment failure, as defined by line advancement or death. The risk of treatment failure was significantly higher with sorafenib and temsirolimus as compared to everolimus.

scholarly journals Histologic Remission Is Associated With Lower Risk of Treatment Failure in Patients With Crohn Disease in Endoscopic Remission

2020 ◽  
Author(s):  
Hyuk Yoon ◽  
Sushrut Jangi ◽  
Parambir S Dulai ◽  
Brigid S Boland ◽  
Vipul Jairath ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Crohn Disease ◽  
Lower Risk ◽  
Hazard Analysis ◽  
Cumulative Risk ◽  
Treatment Optimization ◽  
Cox Proportional Hazard ◽  
Endoscopic Remission ◽  
Risk Of Treatment

Abstract Background Although achieving histologic remission in ulcerative colitis is established, the incremental benefit of achieving histologic remission in patients with Crohn disease (CD) treated to a target of endoscopic remission is unclear. We evaluated the risk of treatment failure in patients with CD in clinical and endoscopic remission by histologic activity status. Methods In a single-center retrospective cohort study, we identified adults with active CD who achieved clinical and endoscopic remission through treatment optimization. We evaluated the risk of treatment failure (composite of clinical flare requiring treatment modification, hospitalization, and/or surgery) in patients who achieved histologic remission vs persistent histologic activity through Cox proportional hazard analysis. Results Of 470 patients with active CD, 260 (55%) achieved clinical and endoscopic remission with treatment optimization; 215 patients with histology were included (median age, 33 years; 46% males). Overall, 132 patients (61%) achieved histologic remission. No baseline demographic, disease, or treatment factor was associated with achieving histologic remission. Over a 2-year follow-up, patients with CD in clinical and endoscopic remission who achieved histologic remission experienced a 43% lower risk of treatment failure (1-year cumulative risk: 12.9% vs 18.2%; adjusted hazard ratio, 0.57 [95% confidence interval, 0.35-0.94]) as compared with persistent histologic activity. Conclusions Approximately 61% of patients with active CD who achieved clinical and endoscopic remission with treatment optimization simultaneously achieved histologic remission, which was associated with a lower risk of treatment failure. Whether histologic remission should be a treatment target in CD requires evaluation in randomized trials.

scholarly journals Chemotherapy alone versus definitive concurrent chemoradiotherapy for cT4b esophageal squamous cell carcinoma: a population-based study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chia-Chin Li ◽  
Chih-Yi Chen ◽  
Ying-Hsiang Chou ◽  
Chih-Jen Huang ◽  
Hsiu-Ying Ku ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Concurrent Chemoradiotherapy ◽  
Statistical Significance ◽  
Treatment Options ◽  
Population Based ◽  
Primary Analysis

Abstract Background The role of radiotherapy for cT4bNanyM0 esophageal squamous cell carcinoma (ESqCC) is relatively unclear, with both chemotherapy (C/T) alone and definitive concurrent chemoradiotherapy (dCCRT) being treatment options in the current guidelines. We aimed to compare the survival of dCCRT versus C/T for these patients via a population-based approach. Methods Eligible cT4b ESqCC patients diagnosed between 2011 and 2017 were identified via the Taiwan Cancer Registry. We used propensity score (PS) weighting to balance the observable potential confounders between groups. The hazard ratio (HR) of death and incidence of esophageal cancer mortality (IECM) were compared between dCCRT and C/T. We also evaluated OS in subgroups of either low or standard radiotherapy doses. Results Our primary analysis consisted of 247 patients in whom covariates were well balanced after PS weighing. The HR for death when dCCRT was compared with C/T was 0.36 (95% confidence interval 0.24–0.53, P < 0.001). Similar results were found for IECM. Statistical significance was only observed in the standard RT dose but not in the low dose in subgroup analyses. Conclusions In this population-based nonrandomized study of cT4bNanyM0 ESqCC patients from Asia (Taiwan), we found that the use of radiotherapy with chemotherapy was associated with better overall survival than chemotherapy alone. Further studies (especially RCTs) are needed to confirm our findings.

Abstract 66: Causal Associations Between Genetically-determined Smoking and Risk of Subarachnoid Hemorrhage

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Julian N Acosta ◽  
Cameron Both ◽  
Stacy Brown ◽  
Audrey Leasure ◽  
Kevin N Vanent ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Smoking Behavior ◽  
Population Based ◽  
European Ancestry ◽  
Ratio Method ◽  
Polygenic Risk Score ◽  
Primary Analysis ◽  
Increased Risk ◽  
Secondary Analyses ◽  
Genetically Determined

Introduction: Animal and observational studies indicate that smoking is a risk factor for aneurysm formation and rupture, leading to subarachnoid hemorrhage (SAH). However, a definitive causal relationship between smoking and SAH has not been established. We leveraged the causal properties of mutation-disease associations to test the hypothesis that smoking is causally linked to SAH. Methods: We conducted a one-sample Mendelian Randomization (MR) study within the UK Biobank, a prospective, population-based observational study. We restricted the analysis to study participants with genetically-confirmed European ancestry. SAH cases were ascertained using previously validated codes. As the instrument, we built a polygenic risk score (PRS) using independent (R2<0.1) genetic variants known to be associated (p<5x10-8) with smoking. For the primary MR analysis, we implemented the ratio method using the estimates obtained from testing the PRS for association with risk of SAH and smoking. In secondary analyses, we implemented the inverse-variance weighted (IVW) and weighted median (WM) methods. Pleiotropy was assessed via the MR-Egger approach. Results: We included a total of 408,622 individuals in this study (mean age 57 [SD 8], female sex 220,944 [54%]). Of these, 132,568 (32%) ever smoked regularly and 904 (0.22%) had an SAH. Each additional standard deviation of the smoking PRS was associated with a 9% increased risk of SAH (OR 1.09, 95%CI 1.03-1.17; p=0.006) and 21% increased risk of smoking (OR 1.21, 95%CI 1.2-1.21; p=1x10-16). In the primary analysis, genetically-determined smoking was associated with a 63% increase in risk of SAH (OR 1.63, 95%CI 1.15-2.30; p=0.006). Secondary analyses using the IVW method (OR 1.57, 95%CI 1.13-2.17; p=0.007) and the WM method (OR 1.74, 95%CI 1.06-2.86; p=0.028) yielded comparable results. There was no significant pleiotropy (MR-Egger intercept p=0.38). Conclusion: Genetically-determined smoking is strongly associated with the risk of SAH. These findings provide evidence for a causal link between smoking and the occurrence of this often-debilitating condition. Interventions aimed at reducing smoking behavior could offer significant benefits, especially to those at high risk of SAH.

Factors associated to first line antiretroviral therapy (ART) failure among HIV/AIDS patients at Sanglah Hospital, Bali

2017 ◽  
pp. 4
Author(s):  
Cok Istri Sri Dharma Astiti ◽  
A.A Sagung Sawitri ◽  
Tuti Parwati
Keyword(s):  
Risk Factors ◽  
Treatment Failure ◽  
Clinical Stage ◽  
Hiv And Aids ◽  
First Line ◽  
Aids Patients ◽  
Factors Associated ◽  
Art Initiation ◽  
Risk Of Treatment ◽  
Hiv Aids

Background and purpose: The incidence of first line ART failure is increasing in the South East Asia region. The main referral hospital in Bali has recorded an increased use of second line ART due to the first line ART failure. This study aims to explore risk factors associated to first line ART failure.Methods: A case control study was conducted among people living with HIV and AIDS at Sanglah Hospital Denpasar who started first line ART between 2004 and 2013. Cases were those who diagnosed as having clinical treatment failure and still on treatment in 2015. Controls were those with no treatment failure. Sex and year of ART initiation were matched between case and control. Data were obtained from medical records that include initial regiments, HIV mode of transmission, the WHO HIV clinical stage, CD4 count, opportunistic infections, body mass index, hemoglobin level, and drug substitution at the beginning and during treatment. Risk factors were analysed using logistic regression.Results: Out of 68 HIV/AIDS patients with clinical ART failure, 72.1% were confirmed with immunological and 36.8% were confirmed with virological failure. Median time before treatment failure was 3.5 years. Factors associated to ART failure were HIV clinical stage IV with (AOR=3.43; 95%CI=1.65-7.13) and being widow/widower (AOR=4.85; 95%CI=1.52-15.53). Patients with TB co-infection have a lower risk for treatment failure due to early diagnosis and treatment through TB-HIV program with (AOR=0.32; 95%CI=0.14-0.70).Conclusions: Higher HIV clinical stage at ART initiation increases the risk of treatment failure. HIV-TB co-infection indirectly reduces the risk of treatment failure.

Attitudes to antipsychotics: a multi-site survey of Canadian psychiatry residents

2018 ◽  
Vol 13 (6) ◽  
pp. 318-338
Author(s):  
Anees Bahji ◽  
Neeraj Bajaj
Keyword(s):  
First Generation ◽  
Treatment Options ◽  
Similar Efficacy ◽  
Psychiatry Residents ◽  
Training Experience ◽  
Content Type ◽  
Electronic Survey ◽  
Site Survey ◽  
Long Acting ◽  
The University

Purpose The purpose of this paper is to identify the training needs of the next generation of psychiatrists, and barriers in prescribing first-generation antipsychotics (FGAs), long-acting injectable (LAIs) antipsychotics and clozapine. Design/methodology/approach An electronic survey was sent to psychiatry residents (N= 75/288, 26 percent) at four Canadian residency programs in late December 2017. The survey was based on an instrument originally developed at the University of Cambridge and consisted of 31 questions in 10 content domains. Findings Nearly 80 percent of residents were aware that FGAs and second-generation antipsychotics (SGAs) have similar efficacy. However, extra-pyramidal symptoms and lack of training experience were the leading concerns associated with the prescribing of FGAs. Although over 90 percent of residents felt confident about initiating an oral SGA as a regular medication, only 40 percent did so with FGAs. Confidence with initiating LAIs and clozapine was 60 and 61 percent, respectively. Practical implications The survey highlights the need for better training in the use of FGAs, clozapine and LAIs. These medications can be effectively used in providing patients with the most appropriate evidence-based treatment options to improve treatment outcomes, while ensuring that these resources are not lost to the future generations of psychiatrists. Originality/value The survey may be the first of its kind to assess antipsychotic prescribing attitudes in Canadian psychiatry residents in multiple sites.

Sign in / Sign up

Export Citation Format

Share Document