55 research outputs found

    Development of an evidence-based checklist for the detection of drug related problems in type 2 diabetes

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    Objective To develop an evidence-based checklist to identify potential drug related problems (PDRP) in patients with type 2 diabetes. Setting The evidence based checklist was applied to records of ambulatory type 2 diabetes patients in New South Wales, Australia. Method After comprehensive review of the literature, relevant medication groups and potential drug related problems in type 2 diabetes were identified. All the relevant information was then structured in the form of a checklist. To test the utility of the evidence-based checklist a cross-sectional retrospective study was conducted. The PDRP checklist was applied to the data of 148 patients with established type 2 diabetes and poor glycaemic control. The range and extent of DRPs in this population were identified, which were categorized using the PCNE classification. In addition, the relationship between the total as well as each category of DRPs and several of the patients’ clinical parameters was investigated. Main outcome measure: Number and category of DRPs per patient. Results The PDRP checklist was successfully developed and consisted of six main sections. 682 potential DRPs were identified using the checklist, an average of 4.6 (SD = 1.7) per patient. Metabolic and blood pressure control in the study subjects was generally poor: with a mean HbA1c of 8.7% (SD = 1.5) and mean blood pressure of 139.8 mmHg (SD = 18.1)/81.7 mmHg (SD = 11.1). The majority of DRPs was recorded in the categories ‘therapy failure’ (n = 264) and ‘drug choice problem’ (n = 206). Potentially non-adherent patients had a significantly higher HbA1c than patients who adhered to therapy (HbA1c of 9.4% vs. 8.5%; P = 0.01). Conclusion This is the first tool developed specifically to detect potential DRPs in patients with type 2 diabetes. It was used to identify DRPs in a sample of type 2 diabetes patients and demonstrated the high prevalence of DRPs per patient. The checklist may assist pharmacists and other health care professionals to systematically identify issues in therapy and management of their type 2 diabetes patients and enable earlier intervention to improve metabolic control

    Antipsychotics and Torsadogenic Risk: Signals Emerging from the US FDA Adverse Event Reporting System Database

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    Background: Drug-induced torsades de pointes (TdP) and related clinical entities represent a current regulatory and clinical burden. Objective: As part of the FP7 ARITMO (Arrhythmogenic Potential of Drugs) project, we explored the publicly available US FDA Adverse Event Reporting System (FAERS) database to detect signals of torsadogenicity for antipsychotics (APs). Methods: Four groups of events in decreasing order of drug-attributable risk were identified: (1) TdP, (2) QT-interval abnormalities, (3) ventricular fibrillation/tachycardia, and (4) sudden cardiac death. The reporting odds ratio (ROR) with 95 % confidence interval (CI) was calculated through a cumulative analysis from group 1 to 4. For groups 1+2, ROR was adjusted for age, gender, and concomitant drugs (e.g., antiarrhythmics) and stratified for AZCERT drugs, lists I and II (http://www.azcert.org, as of June 2011). A potential signal of torsadogenicity was defined if a drug met all the following criteria: (a) four or more cases in group 1+2; (b) significant ROR in group 1+2 that persists through the cumulative approach; (c) significant adjusted ROR for group 1+2 in the stratum without AZCERT drugs; (d) not included in AZCERT lists (as of June 2011). Results: Over the 7-year period, 37 APs were reported in 4,794 cases of arrhythmia: 140 (group 1), 883 (group 2), 1,651 (group 3), and 2,120 (group 4). Based on our criteria, the following potential signals of torsadogenicity were found: amisulpride (25 cases; adjusted ROR in the stratum without AZCERT drugs = 43.94, 95 % CI 22.82-84.60), cyamemazine (11; 15.48, 6.87-34.91), and olanzapine (189; 7.74, 6.45-9.30). Conclusions: This pharmacovigilance analysis on the FAERS found 3 potential signals of torsadogenicity for drugs previously unknown for this risk

    Global Biodiversity and Phylogenetic Evaluation of Remipedia (Crustacea)

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    Remipedia is one of the most recently discovered classes of crustaceans, first described in 1981 from anchialine caves in the Bahamas Archipelago. The class is divided into the order Enantiopoda, represented by two fossil species, and Nectiopoda, which contains all known extant remipedes. Since their discovery, the number of nectiopodan species has increased to 24, half of which were described during the last decade. Nectiopoda exhibit a disjunct global distribution pattern, with the highest abundance and diversity in the Caribbean region, and isolated species in the Canary Islands and in Western Australia. Our review of Remipedia provides an overview of their ecological characteristics, including a detailed list of all anchialine marine caves, from which species have been recorded. We discuss alternative hypotheses of the phylogenetic position of Remipedia within Arthropoda, and present first results of an ongoing molecular-phylogenetic analysis that do not support the monophyly of several nectiopodan taxa. We believe that a taxonomic revision of Remipedia is absolutely essential, and that a comprehensive revision should include a reappraisal of the fossil record

    Evaluating the relationship between amyloid-β and α-synuclein phosphorylated at Ser129 in dementia with Lewy bodies and Parkinson’s disease

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    INTRODUCTION: Lewy body and Alzheimer-type pathologies often co-exist. Several studies suggest a synergistic relationship between amyloid-β (Aβ) and α-synuclein (α-syn) accumulation. We have explored the relationship between Aβ accumulation and the phosphorylation of α-syn at serine-129 (pSer129 α-syn), in post-mortem human brain tissue and in SH-SY5Y neuroblastoma cells transfected to overexpress human α-syn. METHODS: We measured levels of Aβ40, Aβ42, α-syn and pSer129 α-syn by sandwich enzyme-linked immunosorbent assay, in soluble and insoluble fractions of midfrontal, cingulate and parahippocampal cortex and thalamus, from cases of Parkinson’s disease (PD) with (PDD; n = 12) and without dementia (PDND; n = 23), dementia with Lewy bodies (DLB; n = 10) and age-matched controls (n = 17). We also examined the relationship of these measurements to cognitive decline, as measured by time-to-dementia and the mini-mental state examination (MMSE) score in the PD patients, and to Braak tangle stage. RESULTS: In most brain regions, the concentration of insoluble pSer129 α-syn correlated positively, and soluble pSer129 α-syn negatively, with the levels of soluble and insoluble Aβ. Insoluble pSer129 α-syn also correlated positively with Braak stage. In most regions, the levels of insoluble and soluble Aβ and the proportion of insoluble α-syn that was phosphorylated at Ser129 were significantly higher in the PD and DLB groups than the controls, and higher in the PDD and DLB groups than the PDND brains. In PD, the MMSE score correlated negatively with the level of insoluble pSer129 α-syn. Exposure of SH-SY5Y cells to aggregated Aβ42 significantly increased the proportion of α-syn that was phosphorylated at Ser129 (aggregated Aβ40 exposure had a smaller, non-significant effect). CONCLUSIONS: Together, these data show that the concentration of pSer129 α-syn in brain tissue homogenates is directly related to the level of Aβ and Braak tangle stage, and predicts cognitive status in Lewy body diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13195-014-0077-y) contains supplementary material, which is available to authorized users
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