Weight of salivary gland ultrasonography compared to other items of the 2016 ACR/EULAR classification criteria for Primary Sjögren's syndrome.

OBJECTIVE: Major salivary gland ultrasonography (SGUS) is widely used for the diagnosis of primary Sjögren's syndrome (pSS). Our objective was to assess the contribution of SGUS compared to other items of the 2016 ACR/EULAR pSS classification criteria, based on expert opinion. METHODS: A secure web-based relational database was used by 24 experts from 14 countries to assess 512 realistic vignettes developed from data of patients with suspected pSS. Each vignette provided classification criteria items and information on history, clinical symptoms and SGUS findings. Each expert assessed 64 vignettes, and each vignette was assessed by 3 experts. A diagnosis of pSS was defined according to at least 2 of 3 experts. Validation was performed in the independent French DiapSS cohort of patients with suspected pSS. RESULTS: A criteria-based pSS diagnosis and SGUS findings were independently associated with an expert diagnosis of pSS (P < 0.001). The derived diagnostic weights of individual items in the 2016 ACR/EULAR criteria including SGUS were as follows: anti-SSA, 3; focus score ≥ 1, 3; SGUS score ≥ 2, 1; positive Schirmer's test, 1; dry mouth, 1; and salivary flow rate < 0.1 mL/min, 1. The corrected C statistic area under the curve for the new weighted score was 0.96. Adding SGUS improves the sensitivity from 90.2 % to 95.6% with a quite similar specificity 84.1% versus 82.6%. Results were similar in the DiapSS cohort: adding SGUS improves the sensitivity from 87% to 93%. CONCLUSION: SGUS had similar weight compared to minor items, and its addition improves the performance of the 2016 ACR/EULAR classification criteria.

The Oral HIV/AIDS Research Alliance Program: lessons learned and future directions.

The Oral HIV/AIDS Research Alliance (OHARA) was established in 2006 to provide the capacity to investigate the oral complications associated with HIV/AIDS within the ACTG infrastructure. Its goals were to explore the effects of potent antiretroviral therapy (ART) on the development of opportunistic infections, and variation and resistance of opportunistic pathogens in the context of immune suppression and long-term ART. The objectives of this talk, presented as part of a plenary session at the 7th World Workshop on Oral Health and Disease in AIDS, were to (i) provide an overview of OHARA's most recent research agenda, and how it evolved since OHARA's inception; (ii) describe OHARA's main accomplishments, including examples of research protocols completed and their key findings; and (iii) describe spin-off projects derived from OHARA, lessons learned, and future directions. OHARA has met its central goal and made key contributions to the field in several ways: (i) by developing/updating diagnostic criteria for oral disease endpoints commonly measured in OHARA protocols and in HIV/AIDS research in general and has creating standardized training modules, both for measuring these oral disease endpoints across clinical specialties, and for collecting oral fluid specimens; (ii) by implementing a total of nine protocols, six of which are completed. Three protocols involved domestic research sites, while three involved international research sites (in Africa, India, and South America); (iii) and by developing and validating a number of laboratory assays used in its protocols and in the field of oral HIV/AIDS research.

Overview and research agenda arising from the 7th World Workshop on Oral Health and Disease in AIDS.

The Research Agenda generated by the 7th World Workshop on Oral Health and Disease in AIDS (WW7) is delivered in this paper. Panels of international experts presided over nine workshops that constituted the conference held in November 2014 in Hyderabad, India. The main goal of the Workshop was to bring together clinician and scientists interested in the subject to debate with world-wide perspectives current issues related to the oral manifestations in HIV/AIDS. The workshops were structured around three themes; basic science, clinical/translational science and social science and were attended by 135 participants from 31 countries. The research questions debated at the workshops are presented in nine consensus papers published in this issue and are summarised in this paper along with an outline of the identified research needs in the field.

Role of oral candidiasis in TB and HIV co-infection: AIDS Clinical Trial Group Protocol A5253.

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 HIV-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.

Screening for pulmonary tuberculosis in HIV-infected individuals: AIDS Clinical Trials Group Protocol A5253.

BACKGROUND: Improved tuberculosis (TB) screening is urgently needed for human immunodeficiency virus (HIV) infected patients. METHODS: 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. RESULTS: 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. CONCLUSIONS: Symptom-based screening with smear microscopy was insufficiently sensitive. More sensitive diagnostic testing is required for HIV-infected patients.

American College of Rheumatology classification criteria for Sjögren's syndrome: a data-driven, expert consensus approach in the Sjögren's International Collaborative Clinical Alliance cohort.

OBJECTIVE: 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. METHODS: 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 American­European 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. RESULTS: 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. CONCLUSION: 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.

Global oral health inequalities: oral infections-challenges and approaches.

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.

Overview of the oral HIV/AIDS Research Alliance Program.

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.

[The transfusion center, the blood donor and the given blood in francophone African countries]. / Le centre de transfusion, le donneur de sang et le sang donné dans les pays d'Afrique francophone.

In subsaharan Africa, knowledge of the organization and methods of transfusion centers, as well as blood donor characteristics, is essential in choosing strategies to improve transfusion practices and the security of blood products on this Continent. The present study was based on a analysis led in partnership with the transfusion of seven francophone African countries (Burkina-Faso, Cameroon, Congo, Ivory Cost, Mali, Niger, and Rwanda). The results showed that withstanding significant progress has been realized in the organization and safety, but much remains to be undertaken over the years to come in order to improve the organization of the centers, the providing of blood products and the infectious and immunohematologic safety. This evolution, for the moment, is limited by the financial resources, insufficient training of personnel and cultural obstacles, but will necessarily pass through the pursuit of conjugated efforts of the scientific, international and local communities.

[Teaching transfusion medicine research in the francophone world]. / Une formation à la recherche en médecine transfusionnelle dans le monde francophone.

A two-week, French language, clinical research course in transfusion medicine has recently been created at the Pasteur Institute in Paris under the joint leadership of faculty members from the University of California San Francisco (UCSF), the Blood Systems Research Institute (BSRI) and the National Institute of Transfusion of Paris. The goal is to train transfusion professionals from the developing world to conduct clinical research that will contribute to improving the quality of care and safety in transfusion practices in their respective countries. The course provides training on clinical and epidemiological research methods and their potential applications in transfusion medicine. As part of the course, each student develops a study protocol that can be implemented in his/her blood center of hospital.

The Oral HIV/AIDS Research Alliance: updated case definitions of oral disease endpoints.

The Oral HIV/AIDS Research Alliance (OHARA) is part of the AIDS Clinical Trials Group (ACTG), the largest HIV clinical trials organization in the world. Its main objective is to investigate oral complications associated with HIV/AIDS as the epidemic is evolving, in particular, the effects of antiretrovirals on oral mucosal lesion development and associated fungal and viral pathogens. The OHARA infrastructure comprises: the Epidemiologic Research Unit (at the University of California San Francisco), the Medical Mycology Unit (at Case Western Reserve University) and the Virology/Specimen Banking Unit (at the University of North Carolina). The team includes dentists, physicians, virologists, mycologists, immunologists, epidemiologists and statisticians. Observational studies and clinical trials are being implemented at ACTG-affiliated sites in the US and resource-poor countries. Many studies have shared end-points, which include oral diseases known to be associated with HIV/AIDS measured by trained and calibrated ACTG study nurses. In preparation for future protocols, we have updated existing diagnostic criteria of the oral manifestations of HIV published in 1992 and 1993. The proposed case definitions are designed to be used in large-scale epidemiologic studies and clinical trials, in both US and resource-poor settings, where diagnoses may be made by non-dental healthcare providers. The objective of this article is to present updated case definitions for HIV-related oral diseases that will be used to measure standardized clinical end-points in OHARA studies, and that can be used by any investigator outside of OHARA/ACTG conducting clinical research that pertains to these end-points.

Prevalence of oral disease among adults with primary HIV infection.

OBJECTIVE: To explore the type and prevalence of oral mucosal lesions among adults with primary HIV infection (PHI) compared with HIV-negative adults at high risk for HIV disease, and in relation to HIV viral load. METHODS: We conducted standardized oral examinations to identify specific oral mucosal lesions among adults with PHI, both pre-seroconversion and post- seroconversion-recently infected, compared with HIV-negative adults. We compared the group with oral lesions to those without oral lesions with respect to HIV-RNA load and CD4 + T-cell count. RESULTS: Among 115 adults (predominantly men), pseudomembranous candidiasis was the most common oral lesion among those with PHI, and was found in 4% of the 23 participants in pre-seroconversion and in 9% of 69 participants with post-seroconversion recent infection, compared with none found among 23 HIV negatives. Among those with PHI, the median viral load was higher and the median CD4 + T-cell count lower among the 15 participants with an oral lesion of any type than among the 77 participants without oral lesions (P = 0.02 and 0.04, respectively). CONCLUSION: This finding suggests that individuals with PHI who have oral lesions may be more likely to transmit HIV because of their higher viral load.

(A1) Identification of oral health care needs in children and adults, management of oral diseases.

The workshop considered five questions reviewing the identification of international oral health care needs of children and adults, and the management of oral diseases in resource-poor countries: (1) What is the role of the dental profession in the management of the HIV-infected individual? (2) Identifying health care needs-What are the epidemiology and disparities of HIV-associated oral lesions in children from different continents? (3) How effective is HIV treatment in controlling oral diseases? (4) Could we develop basic inexpensive oral and dental care protocols for economically deprived HIV-infected patients? and (5) What is the best method of arranging resources to meet the oral health care needs of people with HIV disease? The consensus of the workshop participants was that there is a need to re-target research efforts to non-established market economy countries and prioritize research in these regions to children with HIV disease. It will be important to assess commonalities and variations in oral health needs across geographical and cultural boundaries, and research efforts should be centralized in resource-poor countries to support multi-center longitudinal standardized studies. It is essential that oral health research be integrated into other health care research programs, to make these research priorities and public health initiatives feasible.

HIV-related oral disease epidemiology among women: year 2000 update.

OBJECTIVES: The goals of this literature review were to (1) update a prior review [Shiboski CH (1997) The epidemiology of HIV-related oral manifestations in women: a review. Oral Dis 3: S18-S27] of studies on the epidemiology of HIV-related oral manifestations in women prior to the availability of highly active antiretroviral therapy (HAART); (2) explore the effect of HAART on HIV-related oral disease among women; and (3) explore future research directions with respect to HIV-related oral disease epidemiology among African women. METHODS: A computer-assisted search was conducted to identify studies on the prevalence of oral conditions in HIV-infected women in relation to immunological markers and HAART [excluding studies reviewed in Shiboski CH (1997) The epidemiology of HIV-related oral manifestations in women: a review. Oral Dis 3: S18-S27]. Results were summarized and discussed for (1) studies conducted in the developed world prior to and during the era of HAART; and (2) studies conducted in sub-Saharan Africa. RESULTS: Candidiasis (OC) is the most common oral lesion among HIV-infected women, and has been found to be associated with a low CD4 count and a high plasma viral load. Preliminary findings suggest that HAART is associated with a decreasing OC incidence. The few studies identified on HIV-related oral disease in African women suggest that OC is also a common condition in this setting. CONCLUSION: Future oral epidemiology research efforts in Africa should focus on the potential role of OC as sentinel marker of HIV infection and disease progression, to improve detection and prevention of selected opportunistic illnesses.

Prevalence and classification of HIV-associated oral lesions.

OBJECTIVES: An International Workshop addressed the prevalence and classification of HIV/ AIDS associated oral lesions. DESIGN: Five questions provided the framework for discussion and literature review. What is the prevalence of oral lesions in children and adults? Should the accepted classification of HIV-related oral lesions be modified in the light of recent findings? Why is there a gender difference in the prevalence of oral lesions in developed and developing countries? Are there unusual lesions present in developing countries? Is there any association between modes of transmission and the prevalence of oral lesions? RESULTS: Workshop discussion emphasized the urgent need for assistance in the development of expertise to obtain accurate global prevalence data for HIV-associated oral lesions. Oral candidiasis has been consistently reported as the most prevalent HIV-associated oral lesion in all ages. Penicilliosis marneffei, a newly described fungal infection, has emerged in South-east Asia. Oral hairy leukoplakia and Kaposi's sarcoma appear to be associated with male gender and male-to-male HIV transmission risk behaviours. These lesions occur only rarely in children. CONCLUSIONS: Additional prevalence data are needed from developing countries prior to substantially altering the 1993 ECC/WHO Classification of oral lesions associated with adult HIV infection. The workshop confirmed current oral disease diagnostic criteria.

HIV-related oral manifestations among adolescents in a multicenter cohort study.

PURPOSE: To describe baseline prevalence of oral mucosal diseases among HIV infected adolescents in relationship to biological and behavioral risk factors. METHODS: Participants in Reaching for Excellence in Adolescent Care and Health (REACH), a multicenter longitudinal observational study of HIV/AIDS in adolescents, received physical examinations, blood tests, and oral examinations at 3-month intervals. We evaluated participants for oral conditions commonly seen in relationship to HIV, and explored the association of the most common lesion with selected biological and behavioral variables at baseline using contingency tables and Fisher's Exact test. RESULTS: Among 294 HIV infected adolescents recruited between March 1996 and March 1999, the majority were female (75%), aged 17 to 18 years (69%), and African-American (73%). More than 90% had a CD4(+) T-lymphocyte count > 200 cells/mm(3) at baseline and 57% had a plasma HIV-1 RNA concentration

Trends in oral cancer rates in the United States, 1973-1996.

OBJECTIVES: To explore changes in demographic distribution, incidence and survival rates of oral cancer in the United States from 1973 through 1996. METHODS: From the Surveillance, Epidemiology, and End Results (SEER) data, we computed the proportion of oral cancer by demographic characteristics, site, and stage at diagnosis for 1973-84 and 1985-96. We estimated incidence and 5-year relative survival rates of oral cancer by age, gender, and race/ethnicity, and compared survival rates between the two periods. The estimated annual percent change (EAPC) was used to explore trends in incidence rate from 1973 through 1996. RESULTS: Most of the tongue and floor of mouth cancers (>54%) reported during 1973-84 and 1985-96 had spread to a distant site at time of diagnosis. The age-adjusted annual incidence rates of oral cancer decreased among white men from 1973 through 1996, but increased among black men aged 65-69 years, and among young white men (aged 30-34 years) and women (aged 25-29 years). These changes in trend were all statistically significant (testing EAPC=0 at the 0.05 level). Overall, there was no improvement in the 5-year relative survival rate of either whites or blacks with oral cancer. CONCLUSION: There was little change in early detection of oral cancer or in 5-year relative survival rates between 1973-84 and 1985-96 in nine SEER regions. This suggests a deficiency in professional and public education regarding early diagnosis of oral cancer. Furthermore, the increasing trend of oral cancer among older black men and among younger whites merits further investigation.

Effect of receptive oral sex and smoking on the incidence of hairy leukoplakia in HIV-positive gay men.

We sought to determine whether hairy leukoplakia (HL), an Epstein-Barr virus-related oral lesion, is associated with receptive oral sex activity and cigarette smoking among HIV-positive gay men. Oral examinations were conducted every 6 months among San Francisco Men's Health Study participants over a 6-year period. We fitted time-to-lesion regression models to compare the incidence of HL among men who had mouth-to-penis contact with various numbers of partners, while controlling for cigarette smoking and CD4 count. The 6-year incidence of HL was 32% among 291 HIV-positive men. We found no significant increase in the hazard of developing HL for each additional insertive-oral-sex male partner in the past 6 months (relative hazard = 1.01; 95% confidence interval [CI], 0.99, 1.02), and a similar lack of association when number of sex partners was categorized. However, the hazard of developing HL doubled with any 300-unit decrease in CD4 count (95% CI, 1.4, 2.7), or if men smoked > or =20 cigarettes/day compared with nonsmokers (95% CI, 1.2, 3.9). This finding, which may suggest one effect that smoking produces on the oral mucosa's local immune response, merits further investigation.