111 research outputs found
BICEPP: an example-based statistical text mining method for predicting the binary characteristics of drugs
<p>Abstract</p> <p>Background</p> <p>The identification of drug characteristics is a clinically important task, but it requires much expert knowledge and consumes substantial resources. We have developed a statistical text-mining approach (BInary Characteristics Extractor and biomedical Properties Predictor: BICEPP) to help experts screen drugs that may have important clinical characteristics of interest.</p> <p>Results</p> <p>BICEPP first retrieves MEDLINE abstracts containing drug names, then selects tokens that best predict the list of drugs which represents the characteristic of interest. Machine learning is then used to classify drugs using a document frequency-based measure. Evaluation experiments were performed to validate BICEPP's performance on 484 characteristics of 857 drugs, identified from the Australian Medicines Handbook (AMH) and the PharmacoKinetic Interaction Screening (PKIS) database. Stratified cross-validations revealed that BICEPP was able to classify drugs into all 20 major therapeutic classes (100%) and 157 (of 197) minor drug classes (80%) with areas under the receiver operating characteristic curve (AUC) > 0.80. Similarly, AUC > 0.80 could be obtained in the classification of 173 (of 238) adverse events (73%), up to 12 (of 15) groups of clinically significant cytochrome P450 enzyme (CYP) inducers or inhibitors (80%), and up to 11 (of 14) groups of narrow therapeutic index drugs (79%). Interestingly, it was observed that the keywords used to describe a drug characteristic were not necessarily the most predictive ones for the classification task.</p> <p>Conclusions</p> <p>BICEPP has sufficient classification power to automatically distinguish a wide range of clinical properties of drugs. This may be used in pharmacovigilance applications to assist with rapid screening of large drug databases to identify important characteristics for further evaluation.</p
Extent of Height Variability Explained by Known Height-Associated Genetic Variants in an Isolated Population of the Adriatic Coast of Croatia
BACKGROUND: Human height is a classical example of a polygenic quantitative trait. Recent large-scale genome-wide association studies (GWAS) have identified more than 200 height-associated loci, though these variants explain only 2âŒ10% of overall variability of normal height. The objective of this study was to investigate the variance explained by these loci in a relatively isolated population of European descent with limited admixture and homogeneous genetic background from the Adriatic coast of Croatia. METHODOLOGY/PRINCIPAL FINDINGS: In a sample of 1304 individuals from the island population of Hvar, Croatia, we performed genome-wide SNP typing and assessed the variance explained by genetic scores constructed from different panels of height-associated SNPs extracted from five published studies. The combined information of the 180 SNPs reported by Lango Allen el al. explained 7.94% of phenotypic variation in our sample. Genetic scores based on 20~50 SNPs reported by the remaining individual GWA studies explained 3~5% of height variance. These percentages of variance explained were within ranges comparable to the original studies and heterogeneity tests did not detect significant differences in effect size estimates between our study and the original reports, if the estimates were obtained from populations of European descent. CONCLUSIONS/SIGNIFICANCE: We have evaluated the portability of height-associated loci and the overall fitting of estimated effect sizes reported in large cohorts to an isolated population. We found proportions of explained height variability were comparable to multiple reference GWAS in cohorts of European descent. These results indicate similar genetic architecture and comparable effect sizes of height loci among populations of European descent
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How do pharmacists in English general practices identify their impact? An exploratory qualitative study of measurement problems
Background: In England, there is an ongoing national pilot to expand pharmacistsâ presence in general practice. Evaluation of the pilot includes numerical and survey-based Key Performance Indicators (KPIs) and requires pharmacists to electronically record their activities, possibly by using activity codes. At the time of the study (2016), no national evaluation of pharmacistsâ impact in this environment had been formally announced. The aim of this qualitative study was to identify problems that English pharmacists face when
measuring and recording their impact in general practice.
Methods: All pharmacists, general practitioners (GPs) and practice managers working
across two West London pilot sites were invited, via e-mail, to participate in a focus group study. Appropriately trained facilitators conducted two audio-recorded, semi-structured
focus groups, each lasting approximately one hour, to explore experiences and
perceptions associated with the KPIs. Audio-recordings were transcribed verbatim and
the data analysed thematically. Results: In total, 13 pharmacists, one GP and one practice manager took part in the study. Four major themes were discerned: inappropriateness of the numerical national KPIs (âwhether or not we actually have positive impact on KPIs is beyond our controlâ); depth and breadth of pharmacistsâ activity (âwe see a huge plethora of different patients and go through this holistic approach - everything is looked atâ); awareness of practice based pharmacistsâ roles (âI think the really important [thing] is that everyone knows what pharmacists in general practice are doingâ); and central evaluation versus local initiatives (âthe KPIs will be measured by National Health Service England regardless of what we thinkâ versus âwhat I think is more pertinent, are there some local things weâre going to measure?â). Conclusions: Measures that will effectively capture pharmacistsâ impact in general practice should be developed, along with a set of codes reflecting the whole spectrum of pharmacistsâ activities. Our study also points out the significance of a transparent, robust national evaluation, including exploring the needs/expectations of practice staff and patients regarding pharmacistsâ presence in general practice
Genome-wide association trans-ethnic meta-analyses identifies novel associations regulating coagulation Factor VIII and von Willebrand Factor plasma levels
BACKGROUND: Factor VIII (FVIII) and its carrier protein von Willebrand factor (VWF) are associated with risk of arterial and venous thrombosis and with hemorrhagic disorders. We aimed to identify and functionally test novel genetic associations regulating plasma FVIII and VWF. METHODS: We meta-analyzed genome-wide association results from 46 354 individuals of European, African, East Asian, and Hispanic ancestry. All studies performed linear regression analysis using an additive genetic model and associated â35 million imputed variants with natural log-transformed phenotype levels. In vitro gene silencing in cultured endothelial cells was performed for candidate genes to provide additional evidence on association and function. Two-sample Mendelian randomization analyses were applied to test the causal role of FVIII and VWF plasma levels on the risk of arterial and venous thrombotic events. RESULTS: We identified 13 novel genome-wide significant ( Pâ€2.5Ă10-8) associations, 7 with FVIII levels ( FCHO2/TMEM171/TNPO1, HLA, SOX17/RP1, LINC00583/NFIB, RAB5C-KAT2A, RPL3/TAB1/SYNGR1, and ARSA) and 11 with VWF levels ( PDHB/PXK/KCTD6, SLC39A8, FCHO2/TMEM171/TNPO1, HLA, GIMAP7/GIMAP4, OR13C5/NIPSNAP, DAB2IP, C2CD4B, RAB5C-KAT2A, TAB1/SYNGR1, and ARSA), beyond 10 previously reported associations with these phenotypes. Functional validation provided further evidence of association for all loci on VWF except ARSA and DAB2IP. Mendelian randomization suggested causal effects of plasma FVIII activity levels on venous thrombosis and coronary artery disease risk and plasma VWF levels on ischemic stroke risk. CONCLUSIONS: The meta-analysis identified 13 novel genetic loci regulating FVIII and VWF plasma levels, 10 of which we validated functionally. We provide some evidence for a causal role of these proteins in thrombotic events
Meta-analysis of exome array data identifies six novel genetic loci for lung function
Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease.
Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals.
Results: We identified significant (P<2·8x10-7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs (SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU.
Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease
Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain
Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of ch
Publisher Correction: Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.
Correction to: Nature Communications https://doi.org/10.1038/s41467-020-19366-9, published online 5 January 2021.
The original version of this Article contained an error in Fig. 2, in which panels a and b were inadvertently swapped.
This has now been corrected in the PDF and HTML versions of the Article
Publisher Correction: Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.
Correction to: Nature Communications https://doi.org/10.1038/s41467-020-19366-9, published online 5 January 2021.
The original version of this Article contained an error in Fig. 2, in which panels a and b were inadvertently swapped.
This has now been corrected in the PDF and HTML versions of the Article
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