Clozapine treatment and discontinuation in Iceland: A national longitudinal study using electronic patient records.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Clozapine is the only drug approved for treatment-resistant schizophrenia. There is evidence that clozapine is underutilized.To evaluate the initiation and discontinuation of clozapine at Landspitali University Hospital in Iceland and the prevalence of antipsychotic polypharmacy in clozapine-treated patients.The study is a part of an ongoing longitudinal study of schizophrenia in Iceland. We identified 201 patients on clozapine or who have been on clozapine by using a keyword search in the electronic health records and by reviewing their medical records.Mean age at first treatment with clozapine was 37.8 years. Mean follow-up period on clozapine was 11 years. After 20 years of treatment 71.2% of patients were still on clozapine. After one year of treatment 84.4% of patients were still receiving clozapine treatment. We estimate that 11.4% of patients with schizophrenia in Iceland are taking clozapine and that 16% have been treated with clozapine at some point. Polypharmacy is common, since nearly 2/3, 65.6%, of patients taking clozapine use at least one other antipsychotic and 16.9% are also receiving depot injections.We need to increase the awareness of psychiatrists in Iceland with regard to treatment with clozapine, since only about half of the estimated population of patients with treatment-resistant schizophrenia in Iceland have ever been treated with clozapine. Nearly two thirds of patients who are prescribed clozapine in Iceland remain on it long-term.info:eu-repo/grantAgreement/EC/FP7/279227 National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College Londo

Neutropenia and agranulocytosis during treatment of schizophrenia with clozapine versus other antipsychotics: an observational study in Iceland

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files.Data on the haematological outcomes of patients who continue clozapine treatment following neutropenia are very rare as even mild neutropenia results in mandatory discontinuation of clozapine in most countries. However, in Iceland where clozapine monitoring is less stringent allows an observational study to be done on the risk of agranulocytosis and neutropenia during treatment with clozapine compared with other antipsychotics among patients with schizophrenia.The present study is a part of a wider ongoing longitudinal study of schizophrenia in Iceland. We identified 201 patients with schizophrenia treated with clozapine and 410 patients with schizophrenia who had never been on clozapine by searching the electronic health records of Landspitali, the National University Hospital. Neutrophil counts were searched in electronic databases to identify patients who developed neutropenia/agranulocytosis and the frequency of neutrophil measurements was examined as well.The median number of days between neutrophil measurements during the first 18 weeks of clozapine treatment was 25 days but after the first 18 weeks on the drug the median became 124 days. Thirty four cases of neutropenia were identified during clozapine treatment with an average follow up time of 9.2 years. The majority, 24 individuals developed mild neutropenia (1500-1900 neutrophils/mm(3)). None of these progressed to agranulocytosis. The remaining 10 patients developed neutropenia in the range 500-1400 /mm(3) of whom one developed agranulocytosis, three stopped clozapine use and 6 patients continued on clozapine for at least a year without developing agranulocytosis. Unexpectedly, schizophrenia patients on other antipsychotics had an equal risk of developing neutropenia as those on clozapine.Neutropenia is common both in patients with schizophrenia on clozapine treatment and in those never on clozapine. Therefore a large part of neutropenia during clozapine treatment is probably not caused by clozapine. These findings have implications in assessing the balance between the risk of progression from neutropenia to agranulocytosis against the morbidity resulting from the premature discontinuation of clozapine under the current monitoring regulations in the US and in most of Europe.info:eu-repo/grantAgreement/EC/FP7/279227 National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London, Maudsley NHS Foundation Trust and King’s College London

Elevation Change of Drangajokull, Iceland, from Cloud-Cleared ICESat Repeat Profiles and GPS Ground-Survey Data

Located on the Vestfirdir Northwest Fjords), DrangaJokull is the northernmost ice map in Iceland. Currently, the ice cap exceeds 900 m in elevation and covered an area of approx.l46 sq km in August 2004. It was about 204 sq km in area during 1913-1914 and so has lost mass during the 20th century. Drangajokull's size and accessibility for GPS surveys as well as the availability of repeat satellite altimetry profiles since late 2003 make it a good subject for change-detection analysis. The ice cap was surveyed by four GPS-equipped snowmobiles on 19-20 April 2005 and has been profiled in two places by Ice, Cloud. and land Elevation Satellite (ICESat) 'repeat tracks,' fifteen times from late to early 2009. In addition, traditional mass-balance measurements have been taken seasonally at a number of locations across the ice cap and they show positive net mass balances in 2004/2005 through 2006/2007. Mean elevation differences between the temporally-closest ICESat profiles and the GPS-derived digital-elevation model (DEM)(ICESat - DEM) are about 1.1 m but have standard deviations of 3 to 4 m. Differencing all ICESat repeats from the DEM shows that the overall elevation difference trend since 2003 is negative with losses of as much as 1.5 m/a from same season to same season (and similar elevation) data subsets. However, the mass balance assessments by traditional stake re-measurement methods suggest that the elevation changes where ICESat tracks 0046 and 0307 cross Drangajokull are not representative of the whole ice cap. Specifically, the area has experienced positive mass balance years during the time frame when ICESat data indicates substantial losses. This analysis suggests that ICESat-derived elevations may be used for multi-year change detection relative to other data but suggests that large uncertainties remain. These uncertainties may be due to geolocation uncertainty on steep slopes and continuing cloud cover that limits temporal and spatial coverage across the area

Geosynthetic stabilization of unpaved roads on soft ground : a field evaluation

A full scale field trial was carried out to investigate the performance of different geosynthetics in unpaved road construction over soft ground. The test site comprises five 16 m long, by 4.5 m wide test sections, built on a subgrade of undrained shear strength approximately 40 kPa. One is unreinforced and serves as a control section in the study, three sections include a geotextile, and one includes a geogrid. Each test section incorporated a variable thickness of sandy gravel base course material, between 25 and 50 cm thick. They were trafficked in sequence by a vehicle of standard axle load. An important governing parameter for interpretation of behavior is the influence of base course thickness on the relationship between number of passes and rut depth. Performance of the test sections was evaluated from measurements of rut depth, base course thickness, base course deformations, geosynthetic strain, and deformed profile of the geosynthetic, with increasing number of vehicle passes. Vehicle trafficking was continued to a rut depth of about 20 cm, which constitutes a serviceability failure. Results from the full scale field trial show a better performance in the reinforced sections than the unreinforced section. The performance of the unreinforced section shows good agreement with other well-documented field data at large rut depths, between 10 and 15 cm, but not at small ruts. Although the four geosynthetics exhibited a broad range of stiffness and material properties, the general performance of the four reinforced sections was similar on the thicker base course layers. This is attributed to a reinforced mechanism governed by stiffness and separation, and all materials appear adequately stiff for the site condition and vehicle loading. On the thinner subgrades, a tensioned-membrane effect is mobilized, and a significant difference is observed between the geosynthetics.Applied Science, Faculty ofCivil Engineering, Department ofGraduat

Constipation, ileus and medication use during clozapine treatment in patients with schizophrenia in Iceland

To access publisher's full text version of this article click on the hyperlink belowPurpose of the article: Clozapine is the only evidence based treatment for treatment-resistant schizophrenia. Constipation is a well known side effect of clozapine treatment. The aims of this study are to describe the prevalence of constipation and ileus during clozapine treatment of patients with schizophrenia in Iceland and to assess the concomitant use of medication that can cause constipation, and laxatives used to treat constipation. We identified 188 patients treated with clozapine by searching the electronic health records of Landspitali, the National University Hospital, during the study period 1.1.1998 - 21.11.2014. Cases of constipation and ileus were identified using an electronic search with keywords related to ileus in the patients' electronic health records. Detailed medication use was available for 154 patients that used clozapine for at least one year. Four out of 188 patients were diagnosed with ileus that resulted in admission to hospital. Two of these required a permanent stoma as a consequence of their ileus. Laxatives were prescribed for 24 out of 154 patients (15.4%) while on clozapine. In total 40.9% of the patients either had laxatives prescribed or had constipation documented in the medical records. Apart from clozapine, other medications known to cause constipation were prescribed to 28 out of 154 patients (18.2%). Constipation is a common problem during clozapine treatment which can progress to full-blown ileus which can be fatal. Clinicians need to monitor signs of constipation during treatment with clozapine and respond to it with lifestyle advice and laxative treatment.European Unio

Risk of diabetes and dyslipidemia during clozapine and other antipsychotic drug treatment of schizophrenia in Iceland.

To access publisher's full text version of this article click on the hyperlink belowType 2 diabetes (T2D) and raised blood lipids are associated with the use of antipsychotics, not least clozapine.To describe the prevalence of high blood glucose levels, T2D, and dyslipidemia, in association with the use of clozapine or other antipsychotics in patients with schizophrenia in Iceland.This study identified 188 patients treated with clozapine and 395 patients never treated with clozapine by searching the electronic health records of Landspitali, the National University Hospital. The comparison group consisted of Icelandic population controls. Data were obtained on blood glucose, HbA1c, and blood lipid levels from these health records.The prevalence of T2D was 14.3% in the clozapine group, where the mean age was 51.2 years, and 13.7% in the never-on-clozapine group, where the mean age was 58.6 years. Males on clozapine were 2.3-times more likely and females 4.4-times more likely to have developed T2D than controls from an age-adjusted Icelandic cohort, while males on other antipsychotics were 1.5-times more likely and females 2.3-times as likely to have T2D than controls. Only one case of ketoacidosis was identified. Triglyceride levels were significantly higher in both treatment groups compared to controls in the age-adjusted Icelandic cohort.Clinicians must take active steps to reduce the risk of T2D and raised triglycerides in patients with schizophrenia. Antipsychotics were associated with a greater risk of T2D developing in females compared to males.European Union National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London Maudsley NHS Foundation Trust King's College Londo