Caroline H Shiboski

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

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Publications (53)128.3 Total impact

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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.
    IADR General Session and Exhibition 2014; 06/2014
  • 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)
    IADR General Session and Exhibition 2014; 06/2014
  • C. SHIBOSKI
    IADR General Session and Exhibition 2014; 06/2014
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    ABSTRACT: 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.
    06/2014; 18(6):682-8.
  • 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.
    The journal of evidence-based dental practice 12/2013; 13(4):180-2.
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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.
    Virology 11/2013; 446(1-2):378-88. · 3.35 Impact Factor
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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.
    The International Journal of Tuberculosis and Lung Disease 04/2013; 17(4):532-9. · 2.76 Impact Factor
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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.
    Journal of the American Dental Association (1939) 09/2012; 143(9):992-1001. · 1.82 Impact Factor
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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.
    Arthritis care & research. 04/2012; 64(4):475-87.
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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.
    Arthritis care & research. 01/2012; 64(6):911-8.
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    ABSTRACT: Four oral mucosal infections were identified as Global Oral Health Priorities: (a) HIV and associated viral, bacterial, and fungal infections; (b) tuberculosis; (c) NOMA; and (d) sexually transmitted diseases. Huge global inequalities exist in all four. HIV-associated infections constitute the major challenge. Oral manifestations of AIDS can be specifically diagnostic, indicating a significant role for dentists within health teams. The World Workshops in Oral Health & Disease in AIDS have identified a research program, elements of which are being implemented. Data on oral mucosal involvement in tuberculosis, syphilis, and gonorrhea are incomplete in developed countries and virtually non-existent in low- and middle-income countries, indicating the need for further epidemiological studies. Oral manifestations of tuberculosis and sexually transmitted diseases are largely associated with general health, so action programs should be integrated with agencies treating the systemic diseases. NOMA is very much in the oral health domain. It is a preventable disease associated with malnutrition and unidentified bacterial factors. Prevalence is probably grossly overestimated at present; but nevertheless it constitutes a challenge to the profession, especially in the NOMA belt. Current treatment is surgical, but plans for its eradication should be achievable. The global oral health community, especially the IADR, has a major role to play.
    Advances in dental research 05/2011; 23(2):227-36.
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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.
    Arthritis & Rheumatology 04/2011; 63(7):2021-30. · 7.48 Impact Factor
  • C Shiboski, T Hodgson, S J Challacombe
    Advances in dental research 04/2011; 23(1):7-9.
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    ABSTRACT: The Oral HIV/AIDS Research Alliance is part of the AIDS Clinical Trials Group, the largest HIV clinical trial organization in the world, and it is funded by the National Institute of Dental and Craniofacial Research, in collaboration with the National Institute of Allergy and Infectious Diseases. The alliance's main objective is to investigate the oral complications associated with HIV/AIDS as the epidemic is evolving-in particular, the effects of potent antiretrovirals on the development of oral mucosal lesions and associated fungal and viral pathogens. Furthermore, oral fluids are being explored for their potential monitoring and diagnostic role with respect to HIV disease and coinfections. This article presents an overview of the alliance, its scientific agenda, and an outline of the novel interventional and noninterventional clinical studies ongoing and developing within the AIDS Clinical Trials Group infrastructure in the United States and internationally.
    Advances in dental research 04/2011; 23(1):28-33.
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    ABSTRACT: Objectives: The Sjgren's International Collaborative Clinical Alliance (SICCA) is an NIH-funded international registry created to 1) develop standardized classification criteria for Sjgren's syndrome (SS); and 2) develop a data and biospecimen repository for future SS research. The objective of this analysis is to explore changes in the phenotypic features (serologic, oral, and ocular) of SS among participants seen for 2-year follow-up as part of the SICCA cohort. Methods: Participants are recruited from 7 countries in 3 continents using broad criteria to include adults who have symptoms or signs indicating they may have or may develop SS. A standardized set of clinical and biological parameters and information from standardized questionnaires are collected at both study entry and 2-year follow-up. Results: As of March 8, 2010, among 1618 participants in the SICCA cohort, 445 had been seen for a 2-year follow-up visit. The majority were women (93%) over the age of 50 years (61%). The phenotypic features of SS that changed over time were: abnormal ocular staining score indicative of keratoconjunctivitis sicca (KCS) found in 73% at entry and 77% at follow-up (p < 0.02), serum level of complement C4 (median at baseline versus follow-up was 25 versus 24 mg/DL; p<0.001), bilateral parotid enlargement seen in 10% at entry versus 14% at follow-up (p < 0.005), and stimulated parotid flow rate that decreased from 0.12mL/min to 0.08 mL/min (p<0.001). Other features such as having focal lymphocytic sialadenitis with focus score ≥ 1, ANA titer, positive antiSS-A/B serology, unstimulated whole saliva flow rate, and tear break-up time remained stable over time. Conclusion: The prevalence of KCS and parotid enlargement increased over time while stimulated parotid flow rate decreased and hypocomplementemia worsened. Future analyses will explore the predictive value of hypocomplementemia on any change in the phenotypic features of SS. Supported by NIH/NIDCR DE32636
    IADR General Session 2011; 03/2011
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    ABSTRACT: Few existing studies have examined health and oral health needs and treatment-seeking behavior among the homeless and injection drug users (IDUs). This paper describes the prevalence and correlates of health and oral health care needs and treatment-seeking behaviors in homeless IDUs recruited in San Francisco, California, from 2003 to 2005 (N = 340). We examined sociodemographic characteristics, drug use patterns, HIV status via oral fluid testing, physical health using the Short Form 12 Physical Component Score, self-reported needs for physical and oral health care, and the self-reported frequency of seeking medical and oral health care. The sample had a lower health status as compared to the general population and reported a frequent need for physical and oral health care. In bivariate analysis, being in methadone treatment was associated with care-seeking behavior. In addition, being enrolled in Medi-Cal, California's state Medicaid program, was associated with greater odds of seeking physical and oral health care. Methamphetamine use was not associated with higher odds of needing oral health care as compared to people who reported using other illicit drugs. Homeless IDUs in San Francisco have a large burden of unmet health and oral health needs. Recent cuts in Medi-Cal's adult dental coverage may result in a greater burden of oral health care which will need to be provided by emergency departments and neighborhood dental clinics.
    Journal of Urban Health 10/2010; 87(6):920-30. · 1.89 Impact Factor
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    ABSTRACT: Objectives: The Sjgren's International Collaborative Clinical Alliance (SICCA) is a disease registry focused on understanding the phenotypic characteristics of Sjgren's syndrome (SS), and on developing classification criteria for the disease. Because no gold standard classification exists, validation of criteria typically involves application to disease cases and controls determined by experts. This may result in biased estimates of sensitivity and specificity when expert decisions are based on diagnostic tests used in criteria definition. Further, because diagnosis of SS involves multiple clinical specialties, eliciting expert opinions is problematic. To address these issues, validation of proposed criteria for SICCA is data based, involving use of statistical models to identify disease classes, and analytic comparisons of the consistency of classification results between cohort subgroups, and within individuals over time. We describe our approach to validation, and present results using data collected on > 1000 participants from six international sites. Methods: Candidate criteria include a standard classification approach based on objective tests representing the serological, ocular, and salivary components of SS, and alternate versions that supplement/replace components with less invasive and/or more practical measures. Statistical models applied to a wide range of diagnostic tests and phenotypic features are used to derive disease classifications, against which these alternate criteria and the working standard can be compared. Additional validation is provided by assessments of stability of results among participants not used in deriving the criteria, and over the course of follow-up. Results: Sensitivities and specificities for various criteria sets estimated using a range of model-based disease classes exhibited high levels of stability, both within subgroups of the cohort, and within individuals over time. Conclusions: Our proposed methods avoid circularity in previously applied methods to validate proposed criteria for SS, and provide an objective and broadly applicable data based approach to criteria development. No1-DE-32636
    IADR General Session 2010; 07/2010
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    ABSTRACT: Objectives: HCV is postulated to be a sialotropic virus. We compared unstimulated whole salivary flow rate (UWSR) in HCV and non-HCV patients and examined UWSR in relation to various factors, including patient's subjective assessment of xerostomia. Methods: 76 HCV and 52 non-HCV (31 hepatitis-B; 21 fatty-liver disease/cryptogenic) patients (n=128) were recruited from a tertiary-referral liver clinic. None had known predisposing conditions for salivary hypofunction. UWSR was measured and a 6-item visual analog scale (VAS) was administered to assess oral dryness (OD), oral discomfort, difficulty swallowing & speaking, and lip dryness. Student's t-test, linear regression and Pearson's correlation tests were used for comparison between groups. Results: HCV and non-HCV groups had comparable mean age (yearsSD) (52.414.7 & 54.88.2), % male (70% & 60%) and % with cirrhosis (57% vs 58%). Mean UWSR (ml/minSEM) were 0.2640.017 and 0.3020.029 in HCV and non-HCV groups (p=0.223), respectively. After controlling for possible confounders, HCV status was associated with lower UWSR, but only male gender and presence of cirrhosis were statistically significant predictors in multivariate regression models (Table 1). All VAS scores for xerostomia were significantly higher in HCV than non-HCV groups (p<0.05). In HCV patients, correlation between VAS scores & UWSR showed r-values ranging from -0.43 to -0.30, with OD having the strongest correlation with low UWSR (r=-0.43). Table 1. Univariate & Multivariate regression for predictors of UWSR Predictors Univariate Multivariate b1 95% CI p-value HCV -0.034 -0.048 -0.100-0.023 -0.108-0.012 0.223 0.114 Male Gender 0.081 0.090 0.018-0.143 0.029-0.152 0.012 0.004 Cirrhosis -0.054 -0.061 -0.115-0.006 -0.120-0.350 0.078 0.043 Conclusions: UWSR was lower in HCV than non-HCV patients, though the difference was not statistically significant. Cirrhosis and gender are strong predictors of UWSR in this population. A subjective complaint of OD was more severe in HCV than non-HCV groups and correlated with UWSR. Further research is needed to identify underlying mechanisms of salivary dysfunction in this population.
    IADR General Session 2010; 07/2010
  • C. SHIBOSKI
    IADR General Session 2010; 07/2010
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    ABSTRACT: To describe, apply, and test a new ocular grading system for assessing keratoconjunctivitis sicca (KCS) using lissamine green and fluorescein. Prospective, observational, multicenter cohort study. The National Institutes of Health-funded Sjögren's Syndrome International Registry (called Sjögren's International Collaborative Clinical Alliance [SICCA]) is developing standardized classification criteria for Sjögren syndrome (SS) and is creating a biospecimen bank for future research. Eight SICCA ophthalmologists developed a new quantitative ocular grading system (SICCA ocular staining score [OSS]), and we analyzed OSS distribution among the SICCA cohort and its association with other phenotypic characteristics of SS. The SICCA cohort includes participants ranging from possibly early SS to advanced disease. Procedures include sequenced unanesthetized Schirmer test, tear break-up time, ocular surface staining, and external eye examination at the slit lamp. Using statistical analyses and proportional Venn diagrams, we examined interrelationships between abnormal OSS (>or=3) and other characteristics of SS (labial salivary gland [LSG] biopsy with focal lymphocytic sialadenitis and focus score >1 positive anti-SS A antibodies, anti-SS B antibodies, or both). Among 1208 participants, we found strong associations between abnormal OSS, positive serologic results, and positive LSG focus scores (P < .0001). Analysis of the overlapping relationships of these 3 measures defined a large group of participants who had KCS without other components of SS, representing a clinical entity distinct from the KCS associated with SS. This new method for assessing KCS will become the means for diagnosing the ocular component of SS in future classification criteria. We find 2 forms of KCS whose causes may differ.
    American Journal of Ophthalmology 03/2010; 149(3):405-15. · 4.02 Impact Factor

Publication Stats

1k Citations
128.30 Total Impact Points

Institutions

  • 1993–2014
    • University of California, San Francisco
      • • Department of Orofacial Sciences
      • • Division of Hospital Medicine
      • • Division of Periodontology
      • • Center for AIDS Prevention Studies
      • • School of Dentistry
      San Francisco, California, United States
  • 2008
    • Obafemi Awolowo University
      • Department of Oral and Maxillofacial Surgery and Oral Pathology
      Ilesa, Osun State, Nigeria
    • University of Zimbabwe
      • College of Health Sciences
      Harare, Harare Province, Zimbabwe
  • 2006
    • University College London
      • Division of Medicine
      London, ENG, United Kingdom