Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109971/1/cptclpt20132.pd

Reliability testing of tendon disease using two different scanning methods in patients with rheumatoid arthritis

Objective. To assess the intra- and interobserver reliability of musculoskeletal ultrasonography (US) in detecting inflammatory and destructive tendon abnormalities in patients with RA using two different scanning methods.Methods. Thirteen observers examined nine patients with RA and one healthy individual in two rounds independently and blindly of each other. Each round consisted of two consecutive examinations, an anatomy-based examination and a free examination according to personal preferences. The following tendons were evaluated: wrist extensor compartments 2, 4 and 6, finger flexor tendons 3 and 4 at MCP level, tibialis posterior tendon and both peronei tendons. Overall, positive and negative agreements and \u3ba-values for greyscale (GS) tenosynovitis, peritendinous power Doppler (PPD) signal, intratendinous power Doppler (IPD) signal and GS tendon damage were calculated.Results. Intraobserver \u3ba-value ranges were 0.53-0.55 (P < 0.0005) for GS tenosynovitis, 0.61-0.64 (P < 0.0005) for PPD signal, 0.65-0.66 (P < 0.0005) for IPD signal and 0.44-0.53 (P < 0.0005) for GS tendon damage. For interobserver reliability, substantial overall agreement ranged from 80 to 89% for GS tenosynovitis, 97 to 100% for PPD signal, 97 to 100% for IPD signal and 97 to 100% for GS tendon damage. Results were independent of scanning technique.Conclusion. Intraobserver reliability for tenosynovitis and tendon damage varied from moderate for GS to good for PD. Overall interobserver reliability for tenosynovitis and tendon damage was excellent both for GS and PD. This qualitative scoring system may serve as the first step to a semi-quantitative score for tendon pathology. \ua9 The Author 2012. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved

Social capital and HIV/AIDS in the United States: Knowledge, gaps, and future directions

Purpose Social capital is a well-established predictor of several behavioral health outcomes. However, we know less about the relationship with prevention, transmission, and treatment of HIV/AIDS outcomes in the United States (US). Methods In 2017, we conducted a scoping review of empirical studies investigating the relationships between social capital and HIV/AIDS in the US by searching PubMed, Embase, PsycINFO, Web of Science, and Sociological Abstracts with no restriction on publication date, for articles in English language. Sample search terms included: HIV infections OR HIV OR AIDS OR acquired immunodeficiency syndrome OR human immunodeficiency virus AND social capital OR social control, informal OR social participation OR social cohesion OR generalized trust OR social trust OR collective efficacy OR community mob* OR civic participation. Results We identified 1581 unique manuscripts and reviewed 13 based on eligibility criteria. The earliest eligible study was published in 2003. More than half (n=7/13) focused on HIV or AIDS diagnosis, then prescribing ART and/or adherence (n=5/13), then linkage and or engagement in HIV care (n=4/13). Fifty eight percent (58%) documented a protective association between at least one social capital measure and an HIV/AIDS outcome. Seven studies used validated social capital scales, however there was substantial variation in conceptual/operational definitions and measures used. Most studies were based on samples from the Northeast. Three studies directly focused on or stratified analyses among subgroups or key populations. Studies were cross-sectional, so causal inference is unknown. Conclusion Our review suggests that social capital may be an important determinant of HIV/AIDS prevention, transmission, and treatment outcomes. We recommend future research assess these associations using qualitative and mixed-methods approaches, longitudinally, examine differences across subgroups and geographic region, include a wider range of social capital constructs, and examine indicators beyond HIV diagnosis, as well as how mechanisms like stigma link social capital to HIV/AIDS

Preliminary definitions for the sonographic features of synovitis in children

Objectives Musculoskeletal ultrasonography (US) has the potential to be an important tool in the assessment of disease activity in childhood arthritides. To assess pathology, clear definitions for synovitis need to be developed first. The aim of this study was to develop and validate these definitions through an international consensus process. Methods The decision on which US techniques to use, the components to be included in the definitions as well as the final wording were developed by 31 ultrasound experts in a consensus process. A Likert scale of 1-5 with 1 indicating complete disagreement and 5 complete agreement was used. A minimum of 80% of the experts scoring 4 or 5 was required for final approval. The definitions were then validated on 120 standardized US images of the wrist, MCP and tibiotalar joints displaying various degrees of synovitis at various ages. Results B-Mode and Doppler should be used for assessing synovitis in children. A US definition of the various components (i.e. synovial hypertrophy, effusion and Doppler signal within the synovium) was developed. The definition was validated on still images with a median of 89% (range 80-100) of participants scoring it as 4 or 5 on a Likert scale. Conclusions US definitions of synovitis and its elementary components covering the entire pediatric age range were successfully developed through a Delphi process and validated in a web-based still images exercise. These results provide the basis for the standardized US assessment of synovitis in clinical practice and research

A Method to Exchange Recombinant Differentially Phosphorylated Rhodamine-Labeled Cardiac RLC into Permeabilized Cardiac Trabeculae

Cyclosporine, everolimus, and tacrolimus are the cornerstone of immunosuppressive therapy in renal transplantation. These drugs are characterized by narrow therapeutic windows, highly variable pharmacokinetics (PK), and metabolism by CYP3A enzymes. Recently, the decreased activity allele, CYP3A4*22, was described as a potential predictive marker for CYP3A4 activity. This study investigated the effect of CYP3A4*22, CYP3A5*3, and CYP3A combined genotypes on cyclosporine, everolimus, and tacrolimus PK in renal transplant patients. CYP3A4*22 carriers showed a significant lower clearance for cyclosporine (−15%), and a trend was observed for everolimus (−7%) and tacrolimus (−16%). Patients carrying at least one CYP3A5*1 allele had 1.5-fold higher tacrolimus clearance compared with noncarriers; however, CYP3A5*3 appeared to be nonpredictive for everolimus and cyclosporine. CYP3A combined genotype did not significantly improve prediction of clearance compared with CYP3A5*3 or CYP3A4*22 alone. These data suggest that dose individualization of cyclosporine, everolimus, or tacrolimus therapy based on CYP3A4*22 is not indicated

Meta-analysis on the association of VEGFR1 genetic variants with sunitinib outcome in metastatic renal cell carcinoma patients

VEGFR1 rs9582036 and rs9554320 were previously reported the association with sunitinib progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC). Hereafter, the association of both single nucleotide polymorphisms (SNPs) with PFS/OS was confirmed in two independent mRCC cohorts. The aim of the current study was to validate the associations of both SNPs with sunitinib outcome in three independent well-characterized cohorts (SUTOX, CCF and SOGUG) including 286 sunitinib-treated mRCC patients, as well as to perform a meta-analysis of current and published data combined. We found that rs9582036 and rs9554320 showed a significant association with sunitinib PFS in the CCF cohort (HR: 0.254, 95%CI: 0.092-0.703; P=0.008 and HR: 0.430, 95%CI: 0.200- 0.927

Predictors of response to anti-TNF therapy in ankylosing spondylitis: results from the British Society for Rheumatology Biologics Register

Objective. Few data exist on the use of anti-TNF drugs for AS during routine clinical use in the UK. This report describes an improvement in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) after 6 months of therapy in 261 patients enrolled in a national prospective observational register

How does a cadaver model work for testing ultrasound diagnostic capability for rheumatic-like tendon damage?

To establish whether a cadaver model can serve as an effective surrogate for the detection of tendon damage characteristic of rheumatoid arthritis (RA). In addition, we evaluated intraobserver and interobserver agreement in the grading of RA-like tendon tears shown by US, as well as the concordance between the US findings and the surgically induced lesions in the cadaver model. RA-like tendon damage was surgically induced in the tibialis anterior tendon (TAT) and tibialis posterior tendon (TPT) of ten ankle/foot fresh-frozen cadaveric specimens. Of the 20 tendons examined, six were randomly assigned a surgically induced partial tear; six a complete tear; and eight left undamaged. Three rheumatologists, experts in musculoskeletal US, assessed from 1 to 5 the quality of US imaging of the cadaveric models on a Likert scale. Tendons were then categorized as having either no damage, (0); partial tear, (1); or complete tear (2). All 20 tendons were blindly and independently evaluated twice, over two rounds, by each of the three observers. Overall, technical performance was satisfactory for all items in the two rounds (all values over 2.9 in a Likert scale 1-5). Intraobserver and interobserver agreement for US grading of tendon damage was good (mean κ values 0.62 and 0.71, respectively), with greater reliability found in the TAT than the TPT. Concordance between US findings and experimental tendon lesions was acceptable (70-100 %), again greater for the TAT than for the TPT. A cadaver model with surgically created tendon damage can be useful in evaluating US metric properties of RA tendon lesions

Reliability testing of tendon disease using two different scanning methods in patients with rheumatoid arthritis

Objective. To assess the intra- and interobserver reliability of musculoskeletal ultrasonography (US) in detecting inflammatory and destructive tendon abnormalities in patients with RA using two different scanning methods.Methods. Thirteen observers examined nine patients with RA and one healthy individual in two rounds independently and blindly of each other. Each round consisted of two consecutive examinations, an anatomy-based examination and a free examination according to personal preferences. The following tendons were evaluated: wrist extensor compartments 2, 4 and 6, finger flexor tendons 3 and 4 at MCP level, tibialis posterior tendon and both peronei tendons. Overall, positive and negative agreements and κ-values for greyscale (GS) tenosynovitis, peritendinous power Doppler (PPD) signal, intratendinous power Doppler (IPD) signal and GS tendon damage were calculated.Results. Intraobserver κ-value ranges were 0.53-0.55 (P < 0.0005) for GS tenosynovitis, 0.61-0.64 (P < 0.0005) for PPD signal, 0.65-0.66 (P < 0.0005) for IPD signal and 0.44-0.53 (P < 0.0005) for GS tendon damage. For interobserver reliability, substantial overall agreement ranged from 80 to 89% for GS tenosynovitis, 97 to 100% for PPD signal, 97 to 100% for IPD signal and 97 to 100% for GS tendon damage. Results were independent of scanning technique.Conclusion. Intraobserver reliability for tenosynovitis and tendon damage varied from moderate for GS to good for PD. Overall interobserver reliability for tenosynovitis and tendon damage was excellent both for GS and PD. This qualitative scoring system may serve as the first step to a semi-quantitative score for tendon pathology. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved

Association of single nucleotide polymorphisms in IL8 and IL13 with sunitinib-induced toxicity in patients with metastatic renal cell carcinoma

Purpose: Earlier, the association of single nucleotide polymorphisms (SNPs) with toxicity and efficacy of sunitinib has been explored in patients with metastatic renal cel