Beyza Doğanay Erdoğan

Minimal Clinically Important Difference as Applied in Rheumatology: An OMERACT Rasch Working Group Systematic Review and Critique

Objective. We aimed to evaluate how minimal (clinically) important differences (MCID/MID) were calculated in rheumatology in the past 2 decades and demonstrate how the calculation is compromised by the lack of interval scaling. Methods. We conducted a systematic literature review on articles reporting MCID calculation in osteoarthritis (OA) and rheumatoid arthritis (RA) from January 1, 1989, to May 9, 2014. We evaluated the methods of MCID calculation and recorded the ranges of MCID for common patient-reported outcome measures (PROM). Taking data from the Health Assessment Questionnaire (HAQ), we showed the effects of performing mathematical calculations on ordinal data. Results. A total of 330 abstracts were reviewed and 123 articles chosen for full text review. Thirty-six (19 OA, 16 RA and 1 OA-RA) articles were included in the final evaluation. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was the most frequently reported PROM with relevant calculations in OA, and the HAQ in RA. Sixteen articles used anchor-based methods alone for calculation of MCID, and 1 article used distribution-based methods alone. Nineteen articles used both anchor and distribution-based methods. Only 1 article calculated MCID using an interval scale. Wide ranges in MCID for the WOMAC in OA and HAQ in RA were noted. Ordinal-based derivations of MCID are shown to understate true change at the margins, and overstate change in the mid-range of a scale. Conclusion. The anchor-based method is commonly used in the calculation of MCID. However, the lack of interval scaling is shown to compromise validity of MCID calculation.

Nonalcoholic fatty liver disease is associated with significant coronary artery disease in type 2 diabetic patients: A computed tomography angiography study 在2型糖尿病患者中非酒精性脂肪性肝病与严重冠心病有关：一项计算机断层扫描血管造影研究

To investigate whether nonalcoholic fatty liver disease (NAFLD) is associated with coronary artery disease (CAD) in type 2 diabetic patients, who underwent coronary computed tomography angiography (CTA).

Optimization of gene expression microarray protocol for formalin-fixed paraffin-embedded tissues.

Formalin-fixed paraffin-embedded (FFPE) tissue is a widely available clinical specimen for retrospective studies. The possibility of long-term clinical follow-up of FFPE samples makes them a valuable source to evaluate links between molecular and clinical information. Working with FFPE samples in the molecular research area, especially using high-throughput molecular techniques such as microarray gene expression profiling, has come into prominence. Because of the harmful effects of formalin fixation process such as degradation of nucleic acids, cross-linking with proteins, and chemical modifications on DNA and RNA, there are some limitations in gene expression profiling studies using FFPE samples. To date many studies have been conducted to evaluate gene expression profiling using microarrays (Thomas et al., Thomas et al. (2013) [1]; Scicchitano et al., Scicchitano et al. (2006) [2]; Frank et al., Frank et al. (2007) [3]; Fedorowicz et al., Fedorowicz et al. (2009) [4]). However, there is still no generally accepted, efficient and standardized procedure for microarray analysis of FFPE samples. This paper describes the microarray data presented in our recently accepted to be published article showing a standard protocol from deparaffinization of FFPE tissue sections and RNA extraction to microarray gene expression analysis. Here we represent our data in detail, deposited in the gene expression omnibus (GEO) database with the accession number GSE73883. Four combinations of two different cRNA/cDNA preparation and labeling protocols with two different array platforms (Affymetrix Human Genome U133 Plus 2.0 and U133_X3P) were evaluated to determine which combination gives the best percentage of present call. The study presents a dataset for comparative analysis which has a potential in terms of providing a robust protocol for gene expression profiling with FFPE tissue samples.

Familial Mediterranean fever in siblings.

Objective. Genetic and environmental factors have been implicated in disease severity and development of amyloidosis in familial Mediterranean fever (FMF). We investigated similarities in clinical characteristics, disease severity, and treatment response within siblings with FMF. Methods. The study group consisted of 2 or more siblings who were followed in our center with the diagnosis of FMF. Siblings were evaluated for demographic data, clinical and laboratory disease features, genetic analysis of MEFV mutations, and disease severity score. The intraclass correlation coefficient (ICC), which can be interpreted as the expected correlation between 2 siblings, was used to reflect within-family similarity. Results. The study included 67 pediatric patients from 31 different families. When we investigated the similarity of siblings after adjusting for genetic effects, we found very low ICC with p > 0.05 in the majority of clinical features, disease severity, and colchicine dosages. However, age at disease onset, age at onset of therapy, attack-free acute-phase reactant levels, and presence of amyloidosis were found to be similar within siblings (relatively high ICC with p < 0.05). Conclusion. Siblings with FMF had different clinical findings and disease severity. They had similar amyloidogenic potential, proven by both similar presence of amyloid and increased levels of acute-phase reactants between attacks. Our findings strongly support that genetic factors may be more dominant in the development of amyloidosis.

Integrating patient reported outcome measures and computerized adaptive test estimates on the same common metric: an example from the assessment of activities in rheumatoid arthritis

This study aimed to explore the potential of an inclusive and fully integrated measurement system for the Activities component of the International Classification of Functioning, Disability and Health (ICF), incorporating four classical scales, including the Health Assessment Questionnaire (HAQ), and a Computerized Adaptive Testing (CAT).

Foetal biometry in polyhydramnios: Does femur length fall behind?

We aimed to identify the growth patterns in polyhydramnios, and therefore evaluated 108 singleton pregnancies complicated with polyhydramnios according to the changes in biparietal diameter (BPD), abdominal circumference (AC) and femur length (FL) percentiles. The pregnancy outcomes according to the growth features were analysed. In the study population, BPD and AC percentiles exhibited a significant increase (p = 0.023 and 0.05, respectively), although FL percentiles showed a significant decrease (p = 0.006) according to the changes in third trimester relative to second trimester. In the overgrown group (n = 52), the FL/BPD ratio was lower (p < 0.001), with more foetuses with FL/BPD ratios below 71 (p = 0.05). In conclusion, there was a significant increase in BPD and AC percentiles and a decrease in FL percentiles in third trimester relative to second trimester in foetuses with polyhydramnios. However, we observed a shorter FL and a lower FL/BPD ratio without associated skeletal dysplasia in overgrown foetuses.

The Interaction of Nepafenac and Prostaglandin Analogs in Primary Open-angle Glaucoma Patients.

Purpose:To investigate the effect of nepafenac on intraocular pressure (IOP) in primary open-angle glaucoma (POAG) patients treated with prostaglandin (PG) analogs. Materials and Methods:This prospective clinical study included 35 patients who had been receiving latanoprost (n=12), travoprost (n=12), or bimatoprost (n=11) for POAG. Nepafenac 0.1% and placebo drops were administered to the right and left eyes of patients, respectively, 3 times a day for 7 days. IOP measurements were taken at 9:00 AM, 12:00 PM, and 4:00 PM at baseline and all consecutive visits. The visits were scheduled on days 1 and 7 during treatment and 1 and 7 days after discontinuation of the treatment. Results:The mean age of the patients was 60.28±7.51 years (range, 48 to 75 y). The baseline IOP was similar in the nepafenac and placebo groups (15.33±1.45 vs. 15.41±1.41, respectively, P>0.05). The decrease in the mean IOP was significant in the nepafenac group compared with the placebo group throughout the treatment period (P<0.001). After the discontinuation of nepafenac treatment, the mean IOP became similar with the placebo group from the first day (P>0.05). The change in mean IOP was not significant between the PG subgroups during treatment and discontinuation periods (P=0.712). Conclusions:Nepafenac potentiates the IOP-lowering effects of 3 different PG analogs in POAG patients.

Nonalcoholic fatty liver disease is associated with significant coronary artery disease in type 2 diabetic patients: A computed tomography angiography study 在2型糖尿病患者中非酒精性脂肪性肝病与严重冠心病有关：一项计算机断层扫描血管造影研究: NAFLD is associated with significant CAD

To investigate whether nonalcoholic fatty liver disease (NAFLD) is associated with coronary artery disease (CAD) in type 2 diabetic patients, who underwent coronary computed tomography angiography (CTA).

Genome projects 5W1H: what, where, when, why, how and in which population?

Genome projects aim to decode an organism’s complete set of deoxyribonucleic acid (DNA), which can be described as the living code of organism. The idea of the Human Genome Project (HGP) was conceived in the early 1980s. The project was started at 1990 and finished at 2003. The sequencing of the whole human genome derived from the DNA of several anonymous volunteers, costed 3.8 billion dollars. In order to annotate the genome data, the “topography of the genome” and the anatomy of the genes should have been revealed. For this purpose, genome projects of several model organisms was carried out in parallel with HGP with the aim to identify basic structural components, organizational structure and evolutionarily development of the genome. With the advent of microarray technology in the early 2000s, high-throughput screening of Single Nucleotide Polymorphisms (SNPs) and Copy Number Variations (CNVs) became feasible. After the completion of HGP in 13 years, James D. Watson’s genome was sequenced with 1 million dollar budget in just 2 months using next generation sequencing technology. Today a human