scholarly journals A retrospective study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis

2020 ◽  
Vol 217 (3) ◽  
pp. 506-513 ◽  
Author(s):  
Cecilia Casetta ◽  
Ebenezer Oloyede ◽  
Eromona Whiskey ◽  
David Michael Taylor ◽  
Fiona Gaughran ◽  
...  
Keyword(s):  
Propensity Scores ◽  
Treatment Initiation ◽  
Clinical Effectiveness ◽  
Hazard Ratio ◽  
Psychotic Symptoms ◽  
Treatment Resistant ◽  
Post Discharge ◽  
The Uk ◽  
Lower Hazard

BackgroundClozapine is uniquely effective in treatment-resistant psychosis but remains underutilised, partly owing to psychotic symptoms leading to non-adherence to oral medication. An intramuscular formulation is available in the UK but outcomes remain unexplored.AimsThis was a retrospective clinical effectiveness study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis over a 3-year period.MethodSuccessful initiation of oral clozapine after intramuscular prescription was the primary outcome. Secondary outcomes included all-cause clozapine discontinuation 2 years following initiation, and 1 year after discharge. Discontinuation rates were compared with a cohort prescribed only oral clozapine. Propensity scores were used to address confounding by indication.ResultsAmong 39 patients prescribed intramuscular clozapine, 19 received at least one injection, whereas 20 accepted oral clozapine when given an enforced choice between the two. Thirty-six (92%) patients successfully initiated oral clozapine after intramuscular prescription; three never transitioned to oral. Eight discontinued oral clozapine during the 2-year follow-up, compared with 83 out of 162 in the comparator group (discontinuation rates of 24% and 50%, respectively). Discontinuation rates at 1-year post-discharge were 21%, compared with 44% in the comparison group. Intramuscular clozapine prescription was associated with a non-significantly lower hazard of discontinuation 2 years after initiation (hazard ratio 0.39, 95% CI 0.14–1.06) and 1 year after discharge (hazard ratio 0.37, 95% CI 0.11–1.24). The only reported adverse event specific to the intramuscular formulation was injection site pain and swelling.ConclusionsIntramuscular clozapine prescription allowed transition to oral maintenance in an initially non-adherent cohort. Discontinuation rates were similar to patients only prescribed oral clozapine and comparable to existing literature.

scholarly journals Symptom remission at 12-weeks strongly predicts long-term recovery from the first episode of psychosis

2019 ◽  
Vol 50 (9) ◽  
pp. 1452-1462 ◽  
Author(s):  
Paola Dazzan ◽  
Julia M. Lappin ◽  
Margaret Heslin ◽  
Kim Donoghue ◽  
Ben Lomas ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Strong Predictor ◽  
Population Based ◽  
Individual Characteristics ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Symptom Remission ◽  
Symptom Recovery ◽  
The Uk

AbstractBackgroundTo determine the baseline individual characteristics that predicted symptom recovery and functional recovery at 10-years following the first episode of psychosis.MethodsAESOP-10 is a 10-year follow up of an epidemiological, naturalistic population-based cohort of individuals recruited at the time of their first episode of psychosis in two areas in the UK (South East London and Nottingham). Detailed information on demographic, clinical, and social factors was examined to identify which factors predicted symptom and functional remission and recovery over 10-year follow-up. The study included 557 individuals with a first episode psychosis. The main study outcomes were symptom recovery and functional recovery at 10-year follow-up.ResultsAt 10 years, 46.2% (n = 140 of 303) of patients achieved symptom recovery and 40.9% (n = 117) achieved functional recovery. The strongest predictor of symptom recovery at 10 years was symptom remission at 12 weeks (adj OR 4.47; CI 2.60–7.67); followed by a diagnosis of depression with psychotic symptoms (adj OR 2.68; CI 1.02–7.05). Symptom remission at 12 weeks was also a strong predictor of functional recovery at 10 years (adj OR 2.75; CI 1.23–6.11), together with being from Nottingham study centre (adj OR 3.23; CI 1.25–8.30) and having a diagnosis of mania (adj OR 8.17; CI 1.61–41.42).ConclusionsSymptom remission at 12 weeks is an important predictor of both symptom and functional recovery at 10 years, with implications for illness management. The concepts of clinical and functional recovery overlap but should be considered separately.

Abstract 3395: Potassium Supplement Use May Increase Hospitalization without Affecting Mortality in Chronic Heart Failure: Implications for Use of Aldosterone Antagonists to Maintain Potassium Balance in Chronic Heart Failure

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Ali Ahmed ◽  
Chris Adamopoulos ◽  
Xuemei Sui ◽  
Thomas E Love
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Propensity Scores ◽  
Cox Regression ◽  
Hazard Ratio ◽  
Aldosterone Antagonists ◽  
Potassium Supplement ◽  
Supplement Use ◽  
Group Trial

Background: Hypokalemia is common in heart failure (HF). Aldosterone antagonists can raise serum potassium (K) and also improve survival. Yet, K-supplements are often used to correct hypokalemia; although little is known about the effects of K-supplements in HF. Methods: Of the 7788 ambulatory chronic HF patients in the Digitalis Investigation Group trial, 2199 (28%) were receiving K-supplements. Propensity scores for K-supplement use was calculated for each patient and were used to match 2131 patients receiving K-supplements with 2131 no-K-supplements patients (absolute standardized differences <10% for all measured covariates). Matched Cox regression models were used to estimate effects of K-supplements on outcomes during 40 months of median follow-up. Results: Compared with 68% (rate, 4120/10000 person-years) of no-K-supplement patients, 71% (rate, 4777/10000 person-years) of patients receiving K-supplements were hospitalized from all causes (hazard ratio, 1.15; 95% CI, 1.05–1.26; P=0.004). Compared with 38% (rate, 1313/10000 person-years) of no-K-supplement patients, 38% (rate, 1327/10000 person-years) of patients receiving K-supplements died from all causes (hazard ratio, 1.05; 95% CI, 0.94–1.18; P=0.390). Conclusion: K-supplement use was associated with no mortality reduction but increased hospitalization. This first report on the effect of K-supplement in HF raises question about the wisdom of K-supplement use to correct hypokalemia and maintain normokalemia in HF. Given the proven mortality benefits of aldosterone antagonists and their ability to raise serum K, spironolactone may be preferable to maintain normokalemia in chronic HF. Figure 1. Association of potassium supplement use and all-cause hospitalization

scholarly journals Vitamin D levels and risk of delirium

Neurology ◽  
2019 ◽  
Vol 92 (12) ◽  
pp. e1387-e1394 ◽  
Author(s):  
Kirsty Bowman ◽  
Lindsay Jones ◽  
Luke C. Pilling ◽  
João Delgado ◽  
George A. Kuchel ◽  
...  
Keyword(s):  
Vitamin D ◽  
Confidence Interval ◽  
Hospital Admissions ◽  
Mendelian Randomization ◽  
Hazard Ratio ◽  
Nucleotide Polymorphisms ◽  
Community Based ◽  
Vitamin D Levels ◽  
The Uk

ObjectiveTo estimate effects of vitamin D levels on incident delirium hospital admissions using inherited genetic variants in mendelian randomization models, which minimize confounding and exclude reverse causation.MethodsLongitudinal analysis using the UK Biobank, community-based, volunteer cohort (2006–2010) with incident hospital-diagnosed delirium (ICD-10 F05) ascertained during ≤9.9 years of follow-up of hospitalization records (to early 2016). We included volunteers of European descent aged 60-plus years by end of follow-up. We used single-nucleotide polymorphisms previously shown to increase circulating vitamin D levels, and APOE variants. Cox competing models accounting for mortality were used.ResultsOf 313,121 participants included, 544 were hospitalized with delirium during follow-up. Vitamin D variants were protective for incident delirium: hazard ratio = 0.74 per 10 nmol/L (95% confidence interval 0.62–0.87, p = 0.0004) increase in genetically instrumented vitamin D, with no evidence for pleiotropy (mendelian randomization–Egger p > 0.05). Participants with ≥1 APOE ε4 allele were more likely to develop delirium (e.g., ε4ε4 hazard ratio = 3.73, 95% confidence interval 2.68–5.21, p = 8.0 × 10−15 compared to ε3ε3), but there was no interaction with vitamin D variants.Conclusions and relevanceIn a large community-based cohort, there is genetic evidence supporting a causal role for vitamin D levels in incident delirium. Trials of correction of low vitamin D levels in the prevention of delirium are needed.

scholarly journals Amisulpride augmentation in clozapine-unresponsive schizophrenia (AMICUS): a double-blind, placebo-controlled, randomised trial of clinical effectiveness and cost-effectiveness

2017 ◽  
Vol 21 (49) ◽  
pp. 1-56 ◽  
Author(s):  
Thomas RE Barnes ◽  
Verity C Leeson ◽  
Carol Paton ◽  
Louise Marston ◽  
Linda Davies ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Side Effects ◽  
Side Effect ◽  
Clinical Effectiveness ◽  
Health Technology ◽  
Treatment Resistant ◽  
Double Blind ◽  
Insufficient Response ◽  
Economic Analyses

BackgroundWhen treatment-refractory schizophrenia shows an insufficient response to a trial of clozapine, clinicians commonly add a second antipsychotic, despite the lack of robust evidence to justify this practice.ObjectivesThe main objectives of the study were to establish the clinical effectiveness and cost-effectiveness of augmentation of clozapine medication with a second antipsychotic, amisulpride, for the management of treatment-resistant schizophrenia.DesignThe study was a multicentre, double-blind, individually randomised, placebo-controlled trial with follow-up at 12 weeks.SettingsThe study was set in NHS multidisciplinary teams in adult psychiatry.ParticipantsEligible participants were people aged 18–65 years with treatment-resistant schizophrenia unresponsive, at a criterion level of persistent symptom severity and impaired social function, to an adequate trial of clozapine monotherapy.InterventionsInterventions comprised clozapine augmentation over 12 weeks with amisulpride or placebo. Participants received 400 mg of amisulpride or two matching placebo capsules for the first 4 weeks, after which there was a clinical option to titrate the dosage of amisulpride up to 800 mg or four matching placebo capsules for the remaining 8 weeks.Main outcome measuresThe primary outcome measure was the proportion of ‘responders’, using a criterion response threshold of a 20% reduction in total score on the Positive and Negative Syndrome Scale.ResultsA total of 68 participants were randomised. Compared with the participants assigned to placebo, those receiving amisulpride had a greater chance of being a responder by the 12-week follow-up (odds ratio 1.17, 95% confidence interval 0.40 to 3.42) and a greater improvement in negative symptoms, although neither finding had been present at 6-week follow-up and neither was statistically significant. Amisulpride was associated with a greater side effect burden, including cardiac side effects. Economic analyses indicated that amisulpride augmentation has the potential to be cost-effective in the short term [net saving of between £329 and £2011; no difference in quality-adjusted life-years (QALYs)] and possibly in the longer term.LimitationsThe trial under-recruited and, therefore, the power of statistical analysis to detect significant differences between the active and placebo groups was limited. The economic analyses indicated high uncertainty because of the short duration and relatively small number of participants.ConclusionsThe risk–benefit of amisulpride augmentation of clozapine for schizophrenia that has shown an insufficient response to a trial of clozapine monotherapy is worthy of further investigation in larger studies. The size and extent of the side effect burden identified for the amisulpride–clozapine combination may partly reflect the comprehensive assessment of side effects in this study. The design of future trials of such a treatment strategy should take into account that a clinical response may be not be evident within the 4- to 6-week follow-up period usually considered adequate in studies of antipsychotic treatment of acute psychotic episodes. Economic evaluation indicated the need for larger, longer-term studies to address uncertainty about the extent of savings because of amisulpride and impact on QALYs. The extent and nature of the side effect burden identified for the amisulpride–clozapine combination has implications for the nature and frequency of safety and tolerability monitoring of clozapine augmentation with a second antipsychotic in both clinical and research settings.Trial registrationEudraCT number 2010-018963-40 and Current Controlled Trials ISRCTN68824876.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 21, No. 49. See the NIHR Journals Library website for further project information.

Abstract 17212: 30-day All-cause Readmission is Associated With a Significantly Higher Subsequent All-cause Mortality and Costly Readmissions Among Older Medicare Beneficiaries Hospitalized for Heart Failure

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Cherinne Arundel ◽  
Rahul Khosla ◽  
Charles Faselis ◽  
Charity J Morgan ◽  
Sijian Zhang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Length Of Stay ◽  
Propensity Scores ◽  
Matched Cohort ◽  
Medicare Beneficiaries ◽  
Post Discharge ◽  
Patients With Heart Failure ◽  
All Cause Mortality ◽  
Cumulative Length

Background: Among ambulatory patients with heart failure (HF), hospital admission is associated with higher subsequent mortality. HF is the leading cause of 30-day all-cause readmission, reduction of which is a goal of the Affordable Care Act. We examined the association of 30-day all-cause readmission with subsequent all-cause mortality in a propensity-matched cohort of hospitalized HF patients. Methods: Of the 8049 Medicare beneficiaries hospitalized for HF and discharged alive from 106 U.S. hospitals (1998-2001), 7578 were alive 30-day post-discharge, of which 1519 had 30-day all-cause readmission. Using propensity scores for 30-day all-cause readmission, we assembled a matched cohort of 1516 pairs of patients with and without 30-day all-cause readmission, balanced on 34 baseline characteristics. Results: During 2-12 months of post-discharge follow-up, all-cause mortality occurred in 41% and 27% of matched patients with and without 30-day all-cause readmission, respectively (HR, 1.68; 95% CI, 1.48-1.90; p<0.001; Figure). During a mean post-index follow up of 3 (max 9) years, patients with 30-day all-cause readmissions (vs. without) had higher total of post-index readmissions (mean, 6.9 vs 5.1; p<0.001), longer cumulative length of stay (mean, 51 vs 43 days; p<0.001), and higher charges (mean, $129,175 vs. $114,787; p=0.012) and payments (mean, $38,972 vs. $34,025; p=0.001) from those readmissions. Conclusions: Among hospitalized patients with HF 30-day all-cause readmission is associated with higher subsequent mortality, number of readmissions and costs, and longer cumulative length of stay.

scholarly journals Clinical effectiveness of the Manchester Glaucoma Enhanced Referral Scheme

2018 ◽  
Vol 103 (8) ◽  
pp. 1066-1071 ◽  
Author(s):  
Patrick J G Gunn ◽  
Joanne R Marks ◽  
Evgenia Konstantakopoulou ◽  
David F Edgar ◽  
John G Lawrenson ◽  
...  
Keyword(s):  
Usual Care ◽  
False Positive ◽  
False Negative ◽  
Clinical Effectiveness ◽  
Outcome Data ◽  
Reference Standard ◽  
Referral Criteria ◽  
Standard Assessment ◽  
The Uk

BackgroundGlaucoma referral filtering schemes have operated in the UK for many years. However, there is a paucity of data on the false-negative (FN) rate. This study evaluated the clinical effectiveness of the Manchester Glaucoma Enhanced Referral Scheme (GERS), estimating both the false-positive (FP) and FN rates.MethodOutcome data were collected for patients newly referred through GERS and assessed in ‘usual-care’ clinics to determine the FP rate (referred patients subsequently discharged at their first visit). For the FN rate, glaucoma suspects deemed not requiring referral following GERS assessment were invited to attend for a ‘reference standard’ examination including all elements of assessment recommended by National Institute for Health and Care Excellence (NICE) by a glaucoma specialist optometrist. A separate 33 cases comprising randomly selected referred and non-referred cases were reviewed independently by two glaucoma specialist consultant ophthalmologists to validate the reference standard assessment.Results1404 patients were evaluated in GERS during the study period; 651 (46.3%) were referred to the Hospital Eye Service (HES) and 753 (53.6%) were discharged. The FP rate in 307 assessable patients referred to the HES was 15.5%. This study reviewed 131 (17.4%) of those patients not referred to the HES through the GERS scheme; 117 (89.3%) were confirmed as not requiring hospital follow-up; 14 (10.7%) required follow-up, including 5 (3.8%) offered treatment. Only one patient (0.8%) in this sample met the GERS referral criteria and was not referred (true FN). There were no cases of missed glaucoma or non-glaucomatous pathology identified within our sample.ConclusionThe Manchester GERS is an effective glaucoma filtering scheme with a low FP and FN rate.

Abstract 2453: Exercise Capacity is Inversely Associated with Mortality Risk in Pre-Hypertensive Men

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Andreas E Pittaras ◽  
Jonathan Myers ◽  
Puneet Narayan ◽  
Athanasios Manolis ◽  
Charles Faselis ◽  
...  
Keyword(s):  
Exercise Capacity ◽  
Mortality Risk ◽  
Strong Association ◽  
Hazard Ratio ◽  
Peak Exercise ◽  
Adjusted Risk ◽  
Epidemiologic Evidence ◽  
Increased Risk ◽  
Lower Hazard

Introduction: Epidemiologic evidence supports an inverse and strong association between fitness status, and mortality in healthy individuals. Pre-hypertensive individuals are at increased risk for cardiovascular events compared to those with normal blood pressure. However, there is no information on the association between exercise capacity and mortality in pre-hypertensive individuals. Methods: We assessed the association between peak exercise capacity (METs) and all-cause mortality in pre-hypertensive men (n=4,735; age=56±12). We established four fitness categories based on the MET level achieved. Those who achieved <5 METs (n=674); 5–7 METs (n=1,170); 7.1 to 10 METs (1,784); and > 10 METs (n= n=1,107). There were 943 deaths over 22 years of follow-up (mean=8.0±5.5). Results : After adjusting for age, BMI, diabetes and dyslipidemia, exercise capacity was the strongest predictor of risk for mortality. The adjusted risk was reduced by 14% for every 1-MET increase in exercise capacity (Hazard Ratio= 0.86; CI: 0.84 – 0.88; p<0.001). When compared to those who achieved ≥5 METs, the mortality risk in those who achieved 5.1–7 METs was 25% lower (hazard ratio= 0.75; CI: 0.64 – 0.87; p<0.001); 60% lower for those who achieved 7.1–10 METs (hazard ratio= 0.40; CI: 0.33– 0.48; p<0.001), and 75% lower for those achieving >10 METs (Hazard Ratio= 0.25; CI: 0.19 – 0.33; p<0.001). Conclusions: The association between exercise capacity and mortality in pre-hypertensive individuals was strong, inverse and graded. The mortality risk was lowered by 14% for each 1-MET increase in exercise capacity. The overall reduction in mortality was 25% to 75% for those with an exercise capacity of >7 METs compared to those who achieved <5 METs.

scholarly journals G-CSF mediated neutrophil augmentation in a unique case of comorbid idiopathic Parkinson’s disease and treatment-resistant schizophrenia on clozapine

2020 ◽  
Vol 10 ◽  
pp. 204512532095641 ◽  
Author(s):  
Olivia Morrow ◽  
Lucy Gibson ◽  
Manraj Bhamra ◽  
Anthony S. David ◽  
Sotirios Posporelis
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Adverse Events ◽  
Psychotic Symptoms ◽  
Treatment Resistant ◽  
Unique Case ◽  
Clozapine Therapy ◽  
Stimulating Factor ◽  
Sustained Increase

Treatment of psychosis in Parkinson’s disease (PD) is challenging; pharmacological options are limited, with clozapine considered most effective. The risk of agranulocytosis restricts the use of clozapine, but, where this occurs, cautious re-challenge with granulocyte stimulating factor can be successful. We present a unique case of a patient who developed early-onset PD on a background of antecedent treatment-resistant schizophrenia, who had been treated effectively with clozapine for over 15 years with no adverse events. However, during a hospital admission intended to optimise her Parkinsonian medications, she developed persistent neutropenia necessitating clozapine discontinuation. Numerous attempts to re-challenge with clozapine failed until augmentation with lithium and G-CSF was trialled. Two doses of G-CSF led to a sustained increase in the neutrophil count, allowing the continuation of clozapine therapy in the 1 year of follow up. This illustrates the potential for G-CSF to be used to facilitate clozapine use in a patient population not described previously. Neutrophil augmentation allowed the sustained continuation of this effective therapy, treating her psychotic symptoms without detriment to her movement disorder. We suggest that G-CSF might be considered as a treatment option in other cases where clozapine-associated neutropenia obstructs its use.

Post Discharge Clinically Overt Venous Thromboembolism in Orthopaedic Surgery Patients with Negative Venography -an Overview Analysis

1996 ◽  
Vol 76 (06) ◽  
pp. 0887-0892 ◽  
Author(s):  
Serena Ricotta ◽  
Alfonso lorio ◽  
Pasquale Parise ◽  
Giuseppe G Nenci ◽  
Giancarlo Agnelli
Keyword(s):  
Venous Thromboembolism ◽  
Orthopaedic Surgery ◽  
Diagnostic Methods ◽  
Future Research ◽  
Post Discharge ◽  
Pharmacological Prophylaxis ◽  
Vein Thrombosis ◽  
Overview Analysis ◽  
Major Orthopaedic Surgery

SummaryA high incidence of post-discharge venous thromboembolism in orthopaedic surgery patients has been recently reported drawing further attention to the unresolved issue of the optimal duration of the pharmacological prophylaxis. We performed an overview analysis in order to evaluate the incidence of late occurring clinically overt venous thromboembolism in major orthopaedic surgery patients discharged from the hospital with a negative venography and without further pharmacological prophylaxis. We selected the studies published from January 1974 to December 1995 on the prophylaxis of venous thromboembolism after major orthopaedic surgery fulfilling the following criteria: 1) adoption of pharmacological prophylaxis, 2) performing of a bilateral venography before discharge, 3) interruption of pharmacological prophylaxis at discharge in patients with negative venography, and 4) post-discharge follow-up of the patients for at least four weeks. Out of 31 identified studies, 13 fulfilled the overview criteria. The total number of evaluated patients was 4120. An adequate venography was obtained in 3469 patients (84.1%). In the 2361 patients with negative venography (68.1%), 30 episodes of symptomatic venous thromboembolism after hospital discharge were reported with a resulting cumulative incidence of 1.27% (95% C.I. 0.82-1.72) and a weighted mean incidence of 1.52% (95% C.I. 1.05-1.95). Six cases of pulmonary embolism were reported. Our overview showed a low incidence of clinically overt venous thromboembolism at follow-up in major orthopaedic surgery patients discharged with negative venography. Extending pharmacological prophylaxis in these patients does not appear to be justified. Venous thrombi leading to hospital re-admission are likely to be present but asymptomatic at the time of discharge. Future research should be directed toward improving the accuracy of non invasive diagnostic methods in order to replace venography in the screening of asymptomatic post-operative deep vein thrombosis.

Sign in / Sign up

Export Citation Format

Share Document