Publications by authors named "Haikady N Nagaraja"

75 Publications

Prevalence of cancer and the benign call rate of afirma gene classifier in F-Fluorodeoxyglucose positron emission tomography positive cytologically indeterminate thyroid nodules.

Cancer Med 2021 Feb 15;10(3):1084-1090. Epub 2021 Jan 15.

Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University Wexner Medical Center and Arthur G. James Cancer Center, Columbus, Ohio, USA.

Background: F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) positive (PET+) cytologically indeterminate thyroid nodules (ITNs) have variable cancer risk in the literature. The benign call rate (BCR) of Afirma Gene Classifier (Gene Expression Classifier, GEC, or Genome Sequence Classifier, GSC) in (PET +) ITNs is unknown.

Methods: This is a retrospective study at our institution of all patients with (PET+) ITNs (Bethesda III/IV) from 1 January 2010 to 21 May 2019 who underwent Afirma testing and/or surgery or repeat FNA with benign cytology.

Results: Forty-five (PET+) ITNs were identified: 31 Afirma-tested (GEC = 20, GSC = 11) and 14 either underwent surgery (n = 13) or repeat FNA (Benign cytology) (n = 1) without Afirma. The prevalence of cancer and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) including only resected nodules and ITN with repeat benign FNA (n = 33) was 36.4% (12/33). Excluding all Afirma "suspicious" non-resected ITNs and assuming all Afirma "benign" ITNs were truly benign, that prevalence was 28.6% (12/42). The BCR with GSC was 64% compared to 25% with GEC (p = 0.056). Combining GSC/GEC-tested ITNs, the BCR was higher in ITNs demonstrating low/very low-risk sonographic pattern by the American Thyroid Association (ATA) classification and ITNs scoring <4 by the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR-TI-RADS) than ITNs with higher sonographic pattern/score (p = 0.025).

Conclusions: The prevalence of cancer/NIFTP in (PET+) ITNs was 28.6-36.4% depending on the method of calculation. The BCR of Afirma GSC was 64%. Combining Afirma GEC/GSC-tested ITNs, BCR was higher in ITNs with a lower risk sonographic pattern.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.3704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897903PMC
February 2021

Differentiating Staphylococcus infection-associated glomerulonephritis and primary IgA nephropathy: a mass spectrometry-based exploratory study.

Sci Rep 2020 10 14;10(1):17179. Epub 2020 Oct 14.

Division of Nephrology, Department of Internal Medicine, Ground Floor, The Ohio State University Wexner Medical Center, 395 West 12th Avenue, Columbus, OH, 43210, USA.

Staphylococcus infection-associated glomerulonephritis (SAGN) and primary IgA nephropathy (IgAN) are separate disease entities requiring different treatment approaches. However, overlapping histologic features may cause a diagnostic dilemma. An exploratory proteomic study to identify potential distinguishing biomarkers was performed on formalin fixed paraffin embedded kidney biopsy tissue, using mass spectrometry (HPLC-MS/MS) (n = 27) and immunohistochemistry (IHC) (n = 64), on four main diagnostic groups-SAGN, primary IgAN, acute tubular necrosis (ATN) and normal kidney (baseline transplant biopsies). Spectral counts modeled as a negative binomial distribution were used for statistical comparisons and in silico pathway analysis. Analysis of variance techniques were used to compare groups and the ROC curve to evaluate classification algorithms. The glomerular proteomes of SAGN and IgAN showed remarkable similarities, except for significantly higher levels of monocyte/macrophage proteins in SAGN-mainly lysozyme and S100A9. This finding was confirmed by IHC. In contrast, the tubulointerstitial proteomes were markedly different in IgAN and SAGN, with a lower abundance of metabolic pathway proteins and a higher abundance of extracellular matrix proteins in SAGN. The stress protein transglutaminase-2 (TGM2) was also significantly higher in SAGN. IHC of differentially-expressed glomerular and tubulointerstitial proteins can be used to help discriminate between SAGN and IgAN in ambiguous cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-73847-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560901PMC
October 2020

Association Between Urinary Epidermal Growth Factor and Renal Prognosis in Lupus Nephritis.

Arthritis Rheumatol 2021 02 12;73(2):244-254. Epub 2021 Jan 12.

The Ohio State University Wexner Medical Center, Columbus.

Objective: To evaluate the role of urinary epidermal growth factor (EGF) as a biomarker of chronic kidney damage in lupus nephritis (LN).

Methods: A proteomics approach was used to identify urinary EGF as a biomarker of interest in a discovery cohort of patients with LN. The expression of urinary EGF was characterized in 2 large multiethnic LN cohorts, and the association between urinary EGF levels at the time of flare and kidney outcomes was evaluated in a subset of 120 patients with long-term follow-up data. For longitudinal studies, the expression of urinary EGF over time was determined in 2 longitudinal cohorts of patients with LN from whom serial urine samples were collected.

Results: Discovery analysis showed the urinary EGF levels as being low in patients with active LN (median peptide count 8.4, interquartile range [IQR] 2.8-12.3 in patients with active LN versus median 48.0, IQR 45.3-64.6 in healthy controls). The peptide sequence was consistent with that of proEGF, and this was confirmed by immunoblotting. The discovery findings were verified by enzyme-linked immunosorbent assay. Patients with active LN had a significantly lower level of urinary EGF compared to that in patients with active nonrenal systemic lupus erythematosus (SLE), patients with inactive SLE, and healthy kidney donors (each P < 0.05). The urinary EGF level was inversely correlated with the chronicity index of histologic features assessed in kidney biopsy tissue (Spearman's r = -0.67, P < 0.001). Multivariate survival analysis showed that the urinary EGF level was associated with time to doubling of the serum creatinine level (DSCr), a marker of future end-stage kidney disease (ESKD) (hazard ratio 0.88, 95% confidence interval 0.77-0.99, P = 0.045). Patients whose LN symptoms progressed to DSCr and those who experienced progression to ESKD had a lower urinary EGF level at the time of flare, and urinary EGF levels decreased over the 12 months following flare. All patients who experienced progression to ESKD were identified based on a urinary EGF cutoff level of <5.3 ng/mg.

Conclusion: Urinary EGF levels are correlated with histologic kidney damage in patients with LN. Low urinary EGF levels at the time of flare and decreasing urinary EGF levels over time are associated with adverse long-term kidney outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.41507DOI Listing
February 2021

Adverse effects of electronic cigarettes on the disease-naive oral microbiome.

Sci Adv 2020 May 27;6(22):eaaz0108. Epub 2020 May 27.

Division of Periodontology, The Ohio State University, Columbus, OH, USA.

Six percent of Americans, including 3 million high schoolers, use e-cigarettes, which contain potentially toxic substances, volatile organic compounds, and metals. We present the first human study on the effects of e-cigarette exposure in the oral cavity. By interrogating both immunoinflammatory responses and microbial functional dynamics, we discovered pathogen overrepresentation, higher virulence signatures, and a brisk proinflammatory signal in clinically healthy e-cigarette users, equivalent to patients with severe periodontitis. Using RNA sequencing and confocal and electron microscopy to validate these findings, we demonstrate that the carbon-rich glycol/glycerol vehicle is an important catalyst in transforming biofilm architecture within 24 hours of exposure. Last, a machine-learning classifier trained on the metagenomic signatures of e-cigarettes identified as e-cigarette users both those individuals who used e-cigarettes to quit smoking, and those who use both e-cigarettes and cigarettes. The present study questions the safety of e-cigarettes and the harm reduction narrative promoted by advertising campaigns.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.aaz0108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253170PMC
May 2020

Urinary Soluble CD163: a Novel Noninvasive Biomarker of Activity for Lupus Nephritis.

J Am Soc Nephrol 2020 06 16;31(6):1335-1347. Epub 2020 Apr 16.

Division of Nephrology, Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, Ohio

Background: Clinical distinction between patients with lupus nephritis who have active inflammation or chronic kidney damage is challenging. Studies have shown soluble CD163, which derives from cleavage of the CD163 M2c macrophage receptor and can be quantified in urine, correlates with active lupus nephritis.

Methods: We measured urine CD163 at lupus nephritis flares in patients from a Mexican cohort and cross-sectional and longitudinal United States cohorts. We also performed serial urine CD163 measurements during the treatment of flares in a subset of patients from the Mexican and longitudinal United States cohorts, and assessed response to therapy at 12 months. In addition, we evaluated urinary CD163 agreement with histologic activity in 19 patients from the Mexican cohort who had repeated kidney biopsies on follow-up.

Results: Urinary CD163 levels were significantly higher in patients with active lupus nephritis than in patients with active extrarenal SLE, inactive SLE, and other glomerular diseases, and correlated with disease clinical severity, histologic class, and the histologic activity index. Urinary CD163 increased from 6 months preflare to flare, diminishing progressively in complete and partial responders, whereas it remained elevated in nonresponders. Urinary CD163 <370 ng/mmol at 6 months predicted complete renal response at 12 months with >87% sensitivity and >87% specificity. Urinary CD163 <370 ng/mmol or >370 ng/mmol perfectly agreed (=1.0) with a histologic activity index ≤1 or >1 in repeated biopsies, respectively. Evaluation of urinary CD163 in patients with persistent proteinuria at 6 months improved the prediction of who would achieve complete renal response at 12 months.

Conclusions: Urinary CD163 reflects histologic inflammation in lupus nephritis and is a promising activity biomarker that varies over time with lupus nephritis activity and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1681/ASN.2019121285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269356PMC
June 2020

The aggregation paradox for statistical rankings and nonparametric tests.

PLoS One 2020 12;15(3):e0228627. Epub 2020 Mar 12.

Syracuse University, David B. Falk College of Sport & Human Dynamics, Syracuse, NY, United States of America.

The relationship between social choice aggregation rules and non-parametric statistical tests has been established for several cases. An outstanding, general question at this intersection is whether there exists a non-parametric test that is consistent upon aggregation of data sets (not subject to Yule-Simpson Aggregation Paradox reversals for any ordinal data). Inconsistency has been shown for several non-parametric tests, where the property bears fundamentally upon robustness (ambiguity) of non-parametric test (social choice) results. Using the binomial(n, p = 0.5) random variable CDF, we prove that aggregation of r(≥2) constituent data sets-each rendering a qualitatively-equivalent sign test for matched pairs result-reinforces and strengthens constituent results (sign test consistency). Further, we prove that magnitude of sign test consistency strengthens in significance-level of constituent results (strong-form consistency). We then find preliminary evidence that sign test consistency is preserved for a generalized form of aggregation. Application data illustrate (in)consistency in non-parametric settings, and links with information aggregation mechanisms (as well as paradoxes thereof) are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228627PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067399PMC
June 2020

Masked uncontrolled hypertension.

J Hypertens 2019 12;37(12):2501-2502

Division of Nephrology, Department of Internal Medicine, Davis Heart and Lung Research Institute, Ohio State University Medical Center, Columbus, Ohio.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0000000000002266DOI Listing
December 2019

Kidney biopsy-based management of maintenance immunosuppression is safe and may ameliorate flare rate in lupus nephritis.

Kidney Int 2020 01 20;97(1):156-162. Epub 2019 Aug 20.

Department of Internal Medicine and Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. Electronic address:

The optimal duration of maintenance immunosuppressive therapy for patients with lupus nephritis who have achieved clinical remission has not been established. Furthermore, clinical and histologic remissions are often discordant. We postulated that continuing therapy for patients with persistent histologic activity on kidney biopsies done during maintenance and discontinuing therapy only for patients without histologic activity would minimize subsequent lupus nephritis flares. To test this, a cohort of 75 prospectively-followed patients with proliferative lupus nephritis was managed using kidney biopsies performed during maintenance therapy. These patients had been on immunosuppression for at least 42 months, had responded, and had maintained their clinical response for at least 12 months before the kidney biopsy was repeated. Maintenance therapy was withdrawn if the biopsy showed an activity index of zero, but was continued if the biopsy showed an activity index of one or more. A lupus nephritis flare developed in seven patients during the average 50 months from the third biopsy and the final clinic visit for a flare rate of 1.5/year; significantly less than reported flare rates. Baseline clinical parameters (serum creatinine, proteinuria) and serologic parameters (complement C3, C4 and anti-dsDNA) did not predict an activity index of zero on the third biopsy or who would have a lupus nephritis flare. No patients developed end-stage kidney disease. Four patients developed de novo chronic kidney disease. There were no serious adverse events related to biopsy. Thus, at an experienced center, biopsy-informed management of maintenance immunosuppression is safe and may improve the lupus nephritis flare rate compared to conventional clinical management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2019.07.018DOI Listing
January 2020

Elevated serum complement levels and higher gene copy number of complement are associated with hypertension and effective response to statin therapy in childhood-onset systemic lupus erythematosus (SLE).

Lupus Sci Med 2019 31;6(1):e000333. Epub 2019 Jul 31.

Division of Rheumatology, Nationwide Children's Hospitatl, Columbus, OH, USA.

Objective: Systemic lupus erythematosus (SLE) features high frequency of cardiovascular disease (CVD) and fluctuating complement levels. The clinical trial Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) aimed to evaluate whether atorvastatin treatment reduced the progression of atherosclerosis in 221 patients with childhood-onset SLE (cSLE), using carotid intima media thickness (CIMT) as surrogates. We leveraged APPLE biorepository and trial data to investigate the relationship between and CVD in cSLE.

Methods: Gene copy numbers (GCNs) for total , and were measured by TaqMan-based real-time PCR and Southern blotting, and analysed with laboratory and clinical parameters through Student's t-test and χ analyses. Effects of total , and GCNs on the response to placebo or atorvastatin treatment and progression of CIMT were examined by regression analyses.

Results: At baseline, C4 protein levels strongly correlated with GCNs of total (p=1.8×10). Each copy of gene increased mean serum C4 by 3.28 mg/dL. Compared with those without hypertension (N=142), individuals with hypertension demonstrated significantly elevated serum levels for C4 and C3 at baseline and serially (C4: P=5.0×10; C3: P=5.84×10). Individuals with ≥2 genes had 2.5 times the odds of having hypertension (p=0.016) and higher diastolic blood pressure (p=0.015) compared with those with deficiency. At the study end, subjects with ≥2 and atorvastatin treatment had significantly slower increase in CIMT compared with those treated with placebo (p=0.018).

Conclusions: cSLE with hypertension had elevated serum levels of C4 and C3 and higher GCN of ; cSLE with ≥2 genes would benefit from statins therapy to prevent atherosclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/lupus-2019-000333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687033PMC
July 2019

Immunostaining for galactose-deficient immunoglobulin A is not specific for primary immunoglobulin A nephropathy.

Nephrol Dial Transplant 2020 12;35(12):2123-2129

Department of Pathology, Division of Renal Pathology, Ohio State University Wexner Medical Center, Columbus, OH, USA.

Background: Primary immunoglobulin A nephropathy (IgAN) is characterized by IgA1-dominant or codominant glomerular deposits, postulated to be galactose deficient (Gd). However, glomerular IgA deposition can also occur in nonrenal diseases such as liver cirrhosis, psoriasis and inflammatory bowel disease ('secondary IgAN') or be an incidental finding in biopsies with other pathologies. A glomerulonephritis resembling IgAN can develop in patients with bacterial, mainly staphylococcal infections [staphylococcal infection-associated glomerulonephritis (SAGN)]. There are no specific histological features to distinguish between these, but differentiation is critical for appropriate management. The aim of this study was to investigate whether a recently described antibody to Gd-IgA1 (KM-55) could aid in differentiating primary IgAN from other conditions with glomerular IgA deposition, especially SAGN.

Methods: We performed a retrospective cohort study of patients who underwent kidney biopsy for clinical indications and were found to have glomerular IgA deposits.

Results: We evaluated 100 biopsies, including primary IgAN (n = 44), secondary IgAN (n = 27), SAGN (n = 13), incidental IgA deposition (n = 8) and lupus nephritis (n = 8). There was no difference in Gd-IgA staining intensity or the proportion of positive cases between primary and secondary IgAN. SAGN and cases with incidental IgA deposits had significantly lower Gd-IgA staining intensity than primary IgAN, but up to 69% of SAGN cases were positive (albeit weaker).

Conclusions: Gd-IgA staining is present not only in primary IgAN, but also in biopsies with secondary IgAN, SAGN and incidental IgA. Weak or negative staining may favor SAGN, especially in the setting of infection, or incidental IgA in the absence of nephritic symptoms or in the presence of other unrelated glomerular pathologies. However, positive staining for Gd-IgA alone is not specific enough for a diagnosis of primary IgAN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfz152DOI Listing
December 2020

Opposite Profiles of Complement in Antiphospholipid Syndrome (APS) and Systemic Lupus Erythematosus (SLE) Among Patients With Antiphospholipid Antibodies (aPL).

Front Immunol 2019 7;10:885. Epub 2019 May 7.

The Research Institute at Nationwide Children's Hospital, Columbus, OH, United States.

APS is the association of antiphospholipid antibodies (aPL) with thromboses and/or recurrent pregnancy loss (RPL). Among patients with SLE, one-third have aPL and 10-15% have a manifestation of secondary APS. Animal studies suggested that complement activation plays an important role in the pathogenesis of thrombosis and pregnancy loss in APS. We performed a cross-sectional study on complement proteins and genes in 525 patients with aPL. Among them, 237 experienced thromboses and 293 had SLE; 111 had both SLE and thromboses, and 106 had neither SLE nor thrombosis. Complement protein levels were determined by radial immunodiffusion for C4, C3 and factor H; and by functional ELISA for mannan binding lectin (MBL). Total and gene copy numbers (GCN) were measured by TaqMan-based realtime PCR. Two to six copies of genes are frequently present in a diploid genome, and each copy may code for an acidic C4A or a basic C4B protein. We observed significantly (a) protein levels of total C4, C4A, C4B, C3, and anticardiolipin (ACLA) IgG, (b) increased frequencies of lupus anticoagulant and males, and (c) decreased levels of complement factor H, MBL and ACLA-IgM among patients with thrombosis than those without thrombosis ( = 288). We also observed significantly GCNs of total and among aPL-positive patients with both SLE and thrombosis than others. By contrast, aPL-positive subjects with SLE had significantly reduced protein levels of C3, total C4, C4A, C4B and ACLA-IgG, and higher frequency of females than those without SLE. Patients with thrombosis but SLE ( = 126), and patients with SLE but thrombosis ( = 182) had the greatest differences in mean protein levels of C3 ( = 2.6 × 10), C4 ( = 2.2 × 10) and ACLA-IgG ( = 1.2 × 10). RPL occurred in 23.7% of female patients and thrombotic SLE patients had the highest frequency of RPL (41.0%; = 3.8 × 10). Compared with non-RPL females, RPL had significantly higher frequency of thrombosis and elevated C4 protein levels. Female patients with homozygous C4A deficiency experienced RPL ( = 0.0001) but the opposite was true for patients with homozygous C4B deficiency ( = 0.017). These results provide new insights and biomarkers for diagnosis and management of APS and SLE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2019.00885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514053PMC
September 2020

Left atrial volume quantification using coronary calcium score scan: Feasibility, reliability and reproducibility analysis of a standardized approach.

Int J Cardiol Heart Vasc 2019 Jun 30;23:100351. Epub 2019 Mar 30.

The Ohio State University Wexner Medical Center, 473 W 12th Avenue, Suite 200, Columbus, OH, 43210, United States of America.

Background: Left atrial volume (LAV) is an independent prognosticator of cardiovascular events. We investigated whether LAV could be accurately and reliably measured using coronary calcium score (CAC) scan.

Methods: We retrospectively selected consecutive patients that underwent coronary CT angiography (CCTA) and CAC scans. A standardized approach to calculate LAV on images was implemented. The measurements of the LAV on CAC scans and CCTA were performed one to three weeks apart in a random fashion by two readers blinded to the results of each other. The LAV measurements from CAC scan were compared to those from CCTA using correlation analysis. Inter-observer and intra-observer agreement of LAV measurement using CAC scan was evaluated.

Results: Final analysis included one hundred subjects, mean age 52 ± 12 years, 48% male. There was a trend of a marginally larger, albeit not clinically significant, mean LAV calculated using CAC scan compared to that using CCTA: 74.3 vs. 71.0 mL:  < 0.001; for reader 1, and 71.7 vs. 71.2 mL  = 0.06 for reader 2, respectively. LAV using CAC scan and CCTA were highly correlated ( = 0.954,  < 0.001 for reader1 and  = 0.945,  < 0.001 for reader 2). There was high reproducibility within each reader with ICC of 0.951 and 0.989 for readers 1 and 2, respectively ( < 0.001). Finally, there was high inter-observer agreement as indicated by of 0.97 and ICC of 0.96 ( < 0.001 for both).

Conclusions: Quantification of LAV from CAC scan using the proposed standardized approach is feasible, highly reliable and reproducible as compared to CCTA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcha.2019.100351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441762PMC
June 2019

Tobacco product transition patterns in rural and urban cohorts: Where do dual users go?

Prev Med Rep 2018 Dec 22;12:241-244. Epub 2018 Oct 22.

The Ohio State University College of Public Health, Division of Health Behavior & Health Promotion, Columbus, OH, USA.

Introduction: Understanding diverse tobacco product consumption represents a crucial area for tobacco regulatory science. With the increase in dual/poly use of tobacco products, transition patterns among exclusive and dual users are of considerable interest. We describe transition patterns of dual users over 18 months.

Methods: A cohort of 145 adults in urban and rural Ohio who reported dual tobacco product use at least some days/week was enrolled during 2014-17. Participants completed follow-up interviews every six months where they were classified into one of five categories: 1) exclusive combustible, 2) exclusive smokeless, 3) exclusive e-cigarette, 4) dual (at least 2 of the previous 3 categories), and 5) less than some days/week. Participants categorized as exclusive and dual (1-4) used their products at least some days per week. Separately within the rural and urban cohorts, 6, 12, and 18 month transition probabilities between the categories were estimated.

Results: The probability of remaining a dual user after 6 months is 43% in the rural and 37% in the urban cohort. The decline continues through 18 months with 24% of rural and 22% of urban dual users remaining in the category. The probability of a dual user consuming combustibles and e-cigarettes transitioning to exclusive combustible use in 6 months is over 50% in both the rural and urban cohorts.

Conclusions: Dual use is an unstable state with users being more likely to transition to exclusive combustible use than to remain in the dual use category. Transitions are similar in the rural and urban cohorts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pmedr.2018.10.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205333PMC
December 2018

Odds ratios from logistic, geometric, Poisson, and negative binomial regression models.

BMC Med Res Methodol 2018 10 20;18(1):112. Epub 2018 Oct 20.

Division of Biostatistics, The Ohio State University, 1841 Neil Avenue, Columbus, OH, 43210-1240, USA.

Background: The odds ratio (OR) is used as an important metric of comparison of two or more groups in many biomedical applications when the data measure the presence or absence of an event or represent the frequency of its occurrence. In the latter case, researchers often dichotomize the count data into binary form and apply the well-known logistic regression technique to estimate the OR. In the process of dichotomizing the data, however, information is lost about the underlying counts which can reduce the precision of inferences on the OR.

Methods: We propose analyzing the count data directly using regression models with the log odds link function. With this approach, the parameter estimates in the model have the exact same interpretation as in a logistic regression of the dichotomized data, yielding comparable estimates of the OR. We prove analytically, using the Fisher information matrix, that our approach produces more precise estimates of the OR than logistic regression of the dichotomized data. We also show the gains in precision using simulation studies and real-world datasets. We focus on three related distributions for count data: geometric, Poisson, and negative binomial.

Results: In simulation studies, confidence intervals for the OR were 56-65% as wide (geometric model), 75-79% as wide (Poisson model), and 61-69% as wide (negative binomial model) as the corresponding interval from a logistic regression produced by dichotomizing the data. When we analyzed existing datasets using our approach, we found that confidence intervals for the OR could be up to 64% shorter (36% as wide) compared to if the data had been dichotomized and analyzed using logistic regression.

Conclusions: More precise estimates of the OR can be obtained directly from the count data by using the log odds link function. This analytic approach is easy to implement in software packages that are capable of fitting generalized linear models or of maximizing user-defined likelihood functions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12874-018-0568-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195979PMC
October 2018

A prospective observational cohort study highlights kidney biopsy findings of lupus nephritis patients in remission who flare following withdrawal of maintenance therapy.

Kidney Int 2018 10 23;94(4):788-794. Epub 2018 Jul 23.

The Ohio State University Wexner Medical Center Department of Internal Medicine-Nephrology, Columbus, Ohio, USA. Electronic address:

One of the most difficult management issues in lupus nephritis (LN) is the optimal duration of maintenance immunosuppression after patients are in clinical remission. Most patients receive immunosuppression for years, based mainly on expert opinion. Prospective data are unavailable. Complicating this issue are data that patients in clinical remission can still have histologically active LN; however, the implications of this are unknown. To study this, the Lupus Flares and Histological Renal Activity at the end of Treatment study (ClinicalTrial.gov, NCT02313974) was designed to examine whether residual histologic activity predisposes to LN flares in class III and IV LN. Patients in complete clinical remission for at least 12 months who had received at least 36 months of immunosuppression were eligible. Patients consented to a second kidney biopsy, were tapered off maintenance immunosuppression and were then followed prospectively for LN flares over 24 months. Forty-four patients were enrolled, and 36 completed the study. LN flares occurred in 11 patients, and ten of these had residual histologic activity on the second biopsy. All patients with an NIH activity index over two flared. The activity index and duration of systemic lupus erythematosus at the second biopsy were independent predictors of flare. A predictive equation based on these variables discriminated between flare and no flare with a sensitivity of 100%, specificity of 88%, and a misclassification rate of 8.3%. Thus, a repeat kidney biopsy may be useful in managing maintenance immunosuppression in LN, and patients in histologic remission may be candidates for withdrawal of therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2018.05.021DOI Listing
October 2018

Characteristics of the Tobacco User Adult Cohort in Urban and Rural Ohio.

Tob Regul Sci 2018 Jan 1;4(1):614-630. Epub 2018 Jan 1.

Professor, The Ohio State University Center of Excellence in Regulatory Tobacco Science, Columbus, OH.

Objectives: Identifying characteristics associated with the use of new and emerging tobacco products is a priority. The enumeration and baseline characteristics of a new cohort of adult tobacco users are described.

Methods: Residents, ≥18 years of age, in urban Franklin County, or one of 6 rural Appalachian counties, and who were exclusive users of combustible, smokeless (SLT), or electronic nicotine delivery systems (ENDS) tobacco products, or were dual users, were targeted for recruitment. Participants were interviewed in-person at baseline on sociodemographic characteristics, tobacco product use, and cognitive/affective and purchasing factors.

Results: We recruited 1210 participants (urban, N = 595; rural, N = 615). Urban participants were less likely to use tobacco daily, began using tobacco later, used tobacco for less time, and had higher cessation interest. ENDS users were significantly less likely to have made a quit attempt than users of other tobacco products. Duration of tobacco use and nicotine dependence also differed by product type.

Conclusion: This cohort's enumeration allowed us to compare factors associated with tobacco product preferences and the use of novel products. The inclusion of rural Appalachia-a region with high tobacco use and disease burden-may provide additional insights into the implementation of tobacco control interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18001/TRS.4.1.8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5978725PMC
January 2018

The role of travel distance and price promotions in tobacco product purchase quantity.

Health Place 2018 05 3;51:151-157. Epub 2018 Apr 3.

The Ohio State University College of Public Health, Cunz Hall, 1841 Neil Ave., Columbus, OH 43210, United States.

Introduction: Rural Americans are particularly vulnerable to tobacco price reducing promotions are known to be directed to and used by vulnerable populations. Tobacco purchasing decisions, such as unit quantity purchased, may vary by rurality, by price promotion use, and possibly by the interaction between the two. Purchase decisions are likely to affect tobacco use behavior. Therefore, explanation of variation in tobacco purchase quantity by factors associated with rural vulnerability and factors that fall under the regulatory scope of the Tobacco Control Act (TCA) of 2009 could be of value to regulatory proposals intended to equitably benefit public health.

Methods: Our sample included 54 combustible tobacco users (298 purchase events) and 27 smokeless tobacco users (112 purchase events), who were asked to report all tobacco purchases on a smartphone application. We used an ecological momentary assessment methodology to collect data about tobacco users' purchasing patterns, including products, quantity purchased, and use of price promotions. A parent cohort study provided relevant data for home-outlet distance calculation and covariates. Our analysis examined associations between our outcome-purchase quantity per purchase event-and distance from participant's home to the nearest outlet, whether a price reducing promotion was used, and the interaction of these two factors.

Results: Combustible users showed an increased cigarette pack purchase quantity if they lived further from an outlet and used a price promotion (i.e., an interaction effect; RR = 1.70, 95% CI [1.11, 2.62]). Smokeless users purchased more units of snuff when they used price promotions (RR = 1.81, 95% CI [1.02, 3.20]).

Conclusions: Regulatory action that imposes restrictions on the availability or use of price promotions could alter the purchasing behavior of rural Americans in such a way that makes it easier to reduce tobacco use or quit. Such action would also restrict flexibility in the price of tobacco products, which is known as a powerful tobacco control lever.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.healthplace.2018.03.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964010PMC
May 2018

T-Wave Abnormality as Electrocardiographic Signature of Myocardial Edema in Non-ST-Elevation Acute Coronary Syndromes.

J Am Heart Assoc 2018 01 26;7(3). Epub 2018 Jan 26.

The Ohio State University Heart and Vascular Center, Columbus, OH

Background: T-wave abnormalities are common during the acute phase of non-ST-segment elevation acute coronary syndromes, but mechanisms underlying their occurrence are unclear. We hypothesized that T-wave abnormalities in the presentation of non-ST-segment elevation acute coronary syndromes correspond to the presence of myocardial edema.

Methods And Results: Secondary analysis of a previously enrolled prospective cohort of patients presenting with non-ST-segment elevation acute coronary syndromes was conducted. Twelve-lead electrocardiography (ECG) and cardiac magnetic resonance with T2-weighted imaging were acquired before invasive coronary angiography. ECGs were classified dichotomously (ie, ischemic versus normal/nonischemic) and nominally according to patterns of presentation: no ST- or T-wave abnormalities, isolated T-wave abnormality, isolated ST depression, ST depression+T-wave abnormality. Myocardial edema was determined by expert review of T2-weighted images. Of 86 subjects (65% male, 59.4 years), 36 showed normal/nonischemic ECG, 25 isolated T-wave abnormalities, 11 isolated ST depression, and 14 ST depression+T-wave abnormality. Of 30 edema-negative subjects, 24 (80%) had normal/nonischemic ECGs. Isolated T-wave abnormality was significantly more prevalent in edema-positive versus edema-negative subjects (41.1% versus 6.7%, =0.001). By multivariate analysis, an ischemic ECG showed a strong association with myocardial edema (odds ratio 12.23, 95% confidence interval 3.65-40.94, <0.0001). Among individual ECG profiles, isolated T-wave abnormality was the single strongest predictor of myocardial edema (odds ratio 23.84, 95% confidence interval 4.30-132, <0.0001). Isolated T-wave abnormality was highly specific (93%) but insensitive (43%) for detecting myocardial edema.

Conclusions: T-wave abnormalities in the setting of non-ST-segment elevation acute coronary syndromes are related to the presence of myocardial edema. High specificity of this ECG alteration identifies a change in ischemic myocardium associated with worse outcomes that is potentially reversible.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.117.007118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850236PMC
January 2018

Patients with sporadic and familial amyotrophic lateral sclerosis found value in genetic testing.

Mol Genet Genomic Med 2018 03 20;6(2):224-229. Epub 2017 Dec 20.

Division of Human Genetics, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Background: Amyotrophic lateral sclerosis (ALS) is increasingly recognized as a genetic disease. There is no consensus, however, as to the role of genetic testing in the care of the ALS patient.

Methods: We conducted a survey to study patient access, attitudes, and experience with ALS genetic testing among patients enrolled in a US ALS registry.

Results: Among 449 survey respondents, 156 (34.7%) were offered testing and 105 of 156 (67.3%) completed testing. The majority of respondents with familial ALS (fALS) (31/45, 68.9%) were offered testing, while a minority of respondents with sporadic ALS (sALS) (111/404, 27.5%) were offered testing (p = .00001). Comparison of mean test experience scores between groups revealed that respondents with fALS were no more likely to report a favorable experience with genetic testing than those with sALS (p = .51). Respondents who saw a genetic counselor did not have significantly different test experience scores, compared to those who did not (p = .14). In addition, no differences in test experience scores were observed between those who received positive or negative genetic test results (p = .98).

Conclusion: These data indicate that patients with ALS found value in clinical genetic testing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mgg3.360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902388PMC
March 2018

Digitally translated Self-Administered Gerocognitive Examination (eSAGE): relationship with its validated paper version, neuropsychological evaluations, and clinical assessments.

Alzheimers Res Ther 2017 Jun 27;9(1):44. Epub 2017 Jun 27.

Neuropsychology Laboratory, Department of Psychiatry, The Ohio State University Wexner Medical Center, 1670 Upham Drive, Columbus, OH, 43210, USA.

Background: The original paper Self-Administered Gerocognitive Examination (SAGE) is a valid and reliable cognitive assessment tool used to identify individuals with mild cognitive impairment (MCI) or early dementia. We evaluated identical test questions in a digital format (eSAGE) made for tablet use with the goals of calibrating it against SAGE and establishing its association with other neuropsychological tests and clinical assessments of cognitive impairment.

Methods: Subjects aged 50 and over who had taken SAGE were recruited from community and clinic settings. Subjects were randomly selected to participate in a clinical evaluation including neuropsychological evaluations. SAGE and eSAGE were administered using a crossover design. Subjects were identified as dementia, MCI, or normal based on standard clinical criteria. Associations were investigated using Spearman correlations, linear regression, and sensitivity and specificity measures.

Results: Of the 426 subjects screened, 66 completed the evaluation. eSAGE score correlation to a battery of neuropsychological tests was 0.73 (p < 0.0001) with no significant difference between the paper and digital format. Spearman correlation of SAGE versus eSAGE was 0.88 (p < 0.0001), and they are related by the formula: eSAGE score = -1.05 + 0.99 × SAGE score. Since the slope is very close to 1 (p = 0.86) there is strong evidence that the scaling is identical between eSAGE and SAGE, with no scale bias. Overall, eSAGE scores are lower by an average of 1.21 and the decrease is statistically significant (p < 0.0001). For those subjects familiar with smartphones or tablets (one measure of digital proficiency), eSAGE scores are lower by an average of 0.83 points (p = 0.029). With a score 16 and higher being classified as normal, eSAGE had 90% specificity and 71% sensitivity in detecting those with cognitive impairment from normal subjects.

Conclusions: Tablet-based eSAGE shows a strong association with the validated paper SAGE and a neuropsychological battery. It shows no scale bias compared to SAGE. Both have the advantage of self-administration, brevity, four interchangeable forms, and high sensitivity and specificity in detecting cognitive impairment from normal subjects. Their potential widespread availability will be a major factor in overcoming the many obstacles in identifying early cognitive changes.

Trial Registration: ClinicalTrials.gov, NCT02544074 . Registered on 18 March 2015.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13195-017-0269-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5488440PMC
June 2017

Interrater and Intrarater Reliability of Arthroscopic Measurements of Articular Cartilage Defects in the Knee.

J Bone Joint Surg Am 2017 Jun;99(12):979-988

1Division of Sports Medicine Cartilage Repair Center, Department of Orthopaedics (D.C.F., W.C.G., and A.C.D.), Division of Biostatistics, College of Public Health (H.N.N.), and Wexner Medical Center (D.C.F. and A.C.D.), The Ohio State University, Columbus, Ohio 2Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 3Department of Orthopaedic Surgery, Washington University, St. Louis, Missouri 4OrthoCarolina, Pineville, North Carolina 5University of Kentucky, Lexington, Kentucky.

Background: Cartilage lesions of the knee are difficult to treat. Lesion size is a critical factor in treatment algorithms, and the accurate, reproducible sizing of lesions is important. In this study, we evaluated the interrater and intrarater reliability of, and correlations in relation to, various arthroscopic sizing techniques.

Methods: Five lesions were created in each of 10 cadaveric knees (International Cartilage Repair Society grade 3C). Three orthopaedic surgeons used 4 techniques (visualization and use of a 3-mm probe, a simple metal ruler, and a sliding metallic ruler tool) to estimate lesion size. Repeated-measures data were analyzed using a mixed-effect linear model. The differences between observed and gold-standard (plastic mold) values were used as the response. Intraclass and interclass correlation coefficient (ICC) values for intrarater and interrater reliability were computed, as were overall correlation coefficients between measurements and gold standards.

Results: The mean lesion size was 2.37 cm (range, 0.36 to 6.02 cm). Rater, lesion location and size, and measurement method all affected the cartilage defect measurements. Surgeons underestimated lesion size, and measurements of larger lesions had a higher percentage of error compared with those of smaller lesions. When compared with plastic molds of lesions, 60.5% of surgeon measurements underestimated lesion size. Overall, the correlation between measurements and gold standards was strongest for the simple metal ruler method and weakest for the visualization method.

Conclusions: Several factors may influence arthroscopic estimation of cartilage lesion size: the lesion location, measurement tool, surgeon, and defect size itself. The intrarater and interrater reliability was moderate to good using a 3-mm probe, sliding metallic ruler tool, or simple metal ruler and was fair to moderate using visualization only.

Clinical Relevance: There is a need for more accurate methods of determining the size of articular cartilage lesions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2106/JBJS.16.01132DOI Listing
June 2017

A tale of two risks: smoking, diabetes and the subgingival microbiome.

ISME J 2017 09 23;11(9):2075-2089. Epub 2017 May 23.

Division of Periodontology, College of Dentistry, The Ohio State University, Coloumbus, OH, USA.

Although smoking and diabetes have been established as the only two risk factors for periodontitis, their individual and synergistic impacts on the periodontal microbiome are not well studied. The present investigation analyzed 2.7 million 16S sequences from 175 non-smoking normoglycemic individuals (controls), smokers, diabetics and diabetic smokers with periodontitis as well as periodontally healthy controls, smokers and diabetics to assess subgingival bacterial biodiversity and co-occurrence patterns. The microbial signatures of periodontally healthy smokers, but not diabetics, were highly aligned with the disease-associated microbiomes of their respective cohorts. Diabetics were dominated by species belonging to Fusobacterium, Parvimonas, Peptostreptococcus, Gemella, Streptococcus, Leptotrichia, Filifactor, Veillonella, TM7 and Terrahemophilus. These microbiomes exhibited significant clustering based on HbA1c levels (pre-diabetic (<6.5%), diabetic (6.5-9.9%), diabetics >10%). Smokers with periodontitis evidenced a robust core microbiome (species identified in at least 80% of individuals) dominated by anaerobes, with inter-individual differences attributable largely to the 'rare biosphere'. Diabetics and diabetic smokers, on the other hand, were microbially heterogeneous and enriched for facultative species. In smokers, microbial co-occurrence networks were sparse and predominantly congeneric, while robust inter-generic networks were observed in diabetics and diabetic smokers. Smoking and hyperglycemia impact the subgingival microbiome in distinct ways, and when these perturbations intersect, their synergistic effect is greater than what would be expected from the sum of each effect separately. Thus, this study underscores the importance of early intervention strategies in maintaining health-compatible microbiomes in high-risk individuals, as well as the need to personalize these interventions based on the environmental perturbation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ismej.2017.73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5563960PMC
September 2017

Factors Determining Left Main Coronary Artery Luminal Area.

J Invasive Cardiol 2017 Jul 15;29(7):246-249. Epub 2017 Feb 15.

The Ohio State University, Department of Medicine/Cardiovascular Medicine, Columbus, Ohio 43210 USA.

Background: A certain minimal luminal cross-sectional area has been traditionally used in clinical practice as a cut-off value to determine severity of left main coronary artery (LMCA) stenosis. The severity of stenosis, however, depends on the baseline luminal area (ie, area prior to stenosis), which may vary among individuals. The present study was undertaken to define normal LMCA luminal area using current technology in vivo.

Methods: LMCA luminal area was determined using multislice computed tomography coronary angiography. Eighty-six subjects with normal coronary arteries and calcium score of zero were included in this study. Left ventricular (LV) mass and LV volumes (systolic, diastolic) were also measured.

Results: A wide distribution was found in LMCA luminal area, with median value 17.3 mm² and range 8.1-33.9 mm². A relationship was found between log(LMCA luminal area) and log(LV mass) (r=.515; P<.001) and with body surface area (r=.273; P=.01). Significant relationships were also found between LMCA luminal area and LV volumes (systolic, diastolic). In multiple regression analysis, however, the LV mass was the only independent predictor of LMCA luminal area.

Conclusion: LMCA luminal area varies substantially among individuals with normal coronary arteries and is related to many other factors. The data suggest that the current practice of using a minimal luminal area cut-off when assessing LMCA stenosis may be misleading, and thus available information should be individualized.
View Article and Find Full Text PDF

Download full-text PDF

Source
July 2017

Prevalence, predictors, and outcomes of steroid-induced hyperglycemia in hospitalized patients with hematologic malignancies.

Endocrine 2017 Apr 6;56(1):90-97. Epub 2017 Jan 6.

Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University Wexner Medical Center, 5th Floor McCampbell Hall, 1581 Dodd Drive, Columbus, OH, 43210-1296, USA.

Purpose: To determine prevalence, predictors, and outcomes of steroid-induced hyperglycemia in hospitalized patients with hematologic malignancies METHODS: We performed retrospective analysis of patients who were hospitalized on any of the four hematology services or bone marrow transplant service and who received systemic steroids during a 2-month period. Mean glucoses for days 1-4 and maximum glucose were calculated and the total daily steroid dose was converted to equivalent dose of dexamethasone. Hyperglycemia was defined as any glucose >9.917 mmol/l during days 1-4. We examined associations between variables using Spearman's correlations and multivariable linear regression RESULTS: 168 patients were included in the analysis. Mean age was 57.1 ± 14.4 years with 59% males and 90% Caucasians. The prevalence of hyperglycemia was 39%. Eight patients received intravenous insulin. In patients without diabetes, steroid dose equivalent to >12 mg dexamethasone and longer acting steroids caused greater degree of hyperglycemia compared to a dose <12 mg. Maximum glucose was a predictor of hospital length of stay among patients without diabetes (but not those with diabetes), and with acute leukemia or stem cell transplant (but not other hematologic malignancies). There were no significant differences in in mortality or other outcomes between the groups with and without hyperglycemia CONCLUSIONS: Hyperglycemia is common in patients with hematologic malignancies, which require frequent corticosteroids. Higher steroid dose and long-acting steroids caused a greater degree of hyperglycemia. Maximum glucose was a predictor of length of stay but this was only significant for patients without diabetes, those with acute hematologic malignancy or stem cell transplant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12020-016-1220-2DOI Listing
April 2017

Paired Studies Comparing Clinical Profiles of Lewy Body Dementia with Alzheimer's and Parkinson's Diseases.

J Alzheimers Dis 2016 10;54(3):995-1004

Department of Neurology, The Ohio State University, Columbus, OH, USA.

Limited data compares clinical profiles of Lewy Body Dementia (LBD) with Alzheimer's disease (AD) and Parkinson's disease (PD). Twenty-one mildly demented ambulatory LBD subjects were individually matched by MMSE score with 21 AD subjects and by UPDRS motor score with 21 PD subjects. Matched by age, gender, education, and race, pairs were compared using cognitive, functional, behavioral, and motor measures. LBD group performed worse than PD on axial motor, gait, and balance measures. AD had more amnesia and orientation impairments, but less executive and visuospatial deficits than LBD subjects. LBD group had more sleepiness, cognitive/behavioral fluctuations, hallucinations, and sleep apnea than AD or PD. Axial motor, gait, and balance disturbances correlated with executive, visuospatial, and global cognition deficits. LBD is differentiated from AD and PD by retrieval memory, visuospatial, and executive deficits; axial motor, gait and balance impairments; sleepiness, cognitive/behavioral fluctuations, hallucinations, and sleep apnea.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/JAD-160384DOI Listing
October 2016

Effects of Complement C4 Gene Copy Number Variations, Size Dichotomy, and C4A Deficiency on Genetic Risk and Clinical Presentation of Systemic Lupus Erythematosus in East Asian Populations.

Arthritis Rheumatol 2016 06;68(6):1442-1453

Center for Molecular and Human Genetics, The Research Institute and Division of Pediatric Rheumatology, Nationwide Children's Hospital; and Department of Pediatrics, The Ohio State University, 700 Children's Drive, Columbus, Ohio 43205, USA.

Objective: Human complement C4 is complex, with multiple layers of diversity. The aims of this study were to elucidate the copy number variations (CNVs) of C4A and C4B in relation to disease risk in systemic lupus erythematosus (SLE), and to compare the basis of race-specific C4A deficiency between East Asians and individuals of European descent.

Methods: The East Asian study population included 999 SLE patients and 1,347 healthy subjects. Variations in gene copy numbers (GCNs) of total C4, C4A, and C4B, as well as C4-Long and C4-Short genes, were determined and validated using independent genotyping technologies. Genomic regions with C4B96 were investigated to determine the basis of the most basic C4B protein occurring concurrently with C4A deficiency.

Results: In East Asians, high GCNs of total C4 and C4A were strongly protective against SLE, whereas low and medium GCNs of total C4 and C4A, and the absence of C4-Short genes, were risk factors for SLE. Homozygous C4A deficiency was infrequent in East Asian subjects, but had an odds ratio (OR) of 12.4 (P = 0.0015) for SLE disease susceptibility. Low serum complement levels were strongly associated with low GCNs of total C4 (OR 3.19, P = 7.3 × 10(-7) ) and C4B (OR 2.53, P = 2.5 × 10(-5) ). Patients with low serum complement levels had high frequencies of anti-double-stranded DNA antibodies (OR 4.96, P = 9.7 × 10(-17) ), hemolytic anemia (OR 3.89, P = 3.6 × 10(-10) ), and renal disease (OR 2.18, P = 8.5 × 10(-6) ). The monomodular-Short haplotype found to be prevalent in European Americans with C4A deficiency, which was in linkage disequilibrium with HLA-DRB1*0301, was scarce in East Asians. Instead, most East Asian subjects with C4A deficiency were found to have a recombinant haplotype with bimodular C4-Long and C4-Short genes, encoding C4B1 and C4B96, which was linked to HLA-DRB1*1501. DNA sequencing revealed an E920K polymorphism in C4B96.

Conclusion: C4 CNVs and deficiency of C4A both play an important role in the risk and manifestations of SLE in East Asian and European populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.39589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5114127PMC
June 2016

Impact of a Worksite Diabetes Prevention Intervention on Diet Quality and Social Cognitive Influences of Health Behavior: A Randomized Controlled Trial.

J Nutr Educ Behav 2016 Mar 16;48(3):160-9.e1. Epub 2016 Jan 16.

College of Public Health, Division of Biostatistics, Ohio State University, Columbus, OH.

Objective: To evaluate the impact of a worksite diabetes prevention intervention on secondary outcomes regarding the change in diet quality and components of the Health Action Process Approach (HAPA) theoretical framework.

Design: Pretest-posttest control group design with 3-month follow-up.

Setting: University worksite.

Participants: Employees aged 18-65 years with prediabetes (n = 68).

Intervention: A 16-week group-based intervention adapted from the Diabetes Prevention Program.

Main Outcome Measures: Diet quality was assessed using the Alternative Healthy Eating Index 2010; HAPA components were assessed via written questionnaire.

Analysis: Repeated-measures ANOVA compared the between- and within-group change in outcomes across time.

Results: Significant difference occurred between groups for the change in consumption of nuts/legumes and red/processed meats postintervention and for fruits at 3-month follow-up (all P < .05); a significant increase in total Alternative Healthy Eating Index 2010 score occurred postintervention in the experimental group (P = .002). The changes in action planning, action self-efficacy, and coping self-efficacy from HAPA were significantly different between groups after the intervention; the change in outcome expectancies was significantly different between groups at 3-month follow-up (all P < .05).

Conclusions And Implications: The worksite intervention facilitated improvement in diet quality and in planning and efficacious beliefs regarding diabetes prevention. Further research is needed to evaluate the long-term impact of the intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jneb.2015.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788518PMC
March 2016

Relationship of Circulating Anti-C3b and Anti-C1q IgG to Lupus Nephritis and Its Flare.

Clin J Am Soc Nephrol 2016 Jan 23;11(1):47-53. Epub 2015 Dec 23.

Department of Medicine and Davis Heart and Lung Research Institute, Ohio State University Medical Center, Columbus, Ohio; and.

Background And Objectives: Autoantibodies to complement C1q (anti-C1q) are associated with the diagnosis of lupus nephritis. In this study, we compare anti-C1q IgG with another complement autoantibody, anti-C3b IgG, as a biomarker of lupus nephritis and lupus nephritis flare.

Design, Setting, Participants, & Measurements: Our investigation involved the Ohio SLE Study, a prospective observational cohort of patients with recurrently active lupus who were followed bimonthly. Serum anti-C1q and anti-C3b IgG levels were assessed cross-sectionally by ELISA in 40 normal controls and 114 patients in the Ohio SLE Study (41 nonrenal and 73 lupus nephritis) at study entry, and longitudinally in a subset of patients in the Ohio SLE Study with anti-C1q-positive lupus nephritis in samples collected every 2 months for 8 months leading up to lupus nephritis flare (n=16 patients).

Results: In the cross-sectional analysis, compared with anti-C1q IgG, anti-C3b IgG was less sensitive (36% versus 63%) but more specific (98% versus 71%) for lupus nephritis. Only anti-C3b IgG was associated with patients with lupus nephritis who experienced at least one lupus nephritis flare during the Ohio SLE Study period (P<0.01). In the longitudinal analysis, circulating levels of anti-C1q IgG increased at the time of lupus nephritis flare only in patients who were anti-C3b positive (P=0.02), with significant increases occurring from 6 (38% increase) and 4 months (41% increase) before flare. Anti-C3b IgG levels also trended up at lupus nephritis flare, although the change did not reach statistical significance (P=0.07). Neither autoantibody increased 2 months before flare.

Conclusions: Although not as prevalent as anti-C1q IgG, anti-C3b IgG showed nearly complete specificity for lupus nephritis. The presence of anti-C3b IgG identified patients with lupus nephritis who were prone to flare and in whom serial measurements of markers associated with complement, such as anti-C1q IgG, may be useful to monitor lupus nephritis activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2215/CJN.03990415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702227PMC
January 2016

A Randomized Controlled Trial Translating the Diabetes Prevention Program to a University Worksite, Ohio, 2012-2014.

Prev Chronic Dis 2015 Nov 25;12:E210. Epub 2015 Nov 25.

The Ohio State University Health Plan, Inc, Columbus, Ohio.

Introduction: Working adults spend much time at the workplace, an ideal setting for wellness programs targeting weight loss and disease prevention. Few randomized trials have evaluated the efficacy of worksite diabetes prevention programs. This study evaluated the efficacy of a worksite lifestyle intervention on metabolic and behavioral risk factors compared with usual care.

Methods: A pretest-posttest control group design with 3-month follow-up was used. Participants with prediabetes were recruited from a university worksite and randomized to receive a 16-week lifestyle intervention (n = 35) or usual care (n = 34). Participants were evaluated at baseline, postintervention, and 3-month follow-up. Dietary intake was measured by a food frequency questionnaire and level of physical activity by accelerometers. Repeated measures analysis of variance compared the change in outcomes between and within groups.

Results: Mean (standard error [SE]) weight loss was greater in the intervention (-5.5% [0.6%]) than in the control (-0.4% [0.5%]) group (P < .001) postintervention and was sustained at 3-month follow-up (P < .001). Mean (SE) reductions in fasting glucose were greater in the intervention (-8.6 [1.6] mg/dL) than in the control (-3.7 [1.6] mg/dL) group (P = .02) postintervention; both groups had significant glucose reductions at 3-month follow-up (P < .001). In the intervention group, the intake of total energy and the percentage of energy from all fats, saturated fats, and trans fats decreased, and the intake of dietary fiber increased (all P < .01) postintervention.

Conclusion: The worksite intervention improved metabolic and behavioral risk factors among employees with prediabetes. The long-term impact on diabetes prevention and program sustainability warrant further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5888/pcd12.150301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4674443PMC
November 2015