ABSTRACT
Background: The biologic disease-modifying antirheumatic drugs (bDMARDs) are currently incorporated as part of the pharmacotherapy management of inflammatory arthritis (IA). Adherence to bDMARDs is crucial to ensure treatment success in IA. However, most of the recent studies evaluated adherence level in patients using subcutaneous injections of bDMARDs utilized the indirect methods adapted from adherence assessment for oral medication. Aim: This study aimed to develop a questionnaire to assess adherence to the self-injectable subcutaneous bDMARDs. Methods: The development of the Subcutaneous bDMARDs Adherence Score (SCADS) involved evaluation of content validity. Literature reviews provide the basis for domain identification and item formation. Four experts evaluated the instrument by using a four-point ordinal scale with a rubric scoring on relevance, importance, and clarity of each item in measuring the overarching construct. The item-level content validity index (I-CVI) and the scale-level content validity index (S-CVI) were calculated. The factor structure and internal consistency reliability of SCADS were estimated using principal component analysis (PCA) and Cronbach's alpha, respectively. Results: Both S-CVI/UA (universal agreement) and the average item-level content validity index (S-CVI/Ave) (average) for the entire instrument showed excellent criteria with a value of >0.90. Cronbach's alpha coefficient value for SCADS was 0.707 indicating good internal consistency. All items showed corrected item-total correlation coefficients above 0.244. Questionnaire items with a factor loading of 0.30 or above were considered in the final factor solution. The factor analysis resulted in 3-factor solutions, which corresponded to 66.62% of the total variance. Conclusion: The SCADS is a consistent and reliable instrument for evaluating adherence among IA patients using the subcutaneous bDMARDs. It is simple to use, yet comprehensive but still requiring further clinical and international validation.
ABSTRACT
Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder characterized by tumor growth in multiple organs and caused by mutations in either TSC1 or TSC2 genes. Because of their relatively large genomic sizes, absence of hotspots, and common type of mutations, mutation detection in TSC1 and TSC2 genes has been challenging. We devised a combination of multiple ligation-dependent probe amplification (MLPA) and amplicon sequencing (AS) to simplify the detection strategy, yet we come up with reasonably high detection rate. Thirty-four Malaysian patients diagnosed with TSC were referred to Human Genome Center, Universiti Sains Malaysia. We used a combination of MLPA to detect large copy number changes and AS to detect smaller mutations. TSC1 pathogenic or likely pathogenic mutations were found in 6 patients (18%) and TSC2 in 21 patients (62%), whereas 6 patients (18%) show no mutations and 1 patient (2%) showed only TSC2 missense variant with uncertain significance. Six of the mutations are novel. Our detection strategy costs 81% less and require 1 working week less than the conventional strategy. Confirmatory sequencing using Sanger method on a few representative mutations showed agreement with results of the AS. Combination of MLPA and Illumina MiSeq AS provides a simplified strategy and reasonably high detection rate for TSC1/TSC2 mutation, which suggested application of the strategies into clinical molecular diagnostics.
Subject(s)
High-Throughput Nucleotide Sequencing , Mutation , Nucleic Acid Amplification Techniques , Tuberous Sclerosis/diagnosis , Tuberous Sclerosis/genetics , Tumor Suppressor Proteins/genetics , Adolescent , Adult , Child , Child, Preschool , Cross-Sectional Studies , DNA Mutational Analysis/methods , Female , Genotype , High-Throughput Nucleotide Sequencing/economics , High-Throughput Nucleotide Sequencing/methods , High-Throughput Nucleotide Sequencing/standards , Humans , Infant , Male , Middle Aged , Nucleic Acid Amplification Techniques/economics , Nucleic Acid Amplification Techniques/methods , Nucleic Acid Amplification Techniques/standards , Phenotype , Tuberous Sclerosis Complex 1 Protein , Tuberous Sclerosis Complex 2 Protein , Young AdultABSTRACT
We describe a 5-year-old girl who had sudden onset difficulty in walking after 3 days of febrile illness. In the emergency department her creatine kinase level was elevated but urine myoglobin was normal. She was diagnosed as having benign acute childhood myositis. Because of poor oral intake and dehydration, she was admitted to the pediatric ward. The next day she had a petechial rash over the antecubital fossa, and dengue IgM back was positive. She was treated conservatively and recovered uneventfully. Despite dengue fever being endemic in Malaysia, this is the first case report of myositis following dengue infection in Malaysia.
