Objective:
To provide information for physicians and patients on which to base a decision as to whether to stop mandatory blood testing.
Data Sources:
Articles on drug-induced blood dyscrasias were ...identified by searches of MEDLINE (1966—September 2005) and review of their bibliographies. Novartis was asked to provide additional data on clozapine, leukopenia, agranulocytosis, and suicidality.
Study Selection and Data Extraction:
Data on the chance of clozapine-induced leukopenia and agranulocytosis were combined with data about possible fatality and compared with the risks associated with other medications and with life in general.
Data Synthesis:
The chance of clozapine-induced leukopenia or agranulocytosis decreases exponentially over time. In the US, the chance in the second 6 months of treatment is 0.70/1000 patient-years and, after the first year, 0.39/1000 patient-years. The case fatality rate of clozapine-induced agranulocytosis is estimated as 4.2–16%, depending on whether a granulocyte colony-stimulating factor is used. Nevertheless, treatment with clozapine reduces overall mortality, probably because it reduces suicidality.
Conclusions:
After at least 6 months' treatment with clozapine, the mortality involved in stopping white blood cell monitoring is about the same as the mortality associated with other medications, such as mianserin or phenylbutazone, and with life in general (traffic or occupational accident). If the patient has been well informed and wishes to stop the monitoring, it is a medically justifiable option to do so and is preferable to stopping treatment with clozapine since this drug reduces overall mortality.
Clozapine Intoxication in COVID-19 Tio, Niels; Schulte, Peter F.J; Martens, Harrie J.M
The American journal of psychiatry,
02/2021, Letnik:
178, Številka:
2
Journal Article
Recenzirano
Clozapine is regarded as a very effective antipsychotic. Here, a case of a 46-year-old Caucasian nonsmoker, who lives at an institution for people with intellectual disabilities, is presented. He is ...known to have a severe intellectual disability of unknown cause as well as schizophrenia, for which he takes 200 mg of clozapine twice daily.
Clozapine remains the drug of choice for treatment-resistant schizophrenia. As a consequence of its long history and complex pharmacology, we suspected wide variation in the regulations of clozapine ...use across different countries. The summaries of product characteristics (SPCs) from clozapine manufacturers, as well as local and national guidelines in the following selected countries, were reviewed: China, Denmark, Ireland, Japan, The Netherlands, New Zealand, Romania, the UK and the US. Clozapine is available as tablets in all countries, as an oral suspension in all included countries, with the exception of Japan and Romania, as orally disintegrating tablets in the US and China, and as an injectable in The Netherlands. General practitioner prescribing is only available in The Netherlands, New Zealand, the UK and the US, although with some restrictions in some of the countries. In Ireland and China, clozapine is only dispensed through hospital pharmacies. Hematological monitoring is mandatory in all countries but varies substantially in frequency, e.g. in Denmark hematologic monitoring is mandatory weekly for 18 weeks, followed by monthly monitoring, compared with Japan where blood work is required weekly for 26 weeks, followed by biweekly hematologic monitoring thereafter. In most included countries, with the exception of Denmark, Romania and The Netherlands, the manufacturer provides a mandatory hematological monitoring database, and dispensing of clozapine is not permissible without acceptable white blood count and absolute neutrophil count results. Local guidelines in New Zealand recommend echocardiography and routine troponin during the initial phases of treatment with clozapine. Regulations of clozapine vary widely with regard to rules of prescribing and monitoring. A worldwide update and harmonization of these regulations is recommended.
BackgroundIn a large and comprehensively assessed sample of patients with bipolar disorder type I (BDI), we investigated the prevalence of psychotic features and their relationship with life course, ...demographic, clinical, and cognitive characteristics. We hypothesized that groups of psychotic symptoms (Schneiderian, mood incongruent, thought disorder, delusions, and hallucinations) have distinct relations to risk factors.MethodsIn a cross-sectional study of 1342 BDI patients, comprehensive demographical and clinical characteristics were assessed using the Structured Clinical Interview for DSM-IV (SCID-I) interview. In addition, levels of childhood maltreatment and intelligence quotient (IQ) were assessed. The relationships between these characteristics and psychotic symptoms were analyzed using multiple general linear models.ResultsA lifetime history of psychotic symptoms was present in 73.8% of BDI patients and included delusions in 68.9% of patients and hallucinations in 42.6%. Patients with psychotic symptoms showed a significant younger age of disease onset (β = −0.09, t = −3.38, p = 0.001) and a higher number of hospitalizations for manic episodes (F11 338 = 56.53, p < 0.001). Total IQ was comparable between groups. Patients with hallucinations had significant higher levels of childhood maltreatment (β = 0.09, t = 3.04, p = 0.002).ConclusionsIn this large cohort of BDI patients, the vast majority of patients had experienced psychotic symptoms. Psychotic symptoms in BDI were associated with an earlier disease onset and more frequent hospitalizations particularly for manic episodes. The study emphasizes the strength of the relation between childhood maltreatment and hallucinations but did not identify distinct subgroups based on psychotic features and instead reported of a large heterogeneity of psychotic symptoms in BD.
Abstract Background Bipolar disorder has been associated with a decrease in cognitive functioning affecting the functional outcome of patients independent of mood states. However, there have only ...been few attempts to investigate the effects of functional remediation for patients with bipolar disorder. The current study investigates the feasibility and effectiveness of a combined group and individual functional remediation program for bipolar disorder, including both patients and their caregivers. Methods Twelve participants diagnosed with bipolar I disorder, and their caregivers, were treated with a combined group and individual functional remediation program. The feasibility of the program was evaluated by dropout rates and participants’ evaluations of the program. The effectiveness of the program was explored through the assessment of functional outcome at baseline, immediately post-treatment, and follow-up three months later. Results The results indicate a high degree of satisfaction and a low dropout rate with the current program. Assessment of outcomes suggests improved functioning in the areas of autonomy and occupational functioning, evolving from baseline to follow-up. Limitations Due to a small sample size and the lack of a control group the results are preliminary. Conclusions This relatively brief intervention offers a more tailor-made approach to functional remediation and shows good feasibility, acceptability and improvement of functioning in patients with bipolar I disorder.
It has been suggested that clozapine has one of the largest diabetic effects of all atypical antipsychotics. To confirm these findings, we examined retrospectively the risk of new-onset diabetes in ...long-term clozapine treatment compared to treatment with other antipsychotics in a matched control population with schizophrenia or schizoaffective disorder. Ninety-four adult patients with schizophrenia or schizoaffective disorder who had been treated with clozapine for 5 years or longer were matched on age, diagnosis, and sex to 94 patients without any use of clozapine. The groups were followed up for as long as 20 years. The cumulative incidence of new detection of diabetes in the clozapine group was 22.3% (mean follow-up, 12.3 years; absolute risk difference, 6.3%; 95% confidence interval, -4.9% to 17.5%). An additional rigorous analysis of the 83 matched pairs with normal glucose measurement before end point showed a significant risk difference between the 2 groups (21.7% compared with 8.4%) but may have been biased against clozapine. We conclude that definitive evidence showing a clinically significant larger risk for new-onset diabetes after long-term treatment with clozapine in comparison to other antipsychotics is lacking.
Living donor for liver transplantation Broelsch, Christoph E.; Burdelski, Martin; Rogiers, Xavier ...
Hepatology,
July 1994, Letnik:
20, Številka:
S7
Journal Article, Conference Proceeding
Recenzirano
Odprti dostop
Since living related liver transplantation was first performed in 1989, more than 150 cases have been performed worldwide, mostly in the United States and Japan. This paper reports the first series ...of living related liver transplantation in Europe. Twenty living related liver transplantation surgeries were performed over a 13‐mo period, with an overall patient survival of 85%. For patients who underwent elective transplantation (n=13), the survival rate was 100%. Technical complications included one arterial thrombosis necessitating retransplantation and five bile leaks requiring surgical revision. The technical improvements that permit avoidance of these complications are discussed. A detailed description of the living related liver procurement is given. All procurements yielded grafts of excellent quality. No intraoperative complications occurred, and no reoperations were necessary. No heterologous blood transfusion was needed. In two patients, incisional hernias developed after wound infection. Living related liver transplantation does not absolve the transplant community of efforts to promote cadaveric organ procurement. Nevertheless, living related liver transplantation does have the advantage of a readily available graft of excellent quality, permitting transplantation with optimal timing under elective conditions. Several centers are now preparing living related segmental liver transplants, following the model of our protocol, for three reasons: (a) to obtain superior results compared with cadaveric liver transplantation; (b) to overcome cadaveric organ shortage and further reduce pretransplantation mortality and (c) to provide viable organs in countries where cadaveric organ procurement is not established. When performed by a team experienced in pediatric liver transplantation and in adult liver resection, living related liver transplantation is an excellent modality for the treatment of end‐stage liver disease in children. (Hepatology 1994;20:49S‐55S.)
A series of novel, selective TNF-α converting enzyme inhibitors based on 4-hydroxy and 5-hydroxy pipecolate hydroxamic acid scaffolds is described. The potency and selectivity of TACE inhibition is ...dramatically influenced by the nature of the sulfonamide group which interacts with the S1′ site of the enzyme. Substituted 4-benzyloxybenzenesulfonamides exhibit excellent TACE potency with >100× selectivity over inhibition of matrix metalloprotease-1 (MMP-1). Alkyl substituents on the
ortho position of the benzyl ether moiety give the most potent inhibition of TNF-α release in LPS-treated human whole blood.
A series of novel hydroxamic acids with potent TACE activity is described.
