Cheongeun Oh

Prevalence of Contraindications and Prescription of Pharmacologic Therapies for Gout

BACKGROUND Patients with gout have comorbidities, but the impact of these comorbidities on treatment has not been studied. METHODS A total of 575 patients with gout were stratified according to certainty of diagnosis according to International Classification of Diseases, 9th Revision, Clinical Modification code alone (cohort I), American College of Radiology criteria (cohort II), and crystal diagnosis (cohort III). Comorbid conditions were defined according to International Classification of Diseases, 9th Revision, Clinical Modification codes, and stratified as either moderate or severe. Drug contraindications were defined as moderate or strong, based on Food and Drug Administration criteria and severity of disease. RESULTS The most common comorbidity was hypertension (prevalence 0.89). The presence of comorbidities resulted in a high frequency of contraindications to approved gout medications. More than 90% of patients had at least 1 contraindication to nonsteroidal anti-inflammatory drugs. Many patients demonstrated multiple contraindications to 1 or more gout medications. Frequently, patients were prescribed medications to which they harbored contraindications. The prevalence of patients prescribed colchicine despite having at least 1 strong contraindication was 30% (cohort I), 37% (cohort II), and 39.6% (cohort III). CONCLUSION Patients with gout typically harbor multiple comorbidities that result in contraindications to many of the medications available to treat gout. Frequently, despite contraindications to gout therapies, patients are frequently prescribed these medications.

IgM autoantibodies to distinct apoptosis-associated antigens correlate with protection from cardiovascular events and renal disease in patients with SLE.

Emerging evidence suggests that there are IgM-autoantibodies that may play protective roles in SLE. While IgM are often considered polyreactive, we postulate that there are distinct sets of IgM-autoantibodies of defined autoreactive specificities relevant to different features of SLE. We examined the relationships between levels of IgM natural autoantibodies (NAbs) to apoptosis-associated phosphorylcholine (PC) or malondialdehyde (MDA) antigens, with lupus-associated autoantibodies and features of disease, in 120 SLE patients. IgM anti-PC was significantly higher in patients with low disease activity and less organ damage determined by the SELENA-SLEDAI, the physicians evaluation and the SLICC damage score. Furthermore, IgM anti-PC was significantly higher in patients without cardiovascular events. In contrast, IgM anti-cardiolipin and IgM anti-dsDNA were significantly higher in patients without renal disease. These results support the hypothesis that some IgM autoantibodies are part of a natural immune repertoire that provide homeostatic functions and protection from certain clinical lupus features.

Function of the medial meniscus in force transmission and stability.

We studied the combined role of the medial meniscus in distributing load and providing stability. Ten normal knees were loaded in combinations of compressive and shear loading as the knee was flexed over a full range. A digital camera tracked the motion, from which femoral-tibial contacts were determined by computer modelling. Load transmission was determined from the Tekscan for the anterior horn, central body, posterior horn, and the uncovered cartilage in the centre of the meniscus. For the three types of loading; compression only, compression and anterior shear, compression and posterior shear; between 40% and 80% of the total load was transmitted through the meniscus. The overall average was 58%, the remaining 42% being transmitted through the uncovered cartilage. The anterior horn was loaded only up to 30 degrees flexion, but played a role in controlling anterior femoral displacement. The central body was loaded 10-20% which would provide some restraint to medial femoral subluxation. Overall the posterior horn carried the highest percentage of the shear load, especially after 30 degrees flexion when a posterior shear force was applied, where the meniscus was estimated to carry 50% of the shear force. This study added new insights into meniscal function during weight bearing conditions, particularly its role in early flexion, and in transmitting shear forces.

Evaluation of femoral strains with cementless proximal-fill femoral implants of varied stem length

BACKGROUND The design intent of proximally-filling lateral flare femoral stems is to load the endosteal surface of the proximal femur both laterally and medially, to achieve normal bone strains. However, the long stem can contact the femoral cortex and may offload the proximal region to some extent. Therefore, in this study, we sought to determine if reducing the stem length, would result in physiologic strain patterns. METHODS Using the PhotoStress® method we analyzed 13 femurs intact and with three different stem length implants: stemless, ultra-short and short. The test rig loaded the femoral head by simulating the mid-stance single leg support phase of gait with the ilio-tibial band and the hip abductor forces. The strain distribution with each stem length implant was then compared to the intact strain distribution to determine which was most similar. FINDINGS As the stem length increased the femurs exhibited a typical pattern of reduced proximal strain and increased distal strain. However, there was some variation in this pattern indicating that the exact stem position and the location of its interaction with the endosteal surface of bone was not the same in each femur. INTERPRETATION The stemless design provided the best match compared to the native femur and therefore has the greatest potential to address the shortcomings of a stemmed femoral implant. However, the ultra-short implant also exhibited a strain distribution that closely emulated the intact femur, and may represent the best option as there are still several questions pertaining to stability and alignment of a stemless implant.

Association of Rheumatoid Arthritis Risk Alleles with Response to Anti-TNF Biologics: Results from the CORRONA Registry and Meta-analysis

In this study, we investigated whether genetic variants known to be related with susceptibility to rheumatoid arthritis (RA) are also associated with response to therapy with anti-tumor necrosis factor (anti-TNF) biologics; 233 patients enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) RA registry were studied. Findings were combined with results from an international collaborative study (N = 1,283) in a meta-analysis (N = 1,516). Multivariate models investigating the association between single nucleotide polymorphisms (SNPs) and change in RA disease activity were adjusted for age, gender, concomitant methotrexate, and baseline disease activity. In the CORRONA cohort, nominal associations with disease activity improvement were observed for the rs1980422 SNP of the CD28 gene in multivariate models (coefficient −0.377, p = 0.005) but were not significant after adjustment for multiple comparisons (q = 0.10). In the meta-analysis, the only SNP with nominal associations with change in DAS28 was the rs2812378 SNP of the CCL21 gene (coefficient 1.9195, p = 0.0068). This association was not significant after adjustment for multiple comparisons (q = 0.143). We conclude that the established RA risk alleles studied were not significantly associated with response to anti-TNF biologics in the CORRONA cohort or the meta-analysis.

Precision and Accuracy of TearLab Osmometer in Measuring Osmolarity of Salt Solutions

Abstract Purpose: The purpose of this study was to examine the inherent precision and accuracy of TearLab Osmolarity System using salt solutions, including solutions of very high osmolarity (>360 mOsm/L). Materials and methods: Ten salt solutions with osmolarity between 286 mOsm/L and 394 mOsm/L (increments of 12 mOsm/L) plus an additional solution of 400 mOsm/L were tested twice on both the TearLab osmometer and a freezing point depression osmometer. For precision, we compared the two repeated osmolarity measurements of 11 solutions obtained from TearLab. For accuracy, we compared the averaged osmolarity measurements obtained from TearLab to those from the freezing point depression osmometer. For both precision and accuracy, Bland–Altman test of agreement was used. Results: For precision, the upper 95% limit of agreement was 4.7 mOsm/L, and the lower 95% limit of agreement was −7.1 mOsm/L. The repeatability coefficient was 5.9 mOsm/L. For accuracy, the upper 95% limit of agreement was 4.8 mOsm/L and the lower 95% limit of agreement was −5.3 mOsm/L. Conclusions: The present study is the first study to demonstrate that the TearLab in situ osmometer can precisely and accurately measure osmolarity of salt solutions, including those with very high osmolarity. Future studies to evaluate the precision and the accuracy of the machine in measuring complex fluids, such as tears, need to be done, and the clinical significance of measuring tear osmolarity in patients needs to be further determined.

Anterior–posterior stability of the knee by an MR image subtraction method

The purpose of our study was to test the hypothesis that when a shear force was applied posteriorly to the loaded knee in vivo, there would be no relative motion between the tibia and the medial femoral condyle. Siemens 7 Tesla high-resolution MRI machine was used to scan eight healthy male volunteers with the knee at 15° of flexion. Two scans were obtained: the first with a compressive force of 660 N along the tibial long axis and a second with the compressive force and a posterior shear force of 36 N applied to the tibia. Solid models were created of the femur, tibia, and menisci for both loading conditions. The tibial models were superimposed enabling the displacements of the femur and menisci to be determined, relative to a fixed tibia. On average, the lateral femoral condyle displaced anteriorly by 0.66 mm but the medial femoral condyle displaced posteriorly by 0.36 mm. This indicated an axial rotation with a center between the lateral and medial condyles, but closer to the medial. The menisci displaced with the femoral condyles, but there was no indication that the medial meniscus was contributing to the pivoting action. This study supported the concept of medial anterior-posterior stability under weight-bearing conditions, but with structures other than the medial meniscus providing the stability. This study has application to the treatment of knee injuries and to knee arthroplasty design.

Yale Lung Cancer Model

The age-period-cohort model is known to provide an excellent description of the temporal trends in lung cancer incidence and mortality. This analytic approach is extended to include the contribution of carcinogenesis models for smoking. Usefulness of this strategy is that it offers a way to temporally calibrate a model that is fitted to population data and it can be readily adopted for the consideration of many different models. In addition, it provides diagnostics that can suggest temporal limitations of a particular carcinogenesis model in describing population rates. Alternative carcinogenesis models can be embedded within this framework. The two-stage clonal expansion model is implemented here. The model was used to estimate the impact of tobacco control after dissemination of knowledge of the harmful effects of cigarette smoking by comparing the observed number of lung cancer deaths to those expected if there had been no control compared to an ideal of complete control in 1965. Results indicate that 35.2% and 26.5% of lung cancer deaths that could have been avoided actually were for males and females, respectively.

Predictive model for cervical alignment and malalignment following surgical correction of adult spinal deformity

Study Design. Retrospective review of prospective multicenter database. Objective. Use predictive modeling to identify patient characteristics, radiographic, and surgical variables that predict reaching an outcome threshold of suboptimal cervical alignment after adult spinal deformity (ASD) surgery. Summary of Background Data. Cervical deformity (CD) after ASD correction has been defined with the following criteria: T1S-CL>20°, C2-C7 SVA>40 mm, and/or C2-C7 kyphosis >10°. While studies have analyzed CD predictors, few have defined and identified predictors of optimal cervical alignment after thoracolumbar surgery. Methods. Inclusion criteria were surgical ASD patients with baseline and 2-year follow-up. Postoperative cervical alignment (CA) and malalignment (nonCA) at 2 years was defined with the following radiographic criteria: 0°⩽T1S-CL⩽20°, 0 mm⩽C2-C7 SVA⩽40 mm, or C2-C7 lordosis >0°. Three thresholds classifying malalignment were defined: (T1) missing 1 criterion, (T2) missing 2 criteria, (T3) missing 3 criteria. Multivariable logistic stepwise regression models with bootstrap resampling procedure were performed for demographic, surgical, and radiographic variables. The model was validated with receiver operative characteristic and area under the curve. Results. Two hundred twenty-five surgical ASD patients were included. At 2 years 208 patients (92.4%) were grouped as CA in T3, while 17 (7.6%) were nonCA. Patients were similar in age (CA: 56.10 vs. nonCA: 55.78 years, P = 0.150), BMI (CA: 26.93 vs. nonCA: 26.94 kg/m2, P = 0.716), and sex (CA: 76.5% vs. nonCA: 87.0%, P = 0.194). The final predictive model included C2 slope, C2-T3 CL, T1S-CL, C2–C7 CL, Pelvic Tilt, C2-S1 SVA, PI-LL, and Smith–Peterson osteotomies number. In this model (area under the curve 89.22% [97.49–80.96%]), the following variables were identified as predictors of nonCA: increased Smith–Peterson osteotomies use (OR: 1.336, P = 0.017), and C2-T3 angle (OR: 1.048, P = 0.005). Conclusion. This study created a statistical model that predicts poor 2-year postoperative cervical malalignment in ASD patients. T3 (patients not meeting all three alignment criteria) was the most effective threshold for modeling nonCA, and included increased baseline C2-T3 angle and increased Smith–Peterson osteotomies during index. Level of Evidence: 3

Hospital Readmission Within 2 Years Following Adult Thoracolumbar Spinal Deformity Surgery: Prevalence, Predictors, and Effect on Patient-derived Outcome Measures

Study Design. A retrospective review of prospective multicenter database. Objective. The aim of this study was to identify factors influencing readmission, reoperation, and the impact on health-related quality of life outcomes (HRQoLs) in adult spinal deformity (ASD) surgery. Summary of Background Data. Many ASD patients experience complications requiring readmission. It is important to identify baseline/operative factors leading to rehospitalizations and reoperation, which may impact outcomes. Methods. Inclusion criteria: ASD surgical patients (age >18 yrs, major coronal Cobb ≥20°, sagittal vertical axis ≥5 cm, pelvic tilt ≥25°, and/or thoracic kyphosis >60°) with complete baseline, 1-, and 2-year follow-up. Patients were grouped on the basis of readmission occurrence (yes/no) and type [medical (no reoperation) vs. surgical (revision surgery)]. Readmissions caused by infections requiring surgical treatment (e.g., deep infections) were considered reoperations. Univariate and multivariate analyses determined readmission and reoperation predictors. Repeated measures mixed models evaluated readmission impact on HRQoLs at 1 and 2 years. Results. Three hundred thirty-four patients were included: 76 (22.8%) readmissions, involving 65 (85.5% of 76) reoperations (surgical readmission) and 11 (14.5% of 76) medical readmissions. The most common surgical readmission indication (n = 65) was implant complications (36.9%; rod breakage n = 13); the most common medical readmission indication was infection (36.4%, n = 4), treated with antibiotics. Noninfectious medical readmission (n = 7) included pleural effusion, deep vein thrombosis (DVT), intraoperative blood loss, neurologic, and unspecified. Readmission predictors: increased number of major peri-operative complications [odds ratio (OR) 5.13, P = 0.014], infection presence (OR 25.02, P = 0.001), implant complications (OR 6.12, P < 0.001), and radiographic complications (DJK, proximal junctional kyphosis, pseudoarthrosis, sagittal/coronal imbalance) (OR 16.94, P < 0.001). HRQoL analysis revealed overall improvement of the full cohort (P < 0.01), though the 76 readmitted improved less overall and at each time point P < 0.001) except in 6-week MCS (P = 0.14). Conclusion. Major peri-operative, implant, radiographic, and infection complications during index were associated with increased readmission odds. Implant complications most frequently caused surgical readmissions. Readmitted patients improved in outcome scores, although less compared with the nonreadmitted cohort, yet displayed reduced 6-week SF-36 Mental Component Summary. Level of Evidence: 3