University of South Australia

About: University of South Australia is a education organization based out in Adelaide, South Australia, Australia. It is known for research contribution in the topics: Population & Poison control. The organization has 10086 authors who have published 32587 publications receiving 913683 citations. The organization is also known as: The University of South Australia & UniSA.

Mutations in the mammalian target of rapamycin pathway regulators NPRL2 and NPRL3 cause focal epilepsy

Abstract: Objective Focal epilepsies are the most common form observed and have not generally been considered to be genetic in origin. Recently, we identified mutations in DEPDC5 as a cause of familial focal epilepsy. In this study, we investigated whether mutations in the mammalian target of rapamycin (mTOR) regulators, NPRL2 and NPRL3, also contribute to cases of focal epilepsy. Methods We used targeted capture and next-generation sequencing to analyze 404 unrelated probands with focal epilepsy. We performed exome sequencing on two families with multiple members affected with focal epilepsy and linkage analysis on one of these. Results In our cohort of 404 unrelated focal epilepsy patients, we identified five mutations in NPRL2 and five in NPRL3. Exome sequencing analysis of two families with focal epilepsy identified NPRL2 and NPRL3 as the top candidate-causative genes. Some patients had focal epilepsy associated with brain malformations. We also identified 18 new mutations in DEPDC5. Interpretation We have identified NPRL2 and NPRL3 as two new focal epilepsy genes that also play a role in the mTOR-signaling pathway. Our findings show that mutations in GATOR1 complex genes are the most significant cause of familial focal epilepsy identified to date, including cases with brain malformations. It is possible that deregulation of cellular growth control plays a more important role in epilepsy than is currently recognized.

Pharmacist-led medication review in community settings: An overview of systematic reviews.

Abstract: Background Pharmacist-led medication review is a collaborative service which aims to identify and resolve medication-related problems. Objective To critically evaluate published systematic reviews relevant to pharmacist-led medication reviews in community settings. Methods MEDLINE, EMBASE, International Pharmaceutical Abstracts (IPA), Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane Database of Systematic Reviews (CDSR) were searched from 1995 to December 2015. Systematic reviews of all study designs and outcomes were considered. Methodological quality was assessed using the 11-item Assessment of Multiple Systematic Reviews (AMSTAR) tool. Systematic reviews of moderate or high quality (AMSTAR ≥ 4) were included in the data synthesis. Data extraction and quality assessment was performed independently by two investigators. Results Of the 35 relevant systematic reviews identified, 24 were of moderate and seven of high quality and were included in the data synthesis. The largest overall numbers of unique primary research studies with favorable outcomes were for diabetes control (78% of studies reporting the outcome), blood pressure control (74%), cholesterol (63%), medication adherence (56%) and medication management (47%). Significant reductions in medication and/or healthcare costs were reported in 35% of primary research studies. Meta-analysis was performed in 12 systematic reviews. Results from the meta-analyses suggested positive impacts on glycosylated hemoglobin, blood pressure, cholesterol, and number and appropriateness of medications. Conflicting findings were reported in relation to hospitalization. No meta-analyses reported reduced mortality. Conclusion Moderate and high quality systematic reviews support the value of pharmacist-led medication review for a range of clinical outcomes. Further research including more rigorous cost analyses are required to determine the impact of pharmacist-led medication reviews on humanistic and economic outcomes. Future systematic reviews should consider the inclusion of both qualitative and quantitative studies to comprehensively evaluate medication review.