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1.  Intra-abdominal Pressure Changes Associated with Lifting: Implications for Postoperative Activity Restrictions 
To describe the effect of lifting maneuver and quantity of weight lifted on the generation of intra-abdominal pressure.
Study Design
Forty-one women undergoing urodynamic evaluation performed four lifting maneuvers, each while lifting 0, 2.5, 5, 10, and 15 kg. The lifting maneuvers were routine activities including squatting with and without assistance, lifting from a counter and receiving weight. Pressure was recorded with a rectal microtip catheter. Each lift was performed twice and the average pressure change was analyzed.
Controlling for potential confounding variables, repeated-measures ANOVA revealed a significant interaction between lift weight and lift maneuver (p= <0.001). Squatting was associated with generation of higher intra-abdominal pressure than lifting from a counter or receiving weights into outstretched arms (p= <0.001). Lifting ≥2.5 kg resulted in significant changes in intra-abdominal pressure regardless of lift maneuver (p= <0.001).
Both lifting maneuver and quantity of weight should be considered when counseling patients regarding postoperative lifting.
PMCID: PMC4329922  PMID: 18068145
Intra-abdominal pressure; weight lifting; postoperative instructions; pelvic floor surgery
2.  Simple regression for correcting ΔCt bias in RT-qPCR low-density array data normalization 
BMC Genomics  2015;16(1):82.
Reverse transcription quantitative PCR (RT-qPCR) is considered the gold standard for quantifying relative gene expression. Normalization of RT-qPCR data is commonly achieved by subtracting the Ct values of the internal reference genes from the Ct values of the target genes to obtain ΔCt. ΔCt values are then used to derive ΔΔCt when compared to a control group or to conduct further statistical analysis.
We examined two rheumatoid arthritis RT-qPCR low density array datasets and found that this normalization method introduces substantial bias due to differences in PCR amplification efficiency among genes. This bias results in undesirable correlations between target genes and reference genes, which affect the estimation of fold changes and the tests for differentially expressed genes. Similar biases were also found in multiple public mRNA and miRNA RT-qPCR array datasets we analysed. We propose to regress the Ct values of the target genes onto those of the reference genes to obtain regression coefficients, which are then used to adjust the reference gene Ct values before calculating ΔCt.
The per-gene regression method effectively removes the ΔCt bias. This method can be applied to both low density RT-qPCR arrays and individual RT-qPCR assays.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1274-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4335788
RT-PCR; Normalization; ΔCt; Housekeeping genes; Regression
3.  Prevalence and Trends of Symptomatic Pelvic Floor Disorders in U.S. Women 
Obstetrics and gynecology  2014;123(1):141-148.
To estimate the prevalence and trends of these pelvic floor disorders in U.S. women from 2005–2010.
We utilized the National Health and Nutritional Examination Survey (NHANES) from 2005–2006, 2007–2008, and 2009–2010. A total of 7,924 non-pregnant women (aged 20 years or older) were categorized as having: urinary incontinence – moderate to severe (3 or higher on a validated urinary incontinence (UI) severity index, range 0–12); fecal incontinence – at least monthly (solid, liquid, or mucus stool); and pelvic organ prolapse – seeing or feeling a bulge. Potential risk factors included age, race and ethnicity, parity, education, poverty income ratio, body mass index (BMI) (<25, 25–29, ≥30 kg/m2), co-morbidity count, and reproductive factors. Using appropriate sampling weights, weighted chi square analysis and multivariable logistic regression models with odds ratios (OR) and 95% confidence intervals (95% CI) were reported.
The weighted prevalence rate of one or more pelvic floor disorder was 25.0% (95% CI 23.6, 26.3), including 17.1% (95% CI 15.8, 18.4) of women with moderate-to-severe urinary incontinence, 9.4% (95% CI 8.6, 10.2) with fecal incontinence, and 2.9% (95% CI 2.5, 3.4) with prolapse. From 2005 to 2010, no significant differences were found in the prevalence rates of any individual disorder or for all disorders combined (p>0.05). After adjusting for potential confounders, higher BMI, greater parity, and hysterectomy were associated with higher odds of one or more pelvic floor disorder.
Although rates of pelvic floor disorders did not change from 2005–2010, these condition remain common with one quarter of adult U.S. women reporting at least one disorder.
PMCID: PMC3970401  PMID: 24463674
4.  Risk Factors Associated with Reoperation for Bleeding following Liver Transplantation 
HPB Surgery  2014;2014:816246.
Introduction. This study's objective was to identify risk factors associated with reoperation for bleeding following liver transplantation (LTx). Methods. A retrospective study was performed at a single institution between 2001 and 2012. Operative reports were used to identify patients who underwent reoperation for bleeding within 2 weeks following LTx (operations for nonbleeding etiologies were excluded). Results. Reoperation for bleeding was observed in 101/928 (10.8%) of LTx patients. The following characteristics were associated with reoperation on multivariable analysis: recipient MELD score (OR 1.06/MELD unit, 95% CI 1.03, 1.09), number of platelets transfused (OR 0.73/platelet unit, 95% CI 0.58, 0.91), and aminocaproic acid utilization (OR 0.46, 95% CI 0.27, 0.80). LTx patients who underwent reoperation for bleeding had a longer ICU stay (5 days ± 7 versus 2 days ± 3, P < 0.001) and hospitalization (18 days ± 9 versus 10 days ± 18, P < 0.001). The risk of death increased in patients who underwent reoperation for bleeding (HR 1.89, 95% CI 1.26, 2.85). Conclusion. Reoperation for bleeding following LTx was associated with increased resource utilization and recipient mortality. A lower threshold for intraoperative platelet transfusion and antifibrinolytics, especially in patients with high lab-MELD score, may decrease the incidence of reoperation for bleeding following LTx.
PMCID: PMC4258335  PMID: 25505820
5.  Psychological Profiles and Pain Characteristics of Older Adults With Knee Osteoarthritis 
Arthritis care & research  2013;65(11):1786-1794.
To identify psychological profiles in persons with knee osteoarthritis (OA) and to determine the relationship between these profiles and specific pain and sensory characteristics, including temporal summation and conditioned pain modulation.
Individuals with knee OA (n = 194) completed psychological, health, and sensory assessments. Hierarchical cluster analysis was used to derive psychological profiles that were compared across several clinical pain/disability and experimental pain responses.
Cluster 1 had high optimism with low negative affect, pain vigilance, anger, and depression, along with the lowest self-reported pain/disability and the lowest sensitivity to mechanical, pressure, and thermal pain (P < 0.01 for all). Cluster 2 had low positive affect with high somatic reactivity, while cluster 3 showed high pain vigilance with low optimism. Clusters 2 and 3 had intermediate levels of self-reported pain/disability and cluster 3 experienced central sensitization to mechanical stimuli. Participants in cluster 3 also displayed significant pain facilitation (P < 0.05). Cluster 4 exhibited the highest pain vigilance, reactivity, negative affect, anger, and depression. These individuals experienced the highest self-reported pain/disability, including widespread pain (P < 0.001 for all). Cluster 4 was most sensitive to mechanical, pressure, and thermal stimuli, and showed significant central sensitization to mechanical and thermal stimuli (P < 0.001 for all).
Our findings demonstrate the existence of homogeneous psychological profiles displaying unique sets of clinical and somatosensory characteristics. Multidisciplinary treatment approaches consistent with the biopsychosocial model of pain should provide significant advantages if targeted to profiles such as those in our OA sample.
PMCID: PMC3922880  PMID: 23861288
6.  Multiple Lupus Associated ITGAM Variants Alter Mac-1 Function on Neutrophils 
Arthritis and rheumatism  2013;65(11):2907-2916.
Multiple studies have demonstrated that single-nucleotide polymorphisms (SNPs) in the ITGAM locus (including the non-synonymous SNPs rs1143679, rs1143678, rs1143683) are associated with SLE. ITGAM encodes the protein CD11b, a subunit of the β2 integrin Mac-1. The purpose of this study was to determine the effects of ITGAM genetic variation on the biological functions of neutrophil Mac-1.
Neutrophils from ITGAM genotyped and sequenced healthy donors were isolated for functional studies. The phagocytic capacity of neutrophil ITGAM variants was probed with complement coated erythrocytes, serum treated zymosan, heat treated zymosan and IgG coated erythrocytes. The adhesion capacity of ITGAM variants, in adhering to either purified intercellular adhesion molecule 1 or tumor necrosis factor α-stimulated endothelial cells was assessed in a flow chamber. Expression levels of total CD11b and activation of CD11b were assessed by flow cytometry.
Mac-1–mediated neutrophil phagocytosis, determined in cultures with 2 different complement-coated particles, was significantly reduced in individuals with nonsynonymous variant alleles of ITGAM. This reduction in phagocytosis was related to variation at either rs1143679 (in the β-propeller region) or rs1143678/rs1143683 (highly linked SNPs in the cytoplasmic/calf-1 regions). Phagocytosis mediated by Fcγ receptors was also significantly reduced in donors with variant ITGAM alleles. Similarly, firm adhesion of neutrophils was significantly reduced in individuals with variant ITGAM alleles. These functional alterations were not attributable to differences in total receptor expression or activation.
The nonsynonymous ITGAM variants rs1143679 and rs1143678/rs113683 contribute to altered Mac-1 function on neutrophils. These results underscore the need to consider multiple nonsynonymous SNPs when assessing the functional consequences of ITGAM variation on immune cell processes and the risk of SLE.
PMCID: PMC3969028  PMID: 23918739
7.  Application of the OMERACT filter to measures of core outcome domains in recent clinical studies of acute gout 
The Journal of rheumatology  2014;41(3):574-580.
To determine the extent to which instruments that measure core outcome domains in acute gout fulfil the OMERACT filter requirements of truth, discrimination and feasibility.
Patient-level data from four randomised controlled trials of agents designed to treat acute gout and one observational study of acute gout were analysed. For each available measure construct validity, test-retest reliability, within-group change using effect size, between-group change using the Kruskall-Wallis statistic and repeated measures generalised estimating equations were assessed. Floor and ceiling effects were also assessed and MCID was estimated. These analyses were presented to participants at OMERACT 11 to help inform voting for possible endorsement.
There was evidence for construct validity and discriminative ability for 3 measures of pain (0 to 4 Likert, 0 to 10 numeric rating scale, 0 to 100 mm visual analogue scale). Likewise, there appears to be sufficient evidence for a 4-point Likert scale to possess construct validity and discriminative ability for physician assessment of joint swelling and joint tenderness. There was some evidence for construct validity and within-group discriminative ability for the Health Assessment Questionnaire as a measure of activity limitations, but not for discrimination between groups allocated to different treatment.
There is sufficient evidence to support measures of pain (using Likert, numeric rating scale or visual analogue scales), joint tenderness and swelling (using Likert scale) as fulfilling the requirements of the OMERACT filter. Further research on a measure of activity limitations in acute gout clinical trials is required.
PMCID: PMC4212978  PMID: 24429178
gout; outcome measures; psychometrics
8.  Experimental pain sensitivity differs as a function of clinical pain severity in symptomatic knee osteoarthritis 
Pain in knee osteoarthritis (OA) has historically been attributed to peripheral pathophysiology; however, the poor correspondence between objective measures of disease severity and clinical symptoms suggests that non-local factors, such as altered central processing of painful stimuli, also contribute to clinical pain in knee OA. Consistent with this notion, recent evidence demonstrates that patients with knee OA exhibit increased sensitivity to painful stimuli at body sites unaffected by clinical pain.
In order to further investigate the contribution of altered pain processing to knee OA pain, the current study tested the hypothesis that symptomatic knee OA is associated with enhanced sensitivity to experimental pain stimuli at the knee and at remote body sites unaffected by clinical pain. We further anticipated that pain sensitivity would differ as a function of the OA symptom severity. Older adults with and without symptomatic knee OA completed a series of experimental pain assessments. A median split of the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) was used to stratify participants into low vs. high OA symptom severity.
Compared to controls and the low symptom group, individuals in the high symptom group were more sensitive to suprathreshold heat stimuli, blunt pressure, punctuate mechanical, and cold stimuli. Individuals in the low symptomatic OA group subgroup exhibited experimental pain responses similar to the pain-free group on most measures. No group differences in endogenous pain inhibition emerged.
These findings suggest that altered central processing of pain is particularly characteristic of individuals with moderate to severe symptomatic knee OA.
PMCID: PMC3831366  PMID: 23973137
WOMAC; knee osteoarthritis; experimental pain; severity
9.  Genetic Variants Associated with Methotrexate Efficacy and Toxicity in Early Rheumatoid Arthritis: Results from the Treatment of Early Aggressive Rheumatoid Arthritis Trial 
The pharmacogenomics journal  2013;14(1):48-53.
Methotrexate (MTX) has emerged as first-line therapy for early moderate to severe rheumatoid arthritis (RA), but individual variation in treatment response remains unexplained. We tested the associations between 863 known pharmacogenetic variants and MTX response in 471 TEAR Trial participants with early RA. Efficacy and toxicity were modeled using multiple regression, adjusted for demographic and clinical covariates. Penalized regression models were used to test joint associations of markers and/or covariates with the outcomes. The strongest genetic associations with efficacy were in CHST11 (five markers with P <0.003), encoding carbohydrate (chondroitin 4) sulfotransferase 11. Top markers associated with MTX toxicity were in the cytochrome p450 genes CYP20A1 and CYP39A1, solute carrier genes SLC22A2 and SLC7A7, and the mitochondrial aldehyde dehydrogenase gene ALDH2. The selected markers explained a consistently higher proportion of variation in toxicity than efficacy. These findings could inform future development of personalized therapeutic approaches.
PMCID: PMC3701736  PMID: 23545897
Methotrexate; rheumatoid arthritis; pharmacogenetics
10.  Temporal summation of pain as a prospective predictor of clinical pain severity in adults aged 45 years and above with knee osteoarthritis: ethnic differences 
Psychosomatic medicine  2014;76(4):302-310.
Enhanced pain facilitation is reportedly an important contributor to the clinical pain experiences of individuals with knee osteoarthritis (OA). Ethnic differences in the prevalence and severity of knee OA in addition to associated pain are also well documented. Temporal summation (TS) of pain is a widely applicable quantitative sensory testing method that invokes neural mechanisms related to pain facilitatory processes. This study tested whether TS of pain, an index of pain facilitation, differentially predicts the clinical pain experiences of African Americans and non-Hispanic Whites with symptomatic knee OA.
A total of 225 study participants underwent assessment of TS of mechanical and heat pain stimuli applied to their most symptomatic knee and their ipsilateral hand (mechanical) or forearm (heat). Using telephone-based surveys, participants subsequently reported their average and worst clinical pain severity across four consecutive weeks following assessment of TS.
In predicting future clinical pain, ethnicity interacted with TS of mechanical pain (but not heat pain), such that TS of mechanical pain at the knee significantly predicted greater clinical ratings of average (b = .02, p = .016) and worst (b = .02, p = .044) clinical pain for non-Hispanic Whites but not African Americans (p’s > .30).
These results reveal the importance of considering ethnicity when examining pain facilitation and the clinical pain of individuals with symptomatic knee OA. The results of this study are discussed in terms of ethnic differences in the predictors of clinical pain experiences among African Americans and non-Hispanic Whites with knee OA.
PMCID: PMC4066647  PMID: 24804882
Pain; Knee Osteoarthritis (OA); Ethnicity; Pain Facilitation; Temporal Summation (TS)
11.  Allelic Dependent Expression of an Activating Fc receptor on B cells Enhances Humoral Immune Responses 
Science translational medicine  2013;5(216):216ra175.
B cells are pivotal regulators of acquired immune responses and recent work in both experimental murine models and humans has demonstrated that subtle changes in the regulation of B cell function can significantly alter immunological responses. The balance of negative and positive signals in maintaining an appropriate B cell activation threshold is critical in B lymphocyte immune tolerance and autoreactivity. FcγRIIb (CD32B), the only recognized Fcγ receptor on B cells, provides IgG-mediated negative modulation through a tyrosine-based inhibition motif which down-regulates B cell receptor initiated signaling. These properties make FcγRIIb a promising target for antibody-based therapy. Here we report the discovery of allele-dependent expression of the activating FcγRIIc on B cells. Identical to FcγRIIb in the extracellular domain, FcγRIIc has a tyrosine-based activation motif in its cytoplasmic domain. In both human B cells and in B cells from mice transgenic for human FcγRIIc, FcγRIIc expression counterbalances the negative feedback of FcγRIIb and enhances humoral responses to immunization in mice and to BioThrax® vaccination in a human Anthrax vaccine trial. Moreover, the FCGR2C-ORF allele is associated with the risk of development of autoimmunity in humans. FcγRIIc expression on B cells challenges the prevailing paradigm of uni-directional negative feedback by IgG immune complexes via the inhibitory FcγRIIb, is a previously unrecognized determinant in human antibody/autoantibody responses, and opens the opportunity for more precise personalized use of B cell targeted antibody-based therapy.
PMCID: PMC3982386  PMID: 24353158
12.  Resource Utilization Associated with Procurement of Transplantable Organs from Donors that do not meet OPTN Eligible Death Criteria 
Transplantation  2014;97(10):1043-1048.
The strategy of evaluating every donation opportunity warrants an investigation into the financial feasibility of this practice. The purpose of this investigation is to measure resource utilization required for procurement of transplantable organs in an organ procurement organization (OPO).
Donors were stratified into those that met OPTN-defined eligible death criteria (ED Donors, n=589) and those that did not (NED Donors, n=703). Variable direct costs and time utilization by OPO staff for organ procurement were measured and amortized per organ transplanted using permutation methods and statistical bootstrapping/resampling approaches.
More organs per donor were procured (3.66 ± 1.2 vs. 2.34 ± 0.8, p<0.0001) and transplanted (3.51 ± 1.2 vs. 2.08 ± 0.8, p<0.0001) in ED donors compared to NED donors. The variable direct costs were significantly lower in NED donors ($29,879.4 ± 11590.1 vs. $19,019.6 ± 7599.60, p<0.0001). In contrast, the amortized variable direct costs per organ transplanted were significantly higher in the NED donors ($8,414.5 ± 138.29 vs. $9,272.04 ± 344.56, p<0.0001). ED donors where thoracic organ procurement occurred were 67% more expensive than in abdominal-only organ procurement. The total time allocated per donor was significantly shorter in NED donors (91.2 ± 44.9 hours vs. 86.8 ± 78.6, p=0.01). In contrast, the amortized time per organ transplanted was significantly longer in the NED donors (23.1 ± 0.8 hours vs. 36.9 ± 3.2, p<0.001).
The variable direct costs and time allocated per organ transplanted is significantly higher in donors that do not meet the eligible death criteria.
PMCID: PMC4024080  PMID: 24503760
Eligible Death Donor; Non-Eligible Death Donor; Organ Procurement; Deceased Donor Organs; Variable Direct Cost; Resource Allocation
13.  Comparison of the Disease Activity Score using Erythrocyte Sedimentation Rate and C-reactive Protein in African-Americans with Rheumatoid Arthritis 
The Journal of rheumatology  2013;40(11):1812-1822.
The Disease Activity Score based on 28 joints (DAS28) has been increasingly used in clinical practice and research studies of rheumatoid arthritis (RA). Studies have reported discordance between DAS28 based on erythrocyte sedimentation rate (ESR) versus C-reactive protein (CRP) in RA patients. However such comparison is lacking in African-Americans with RA.
This analysis included participants from the Consortium for the Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis (CLEAR) Registry which enrolls self-declared African-Americans with RA. Using tender and swollen joint counts separate ESR-based and CRP-based DAS28 scores (DAS28-ESR3 and DAS28-CRP3) were calculated, as were DAS28-ESR4 and DAS28-CRP4, which included the patient’s assessment of disease activity. The scores were compared using paired t-test, simple agreement and kappa, correlation coefficient and Bland-Altman plots.
Of the 233 included participants, 85% were women, mean age at enrollment was 52.6 years, and median disease duration at enrollment was 21 months. Mean DAS28-ESR3 was significantly higher than DAS28-CRP3 (4.8 vs. 3.9; p<0.001). Similarly, mean DAS28-ESR4 was significantly higher than DAS28-CRP4 (4.7 vs. 3.9; p<0.001). ESR-based DAS28 remained higher than CRP-based DAS28 even when stratified by age, sex, and disease duration. Overall agreement was not high between DAS28-ESR3 and DAS28-CRP3 (50%) or between DAS28-ESR4 and DAS28-CRP4 (59%). DAS28-CRP3 underestimated disease activity in 47% of the participants relative to DAS28-ESR3 and DAS28-CRP4 in 40% of the participants relative to DAS28-ESR4.
There was significant discordance between the ESR-based and CRP-based DAS28 which could impact clinical treatment decisions in African-Americans with RA.
PMCID: PMC3987124  PMID: 23950187
DAS28; Rheumatoid Arthritis; African-Americans
14.  Complementary and Alternative Medicine Use in African Americans With Rheumatoid Arthritis 
Arthritis care & research  2014;66(2):180-189.
Racial/ethnic differences with regard to complementary and alternative medicine (CAM) use have been reported in the US. However, specific details of CAM use by African Americans with rheumatoid arthritis (RA) are lacking.
Data were collected from African Americans with RA enrolled in a multicenter registry regarding the use of CAM, including food supplements, topical applications, activities, and alternative care providers. Factors associated with CAM use by sex and disease duration were assessed using t-test, Wilcoxon’s rank sum test, chi-square test, and logistic regression analyses.
Of the 855 participants, 85% were women and mean age at enrollment was 54 years. Overall, ever using any of the CAM treatments, activities, and providers was 95%, 98%, and 51%, respectively (median of 3 for number of treatments, median of 5 for activities, and median of 1 for providers). Those with longer disease duration (>2 years) were significantly more likely (odds ratio >2.0, P < 0.05) to use raisins soaked in vodka/gin, to take fish oils, or to drink alcoholic beverages for RA treatment than those with early disease. As compared to men, women were significantly (P < 0.05) more likely to pray/attend church, write in a journal, and use biofeedback, but were less likely to smoke tobacco or topically apply household oils for treatment of RA.
CAM use was highly prevalent in this cohort, even in individuals with early disease. Health care providers need to be aware of CAM use as some treatments may potentially have interactions with conventional medicines. This could be important within this cohort of African Americans, where racial disparities are known to affect access to conventional care.
PMCID: PMC3977347  PMID: 23983105
15.  Gene-body mass index interactions are associated with methotrexate toxicity in rheumatoid arthritis 
Annals of the rheumatic diseases  2013;73(4):785-786.
PMCID: PMC3970399  PMID: 24291656
Gene polymorphism; methotrexate; rheumatoid arthritis
16.  Perceived racial discrimination, but not mistrust of medical researchers, predicts the heat pain tolerance of African Americans with symptomatic knee osteoarthritis 
Studies have shown that perceived racial discrimination is a significant predictor of clinical pain severity among African Americans. It remains unknown whether perceived racial discrimination also alters the nociceptive processing of painful stimuli, which, in turn, could influence clinical pain severity. This study examined associations between perceived racial discrimination and responses to noxious thermal stimuli among African Americans and non-Hispanic whites. Mistrust of medical researchers was also assessed given its potential to affect responses to the noxious stimuli.
One hundred and thirty (52% African American, 48% non-Hispanic white) community-dwelling older adults with symptomatic knee osteoarthritis completed two study sessions. In session one, individuals provided demographic, socioeconomic, physical and mental health information. They completed questionnaires related to perceived lifetime frequency of racial discrimination and mistrust of medical researchers. In session two, individuals underwent a series of controlled thermal stimulation procedures to assess heat pain sensitivity, particularly heat pain tolerance.
African Americans were more sensitive to heat pain and reported greater perceived racial discrimination as well as greater mistrust of medical researchers compared to non-Hispanic whites. Greater perceived racial discrimination significantly predicted lower heat pain tolerance for African Americans but not non-Hispanic whites. Mistrust of medical researchers did not significantly predict heat pain tolerance for either racial group
These results lend support to the idea that perceived racial discrimination may influence the clinical pain severity of African Americans via the nociceptive processing of painful stimuli.
PMCID: PMC3943939  PMID: 24219416
17.  Do Trained Specialists Solicit Familial Authorization at Equal Frequency, Regardless of Deceased Donor Characteristics? 
The Organ Donor Breakthrough collaborative recommended high-leverage changes including “Master Effective Requesting”.
The purpose of this investigation is to measure who approaches decedent families to request organ donation. Our hypothesis is that trained specialists will solicit authorization at equal frequency regardless of donor characteristics.
A retrospective analysis of an organ center donor database was performed for the years 2006 to 2009. Decedents were stratified into those that met OPTN eligible death criteria (ED donors) and those that did not (not eligible death--NED donors).
Of decedents whose families were approached for authorization, 46% were ED donors and 54% were NED donors. Trained specialists solicited authorization from 76% of the total population, but were more likely to solicit authorization from ED donors than NED donors (86% vs. 68%, p<0.0001). Trained specialists were more likely to solicit authorization from donors whose cause of death were over-represented in ED donors, and donors under the age of 50. Trained specialists were more likely to obtain authorization in both ED and NED donors. Multivariable modeling demonstrated that having a trained specialist approach the decedent’s family was associated with the highest odds of obtaining authorization.
Trained specialists approached the majority of families of decedents for authorization, but disproportionately approached fewer families of NED donors. Having a trained specialist approach the decedent family has the strongest impact on obtaining donor authorization. These data suggest that fewer resources are allocated to NED donors, which may adversely impact deceased donor organ supply.
PMCID: PMC3915045  PMID: 23996950
Donor Authorization; Eligible Death Donor; Race; Cause of Death; Deceased Donor Organs
18.  The association of greater dispositional optimism with less endogenous pain facilitation is indirectly transmitted through lower levels of pain catastrophizing 
Dispositional optimism has been shown to beneficially influence various experimental and clinical pain experiences. One possibility that may account for decreased pain sensitivity among individuals who report greater dispositional optimism is less use of maladaptive coping strategies like pain catastrophizing, a negative cognitive/affective response to pain. An association between dispositional optimism and conditioned pain modulation (CPM), a measure of endogenous pain inhibition, has previously been reported. However, it remains to be determined whether dispositional optimism is also associated with temporal summation (TS), a measure of endogenous pain facilitation. The current study examined whether pain catastrophizing mediated the association between dispositional optimism and TS among 140 older, community-dwelling adults with symptomatic knee osteoarthritis. Individuals completed measures of dispositional optimism and pain catastrophizing. TS was then assessed using a tailored heat pain stimulus on the forearm. Greater dispositional optimism was significantly related to lower levels of pain catastrophizing and TS. Bootstrapped confidence intervals revealed that less pain catastrophizing was a significant mediator of the relation between greater dispositional optimism and diminished TS. These findings support the primary role of personality characteristics such as dispositional optimism in the modulation of pain outcomes by abatement of endogenous pain facilitation and less use of catastrophizing.
PMCID: PMC3592576  PMID: 23218934
Optimism; Catastrophizing; Pain Facilitation; Temporal Summation; Osteoarthritis
19.  Gene expression patterns in peripheral blood cells associated with radiographic severity in African Americans with early rheumatoid arthritis 
Rheumatology international  2012;33(1):129-137.
Gene expression profiling may be used to stratify patients by disease severity to test the hypothesis that variable disease outcome has a genetic component. In order to define unique expression signatures in African American rheumatoid arthritis (RA) patients with severe erosive disease, we undertook a gene expression study using samples of RNA from peripheral blood mononuclear cells (PBMCs). RNA from baseline PBMC samples of 96 African American RA patients with early RA (<2 years disease duration) was hybridized to cDNA probes of the Illumina Human HT-V3 expression array. Expression analyses were performed using the ca. 25,000 cDNA probes, and then expression levels were compared to the total number of erosions in radiographs of the hands and feet at baseline and 36 months. Using a false discovery rate cutoff of Q = 0.30, 1,138 genes at baseline and 680 genes at 36 months significantly correlated with total erosions. No evidence of a signal differentiating disease progression, or change in erosion scores between baseline and 36 months, was found. Further analyses demonstrated that the differential gene expression signature was localized to the patients with the most erosive disease (>10 erosions). Ingenuity Pathway Analysis demonstrated that genes with fold change greater than 1.5 implicated immune pathways such as CTLA signaling in cytotoxic T lymphocytes. These results demonstrate that CLEAR patients with early RA having the most severe erosive disease, as compared to more mild cases (<10 erosions), may be characterized by a set of differentially expressed genes that represent biological pathways with relevance to autoimmune disease.
PMCID: PMC3769702  PMID: 22238028
Genome-wide gene expression; Sharp/van der Heijde; Pathway analysis; CLEAR; ABCoN
20.  Is Decedent Race an Independent Predictor of Organ Donor Consent, or Merely a Surrogate Marker of Socioeconomic Status? 
Transplantation  2012;94(8):873-878.
Studies have demonstrated that African American race is a strong predictor of non-donation. However, it is often and correctly argued that African American race is a crude explanatory variable that is a surrogate marker of socioeconomic status (SES), education and access to health care. We hypothesized that when controlling for these factors, African American race would cease to be a predictor of organ donation.
A retrospective review was performed of 1292 Alabama decedents approached for organ donation between 2006 and 2009. Multivariable logistic regression models were constructed to identify the most parsimonious model that could explain the variation in the log-odds of obtaining consent.
Consent for donation was obtained from 49% of the decedent's families. Household income was a predictor of organ donor consent only in Caucasians. Surprisingly, household income was not statistically different between consented and non-consented African American decedents ($25,147 vs. $26,137; p=0.90). On multivariable analysis, education, urban residence and shorter distance between the decedent residence and donor hospital were significantly associated with obtaining consent for organ donation. On univariate analysis, the odds of donor consent in Caucasians compared to African Americans was 2.76 (95% CI 2.17 – 3.57). When controlling for SES and access to healthcare variables, the odds of donor consent increased to 4.36 (95% CI 2.88 – 6.61).
We interpret this result to indicate that there remains unknown but important factor(s) associated with both race and obtaining organ donor consent. Further studies are required to isolate and determine whether this factor(s) is modifiable.
PMCID: PMC3566527  PMID: 23018878
Socioeconomic Status; Organ Donation; Education; Marital Status
21.  Dietary Glycemic Load, Glycemic Index, and Carbohydrate and Risk of Breast Cancer in the Women’s Health Initiative 
Nutrition and cancer  2011;63(6):899-907.
Dietary glycemic load (GL), glycemic index (GI), and carbohydrate could be associated with breast cancer risk by influencing long-term blood glucose and insulin concentrations. We examined associations between GL, GI, and carbohydrate and incident breast cancer in 148,767 Women’s Heath Initiative (WHI) participants. Dietary variables were estimated from food frequency questionnaires administered at baseline. Self-reported breast cancers during follow-up were confirmed by medical records review. Cox proportional hazards regression modeled time to breast cancer within quintiles of GL, GI, and carbohydrate. There were 6,115 total breast cancers after a median follow-up of 8.0 yr. We observed no associations between GL, GI, or carbohydrate and total incident breast cancer, with hazard ratios and 95% confidence intervals for the highest vs. lowest quintiles of 1.08, 0.92–1.29 (P for trend = 0.27); 1.01, 0.91–1.12 (P = 0.74); and 0.95, 0.80–1.14 (P = 0.98), respectively. There was a trend toward significance for the positive association between GL and in situ cancers (1.40, 0.94–2.13; P = 0.07). Although there was no evidence of associations between GL, GI, or carbohydrate and total breast cancer risk in WHI participants, the suggestion of an association between GL and risk of in situ cancers requires further investigation.
PMCID: PMC3791879  PMID: 21714685
22.  How to estimate the measurement error variance associated with ancestry proportion estimates 
Statistics and its interface  2011;4(3):327-337.
To show how the variance of the measurement error (ME) associated with individual ancestry proportion estimates can be estimated, especially when the number of ancestral populations (k) is greater than 2.
We extend existing internal consistency measures to estimate the ME variance, and we compare these estimates with the ME variance estimated by use of the repeated measurement (RM) approach. Both approaches work by dividing the genotyped markers into subsets. We examine the effect of the number of subsets and of the allocation of markers to each subset on the performance of each approach. We used simulated data for all comparisons.
Independently of the value of k, the measures of internal reliability provided less biased and more precise estimates of the ME variance than did those obtained with the RM approach. Both methods tend to perform better when a large number of subsets of markers with similar sizes are considered.
Our results will facilitate the use of ME correction methods to address the ME problem in individual ancestry proportion estimates. Our method will improve the ability to control for type I error inflation and loss of power in association tests and other genomic research involving ancestry estimates.
PMCID: PMC3786624  PMID: 24089627
Population stratification; admixture; type I error inflation; reliability; Cronbach’s alpha; measurement errors; measurement error variance
23.  Correlation and Clinical Utility of pp65 Antigenemia and Quantitative Polymerase Chain Reaction Assays for Detection of Cytomegalovirus in Pediatric Renal Transplant Patients 
Pediatric transplantation  2012;16(6):627-637.
Quantitative polymerase chain reaction (qPCR) and pp65 antigenemia assays are used to monitor cytomegalovirus (CMV) infection in renal transplant recipients, but correlation of assays in a pediatric population has not been evaluated. Paired CMV real-time qPCR and pp65 antigenemia tests from 882 blood samples collected from 115 pediatric renal transplant recipients were analyzed in this retrospective cohort study for strength of association and clinical correlates.
The assays correlated well in detecting infection (κ = 0.61). Higher qPCR values were demonstrated with increasing levels of antigenemia (p < 0.01). Discordant test results were associated with antiviral treatment (OR 4.33, p < 0.01) and low-level viremia, with odds of concordance increasing at higher qPCR values (OR 3.67, p < 0.01), and no discordance occurring above 8500 genomic equivalents/mL. Among discordant samples, neither test preceded the other in detecting initial infection or in returning to negative while on treatment. Only 2 cases of disease occurred during the 2-year study period.
With strong agreement in the detection of CMV infection, either qPCR or pp65 antigenemia assays can be used effectively for monitoring pediatric renal transplant patients for both detection and resolution of infection.
PMCID: PMC3461327  PMID: 22694244
Pediatrics; Kidney Transplantation; Cytomegalovirus Infections; Polymerase Chain Reaction; CMV pp65 Antigen
Introduction and Hypothesis
The goal of this study was to characterize associations between caffeine consumption and severity of urinary incontinence (UI) in US women. We hypothesized that moderate and high caffeine intake would be associated with UI in US women when controlling for other factors associated with UI.
US women participated in the 2005–2006 and 2007–2008 National Health and Nutrition Examination Survey (NHANES), a cross-sectional, nationally representative survey. Using the Incontinence Severity Index, UI was categorized as “any” and “moderate/severe”. Types of UI included stress, urge, mixed, and other. Food diaries were completed and average water (gm/day), total dietary moisture (gm/day), and caffeine (mg/day) intake were calculated into quartiles. Step-wise logistic regression models were constructed adjusting for: sociodemographics, chronic diseases, body mass index, self-rated health, depression, alcohol use, dietary water and moisture in take, and reproductive factors.
From the 4309 non-pregnant women (aged ≥20 years) who had complete UI and dietary data, UI prevalence for any UI was 41.0% and 16.5% for moderate/severe UI, with stress UI the most common UI type (36.6%). Women consumed a mean caffeine intake of 126.7 mg/day. After adjusting for multiple factors, caffeine in take in the highest quartile (≥204 mg/day) was associated with any UI (prevalence odds ratio (POR)1.47, 95% CI 1.07, 2.01), but not moderate/severe UI (POR 1.42, 95% CI 0.98, 2.07). Type of UI (stress, urgency, mixed) was not associated with caffeine intake.
Caffeine intake ≥204 mg/day was associated with any UI, but not moderate/severe UI, in US women.
PMCID: PMC3505252  PMID: 22699886
urinary; incontinence; caffeine; intake; women
25.  One Year Outcomes of Tension-Free Vaginal Tape (TVT) Mid-Urethral Slings in Overweight and Obese Women 
The purpose of this study was to assess the impact of body mass index (BMI) on tension-free vaginal tape (TVT) success rates, patient satisfaction, and complications one year following surgery.
Baseline and one-year post-surgery outcomes were abstracted, including Urogenital Distress Inventory (UDI-6) scores, Incontinence Impact Questionnaire (IIQ-7) scores, and patient satisfaction ratings. Multivariable logistic and linear regression analyses were performed to examine relationships between outcomes and BMI.
195 subjects with a mean age of 59.3 ±12.6 were included. There was significant improvement within each group (all p-values <0.01) in total UDI-6 and IIQ-7 scores from baseline to one year post-surgery; all groups had high patient satisfaction. No differences in improvement or complications rates were observed among the BMI cohorts (all p-values >0.05)
Differential counseling of overweight or obese women regarding outcomes of the TVT procedure is not supported by these results; longer follow-up is warranted.
PMCID: PMC3261075  PMID: 19448965
obesity; outcomes; TVT sling; urinary incontinence

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