Subgingival Microbiota and Longitudinal Glucose Change: The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS).

Microbial communities along mucosal surfaces throughout the digestive tract are hypothesized as risk factors for impaired glucose regulation and the development of clinical cardiometabolic disease. We investigated whether baseline measures of subgingival microbiota predicted fasting plasma glucose (FPG) longitudinally. The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) enrolled 230 diabetes-free adults (77% female) aged 20 to 55 y (mean ± SD, 34 ± 10 y) from whom baseline subgingival plaque and longitudinal FPG were measured. DNA was extracted from subgingival plaque, and V3 to V4 regions of the 16S rRNA gene were sequenced. FPG was measured at baseline and again at 2 y; glucose change was defined as follow-up minus baseline. Multivariable linear models regressed 2-y glucose change onto baseline measures of community diversity and abundances of 369 individual taxa. A microbial dysbiosis index (MDI) summarizing top individual taxa associated with glucose change was calculated and used in regression models. Models were adjusted for age, sex, race/ethnicity, education, smoking status, body mass index, and baseline glucose levels. Statistical significance was based on the false discovery rate (FDR; <0.05) or a Bonferroni-corrected P value of 1 × 10-4, derived from the initial 369 hypothesis tests for specific taxa. Mean 2-y FPG change was 1.5 ± 8 mg/dL. Baseline levels of 9 taxa predicted FPG change (all FDR <0.05), among which Stomatobaculum sp oral taxon 097 and Atopobium spp predicted greater FPG change, while Leptotrichia sp oral taxon 498 predicted lesser FPG change (all 3 P values, Bonferroni significant). The MDI explained 6% of variation in longitudinal glucose change (P < 0.001), and baseline glucose levels explained 10% of variation (P < 0.0001). FPG change values ± SE in the third versus first tertile of the MDI were 4.5 ± 0.9 versus 1.6 ± 0.9 (P < 1 × 10-4). Subgingival microbiota predict 2-y glucose change among diabetes-free men and women.

Periodontal Bacteria and Prediabetes Prevalence in ORIGINS: The Oral Infections, Glucose Intolerance, and Insulin Resistance Study.

Periodontitis and type 2 diabetes mellitus are known to be associated. The relationship between periodontal microbiota and early diabetes risk has not been studied. We investigated the association between periodontal bacteria and prediabetes prevalence among diabetes-free adults. ORIGINS (the Oral Infections, Glucose Intolerance and Insulin Resistance Study) cross sectionally enrolled 300 diabetes-free adults aged 20 to 55 y (mean ± SD, 34 ± 10 y; 77% female). Prediabetes was defined as follows: 1) hemoglobin A1c values ranging from 5.7% to 6.4% or 2) fasting plasma glucose ranging from 100 to 125 mg/dL. In 1,188 subgingival plaque samples, 11 bacterial species were assessed at baseline, including Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Actinomyces naeslundii. Full-mouth clinical periodontal examinations were performed, and participants were defined as having no/mild periodontitis vs. moderate/severe periodontitis per the definition of the Centers for Disease Control and Prevention / American Academy of Periodontology. Modified Poisson regression evaluated prediabetes prevalence across bacterial tertiles. Prevalence ratios and 95% confidence intervals for third vs. first tertiles are presented. All analyses were adjusted for cardiometabolic risk factors. All results presented currently arise from the baseline cross section. Prediabetes prevalence was 18%, and 58% of participants had moderate/severe periodontitis. Prevalence ratios (95% confidence intervals) summarizing associations between bacterial levels and prediabetes were as follows: A. actinomycetemcomitans, 2.48 (1.34, 4.58), P = 0.004; P. gingivalis, 3.41 (1.78, 6.58), P = 0.0003; T. denticola, 1.99 (0.992, 4.00), P = 0.052; T. forsythia, 1.95 (1.0, 3.84), P = 0.05; A. naeslundii, 0.46 (0.25, 0.85), P = 0.01. The prevalence ratio for prediabetes among participants with moderate/severe vs. no/mild periodontitis was 1.47 (0.78, 2.74), P = 0.23. Higher colonization levels of specific periodontal microbiota are associated with higher prediabetes prevalence among diabetes-free adults.

Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011.

Intima-media thickness (IMT) provides a surrogate end point of cardiovascular outcomes in clinical trials evaluating the efficacy of cardiovascular risk factor modification. Carotid artery plaque further adds to the cardiovascular risk assessment. It is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness >1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. The scientific basis for use of IMT in clinical trials and practice includes ultrasound physics, technical and disease-related principles as well as best practice on the performance, interpretation and documentation of study results. Comparison of IMT results obtained from epidemiological and interventional studies around the world relies on harmonization on approaches to carotid image acquisition and analysis. This updated consensus document delineates further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT. Standardized methods will foster homogenous data collection and analysis, improve the power of randomized clinical trials incorporating IMT and plaque measurements and facilitate the merging of large databases for meta-analyses. IMT results are applied to individual patients as an integrated assessment of cardiovascular risk factors. However, this document recommends against serial monitoring in individual patients.

Longitudinal evaluation of viral interactions in treated HIV-hepatitis B co-infected patients with additional hepatitis C and D virus.

Virological interactions of hepatitis B (HBV), hepatitis C (HCV) and hepatitis D (HDV) viruses in HIV-infected patients have been poorly characterized especially under treatment influences. Undetection rates of hepatitis viruses were longitudinally analyzed in a 3-year cohort of 308 HIV-HBV co-infected patients and compared using Generalized Estimating Equation models adjusted for age, HIV-RNA, CD4 cell-count and antiviral treatment. Chronic hepatitis co-infection in HIV-infected patients (age years, SD) was: 265 HBV (40.7, 8.2); 19 HBV-HCV (39.7, 4.1); 12 HBV-HDV (35.2, 9.9); 12 HBV-HCV-HDV (39.2, 5.2). At inclusion, treatment with lamivudine/tenofovir was not significantly different between co-infection groups. HBV suppression was significantly associated with HDV (aOR = 3.85, 95%CI 1.13-13.10, P = 0.03) and HCV tri-infection (aOR = 2.65, 95%CI 1.03-6.81, P = 0.04), but marginally associated with HIV-HBV-HCV-HDV (aOR = 2.32, 95%CI 0.94-5.74, P = 0.07). In quad-infection, lower HDV-undetectability (vs HIV-HBV-HDV, P = 0.2) and higher HCV-undetectability (vs HIV-HBV-HCV, P = 0.1) were demonstrated. The degree of HBV suppression varied between visits and co-infection groups [range of aOR during follow-up (vs HIV-HBV co-infection): HIV-HBV-HCV = 2.23-5.67, HIV-HBV-HDV = 1.53-15.17]. In treated co-infected patients, HDV expressed continuous suppression over HCV- and HBV-replications. Peaks and rebounds from undetectable hepatitis B, C and/or D viremia warrant closer follow-up in this patient population. HDV-replication was uncontrolled even with antiviral treatment.

Mannheim carotid intima-media thickness consensus (2004-2006). An update on behalf of the Advisory Board of the 3rd and 4th Watching the Risk Symposium, 13th and 15th European Stroke Conferences, Mannheim, Germany, 2004, and Brussels, Belgium, 2006.

Intima-media thickness (IMT) is increasingly used as a surrogate end point of vascular outcomes in clinical trials aimed at determining the success of interventions that lower risk factors for atherosclerosis and associated diseases (stroke, myocardial infarction and peripheral artery diseases). The necessity to promote further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT and to standardize IMT measurements is expressed through this updated consensus. Plaque is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness >1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. Standard use of IMT measurements is based on physics, technical and disease-related principles as well as agreements on how to perform, interpret and document study results. Harmonization of carotid image acquisition and analysis is needed for the comparison of the IMT results obtained from epidemiological and interventional studies around the world. The consensus concludes that there is no need to 'treat IMT values' nor to monitor IMT values in individual patients apart from exceptions named, which emphasize that inside randomized clinical trials should be performed. Although IMT has been suggested to represent an important risk marker, according to the current evidence it does not fulfill the characteristics of an accepted risk factor. Standardized methods recommended in this consensus statement will foster homogenous data collection and analysis. This will help to improve the power of randomized clinical trials incorporating IMT measurements and to facilitate the merging of large databases for meta-analyses.

Mannheim intima-media thickness consensus.

Intima-media thickness (IMT) is increasingly used in clinical trials as a surrogate end point for determining the success of interventions that lower risk factors for atherosclerosis. The necessity for unified criteria to distinguish early atherosclerotic plaque formation from thickening of IMT and to standardize IMT measurements is addressed in this consensus statement. Plaque is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness of > or =1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. Standard use of IMT measurements is recommended in all epidemiological and interventional trials dealing with vascular diseases to improve characterization of the population investigated. The consensus concludes that there is no need to 'treat IMT values' nor to monitor IMT values in individual patients apart from few exceptions. Although IMT has been suggested to represent an important risk marker, it does not fulfill the characteristics of an accepted risk factor. Standardized methods recommended in this consensus statement will foster homogenous data collection and analysis. This will help to improve the power of studies incorporating IMT measurements and to facilitate the merging of large databases for meta-analyses.

A novel approach to directly observed therapy for tuberculosis in an HIV-endemic area.

OBJECTIVES: This study evaluated a novel approach to the delivery of directly observed therapy (DOT) for tuberculosis in Haiti. METHODS: A total of 194 patients (152 HIV seropositive, 42 HIV seronegative) received daily unsupervised triple-drug therapy for 4 to 8 weeks, followed by twice-weekly 2-drug therapy for the remainder of the 6-month period. DOT was deferred until initiation of the twice-weekly phase. RESULTS: A total of 169 of 194 patients (87.1%) completed the 6-month course. The program of deferred DOT had an effectiveness of 85%. Overall cost was reduced by approximately 40%. CONCLUSIONS: Flexible approaches to DOT, integrating behavioral knowledge, cost considerations, and practicality may improve completion rates and program effectiveness.

Periodontal disease, race, and vascular disease.

Recently, a number of studies have rekindled the possible hypothesis that oral health has repercussions beyond the oral cavity and is associated with systemic diseases. Interestingly, it is a return to an old theory that chronic infections and inflammation played a crucial role in atherosclerosis. This larger theory was advocated by French physicians, among others, at the beginning of the 20th century. In this article, we will review the epidemiologic evidence pointing to a possible association between oral health and vascular diseases and examine the role of race/ethnicity in the interpretation of this association.

Effect of post-treatment isoniazid on prevention of recurrent tuberculosis in HIV-1-infected individuals: a randomised trial.

BACKGROUND: Patients with HIV-1 infection respond well to treatment for active tuberculosis, but whether such patients are at increased risk of disease recurrence after complete cure is uncertain. We did a randomised trial in Port au Prince, Haiti, to determine whether recurrent tuberculosis after curative tuberculosis treatment is more common in HIV-1-infected individuals than HIV-1-uninfected individuals, and to determine whether post-treatment isoniazid prophylaxis decreases the risk of recurrent tuberculosis. METHODS: Patients older than 18 years who were diagnosed with a first episode of tuberculosis at the national HIV testing centre in Haiti, and who successfully completed a 6-month rifampicin-containing regimen for active pulmonary tuberculosis, were randomly assigned 1 year of post-treatment isoniazid prophylaxis or placebo. The primary outcome measure was rate of recurrent tuberculosis after at least 24 months. An intention-to-treat analysis was used. FINDINGS: Of 354 patients with active pulmonary tuberculosis, 274 successfully completed treatment, and 233 were randomised. Of 142 HIV-1-positive patients, 68 were assigned isoniazid and 74 placebo. Of 91 HIV-1-negative individuals, 51 were assigned isoniazid and 40 placebo. The rate of recurrent tuberculosis was 4.8 per 100 person-years in HIV-1-infected individuals and 0.4 per 100 person-years in uninfected individuals (relative risk 10.7 [95% CI 1.4-81.6]). Among HIV-1-positive patients receiving isoniazid, the tuberculosis recurrence rate was 1.4 per 100 person-years, and among HIV-1-positive patients receiving placebo, it was 7.8 per 100 person-years (0.18 [0.04-0.83]). Among HIV-1-positive individuals, all cases of recurrent tuberculosis occurred in individuals with a history of HIV-1-related symptoms before initial tuberculosis diagnosis. INTERPRETATION: The rate of recurrent tuberculosis is higher in HIV-1-positive individuals than in HIV-1-negative individuals, and is strongly associated with a history of symptomatic HIV-1 disease before initial tuberculosis diagnosis. Post-treatment isoniazid prophylaxis decreases the risk of recurrence in HIV-1-positive individuals, and should be considered for HIV-1-positive individuals with a history of HIV-1-related symptoms at the time of tuberculosis diagnosis.

Directly observed therapy and treatment completion for tuberculosis in the United States: is universal supervised therapy necessary?

OBJECTIVES: This study examined the relationship between directly observed therapy and treatment completion rates in the years before and after infusion of federal funding for tuberculosis (TB) control in 1993. METHODS: An ecological study of estimated directly observed therapy rates and 12-month treatment completion rates from 1990 through 1994 was undertaken for TB control programs in all 25 cities and counties across the nation with 100 or more incident TB cases in any year from 1990 to 1993. Three cohorts were formed: high treatment completion, intermediate completion, and low completion. RESULTS: In 1990, the median 12-month treatment completion rate was 80% for the entire study population, with a median estimated directly observed therapy rate of 16.8%. By 1994, those rates had increased to 87% and 49.4%, respectively, and increases were shown in all 3 cohorts. CONCLUSIONS: Directly observed therapy has had a marked impact on treatment completion rates in jurisdictions with historically low rates. But TB treatment completion rates of more than 90% can be attained with directly observed therapy rates far lower than those proposed by advocates of universal supervised therapy.

Reporting sexual risk behavior for HIV: a practical risk index and a method for improving risk indices.

OBJECTIVES: As a means of enhancing public health efforts to control sexual transmission of human immunodeficiency virus (HIV), methods were developed to report on risk behavior in a manner that is comparable and widely interpretable. METHODS: An elementary sexual behavior risk index (the vaginal episode equivalent index) that is in accord with some of the essential knowledge about sexual transmission of HIV is described, and a multivariate ordinal risk (MOR) method that can be used to improve such risk indices is introduced. RESULTS: An example shows that these approaches are applicable to observational studies of seroconversion. CONCLUSIONS: The MOR represents a powerful new tool to develop valid comparable measures of sexual risk behavior and, thereby, to advance HIV prevention research.

A prospective study of HIV-seropositive asymptomatic women of childbearing age in a developing country.

An observational study of 140 HIV-seropositive asymptomatic women of childbearing age was conducted in Haiti from 1984 to 1992 as part of a larger natural history study. Forty-four women were pregnant or became pregnant during the study period. The progression to HIV-related disease, AIDS, and mortality from AIDS was compared in the pregnant and nonpregnant cohorts. The mean follow-up time was 44 months. Overall, 32 of the 140 women (38%) developed AIDS, and 26 (19%) died from AIDS during the study period, with a cumulative AIDS incidence rate of 16% at 3 years after study entry. There was a trend toward earlier manifestation of HIV-related symptoms among the pregnant cohort, but no significant difference was observed in the rate of progression to AIDS or death between the pregnant and nonpregnant women.

The urge for an AIDS vaccine: perspectives from a developing country.

AIDS is inexorably involving all parts of the country and all strata of society, with 10% of the urban and 3% of the rural population infected with HIV. It is increasingly a disease of women and children. The major cofactors for transmission are also sexually transmitted. For most developing countries, in spite of all education efforts, the "silent epidemic" of AIDS continues. AIDS is known but not understood; counselling modifies behavior in only 10-20% of at-risk persons. Under optimal conditions, HIV discordant females have seroconversion rates of 4.7% per year and pregnancy rates of 10.4% per year. The recent political unrest in Zaire and Haiti will further enhance the spread of AIDS in these countries. Despite these difficult periods, the work can and must continue. After all, during our 10th year of collaboration with a Haitian private research group, the Haitian government and Cornell University, Haiti has known seven different political rulers. Finally, I want to make a pledge on behalf of the millions of people who face a certain death from HIV infection and AIDS and who will never make the front page of any newspaper. For these people, you can make a difference. You must give us the tools to carry on this fight. The clinical trials must be done where they are most needed: the developing countries. Vaccines represent the only viable alternative despite the recognized obstacles of viral heterogeneity, immunogenicity, and delivery.

HIV and AIDS in Haiti: recent developments.

PIP: Both the seroprevalence and epidemiology of human immunodeficiency virus (HIV) infection have demonstrated substantial changes in Haiti since the beginning of the epidemic in the early 1980s. Although seroprevalence rates vary greatly according to the population group tested, surveys of healthy urban adults have indicated an increase in HIV infection from about 8% in 1986 to 11% in 1991. The rate in rural areas remains at about 3%. Tuberculosis, herpes zoster, malignant prurigo, and weight loss are the most common signs of HIV infection before the virus progresses to acquired immunodeficiency syndrome (AIDS). The most significant changes in the pattern of HIV transmission in Haiti have been a decline in the proportion of cases among bisexuals/homosexuals (from 50% in 1983 to 1% since 1987) or related to blood transfusion. Also striking has been a change in the geographic distribution of HIV. In 1982, 80% of those infected with HIV were from the capital Port-au-Prince, 10% were from other major cities, and 10% were from other countries. In 1990, only 65% of cases originated from the Port-au-Prince area. Finally, there has been a shift in the sex distribution of HIV, with women contributing 38% of cases in 1989-90 compared to only 15% in 1979-82. Disturbing are survey findings that HIV-infected women, or those with an infected partner, continue to have unprotected sexual intercourse and to take no steps to avoid pregnancy. As a result of the growing number of AIDS cases among women, children under 14 years of age now comprises 6.6% of all AIDS cases compared to 2.4% in 1988. Development of a form of contraception that is as effective against HIV transmission as the condom yet could be used without the consent of the male partner would be an important advance in AIDS prevention in Haiti.^ieng