International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Automated classification for HEp-2 cells based on linear local distance coding framework

The occurrence of antinuclear antibodies (ANAs) in patient serum has significant relation to some specific autoimmune diseases. Indirect immunofluorescence (IIF) on human epithelial type 2 (HEp-2) cells is the recommended methodology for detecting ANAs in clinic practice. However, the currently practiced manual detection system suffers from serious problems due to subjective evaluation. In this paper, we present an automated system for HEp-2 cells classification. We adopt a bag-of-words (BoW) framework which has shown impressive performance in image classification tasks because it can obtain discriminative and effective image representation. However, the information loss is inevitable in the coding process. Therefore, we propose a linear local distance coding (LLDC) method to capture more discriminative information. Our LLDC method transforms original local feature to more discriminative local distance vector by searching for local nearest few neighbors of the local feature in the class-specific manifolds. The obtained local distance vector is further encoded and pooled together to get salient image representation. The LLDC method is combined with the traditional coding methods to achieve higher classification accuracy. Incorporated with a linear support vector machine classifier, our proposed method demonstrated its effectiveness on two public datasets, namely, the International Conference on Pattern Recognition (ICPR) 2012 dataset and the International Conference on Image Processing (ICIP) 2013 training dataset. Experimental results show that the LLDC framework can achieve superior performance to the state-of-the-art coding methods for staining pattern classification of HEp-2 cells.Published versio

Image1_TPMT and NUDT15 testing for thiopurine therapy: A major tertiary hospital experience and lessons learned.TIF

Variants in thiopurine methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15) are associated with an accumulation of cytotoxic metabolites leading to increased risk of drug-related toxicity with standard doses of thiopurine drugs. We established TPMT and NUDT15 genetic testing for clinical use and evaluated the utilization, service outcomes and potential value of multi-gene PGx testing for 210 patients that underwent pharmacogenetics (PGx) testing for thiopurine therapy with the aim to optimize service delivery for future prescribing. The test was most commonly ordered for Gastroenterology (40.0%) and Neurology (31.4%), with an average turnaround time of 2 days. Following testing, 24.3% patients were identified as intermediate or poor metabolizers, resulting in 51 recommendations for a drug or dose change in thiopurine therapy, which were implemented in 28 (54.9%) patients. In the remaining patients, 14 were not adjusted and 9 had no data available. Focusing on drug gene interactions available for testing in our laboratory, multi-gene PGx results would present opportunities for treatment optimization for at least 33.8% of these patients who were on 2 or more concurrent medications with actionable PGx guidance. However, the use of PGx panel testing in clinical practice will require the development of guidelines and education as revealed by a survey with the test providers. The evaluation demonstrated successful implementation of single gene PGx testing and this experience guides the transition to a pre-emptive multi-gene testing approach that provides the opportunity to improve clinical care.</p

Clinical Study Methotrexate-Associated Nonalcoholic Fatty Liver Disease with Transaminitis in Rheumatoid Arthritis

Background. The aim of this study was to determine the risk factors of MTX-associated nonalcoholic fatty liver disease (NAFLD) with transaminitis in a cohort of rheumatoid arthritis (RA) patients from Singapore. Methods. Patients who developed ultrasound proven NAFLD with transaminitis while on MTX therapy were identified. The demographic and clinical characteristics of the above patients (cases) were compiled and compared with age-and gender-matched controls who were RA patients on long standing MTX therapy without any episode of transaminitis. Results. Among the 978 patients who had received MTX, the prevalence of MTXassociated NAFLD was 4.7% (46 patients). Compared to the controls, the cases had significantly higher mean cumulative dose of MTX (4.03 ± 2.25 g versus 10.04 ± 9.94 g, ≤ 0.05), weekly dose of MTX (11.3 ± 4.8 mg versus 13.1 ± 4.4 mg weekly, = 0.033), and fasting blood glucose ( = 0.029). Following multivariate regression analysis, only cumulative dose of MTX remained significant ( = 0.015). Among the cases, the cumulative dose of MTX was found to have a significant positive correlation with the alanine transaminase (ALT) level ( &lt; 0.05, standardised beta coefficient 0.512). Conclusion. The cumulative dose of MTX was the only independent predictor of MTX-associated NAFLD with transaminitis

Table1_TPMT and NUDT15 testing for thiopurine therapy: A major tertiary hospital experience and lessons learned.DOCX

Variants in thiopurine methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15) are associated with an accumulation of cytotoxic metabolites leading to increased risk of drug-related toxicity with standard doses of thiopurine drugs. We established TPMT and NUDT15 genetic testing for clinical use and evaluated the utilization, service outcomes and potential value of multi-gene PGx testing for 210 patients that underwent pharmacogenetics (PGx) testing for thiopurine therapy with the aim to optimize service delivery for future prescribing. The test was most commonly ordered for Gastroenterology (40.0%) and Neurology (31.4%), with an average turnaround time of 2 days. Following testing, 24.3% patients were identified as intermediate or poor metabolizers, resulting in 51 recommendations for a drug or dose change in thiopurine therapy, which were implemented in 28 (54.9%) patients. In the remaining patients, 14 were not adjusted and 9 had no data available. Focusing on drug gene interactions available for testing in our laboratory, multi-gene PGx results would present opportunities for treatment optimization for at least 33.8% of these patients who were on 2 or more concurrent medications with actionable PGx guidance. However, the use of PGx panel testing in clinical practice will require the development of guidelines and education as revealed by a survey with the test providers. The evaluation demonstrated successful implementation of single gene PGx testing and this experience guides the transition to a pre-emptive multi-gene testing approach that provides the opportunity to improve clinical care.</p

Image2_TPMT and NUDT15 testing for thiopurine therapy: A major tertiary hospital experience and lessons learned.TIF

Variants in thiopurine methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15) are associated with an accumulation of cytotoxic metabolites leading to increased risk of drug-related toxicity with standard doses of thiopurine drugs. We established TPMT and NUDT15 genetic testing for clinical use and evaluated the utilization, service outcomes and potential value of multi-gene PGx testing for 210 patients that underwent pharmacogenetics (PGx) testing for thiopurine therapy with the aim to optimize service delivery for future prescribing. The test was most commonly ordered for Gastroenterology (40.0%) and Neurology (31.4%), with an average turnaround time of 2 days. Following testing, 24.3% patients were identified as intermediate or poor metabolizers, resulting in 51 recommendations for a drug or dose change in thiopurine therapy, which were implemented in 28 (54.9%) patients. In the remaining patients, 14 were not adjusted and 9 had no data available. Focusing on drug gene interactions available for testing in our laboratory, multi-gene PGx results would present opportunities for treatment optimization for at least 33.8% of these patients who were on 2 or more concurrent medications with actionable PGx guidance. However, the use of PGx panel testing in clinical practice will require the development of guidelines and education as revealed by a survey with the test providers. The evaluation demonstrated successful implementation of single gene PGx testing and this experience guides the transition to a pre-emptive multi-gene testing approach that provides the opportunity to improve clinical care.</p

Methotrexate-Associated Nonalcoholic Fatty Liver Disease with Transaminitis in Rheumatoid Arthritis

Background. The aim of this study was to determine the risk factors of MTX-associated nonalcoholic fatty liver disease (NAFLD) with transaminitis in a cohort of rheumatoid arthritis (RA) patients from Singapore. Methods. Patients who developed ultrasound proven NAFLD with transaminitis while on MTX therapy were identified. The demographic and clinical characteristics of the above patients (cases) were compiled and compared with age- and gender-matched controls who were RA patients on long standing MTX therapy without any episode of transaminitis. Results. Among the 978 patients who had received MTX, the prevalence of MTX-associated NAFLD was 4.7% (46 patients). Compared to the controls, the cases had significantly higher mean cumulative dose of MTX (4.03 ± 2.25 g versus 10.04 ± 9.94 g, P≤0.05), weekly dose of MTX (11.3 ± 4.8 mg versus 13.1 ± 4.4 mg weekly, P=0.033), and fasting blood glucose (P=0.029). Following multivariate regression analysis, only cumulative dose of MTX remained significant (P=0.015). Among the cases, the cumulative dose of MTX was found to have a significant positive correlation with the alanine transaminase (ALT) level (P<0.05, standardised beta coefficient 0.512). Conclusion. The cumulative dose of MTX was the only independent predictor of MTX-associated NAFLD with transaminitis

Tensor factorization for missing data imputation in medical questionnaires

10.1109/ICASSP.2012.6288327ICASSP, IEEE International Conference on Acoustics, Speech and Signal Processing - Proceedings2109-2112IPRO

Analysis of Genetic Variation in CYP450 Genes for Clinical Implementation

<div><p>Background</p><p>Genetic determinants of drug response remain stable throughout life and offer great promise to patient-tailored drug therapy. The adoption of pharmacogenetic (PGx) testing in patient care requires accurate, cost effective and rapid genotyping with clear guidance on the use of the results. Hence, we evaluated a 32 SNPs panel for implementing PGx testing in clinical laboratories.</p><p>Methods</p><p>We designed a 32-SNP panel for PGx testing in clinical laboratories. The variants were selected using the clinical annotations of the Pharmacogenomics Knowledgebase (PharmGKB) and include polymorphisms of CYP2C9, CYP2C19, CYP2D6, CYP3A5 and VKORC1 genes. The CYP2D6 gene allele quantification was determined simultaneously with TaqMan copy number assays targeting intron 2 and exon 9 regions. The genotyping results showed high call rate accuracy according to concordance with genotypes identified by independent analyses on Sequenome massarray and droplet digital PCR. Furthermore, 506 genomic samples across three major ethnic groups of Singapore (Malay, Indian and Chinese) were analysed on our workflow.</p><p>Results</p><p>We found that 98% of our study subjects carry one or more CPIC actionable variants. The major alleles detected include CYP2C9*3, CYP2C19*2, CYP2D6*10, CYP2D6*36, CYP2D6*41, CYP3A5*3 and VKORC1*2. These translate into a high percentage of intermediate (IM) and poor metabolizer (PM) phenotypes for these genes in our population.</p><p>Conclusion</p><p>Genotyping may be useful to identify patients who are prone to drug toxicity with standard doses of drug therapy in our population. The simplicity and robustness of this PGx panel is highly suitable for use in a clinical laboratory.</p></div