Caroline H Shiboski

University of California, San Francisco, San Francisco, California, United States

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Publications (68)186.46 Total impact

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    ABSTRACT: To determine the intra-observer and inter-observer reliability of a novel ocular staining score among trained ophthalmologists. Reliability analysis within a prospective, observational, multi-center cohort study. Those enrolled in the National Institutes of Health-funded Sjögren's International Collaborative Clinical Alliance (SICCA) who presented for follow up at the University of California San Francisco, Aravind Eye Hospital, Johns Hopkins University, and the University of Pennsylvania were included. Study participants were graded using the ocular staining score by at least two masked SICCA-trained ophthalmologists. The primary outcome for this study was the intraclass correlation coefficient (ICC) for the total ocular staining score. ICC's were also calculated for tear break up time (TBUT), conjunctival and corneal staining. Total ocular staining score had an ICC of 0.91 for the right eye (95% CI 0.85 - 0.96) and 0.90 for the left eye (95% CI 0.83 - 0.97). Corneal staining (right eye 0.86, 95% CI 0.76 - 0.93, left eye 0.90, 95% CI 0.81 - 0.95) and conjunctival staining (right eye 0.87, 95% CI 0.80 -0.93, left eye 0.85, 95% CI 0.75 - 0.93) demonstrated excellent agreement. The ICC for TBUT was slightly lower (right eye 0.77, 95% CI 0.64 - 0.89; left eye 0.81, 95% CI 0.68 - 0.90). Previous studies have shown that the ocular staining score is correlated with other diagnostic components of Sjögren syndrome. In this study, we demonstrate high reliability in grading among trained ophthalmologists, completing the validation of this test. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Aug 2015 · American Journal of Ophthalmology
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    ABSTRACT: Many studies include oral HIV-related endpoints that may be diagnosed by non-oral-health specialists (non-OHS) like nurses or physicians. Our objective was to assess the accuracy of clinical diagnoses of HIV-related oral lesions made by non-OHS compared to diagnoses made by OHS. A5254, a cross-sectional study conducted by the Oral HIV/AIDS Research Alliance within the AIDS Clinical Trial Group, enrolled HIV-1-infected adults participants from six clinical trial units (CTU) in the US (San Francisco, New York, Chapel Hill, Cleveland, Atlanta) and Haiti. CTU examiners (non-OHS) received standardized training on how to perform an oral examination and make clinical diagnoses of specific oral disease endpoints. Diagnoses by calibrated non-OHS were compared to those made by calibrated OHS, and sensitivity and specificity computed. Among 324 participants, the majority were black (73%), men (66%), and the median CD4+ cell count 138 cells/mm3. The overall frequency of oral mucosal disease diagnosed by OHS was 43% in US sites, and 90% in Haiti. Oral candidiasis (OC) was detected in 153 (47%) by OHS, with erythematous candidiasis (EC) the most common type (39%) followed by pseudomembranous candidiasis (PC; 26%). The highest prevalence of OC (79%) was among participants in Haiti, and among those with CD4+ cell count ≤ 200 cells/mm3 and HIV-1 RNA > 1000 copies/mL (71%). The sensitivity and specificity of OC diagnoses by non-OHS were 90% and 92% (for EC: 81% and 94%; PC: 82% and 95%). Sensitivity and specificity were also high for KS (87% and 94%, respectively), but sensitivity was < 60% for HL and oral warts in all sites combined. The Candida culture confirmation of OC clinical diagnoses (as defined by ≥ 1 colony forming unit per mL of oral/throat rinse) was ≥ 93% for both PC and EC. Trained non-OHS showed high accuracy of clinical diagnoses of OC in comparison with OHS, suggesting their usefulness in studies in resource-poor settings, but detection of less common lesions may require OHS.
    Full-text · Article · Jul 2015 · PLoS ONE
  • C. Shiboski · S. Shiboski

    No preview · Conference Paper · May 2015
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    ABSTRACT: Sjögren's syndrome (SS) is an autoimmune disease targeting salivary and lacrimal glands. While all patients demonstrate inflammatory infiltration and abnormal secretory function in target tissues, disease features, pathology and clinical course can vary. Activation of distinct inflammatory pathways may drive disease heterogeneity. We investigated whether interferon (IFN) pathway activation correlates with key phenotypic features. Clinical data and one frozen labial salivary gland were obtained from each of 82 participants (53 primary SS, 29 controls) in the Sjögren's International Collaborative Clinical Alliance registry. Salivary gland lysates were immunoblotted with markers of type I or II IFN and patterns of IFN activity were determined by hierarchical clustering. Correlations were defined between SS phenotypic features and IFN activity in the salivary gland. 58% of SS participants had high IFN activity and differed significantly from those with low activity (higher prevalence of abnormal sialometry, leukopenia, hyperglobulinemia, high titer ANA, anti-SSA, and high focus score). Furthermore, distinct patterns of IFN were evident: type I-predominant; type II-predominant; and type I/II IFN. These groups were clinically indistinguishable except for focus score which was highest in type II-predominant participants. The SS phenotype includes distinct molecular subtypes, segregated by the magnitude and pattern of IFN responses. Associations between IFN pathways and disease activity suggest that IFNs are relevant therapeutic targets in SS. Patients with distinct patterns of high IFN activity are clinically similar, demonstrating that IFN-targeting therapies must be selected based on prior analyses of which specific pathway(s) are active in vivo in individual patients. This article is protected by copyright. All rights reserved. © 2015, American College of Rheumatology.
    No preview · Article · May 2015 · Arthritis and Rheumatology
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    ABSTRACT: Objective To determine whether the Sjögren's syndrome B (SSB)-positive/Sjögren's syndrome A (SSA)-negative antibody profile is associated with key phenotypic features of SS. Methods Among registrants in the Sjögren's International Collaborative Clinical Alliance (SICCA) with possible or established SS, we compared anti-SSA/anti-SSB reactivity profiles against concurrent phenotypic features. We fitted logistic regression models to explore the association between anti-SSA/anti-SSB reactivity profile and each key SS phenotypic feature, controlling for potential confounders. Results Among 3297 participants, 2061 (63%) had negative anti-SSA/anti-SSB, 1162 (35%) had anti-SSA with or without anti-SSB, and 74 (2%) anti-SSB alone. Key SS phenotypic features were more prevalent and had measures indicative of greater disease activity in those participants with anti-SSA, either alone or with anti-SSB, than in those with anti-SSB alone or negative SSA/SSB serology. These between-group differences were highly significant and not explained by confounding by age, race/ethnicity or gender. Participants with anti-SSB alone were comparable to those with negative SSA/SSB serology in their association with these key phenotypic features. Among SICCA participants classified with SS on the basis of the American-European Consensus Group or American College of Rheumatology criteria, only 2% required the anti-SSB-alone test result to meet these criteria. Conclusions The presence of anti-SSB, without anti-SSA antibodies, had no significant association with SS phenotypic features, relative to seronegative participants. The solitary presence of anti-SSB antibodies does not provide any more support than negative serology for the diagnosis of SS. This serological profile should thus be interpreted cautiously in clinical practice and potentially eliminated from future classification criteria.
    Full-text · Article · Mar 2015 · Annals of the Rheumatic Diseases
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    ABSTRACT: SETTING: Drug resistance threatens tuberculosis (TB) control, particularly among human immunodeficiency virus (HIV) infected persons. OBJECTIVE: To describe practices in the prevention and management of drug-resistant TB under antiretroviral therapy (ART) programs in lower-income countries. DESIGN: We used online questionnaires to collect program-level data on 47 ART programs in Southern Africa (n=14), East Africa (n=8), West Africa (n=7), Central Africa (n=5), Latin America (n=7) and the Asia-Pacific (n=6 programs) in 2012. Patient-level data were collected on 1002 adult TB patients seen at 40 of the participating ART programs. RESULTS: Phenotypic drug susceptibility testing (DST) was available in 36 (77%) ART programs, but was only used for 22% of all TB patients. Molecular DST was available in 33 (70%) programs and was used in 23% of all TB patients. Twenty ART programs (43%) provided directly observed therapy (DOT) during the entire course of treatment, 16 (34%) during the intensive phase only, and 11(23%) did not follow DOT. Fourteen (30%) ART programs reported no access to second-line anti-tuberculosis regimens; 18 (38%) reported TB drug shortages. CONCLUSIONS: Capacity to diagnose and treat drug-resistant TB was limited across ART programs in lower-income countries. DOT was not always implemented and drug supplies were regularly interrupted, which may contribute to the global emergence of drug resistance.
    Full-text · Article · Nov 2014 · The International Journal of Tuberculosis and Lung Disease
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    ABSTRACT: Objective: Many studies of HIV-related opportunistic infections include oral lesion endpoints that may be diagnosed by non-oral health specialists (OHS). Our objective was to assess the accuracy of clinical diagnoses of HIV-related oral lesions made by non-OHS examiners within the AIDS Clinical Trial Group (ACTG) compared to diagnoses made by OHS. Methods: A5254 is a cross-sectional study conducted by the Oral HIV/AIDS Research Alliance within the ACTG. It enrolled HIV-1-infected adults with or without prior antiretroviral therapy from six ACTG Clinical Trial Units (CTU) in San Francisco, New York, Chapel Hill, Cleveland, Atlanta, and Haiti. At study entry, participants were stratified into one of four strata according to their screening CD4+ cell count and plasma HIV-1 RNA levels. CTU examiners received a standardized training on how to perform an oral examination and make presumptive clinical diagnoses of specific oral disease endpoints. Diagnoses made by calibrated CTU examiners were compared to those made by calibrated OHS, and sensitivity and specificity computed. Results: Among 324 participants, the majority were black (73%), men (66%), and never used injection drugs (85%). The median CD4 cell count was 138 cells/mm3. Oral candidiasis (OC) was detected in 153 (47%) by the OHS, with erythematous candidiasis (EC) as the most common type (39%) followed by pseudomembranous candidiasis (PC; 26%). The highest prevalence of OC (71%) was among those with CD4 cell count≤200 cells/mm3and HIV-1 RNA>1000 copies/mL. Other lesions were detected and will be discussed. The sensitivity and specificity of OC diagnoses were 90% and 92% (for EC: 81% and 94%; for PC: 82% and 95%). Conclusion: A high prevalence of OC was detected among HIV-positive participants from various ACTG sites, and we found a high accuracy of clinical diagnoses of OC, EC, and PC made by non-OHS examiners as compared to OHS.
    No preview · Conference Paper · Jun 2014
  • C. SHIBOSKI
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    ABSTRACT: SICCA is an NIH-funded international registry designed to disseminate SICCA data and biospecimens to the Sjögren’s Syndrome (SS) scientific community that will advance the field of SS research, ultimately leading to effective management/preventative strategies and therapies. The presentation will focus on: SICCA’s implementation in nine academically-based Research Groups, located in Argentina, China, Denmark, India, Japan, the United Kingdom, and the United States, and directed from the University of California San Francisco How over a 10-year period, these research groups, including rheumatologists, ophthalmologists, and oral medicine/pathology specialists,enrolled over 3500 participants throughout the world, yielding a unique database and biorepository of well characterized specimens with extensive phenotypic information available to scientists worldwide How new classification criteria for SS were developed and approved by the American College of Rheumatology, and will allow better dissemination of the biorepository to the scientific community for discovery science (pathogenesis, epidemiology, and genetic studies)
    No preview · Conference Paper · Jun 2014
  • C. SHIBOSKI

    No preview · Conference Paper · Jun 2014
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    ABSTRACT: OBJECTIVE: To evaluate the association between oral candidiasis and tuberculosis (TB) in human immunodeficiency virus (HIV) infected individuals in sub-Saharan Africa, and to investigate oral candidiasis as a potential tool for TB case finding. METHODS: Protocol A5253 was a cross-sectional study designed to improve the diagnosis of pulmonary TB in HEY-infected adults in high TB prevalence countries. Participants received an oral examination to detect oral candidiasis. We estimated the association between TB disease and oral candidiasis using logistic regression, and sensitivity, specificity and predictive values. RESULTS: Of 454 participants with TB culture results enrolled in African sites, the median age was 33 years, 71% were female and the median CD4 count was 257 cells/mm(3). Fifty-four (12%) had TB disease; the prevalence of oral candidiasis was significantly higher among TB cases (35%) than among non-TB cases (16%, P < 0.001). The odds of having TB was 2.4 times higher among those with oral candidiasis when controlling for CD4 count and antifungals (95 %CI 1.2-4.7, P = 0.01). The sensitivity of oral candidiasis as a predictor of TB was 35% (95%CI 22-48) and the specificity 85% (95%CI 81-88). CONCLUSION: We found a strong association between oral candidiasis and TB disease, independent of CD4 count, suggesting that in resource-limited settings, oral candidiasis may provide clinical evidence for increased risk of TB and contribute to TB case finding.
    No preview · Article · Jun 2014 · The International Journal of Tuberculosis and Lung Disease
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    ABSTRACT: We describe the association between age at antiretroviral therapy (ART) initiation and 24-month CD4 cell response in West African HIV-infected children. All HIV-infected children from the IeDEA paediatric West African cohort, initiating ART, with at least two CD4 cell count measurements, including one at ART initiation (baseline) were included. CD4 cell gain on ART was estimated using a multivariable linear mixed model adjusted for baseline variables: age, CD4 cell count, sex, first-line ART regimen. Kaplan-Meier survival curves and a Cox proportional hazards regression model compared immune recovery for age within 24 months post-ART. Of the 4808 children initiated on ART, 3014 were enrolled at a median age of 5.6 years; 61.2% were immunodeficient. After 12 months, children at least 4 years at baseline had significantly lower CD4 cell gains compared with children less than 2 years, the reference group (P < 0.001). However, by 24 months, we observed higher CD4 cell gain in children who initiated ART between 3 and 4 years compared with those less than 2 years (P < 0.001). The 24-month CD4 cell gain was also strongest in immunodeficient children at baseline. Among these children, 75% reached immune recovery: 12-month rates were significantly highest in all those aged 2-5 years at ART initiation compared with those less than 2 years. Beyond 12 months on ART, immune recovery was significantly lower in children initiated more than 5 years (adjusted hazard ratio: 0.69, 95% confidence interval: 0.56-0.86). These results suggest that both the initiation of ART at the earliest age less than 5 years and before any severe immunodeficiency is needed for improving 24-month immune recovery on ART.
    Full-text · Article · May 2014 · AIDS (London, England)
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    ABSTRACT: To estimate the prevalence of oral mucosal diseases and dental caries among HIV-infected children receiving antiretroviral treatment (ART) in West Africa and to identify the factors associated with the prevalence of oral mucosal lesions. Multicentre cross-sectional survey in five paediatric HIV clinics in Côte d'Ivoire, Mali and Sénégal. A standardised examination was performed by trained dentists on a random sample of HIV-infected children aged 5-15 years receiving ART. The prevalence of oral and dental lesions and mean number of decayed, missing/extracted and filled teeth (DMFdefT) in temporary and permanent dentition were estimated with their 95% confidence interval (95% CI). We used logistic regression to explore the association between children's characteristics and the prevalence of oral mucosal lesions, expressed as prevalence odds ratio (POR). The median age of the 420 children (47% females) enrolled was 10.4 years [interquartile range (IQR) = 8.3-12.6]. The median duration on ART was 4.6 years (IQR = 2.6-6.2); 84 (20.0%) had CD4 count<350 cells/mm(3) . A total of 35 children (8.3%; 95% CI: 6.1-11.1) exhibited 42 oral mucosal lesions (24 were candidiasis); 86.0% (95% CI = 82.6-89.3) of children had DMFdefT ≥ 1. The presence of oral mucosal lesions was independently associated with CD4 count < 350 cells/mm(3) (POR = 2.96, 95% CI = 1.06-4.36) and poor oral hygiene (POR = 2.69, 95% CI = 1.07-6.76). Oral mucosal lesions still occur in HIV-infected African children despite ART, but rarely. However, dental caries were common and severe in this population, reflecting the need to include oral health in the comprehensive care of HIV.
    Preview · Article · Jan 2014 · Tropical Medicine & International Health
  • Caroline H Shiboski · Stephen C Shiboski
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    ABSTRACT: Smoking as a risk factor for oral candidiasis in HIV-infected adults. Chattopadhyay A, Patton LL. J Oral Pathol Med 2013;42(4):302-08. Caroline H. Shiboski, DDS, MPH, PhD, Stephen C. Shiboski, PhD PURPOSE/QUESTION: Is smoking an independent risk factor for OC among adults with HIV/AIDS, and does smoking modify the relationship between OC and other important risk factors like CD4 cell count? This investigation was supported by USPHS Grant 5T32DE07191, P30-HD27360, and R29DE11369 from the National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA TYPE OF STUDY/DESIGN: Cohort study Level 2: Limited-quality, patient-oriented evidence Not applicable.
    No preview · Article · Dec 2013 · The journal of evidence-based dental practice
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    ABSTRACT: The incidence of human papillomavirus (HPV)-associated epithelial lesions is substantially higher in human immunodeficiency virus (HIV)-infected individuals than in HIV-uninfected individuals. The molecular mechanisms underlying the increased risk of HPV infection in HIV-infected individuals are poorly understood. We found that HIV proteins tat and gp120 were expressed within the oral and anal mucosal epithelial microenvironment of HIV-infected individuals. Expression of HIV proteins in the mucosal epithelium was correlated with the disruption of epithelial tight junctions (TJ). Treatment of polarized oral, cervical and anal epithelial cells, and oral tissue explants with tat and gp120 led to disruption of epithelial TJ and increased HPV pseudovirion (PsV) paracellular penetration in to the epithelium. PsV entry was observed in the basal/parabasal cells, the cells in which the HPV life cycle is initiated. Our data suggest that HIV-associated TJ disruption of mucosal epithelia may potentiate HPV infection and subsequent development of HPV-associated neoplasia.
    Full-text · Article · Nov 2013 · Virology
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    ABSTRACT: Improved tuberculosis (TB) screening is urgently needed for human immunodeficiency virus (HIV) infected patients. An observational, multi-country, cross-sectional study of HIV-infected patients to compare a standardized diagnostic evaluation (SDE) for TB with standard of care (SOC). SOC evaluations included TB symptom review (current cough, fever, night sweats and/or weight loss), sputum Ziehl-Neelsen staining and chest radiography. SDE screening added extended clinical signs and symptoms and fluorescent microscopy (FM). All participants underwent all evaluations. Mycobacterium tuberculosis on sputum culture was the primary outcome. A total of 801 participants were enrolled from Botswana, Malawi, South Africa, Zimbabwe, India, Peru and Brazil. The median age was 33 years; 37% were male, and median CD4 count was 275 cells/mm(3). Thirty-one participants (4%) had a positive culture on Löwenstein-Jensen media and 54 (8%) on MGIT. All but one positive culture came from sub-Saharan Africa, where the prevalence of TB was 54/445 (12%). SOC screening had 54% sensitivity (95%CI 40-67) and 76% specificity (95%CI 72-80). Positive and negative predictive values were respectively 24% and 92%. No elements of the SDE improved the predictive values of SOC. Symptom-based screening with smear microscopy was insufficiently sensitive. More sensitive diagnostic testing is required for HIV-infected patients.
    No preview · Article · Apr 2013 · The International Journal of Tuberculosis and Lung Disease
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    ABSTRACT: Researchers have reported rampant caries among methamphetamine users. The authors investigated the prevalence of dental disease and associated risk behaviors in methamphetamine users compared with those in heroin users. This pilot project was a cross-sectional study of an ongoing cohort of young adult injection-drug users (IDUs) in San Francisco. Participants completed an oral health questionnaire administered by a research assistant, and dentists performed clinical examinations to record the participants' data in terms of scores on the decayed-missing-filled surfaces (DMFS) index, presence of residual roots, scores on an oral hygiene index and whether any salivary hypofunction was observed. The prevalence of dental disease among 58 young adult IDUs was strikingly high compared with that in the U.S. general population; however, the authors found no difference in the level of dental disease between users of methamphetamine and users of heroin. The mean DMFS score and number of decayed surfaces exceeded 28 in both groups. Although the authors detected no difference in dental disease between methamphetamine and heroin users, they found a high prevalence of caries and caries-associated behaviors in the sample of young adult IDUs. Given the high level of dental disease observed in this population of young adult IDUs, one next step may be to explore the feasibility and effectiveness of providing low-intensity preventive measures (such as distribution of chlorhexidine rinses or xylitol gum or application of fluoride varnishes) through outreach workers.
    No preview · Article · Sep 2012 · Journal of the American Dental Association (1939)
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    ABSTRACT: To study the prevalence of extraglandular manifestations in primary Sjögren's syndrome (SS) among participants enrolled in the Sjögren's International Collaborative Clinical Alliance (SICCA) Registry. A total of 1,927 participants in the SICCA registry were studied, including 886 participants who met the 2002 American-European Consensus Group (AECG) criteria for primary SS, 830 "intermediate" cases who had some objective findings of primary SS but did not meet AECG criteria, and 211 control individuals. We studied the prevalence of immunologic and hematologic laboratory abnormalities, specific rheumatologic examination findings, and physician-confirmed thyroid, liver, and kidney disease, as well as lymphoma among SICCA participants. Laboratory abnormalities, including hematologic abnormalities, hypergammaglobulinemia, and hypocomplementemia, frequently occurred among primary SS cases and were more common among the intermediate cases than among control participants. Cutaneous vasculitis and lymphadenopathy were also more common among primary SS cases. In contrast, the frequency of physician-confirmed diagnoses of thyroid, liver, and kidney disease and lymphoma was low and only primary biliary cirrhosis was associated with primary SS case status. Rheumatologic and neurologic symptoms were common among all SICCA participants, regardless of case status. Data from the international SICCA registry support the systemic nature of primary SS, manifested primarily in terms of specific immunologic and hematologic abnormalities. The occurrence of other systemic disorders among this cohort is relatively uncommon. Previously reported associations may be more specific to select patient subgroups, such as those referred for evaluation of certain neurologic, rheumatologic, or other systemic manifestations.
    Full-text · Article · Jun 2012
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    ABSTRACT: We propose new classification criteria for Sjögren's syndrome (SS), which are needed considering the emergence of biologic agents as potential treatments and their associated comorbidity. These criteria target individuals with signs/symptoms suggestive of SS. Criteria are based on expert opinion elicited using the nominal group technique and analyses of data from the Sjögren's International Collaborative Clinical Alliance. Preliminary criteria validation included comparisons with classifications based on the American–European Consensus Group (AECG) criteria, a model-based “gold standard”obtained from latent class analysis (LCA) of data from a range of diagnostic tests, and a comparison with cases and controls collected from sources external to the population used for criteria development. Validation results indicate high levels of sensitivity and specificity for the criteria. Case definition requires at least 2 of the following 3: 1) positive serum anti-SSA and/or anti-SSB or (positive rheumatoid factor and antinuclear antibody titer >1:320), 2) ocular staining score >3, or 3) presence of focal lymphocytic sialadenitis with a focus score >1 focus/4 mm2 in labial salivary gland biopsy samples. Observed agreement with the AECG criteria is high when these are applied using all objective tests. However, AECG classification based on allowable substitutions of symptoms for objective tests results in poor agreement with the proposed and LCA-derived classifications. These classification criteria developed from registry data collected using standardized measures are based on objective tests. Validation indicates improved classification performance relative to existing alternatives, making them more suitable for application in situations where misclassification may present health risks.
    Full-text · Article · Apr 2012
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    ABSTRACT: The goal of selecting a healthy blood donor is to safeguard donors and reduce the risks of infections and immunologic complications for recipients. To evaluate the blood donor selection process, a survey was conducted in 28 blood transfusion centers located in 15 francophone African countries. Data collected included availability of blood products, risk factors for infection identified among blood donor candidates, the processing of the information collected before blood collection, the review process for the medical history of blood donor candidates, and deferral criteria for donor candidates. During the year 2009, participating transfusion centers identified 366,924 blood donor candidates. A mean of 13% (range, 0%-36%) of the donor candidates were excluded based solely on their medical status. The main risk factors for blood-borne infections were having multiple sex partners, sexual intercourse with occasional partners, and religious scarification. Most transfusion centers collected this information verbally instead of having a written questionnaire. The topics least addressed were the possible complications relating to the donation, religious scarifications, and history of sickle cell anemia and hemorrhage. Only three centers recorded the temperature of the blood donors. The deferral criteria least reported were sickle cell anemia, piercing, scarification, and tattoo. The medical selection process was not performed systemically and thoroughly enough, given the regional epidemiologic risks. It is essential to identify the risk factors specific to francophone African countries and modify the current medical history questionnaires to develop a more effective and relevant selection process.
    Full-text · Article · Jan 2012 · Transfusion
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    ABSTRACT: To examine associations between labial salivary gland (LSG) histopathology and other phenotypic features of Sjögren's syndrome (SS). The database of the Sjögren's International Collaborative Clinical Alliance (SICCA), a registry of patients with symptoms of possible SS as well as those with obvious disease, was used for the present study. LSG biopsy specimens from SICCA participants were subjected to protocol-directed histopathologic assessments. Among the 1,726 LSG specimens exhibiting any pattern of sialadenitis, we compared biopsy diagnoses against concurrent salivary, ocular, and serologic features. LSG specimens included 61% with focal lymphocytic sialadenitis (FLS; 69% of which had focus scores of ≥1 per 4 mm²) and 37% with nonspecific or sclerosing chronic sialadenitis (NS/SCS). Focus scores of ≥1 were strongly associated with serum anti-SSA/SSB positivity, rheumatoid factor, and the ocular component of SS, but not with symptoms of dry mouth or dry eyes. Those with positive anti-SSA/SSB were 9 times (95% confidence interval [95% CI] 7.4-11.9) more likely to have a focus score of ≥1 than were those without anti-SSA/SSB, and those with an unstimulated whole salivary flow rate of <0.1 ml/minute were 2 times (95% CI 1.7-2.8) more likely to have a focus score of ≥1 than were those with a higher flow rate, after controlling for other phenotypic features of SS. Distinguishing FLS from NS/SCS is essential in assessing LSG biopsies, before determining focus score. A diagnosis of FLS with a focus score of ≥1 per 4 mm², as compared to FLS with a focus score of <1 or NS/SCS, is strongly associated with the ocular and serologic components of SS and reflects SS autoimmunity.
    Full-text · Article · Jul 2011 · Arthritis & Rheumatology

Publication Stats

2k Citations
186.46 Total Impact Points

Institutions

  • 1993-2015
    • University of California, San Francisco
      • • Department of Orofacial Sciences
      • • Department of Medicine
      • • School of Dentistry
      San Francisco, California, United States
  • 2009
    • Institut Pasteur
      Lutetia Parisorum, Île-de-France, France
  • 2006
    • University of the Western Cape
      • Faculty of Dentistry
      Kaapstad, Western Cape, South Africa