Management of well appearing infants born to afebrile mothers with inadequate GBS prophylaxis: A retrospective comparison of the three approaches recommended by the COFN.

BACKGROUND: There are three different approaches set forth by the Committee on the Fetus and Newborn (COFN) for managing asymptomatic neonates born to mothers with inadequate intrapartum antibiotic prophylaxis (IAP) for early-onset Group B Strep (GBS) infection. The first approach is that of categorical risk factor assessments, and recommends that asymptomatic infants born to afebrile mothers with inadequate IAP for GBS be monitored with clinical observation for 36-48 hours. The second approach recommends serial physical examinations and vital signs for 36-48 hours to closely monitor changes in clinical condition for all patients. The Kaiser Permanente EOS risk calculator (SRC) is an example of the third approach, a multivariate risk assessment, and it takes into consideration several perinatal risk factors. This multivariate risk assessment then provides recommendations for reassessment and management based on presume risk of the infant developing or having Early Onset Sepsis (EOS). The aim of our study was to compare these three recently published recommendations from the COFN for the management of asymptomatic neonates born to afebrile mothers with inadequate IAP for GBS. STUDY DESIGN: This is a retrospective study of asymptomatic neonates with gestational age ≥35 weeks born to afebrile mothers with indicated inadequate IAP for GBS between April 2017 and July 2020. Management recommendations of the SRC were compared to the recommendations of categorical risk assessment and risk assessment based on clinical condition. RESULTS: A total of 7,396 infants were born during the study period, 394 (5.3%. to mothers with inadequate IAP. Recommendations for these infants according to both the categorical risk factor guideline and the clinical condition guideline include extended, close observation. However, the SRC recommended routine newborn care for 99.7%.f these infants. None of the infants developed EOS. CONCLUSION: The SRC recommend routine neonatal care without enhanced and prolonged observation for nearly all asymptomatic infants born to afebrile mothers with inadequate IAP. As none of the infants in this cohort had EOS, further studies in a larger cohort are needed to establish the safety of SRC in neonates born to mothers with inadequate IAP.

Management of infants born to mothers with chorioamnionitis: A retrospective comparison of the three approaches recommended by the committee on fetus and newborn.

BACKGROUND: Based on the most recently published recommendations from the Committee on the Fetus and Newborn (COFN), three approaches currently exist for the use of risk factors to identify infants who are at increased risk of early-onset sepsis (EOS). Categorical risk factor assessments recommend laboratory testing and empiric antibiotic therapy for all infants born to mothers with a clinical diagnosis of chorioamnionitis. Risk assessments based on clinical condition recommend frequent examinations and close vital sign monitoring for infants born to mothers with chorioamnionitis. The Kaiser Permanente EOS risk calculator (SRC) is an example of the third approach, multivariate risk assessments. The aim of our study was to compare the three risk stratification approaches recommended by the COFN for management of chorioamnionitis-exposed infants. METHODS: Retrospective study of 1,521 infants born ≥35 weeks to mothers with chorioamnionitis. Management recommendations of the SRC were compared to the recommendations of categorical risk assessment and risk assessment based on clinical condition (CCA). RESULTS: Hypothetical application of SRC and CCA resulted in 79.6% and 76.8-85.1% respectively fewer infants allocated empiric antibiotic therapy. While CCA recommended enhanced observation for all chorioamnionitis-exposed infants, SRC recommended routine care without enhanced observation in 44.3% infants. For the six infants (0.39%) with EOS, SRC and CCA recommended empiric antibiotics only for three symptomatic infants. CONCLUSION: The SRC and CCA can reduce antibiotic use but potentially delay antibiotic treatment. The SRC does not recommend enhanced observation with frequent and prolonged vital signs for >44% of chorioamnionitis-exposed infants.

Pain Sensitivity Modifies Risk of Injury-Related Temporomandibular Disorder.

This study evaluates contributions of jaw injury and experimental pain sensitivity to risk of developing painful temporomandibular disorder (TMD). Data were from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) nested case-control study of incident painful TMD. Injury and subsequent onset of painful TMD were monitored prospectively for ≤5 y in a community-based sample of 409 US adults who did not have TMD when enrolled. At baseline, thermal-pressure and pinprick pain sensitivity, as potential effect modifiers, were measured using quantitative sensory testing. During follow-up, jaw injury from any of 9 types of potentially traumatic events was determined using quarterly (3-monthly) health update questionnaires. Study examiners classified incident painful TMD, yielding 233 incident cases and 176 matched controls. Logistic regression models, estimated incidence odds ratios (IORs), and 95% confidence limits (CLs) were used for the association between injury and subsequent onset of painful TMD. During follow-up, 38.2% of incident cases and 13.1% of controls reported 1 or more injuries that were 4 times as likely to be intrinsic (i.e., sustained mouth opening or yawning) as extrinsic (e.g., dental visits, whiplash). Injuries due to extrinsic events (IOR = 7.6; 95% CL, 1.6-36.2), sustained opening (IOR = 5.4; 95% CL, 2.4-12.2), and yawning (IOR = 3.4; 95% CL, 1.6-7.3) were associated with increased TMD incidence. Both a single injury (IOR = 6.0; 95% CL, 2.9-12.4) and multiple injuries (IOR = 9.4; 95% CL, 3.4,25.6) predicted greater incidence of painful TMD than events perceived as noninjurious (IOR = 1.9; 95% CL, 1.1-3.4). Injury-associated risk of painful TMD was elevated in people with high sensitivity to heat pain (IOR = 7.4; 95% CL, 3.1-18.0) compared to people with low sensitivity to heat pain (IOR = 3.9; 95% CL, 1.7-8.4). Jaw injury was strongly associated with elevated painful TMD risk, and the risk was amplified in subjects who had enhanced sensitivity to heat pain at enrollment. Commonly occurring but seemingly innocuous events, such as yawning injury, should not be overlooked when judging prognostic importance of jaw injury.

Vigilance behaviors and EEG activity in sustained attention may affect acute pain.

During Sustained Attention to stimuli across many modalities neural activity often decreases over time on task, while Errors in task performance increase (Vigilance Decrement). Sustained Attention to pain has rarely been investigated experimentally despite its clinical significance. We have employed a Sustained Attention protocol (Continuous Performance Task, CPT) in which the subject counts painful laser stimuli (targets) when they occur randomly in a prolonged train of nonpainful nontargets. We hypothesize that the magnitude of the poststimulus oscillatory power divided by baseline power (Event-Related Spectral Perturbation, ERSP - scalp EEG) over Frontoparietal structures will decrease at all frequencies with time on task, while Beta ERSP (14-30Hz) will be correlated with Error Rates in performance of the CPT. During the CPT with a painful target ERSP was found in four separate Windows, as defined by both their frequency band and the time after the stimulus. A Vigilance Decrement was found which confirms that Sustained Attention to pain was produced by this CPT. In addition, Error Rates was correlated inversely with laser energy, and with ratings of pain unpleasantness and salience. Error Rates also were related directly to the Beta ERSP Window at scalp EEG electrodes over the central sulcus. Over time on task, the ERSP magnitude decreased in Alpha (8-14Hz) Window, was unchanged in early and late Delta/Theta Windows (0-8Hz), and increased in the Beta Window. The increase in Beta ERSP and a decrease in the Alpha ERSP occurred at the same EEG electrode over the parietal lobe to a significant degree across subjects. Overall, Beta activity increases with time on task, and with higher Error Rates as in the case of other modalities. In the case of pain increased Errors correspond to misidentification of painful and nonpainful stimuli and so modulate the sensation of pain under the influence of Sustained Attention.

Painful Temporomandibular Disorder: Decade of Discovery from OPPERA Studies.

In 2006, the OPPERA project (Orofacial Pain: Prospective Evaluation and Risk Assessment) set out to identify risk factors for development of painful temporomandibular disorder (TMD). A decade later, this review summarizes its key findings. At 4 US study sites, OPPERA recruited and examined 3,258 community-based TMD-free adults assessing genetic and phenotypic measures of biological, psychosocial, clinical, and health status characteristics. During follow-up, 4% of participants per annum developed clinically verified TMD, although that was a "symptom iceberg" when compared with the 19% annual rate of facial pain symptoms. The most influential predictors of clinical TMD were simple checklists of comorbid health conditions and nonpainful orofacial symptoms. Self-reports of jaw parafunction were markedly stronger predictors than corresponding examiner assessments. The strongest psychosocial predictor was frequency of somatic symptoms, although not somatic reactivity. Pressure pain thresholds measured at cranial sites only weakly predicted incident TMD yet were strongly associated with chronic TMD, cross-sectionally, in OPPERA's separate case-control study. The puzzle was resolved in OPPERA's nested case-control study where repeated measures of pressure pain thresholds revealed fluctuation that coincided with TMD's onset, persistence, and recovery but did not predict its incidence. The nested case-control study likewise furnished novel evidence that deteriorating sleep quality predicted TMD incidence. Three hundred genes were investigated, implicating 6 single-nucleotide polymorphisms (SNPs) as risk factors for chronic TMD, while another 6 SNPs were associated with intermediate phenotypes for TMD. One study identified a serotonergic pathway in which multiple SNPs influenced risk of chronic TMD. Two other studies investigating gene-environment interactions found that effects of stress on pain were modified by variation in the gene encoding catechol O-methyltransferase. Lessons learned from OPPERA have verified some implicated risk factors for TMD and refuted others, redirecting our thinking. Now it is time to apply those lessons to studies investigating treatment and prevention of TMD.

Hairy leukoplakia; lessons learned: 30-plus years.

Well into the fourth decade of the HIV/AIDS pandemic, we can look back on the early years, the initial discoveries, and the broad sweep of the progress of our understanding of the nature, causes, and significance of the oral lesions seen in those infected with the virus. Prominent among these is oral hairy leukoplakia (HL), a previously unknown lesion of the mouth associated with Epstein-Barr virus (EBV) and initially seen only in people with AIDS, in the then-recognized risk groups, or those shown to be HIV positive. Subsequently, it became clear that the distribution of HL extends well beyond the HIV spectrum. In this brief review, we consider the clinical and histological features of HL, discuss how it was discovered, explore its cause, diagnosis, relationship with AIDS, pathogenesis, significance in EBV biology, options for management, and how it changes with HIV/AIDS therapy.

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.

Global burden of oral diseases: emerging concepts, management and interplay with systemic health.

OBJECTIVES: This study presents the global burden of major oral diseases with an exegetical commentary on their current profiles, the critical issues in oral healthcare and future perspectives. METHODS: A narrative overview of current literature was undertaken to synthesise the contexts with critical elaboration and commentary. RESULTS: Oral disease is one of the most common public health issues worldwide with significant socio-economic impacts, and yet it is frequently neglected in public health policy. The oral data extracted from the Global Burden of Disease Study in 2010 (Murray et al, 2012) show that caries, periodontal disease, edentulism, oral cancer and cleft lip/palate collectively accounted for 18 814 000 disability-adjusted life-years; and the global burden of periodontal disease, oral cancer and caries increased markedly by an average of 45.6% from 1990 to 2010 in parallel with the major non-communicable diseases like diabetes by 69.0%. Oral diseases and non-communicable diseases are closely interlinked through sharing common risk factors (e.g. excess sugar consumption and tobacco use) and underlying infection/inflammatory pathways. CONCLUSIONS: Oral disease remains a major public health burden worldwide. It is of great importance to integrate oral health into global health agenda via the common risk factor approach. The long-term sustainable strategy for global oral health should focus on health promotion and disease prevention through effective multidisciplinary teamwork.

COMT Diplotype Amplifies Effect of Stress on Risk of Temporomandibular Pain.

When measured once, psychological stress predicts development of painful temporomandibular disorder (TMD). However, a single measurement fails to characterize the dynamic nature of stress over time. Moreover, effects of stress on pain likely vary according to biological susceptibility. We hypothesized that temporal escalation in stress exacerbates risk for TMD, and the effect is amplified by allelic variants in a gene, catechol-O-methyltransferase (COMT), regulating catechol neurotransmitter catabolism. We used data from the Orofacial Pain: Prospective Evaluation and Risk Assessment prospective cohort study of 2,707 community-dwelling adults with no lifetime history of TMD on enrollment. At baseline and quarterly periods thereafter, the Perceived Stress Scale (PSS) measured psychological stress. Genotyped DNA from blood samples determined COMT diplotypes. During follow-up of 0.25 to 5.2 y, 248 adults developed examiner-verified incident TMD. PSS scores at baseline were 20% greater (P < 0.001) in adults who developed incident TMD compared with TMD-free controls. Baseline PSS scores increased by 9% (P = 0.003) during follow-up in cases but remained stable in controls. This stress escalation was limited to incident cases with COMT diplotypes coding for low-activity COMT, signifying impaired catabolism of catecholamines. Cox regression models confirmed significant effects on TMD hazard of both baseline PSS (P < 0.001), modeled as a time-constant covariate, and change in PSS (P < 0.001), modeled as a time-varying covariate. Furthermore, a significant (P = 0.04) interaction of COMT diplotype and time-varying stress showed that a postbaseline increase of 1.0 standard deviation in PSS more than doubled risk of TMD incidence in subjects with low-activity COMT diplotypes (hazard ratio = 2.35; 95% confidence limits: 1.66, 3.32), an effect not found in subjects with high-activity COMT diplotypes (hazard ratio = 1.42; 95% confidence limits: 0.96, 2.09). Findings provide novel insights into dynamic effects of psychological stress on TMD pain, highlighting that effects are most pronounced in individuals whose genetic susceptibility increases responsiveness to catecholamine neurotransmitters.

Sleep apnea symptoms and risk of temporomandibular disorder: OPPERA cohort.

The authors tested the hypothesis that obstructive sleep apnea (OSA) signs/symptoms are associated with the occurrence of temporomandibular disorder (TMD), using the OPPERA prospective cohort study of adults aged 18 to 44 years at enrollment (n = 2,604) and the OPPERA case-control study of chronic TMD (n = 1,716). In both the OPPERA cohort and case-control studies, TMD was examiner determined according to established research diagnostic criteria. People were considered to have high likelihood of OSA if they reported a history of sleep apnea or ≥ 2 hallmarks of OSA: loud snoring, daytime sleepiness, witnessed apnea, and hypertension. Cox proportional hazards regression estimated hazard ratios (HRs) and 95% confidence limits (CL) for first-onset TMD. Logistic regression estimated odds ratios (OR) and 95% CL for chronic TMD. In the cohort, 248 individuals developed first-onset TMD during the median 2.8-year follow-up. High likelihood of OSA was associated with greater incidence of first-onset TMD (adjusted HR = 1.73; 95% CL, 1.14, 2.62). In the case-control study, high likelihood of OSA was associated with higher odds of chronic TMD (adjusted OR = 3.63; 95% CL, 2.03, 6.52). Both studies supported a significant association of OSA symptoms and TMD, with prospective cohort evidence finding that OSA symptoms preceded first-onset TMD.

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.

Non-invasive electrical stimulation of the brain (ESB) modifies the resting-state network connectivity of the primary motor cortex: a proof of concept fMRI study.

An innovative method to obtain fMRI resting-state network maps during non-invasive electrical stimulation of the brain (ESB) was developed and tested. Five healthy volunteers participated in 2 fMRI sessions. In session one, a transcranial direct current stimulator (tDCS) was applied placing the positive electrode (31.5 cm(2)) over the right M1 of the cortex and the negative electrode (31.5 cm(2)) over the left supra-orbital area of the head. In session two, a monophasic pulsed current stimulator (tPCS) was applied using the identical electrode placement. Imaging was performed on a Siemens 3T Tim Trio scanner with a 12-channel head coil. At each session, five consecutive functional scans were obtained: 1) resting-state without stimulation (Rest-1), 2) a motor scan consisting of self-paced, bilateral finger-thumb opposition task, 3) resting-state with ESB (Stim-1), 4) resting-state without stimulation (Rest-2), and 5) resting-state with ESB, replicating Stim-1 (Stim-2). Data were analyzed using AFNI and MATLAB. For motor task fMRI analysis, a general linear model (GLM) determined the voxels in the right and left M1 that were significantly correlated with the motor task paradigm. The resting-state time series from the voxels in the R-M1 were averaged and the resulting time series used as a regressor in a GLM analysis to identify M1 connectivity maps. Connectivity maps were quantified as R(2) values, and then combined to give overlap maps for each of the experimental conditions. Fourier analysis determined the energy in the normalized signal average time courses extracted from L-M1 and R-M1 for each of the resting-state scans. Both tDCS and tPCS lowered the R(2) values and energy of the averaged time course in the right and left M1 ROI. The effect of the tPCS appeared more pronounced and less variable among subjects. Applying non-invasive ESB during fMRI scanning may down regulate the motor cortex's resting-state network connectivity.

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.

Guidelines and recommendations for assessment of somatosensory function in oro-facial pain conditions--a taskforce report.

The goals of an international taskforce on somatosensory testing established by the Special Interest Group of Oro-facial Pain (SIG-OFP) under the International Association for the Study of Pain (IASP) were to (i) review the literature concerning assessment of somatosensory function in the oro-facial region in terms of techniques and test performance, (ii) provide guidelines for comprehensive and screening examination procedures, and (iii) give recommendations for future development of somatosensory testing specifically in the oro-facial region. Numerous qualitative and quantitative psychophysical techniques have been proposed and used in the description of oro-facial somatosensory function. The selection of technique includes time considerations because the most reliable and accurate methods require multiple repetitions of stimuli. Multiple-stimulus modalities (mechanical, thermal, electrical, chemical) have been applied to study oro-facial somatosensory function. A battery of different test stimuli is needed to obtain comprehensive information about the functional integrity of the various types of afferent nerve fibres. Based on the available literature, the German Neuropathic Pain Network test battery appears suitable for the study of somatosensory function within the oro-facial area as it is based on a wide variety of both qualitative and quantitative assessments of all cutaneous somatosensory modalities. Furthermore, these protocols have been thoroughly described and tested on multiple sites including the facial skin and intra-oral mucosa. Standardisation of both comprehensive and screening examination techniques is likely to improve the diagnostic accuracy and facilitate the understanding of neural mechanisms and somatosensory changes in different oro-facial pain conditions and may help to guide management.

Spatial attention to thermal pain stimuli in subjects with visual spatial hemi-neglect: extinction, mislocalization and misidentification of stimulus modality.

One approach to the study of disordered spatial attention is to carry out tests of extinction, in which stimuli are detected on the left when they are presented on the left alone, but not when both sides are stimulated simultaneously in a dual simultaneous stimulation (DSS) protocol. Extinction has been documented for multiple sensory modalities, but not for thermal pain stimuli, to our knowledge. We now test the hypothesis that subjects with visual spatial neglect (hemi-neglect) will have alterations in thermal pain sensation which are related to abnormal spatial attention. The results demonstrate that thermal pain extinction of hot and cold pain stimuli occurs in a proportion of subjects with hemi-neglect. In the subjects with visual spatial hemi-neglect but without thermal pain extinction, the sensation of the thermal pain stimulus on the affected (left) side was not extinguished but was often localized to the unaffected (right) side, and the submodality of the stimulus (cold or hot) was often misidentified. Ratios indicating the magnitude of extinction, mislocalization and misidentification were significantly larger on the left side of subjects with visual spatial neglect than in healthy controls or in controls with stroke but without hemineglect. The proportion of subjects with thermal pain extinction, mislocalization, or misidentification was significantly higher in subjects with hemi-neglect than those in either control group. These results demonstrate that disordered attention exerts a powerful effect upon the perception of both the location and the quality of thermal pain stimuli.

Altered pain and thermal sensation in subjects with isolated parietal and insular cortical lesions.

Studies of sensory function following cortical lesions have often included lesions which multiple cortical, white matter, and thalamic structures. We now test the hypothesis that lesions anatomically constrained to particular insular and parietal structures and their subjacent white matter are associated with different patterns of sensory loss. Sensory loss was measured by quantitative sensory testing (QST), and evaluated statistically within patients relative to normal values. All seven subjects with insular and/or parietal lesions demonstrated thermal hypoesthesia, although the etiology of the lesions was heterogeneous. Cold and heat hypoalgesia were only found in the subject with the most extensive parietal and insular lesion, which occurred in utero. Cold allodynia occurred clinically and by thresholds in two subjects with isolated ischemic lesions of the posterior insular/retroinsular cortex, and by thresholds in two subjects with a lesion of parietal cortex with little or no insular involvement. Central pain occurred in the two subjects with clinical allodynia secondary to isolated lesions of the posterior insular/retroinsular cortex, which spared the anterior and posterior parietal cortex. These results suggest that nonpainful cold and heat sensations are jointly mediated by parietal and insular cortical structures so that lesions anywhere in this system may diminish sensitivity. In contrast, thermal pain is more robust requiring larger cortical lesions of these same structures to produce hypoalgesia. In addition, cold allodynia can result from restricted lesions that also produce thermal hypoesthesia, but not from all such lesions.

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.