Internal Medicine Commons^™

Interventions To Promote Adherence To Antiretroviral Therapy In Africa: A Network Meta-Analysis, Edward J. Mills, Richard Lester, Kristian Thorlund, Maria Lorenzi, Katherine Muldoon, Steve Kanters, Sebastian Linnemayr, Robert Gross, Yvette Calderon, K Rivet Amico, Harsha Thirumurthy, Cynthia Pearson, Robert H. Remien, Lawrence Mbuagbaw, Lehana Thabane, Michael Chung, Ira B. Wilson, Albert Liu, Olalekan A. Uthman, Jane Simoni, David Bangsberg, Sanni Yaya, Till Bärnighausen, Nathan Ford, Jean B. Nachega

Internal Medicine, East Africa

Background: Adherence to antiretroviral therapy (ART) is necessary for the improvement of the health of patients and for public health. We sought to determine the comparative effectiveness of different interventions for improving ART adherence in HIV-infected people living in Africa.

Methods: We searched for randomised trials of interventions to promote antiretroviral adherence within adults in Africa. We searched AMED, CINAHL, Embase, Medline (via PubMed), and ClinicalTrials.gov from inception to Oct 31, 2014, with the terms “HIV”, “ART”, “adherence”, and “Africa”. We created a network of the interventions by pooling the published and individual patients' data for comparable treatments and comparing …

New Onset Refractory Status Epilepticus As An Unusual Presentation Of A Suspected Organophosphate Poisoning, Shahan Waheed, Amber Sabeen, Nadeem Ullah Khan

Department of Medicine

New onset refractory status epilepticus (NORSE) is a new entity in medical literature. It has different infectious and noninfectious etiologies showing a devastating impact onto the clinical outcome of patients. Therapy with anaesthetic and antiepileptic agents often fails to improve the condition, unless the primary cause is rectified. Here is presented the case of a young female with a history of depression who after a recent bereavement came to the Emergency Department of Aga Khan University Hospital with complaints of drowsiness that lasted for few hours. Though she had no history of organophosphate poisoning, her physical examination and further investigations …

Emerging Antiretroviral Drug Resistance In Sub-Saharan Africa: Novel Affordable Technologies Are Needed To Provide Resistance Testing For Individual And Public Health Benefits, Gert U. Van Zyl, Lisa M. Frenkel, Michael Chung, Wolfgang Preiser, John W. Mellors, Jean B. Nachega

Internal Medicine, East Africa

In industrialized countries, viral load monitoring and genotypic antiretroviral drug resistance testing (GART) play an important role in the selection of initial and subsequent combination antiretroviral therapy (cART) regimens. In contrast, resource constraints in Africa limit access to assays that could detect virologic failure, transmitted drug resistance (TDR) and acquired drug resistance to cART. This has adverse consequences for both individual and public health. Although the further roll-out of antiretrovirals for prevention, including preexposure prophylaxis (PrEP) and universal test and treat (UTT) strategies, could reduce HIV-1 incidence, these strategies may increase TDR [1,2]. Here, we present arguments that the scale …

Current Perspectives On Primary Care Workforce, Kathleen Klink

Health Workforce Speaker Series

No abstract provided.

Oligonucleotide Ligation Assay Detects Hiv Drug Resistance Associated With Virologic Failure Among Antiretroviral-Naive Adults In Kenya, Michael Chung, Ingrid A. Beck, Sandra Dross, Kenneth Tapia, James N. Kiarie, Barbra A. Richardson, Julie Overbaugh, Samah R. Sakr, Grace C. John-Stewart, Lisa M. Frenkel

Internal Medicine, East Africa

Background: Transmitted drug resistance (TDR) is increasing in some areas of Africa. Detection of TDR may predict virologic failure of first-line non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART). We evaluated the utility of a relatively inexpensive oligonucleotide ligation assay (OLA) to detect clinically relevant TDR at time of ART initiation.

Methods: Pre-ART plasmas from ART-naive Kenyans initiating an NNRTI-based fixed-dose combination ART in a randomized adherence trial conducted in 2006 were retrospectively analyzed by OLA for mutations conferring resistance to NNRTI (K103N, Y181C, and G190A) and lamivudine (M184V). Post-ART plasmas were analyzed for virologic failure (≥1,000 copies/mL) at 6 month …

Effects Of Polypharmacy On Adverse Drug Reactions Among Geriatric Outpatients At A Tertiary Care Hospital In Karachi: A Prospective Cohort Study., Bilal Ahmed, Kashmira Nanji, Rakshinda Mujeeb, Muhammad Junaid Patel

Department of Medicine

Background: Adverse drug reactions (ADRs) present a challenging and expensive public health problem. Polypharmacy is defined according to the WHO criteria as the, ‘‘concurrent use of five or more different prescription medication’’. Elderly are more prone to adverse reactions due to comorbid conditions, longer lists of medications and sensitivity to drug effects. The aim of the study is to estimate the incidence and strength of association of ADRs due to polypharmacy among the geriatric cohort attending outpatient clinics at a tertiary care center.

Methods: A hospital based prospective cohort study was conducted at ambulatory care clinics of Aga Khan University …

Gene Expression Profiling Identifies Irf4-Associated Molecular Signatures In Hematological Malignancies, Ling Wang, Zhi Q. Yao, Jonathan P. Moorman, Yanji Xu, Shunbin Ning

ETSU Faculty Works

The lymphocyte-specific transcription factor Interferon (IFN) Regulatory Factor 4 (IRF4) is implicated in certain types of lymphoid and myeloid malignancies. However, the molecular mechanisms underlying its interactions with these malignancies are largely unknown. In this study, we have first profiled molecular signatures associated with IRF4 expression in associated cancers, by analyzing existing gene expression profiling datasets. Our results show that IRF4 is overexpressed in melanoma, in addition to previously reported contexts including leukemia, myeloma, and lymphoma, and that IRF4 is associated with a unique gene expression pattern in each context. A pool of important genes involved in B-cell development, oncogenesis, …

Safety And Immunogenicity Of Human Serum Albumin-Free Mmr Vaccine In Us Children Aged 12–15 Months, Maurice A. Mufson, Clemente Diaz, Michael Leonardi, Christopher J. Harrison, Stanley Grogg, Antonio Carbayo, Simon Carlo-Torres, Robert Jean Freau, Ana Quintero-Del-Rio, Gisele Bautista, Michael Povey, Christopher Da Costa, Ouzama Nicholson, Bruce L. Innis

Internal Medicine

Background: M-M-RTMII (MMRII; Merck & Co) is currently the only measles-mumps-rubella (MMR) vaccine licensed in the United States. Another licensed vaccine would reinforce MMR supply. This study assessed the immunogenicity of a candidate vaccine (PriorixTM, GlaxoSmithKline Vaccines [MMR-RIT]) when used as a first dose among eligible children in the United States.

Methods: In this exploratory Phase-2, multicenter, observer-blind study, 1220 healthy subjects aged 12–15 months were randomized (3:3:3:3) and received 1 dose of 1 of 3 MMR-RIT lots with differing mumps virus titers (MMR-RIT-1 [4.8 log10]; MMR-RIT-2 [4.1 log10]; MMR-RIT-3 [3.7 log10] CCID50) or MMRII co-administered with hepatitis Avaccine (HAV), …

Hypertensive Crisis, Burden, Management, And Outcome At A Tertiary Care Center In Karachi., Aysha Almas, Ayaz Ghouse, Ahmed Raza Iftikhar, Munawar Khursheed

Department of Medicine

Objectives. Hypertension, if uncontrolled, can lead to hypertensive crisis. We aim to determine the prevalence of hypertensive crisis, its management, and outcome in patients presenting to a tertiary care center in Karachi. Methods. This was a cross-sectional study conducted at the Aga Khan University, Karachi, Pakistan. Adult inpatients (>18 yrs) presenting to the ER who were known hypertensive and had uncontrolled hypertension were included. Results. Out of 1336 patients, 28.6% (387) had uncontrolled hypertension. The prevalence of hypertensive crisis among uncontrolled hypertensive was 56.3% (218). Per oral calcium channel blocker; 35.4% (137) and intravenous nitrate; 22.7% (88) were the …

Diuretic Induced Hyponatremia In Hypertensive Patients., Aysha Almas, Nayla Ahmed, Fareed Khawaja, Aamir Hameed

Department of Medicine

Diuretics are the recommended antihypertensive by several international guidelines. This study was designed to determine the association of hyponatremia in hypertensive patients on diuretic therapy. This was a case control study conducted at the Aga KhanUniversity Hospital, Karachi in adult inpatients (> 18 years) who were known hypertensive. Cases were defined as hypertensives with hyponatremia and controls were defined as hypertensives without hyponatremia. Outcome was hyponatremia. Exposed were those using diuretics. Out of 1800 hypertensive patients sampled by the ICD-9-Coding; 1191 (66%) fulfilled the inclusion criteria. Cases n (%) were 553 (46.4) and controls were 638 (53.5). Among 553 cases …

Clinical, Lifestyle, Socioeconomic Determinants And Rate Of Asymptomatic Intracranial Atherosclerosis In Stroke Free Pakistanis., Ayeesha Kamran Kamal, Farzin Majeed, Omrana Pasha, Hasan Rehman, Muhammad Islam, Iqbal Azam Syed, Muhammad Saleem Ilyas, Munawar Hussain, Kamran Masood, Bilal Ahmed, Sumaira Nazir, Zafar Sajjad, Scott E. Kasner

Department of Medicine

Background: Intracranial Atherosclerotic Disease (ICAD) is the most frequent etiology of stroke with high prevalence among Asians. Despite this, early determinants of ICAD have not been described from this region.

Methods: The study is an analytical prospective cross-sectional study of 200 adults from Radiology Departments of two diagnostic centers in Karachi. Eligible participants confirmed the absence of stroke symptoms via the Questionnaire for Verifying Stroke Free Status (QVSFS) and underwent an interview covering medical, socio demographic, lifestyle and anthropometric evaluation using locally validated and standardized definitions. Magnetic Resonance Images (MRI) were centrally reviewed to detect ICAD using the criterion used …

Metastatic Angiosarcoma And Kasabach-Merritt Syndrome, Suleiman Massarweh, Aun Munis, Rouzan Karabakhtsian, Edward Romond, Jessica Moss

Internal Medicine Faculty Publications

Angiosarcomas are exceedingly rare tumors that are often difficult to diagnose. Exceptionally unusual is the presentation of these tumors with Kasabach-Merritt Syndrome, a curious form of intratumoral coagulation that can be impossible to distinguish from intravascular coagulation, which is more common. Instant recognition of this clinical association can help making a prompt diagnosis and timely initiation of therapy.

Mechanical Thrombectomy Versus Intrasinus Thrombolysis For Cerebral Venous Sinus Thrombosis: A Non-Randomized Comparison., Fazeel M. Siddiqui, Chirantan Banerje, Susanna M. Zuurbier, Qing Hao, Chul Ahn, Glenn L. Prid, Mohammad Wasay, Charles B.L.M. . Majoie, David Liebeskind, ,Mark Johnson, Jan Stam

Department of Medicine

Small retrospective studies have shown the benefit of endovascular treatment with intrasinus thrombolysis (IST) or mechanical thrombectomy (MT) with/without IST (MT ± IST) in cases of multifocal cerebral venous thrombosis (CVT). Our study compares the mortality, functional outcome and periprocedural complications among patients treated with MT ± IST versus IST alone. We reviewed clinical and angiographic findings of 63 patients with CVT who received endovascular treatment at three tertiary care centers. Primary outcome variables were discharge mortality and neurological dysfunction, and intermediate (three months) and long-term (>six months) morbidity. The modified Rankin scale (mRS) was used to assess morbidity. …

A Gut Gone To Pot: A Case Of Cannabinoid Hyperemesis Syndrome Due To K2, A Synthetic Cannabinoid., Anene Ukaigwe, Paras Karmacharya, Anthony A. Donato

Reading Hospital Internal Medicine Residency

Cannabinoid Hyperemesis Syndrome (CHS) was first described in 2004. Due to its novelty, CHS is often unrecognized by clinicians leading to expensive workup of these patients with cyclical symptoms. It may take up to 9 years to diagnose CHS. CHS is characterized by cyclical nausea and vomiting, abdominal pain, and an unusual compulsion to take hot showers in the presence of chronic use of cannabinoids. Cannabicyclohexanol is a synthetic cannabinoid, popularly known as K2 spice. It is a popular marijuana alternative among teenagers and young adults since it is readily available as herbal incense. Unlike marijuana, many users know that …

Biomechanical Comparison Of Hybrid Versus Non Locking Screw Fixation For Midshaft Clavicle Fractures, Joseph T. Cox, J Christopher Gayton, Matthew P. Noyes, Gregory C. Gould, Ronald J. Markert, Michael J. Prayson

Internal Medicine Faculty Publications

Objectives: Recent studies report nonunion rates of up to fifteen percent for nonoperative treatment of displaced, comminuted, or shortened midshaft clavicle fractures. Additionally, authors suggest operative treatment of these comminuted displaced midshaft clavicle fractures leads to a more satisfactory clinical outcome. Biomechanically, clavicle fracture plate fixation has been analyzed for locking versus non-locking screw use, but little evidence on hybrid screw use exists. We hypothesized that fixation of a comminuted midshaft clavicle fracture model with a pre-contoured hybrid screw-plate construct would increase stiffness and load-to-failure compared to a non-locking screw construct. Methods: Fourteen matched pairs of fresh frozen cadaveric clavicles …

Relationship Between Alcohol Use Categories And Noninvasive Markers Of Advanced Hepatic Fibrosis In Hiv-Infected, Chronic Hepatitis C Virus-Infected, And Uninfected Patients, J. K. Lim, J. P. Tate, S. L. Fultz, J. L. Goulet, J. Conigliaro, K. J. Bryant, A. J. Gordon, C. Gibert, D. Rimland, V. Lo Re, +4 Additional Authors

Journal Articles

Background. It is unclear if the risk of liver disease associated with different levels of alcohol consumption is higher for patients infected with human immunodeficiency virus (HIV) or chronic hepatitis C virus (HCV). We evaluated associations between alcohol use categories and advanced hepatic fibrosis, by HIV and chronic HCV status. Methods. We performed a cross-sectional study among participants in the Veterans Aging Cohort Study who reported alcohol consumption at enrollment (701 HIV/HCV-coinfected; 1410 HIV-monoinfected; 296 HCV-monoinfected; 1158 HIV/HCV-uninfected). Alcohol use category was determined by the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and alcohol-related diagnoses and was classified as nonhazardous …

Reply: To Pmid 23929808, J. Karkhanis, E. C. Verna, M. S. Chang, R. T. Stravitz, M. L. Schilsky, W. M. Lee, R. S., Jr. Brown

Journal Articles

No abstract provided.

A Role For Noncoding Variation In Schizophrenia, P. Roussos, A. C. Mitchell, G. Voloudakis, J. F. Fullard, V. M. Pothula, J. Tsang, E. A. Stahl, A. Georgakopoulos, P. K. Gregersen, P. Sklar, +15 Additional Authors

Journal Articles

A large portion of common variant loci associated with genetic risk for schizophrenia reside within noncoding sequence of unknown function. Here, we demonstrate promoter and enhancer enrichment in schizophrenia variants associated with expression quantitative trait loci (eQTL). The enrichment is greater when functional annotations derived from the human brain are used relative to peripheral tissues. Regulatory trait concordance analysis ranked genes within schizophrenia genome-wide significant loci for a potential functional role, based on colocalization of a risk SNP, eQTL, and regulatory element sequence. We identified potential physical interactions of noncontiguous proximal and distal regulatory elements. This was verified in prefrontal …

Steroid Use In Acute Liver Failure, J. Karkhanis, E. C. Verna, M. S. Chang, R. T. Stravitz, M. Schilsky, W. M. Lee, R. S., Jr. Brown

Journal Articles

Drug-induced and indeterminate acute liver failure (ALF) might be due to an autoimmune-like hepatitis that is responsive to corticosteroid therapy. The aim of this study was to evaluate whether corticosteroids improve survival in fulminant autoimmune hepatitis, drug-induced, or indeterminate ALF, and whether this benefit varies according to the severity of illness. We conducted a retrospective analysis of autoimmune, indeterminate, and drug-induced ALF patients in the Acute Liver Failure Study Group from 1998-2007. The primary endpoints were overall and spontaneous survival (SS, survival without transplant). In all, 361 ALF patients were studied, 66 with autoimmune (25 steroids, 41 no steroids), 164 …

Brief Motivational Enhancement Intervention To Prevent Or Reduce Postpartum Alcohol Use: A Single-Blinded, Randomized Controlled Effectiveness Trial, D. M. Rubio, N. L. Day, J. Conigliaro, B. H. Hanusa, C. Larkby, M. Mcneil, E. Cohen, B. Jones, M. Watt-Morse, K. L. Kraemer, +2 Additional Authors

Journal Articles

AIMS: The aim of this study is to assess the effect of brief motivational enhancement intervention postpartum alcohol use. DESIGN: This study is a single-blinded, randomized controlled effectiveness trial in which pregnant women were assigned to receive usual care or up to 5 face-to-face brief motivational enhancement sessions lasting 10-30 minutes each and occurring at study enrollment, 4 and 8 weeks after enrollment, 32 weeks of gestation, and 6 weeks postpartum. SETTING: The setting is in a large, urban, obstetrics clinic. PARTICIPANTS: Participants were women who were >/= 18 years old,gestation, and consumed alcohol during pregnancy. Of 3438 women screened, …

D-Dimer And Risk Of Thromboembolic And Bleeding Events In Patients With Atrial Fibrillation - Observations From The Aristotle Trial, C. Christersson, L. Wallentin, U. Andersson, J. H. Alexander, J. Ansell, R. De Caterina, B. J. Gersh, C. B. Granger, M. Hanna, A. Siegbahn, +5 Additional Authors

Journal Articles

BackgroundD-dimer is related to adverse outcomes in arterial and venous thromboembolic diseases. ObjectivesTo evaluate the predictive value of D-dimer level for stroke, other cardiovascular events, and bleeds, in patients with atrial fibrillation (AF) treated with oral anticoagulation with apixaban or warfarin; and to evaluate the relationship between the D-dimer levels at baseline and the treatment effect of apixaban vs. warfarin. MethodsIn the ARISTOTLE trial, 18201 patients with AF were randomized to apixaban or warfarin. D-dimer was analyzed in 14878 patients at randomization. The cohort was separated into two groups; not receiving vitaminK antagonist (VKA) treatment and receiving VKA treatment at …

Direct Oral Anticoagulants New Drugs And New Concepts, J. H. Levy, A. C. Spyropoulos, C. M. Samama, J. Douketis

Journal Articles

Direct oral anticoagulants (DOACs) are approved for multiple thromboembolic disorders and provide advantages over existing agents. As with all anticoagulants, management protocols for the eventuality of bleeding are important. Randomized phase III studies generally show that DOACs have a similar risk of clinically relevant bleeding compared with standard anticoagulants, with reductions in major bleeding in some cases. This may be particularly important in patients with atrial fibrillation, for whom the rate of intracranial hemorrhage was approximately halved with DOACs compared with warfarin. Conversely, the risk of gastrointestinal bleeding may be increased. Specific patient characteristics, such as renal impairment, comedications, and …

Factors Associated With Inconsistent Condom Use In Adolescents With Negative Or Unknown Hiv Status In Northwest Cameroon, L. Morris, F. Kouya, R. Kwalar, M. Pilapil, K. Saito, N. Palmer, R. Posada, P. M. Tih, T. Welty, J. Jao

Journal Articles

The purpose of this study is to evaluate the association between utilization of HIV testing and condom use amongst Cameroonian youths/adolescents who are not known to be HIV-infected. Worldwide, HIV is spreading most quickly amongst youths/adolescents. Between 44% and 82% of sexually active youths in Cameroon report inconsistent condom use. Data regarding utilization of HIV testing and condom use are lacking. A cross-sectional survey was administered to 431 youths ages 12-26 years in Cameroon from September 2011 to December 2011. Data on sociodemographics, sexual risk behaviors, self-reported HIV status, and condom use were collected. We compared rates of inconsistent condom …

Factors Associated With Damage Accrual In Patients With Systemic Lupus Erythematosus: Results From The Systemic Lupus International Collaborating Clinics (Slicc) Inception Cohort, I. N. Bruce, A. G. O'Keeffe, V. Farewell, J. G. Hanly, S. Manzi, L. Su, D. D. Gladman, S. C. Bae, C. Aranow, M. B. Urowitz, +30 Additional Authors

Journal Articles

BACKGROUND AND AIMS: We studied damage accrual and factors determining development and progression of damage in an international cohort of systemic lupus erythematosus (SLE) patients. METHODS: The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort recruited patients within 15 months of developing four or more 1997 American College of Rheumatology (ACR) criteria for SLE; the SLICC/ACR damage index (SDI) was measured annually. We assessed relative rates of transition using maximum likelihood estimation in a multistate model. The Kaplan-Meier method estimated the probabilities for time to first increase in SDI score and Cox regression analysis was used to assess mortality. RESULTS: …

Hla-Drb1-Associated Rheumatoid Arthritis Risk At Multiple Levels In African Americans Hierarchical Classification Systems, Amino Acid Positions, And Residues, R. J. Reynolds, A. F. Ahmed, M. I. Danila, L. B. Hughes, P. K. Gregersen, S. Raychaudhuri, R. M. Plenge, S. L. Bridges, Af Consortium Longitudinal Evaluat

Journal Articles

Objective. To evaluate HLA-DRB1 genetic risk of rheumatoid arthritis (RA) in African Americans by 3 validated allele classification systems and by amino acid position and residue, and to compare genetic risk between African American and European ancestries. Methods. Four-digit HLA-DRB1 genotyping was performed on 561 autoantibody-positive African American cases and 776 African American controls. Associa-tion analysis was performed on Tezenas du Montcel (TdM), de Vries (DV), and Mattey classification system alleles and separately by amino acid position and individual residues. Results. TdM S2 and S3P alleles were associated with RA (odds ratio [95% confidence interval] 2.8 [2.0-3.9] and 2.1 [1.7-2.7], …

Immunochip Identifies Novel, And Replicates Known, Genetic Risk Loci For Rheumatoid Arthritis In Black South Africans, N. Govind, A. Choudhury, B. Hodkinson, C. Ickinger, J. Frost, A. Lee, P. K. Gregersen, R. J. Reynolds, S. L. Bridges, M. Tikly, +2 Additional Authors

Journal Articles

The aim of this study was to identify genetic variants associated with rheumatoid arthritis (RA) risk in black South Africans. Black South African RA patients (n = 263) were compared with healthy controls (n = 374). Genotyping was performed using the Immunochip, and four-digit high-resolution human leukocyte antigen (HLA) typing was performed by DNA sequencing of exon 2. Standard quality control measures were implemented on the data. The strongest associations were in the intergenic region between the HLA-DRB1 and HLA-DQA1 loci. After conditioning on HLA-DRB1 alleles, the effect in the rest of the extended major histocompatibility (MHC) diminished. Non-HLA single …

The Influence Of Polygenic Risk Scores On Heritability Of Anti-Ccp Level In Ra, J. Cui, K. E. Taylor, Y. C. Lee, H. Kallberg, M. E. Weinblatt, J. S. Coblyn, L. Klareskog, L. A. Criswell, P. K. Gregersen, E. W. Karlson, +2 Additional Authors

Journal Articles

The objective of this study was to study genetic factors that influence quantitative anticyclic citrullinated peptide (anti-CCP) antibody levels in RA patients. We carried out a genome-wide association study (GWAS) meta-analysis using 1975 anti-CCP + RA patients from three large cohorts, the Brigham Rheumatoid Arthritis Sequential Study (BRASS), North American Rheumatoid Arthritis Consortium (NARAC) and the Epidemiological Investigation of RA (EIRA). We also carried out a genome-wide complex trait analysis (GCTA) to estimate the heritability of anti-CCP levels. GWAS-meta-analysis showed that anti-CCP levels were most strongly associated with the human leukocyte antigen (HLA) region with a P-value of 2 x …

Lymphoma Risk In Systemic Lupus: Effects Of Disease Activity Versus Treatment, S. Bernatsky, R. Ramsey-Goldman, L. Joseph, J. F. Boivin, K. H. Costenbader, M. B. Urowitz, D. D. Gladman, P. R. Fortin, C. Aranow, A. E. Clarke, +27 Additional Authors

Journal Articles

Objective To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE). Methods We performed case-cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated in regression models, for time-dependent exposures to immunomodulators (cyclophosphamide, azathioprine, methotrexate, mycophenolate, antimalarial drugs, glucocorticoids) demographics, calendar year, Sjogren's syndrome, SLE duration and disease activity. We used adjusted mean SLE Disease Activity Index scores (SLEDAI-2K) over time, and drugs were treated both categorically (ever/never) and as estimated cumulative doses. Results We studied 75 patients with lymphoma (72 non-Hodgkin, three Hodgkin) and …

Mhc Associations With Clinical And Autoantibody Manifestations In European Sle, D. L. Morris, M. M. A. Fernando, K. E. Taylor, S. A. Chung, J. Nititham, M. E. Alarcon-Riquelme, L. F. Barcelloss, T. W. Behrens, P. K. Gregersen, Con Syst Lupus Erythematosus Genet, +13 Additional Authors

Journal Articles

Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease affecting multiple organ systems and characterized by autoantibody formation to nuclear components. Although genetic variation within the major histocompatibility complex (MHC) is associated with SLE, its role in the development of clinical manifestations and autoantibody production is not well defined. We conducted a meta-analysis- of four independent European SLE case collections for associations between SLE sub-phenotypes and MHC single-nucleotide polymorphism genotypes, human leukocyte antigen (HLA) alleles and variant HLA amino acids. Of the 11 American College of Rheumatology criteria and 7 autoantibody sub-phenotypes examined, anti-Ro/SSA and anti-La/SSB antibody subsets exhibited the …

A 129-Kb Deletion On Chromosome 12 Confers Substantial Protection Against Rheumatoid Arthritis, Implicating The Gene Slc2a3, C. D. Veal, K. E. Reekie, J. C. Lorentzen, P. K. Gregersen, L. Padyukov, A. J. Brookes

Journal Articles

We describe a copy-number variant (CNV) for which deletion alleles confer a protective affect against rheumatoid arthritis (RA). This CNV reflects net unit deletions and expansions to a normal two-unit tandem duplication located on human chr12p13.31, a region with conserved synteny to the rat RA susceptibility quantitative trait loci Oia2. Genotyping, using the paralogue ratio test and SNP intensity data, in Swedish samples (2,403 cases, 1,269 controls) showed that the frequency of deletion variants is significantly lower in cases (P=0.0012, OR=0.442 [95%CI 0.258-0.755]). Reduced frequencies of deletion variants were also seen in replication materials comprising 9,201 UK samples (1,846 cases, …