The teeth and faces of twins: providing insights into dentofacial development and oral health for practising oral health professionals.

The continuing studies of the teeth and faces of Australian twins and their families in the Craniofacial Biology Research Group in the School of Dentistry at the University of Adelaide began 30 years ago. Three main cohorts of twins have been recruited, enabling various objectives and specific hypotheses to be addressed about the roles of genetic, epigenetic and environmental influences on human dentofacial growth and development, as well as oral health. This paper highlights some key findings arising from these studies, emphasizing those of direct relevance to practising oral health professionals. We also draw on published literature to review the significant developments in relation to the use of precision 2D and 3D imaging equipment, the application of modern molecular techniques, and the development of sophisticated computer software for analysing genetic relationships and comparing complex shapes. Such developments are valuable for current and future work. Apart from the classical or traditional twin model, there are several other twin models that can be used in research to clarify the relative contributions of genetic, epigenetic and environmental contributions to phenotypic variation. The monozygotic (MZ) co-twin model is one particularly valuable method, given that examination of only one pair of MZ twins can provide considerable insights into underlying causes of observed variation. This model can be used in a dental practice environment, with oral health professionals having the opportunity to explore differences in orofacial structures between MZ co-twins who are attending as patients. As researchers have become more aware of the complexities of the interactions between the genome, the epigenome and the environment during development, there is the need to collect more phenotypic data and define new phenotypes that will better characterize variations in growth processes and health status. When coupled with powerful new genetic approaches, including genome-wide association studies and linkage analyses, exciting opportunities are opening up to unravel the causes of problems in craniofacial growth and common oral diseases in human populations.

30 Years on Selected Issues in the Prevention of HIV among Persons Who Inject Drugs.

After 30 years of extensive research on human immunodeficiency virus (HIV) among persons who inject drugs (PWID), we now have a good understanding of the critical issues involved. Following the discovery of HIV in 1981, epidemics among PWID were noted in many countries, and consensus recommendations for interventions for reducing injection related HIV transmission have been developed. While high-income countries have continued to develop and implement new Harm Reduction programs, most low-/middle-income countries have implemented Harm Reduction at very low levels. Modeling of combined prevention programming including needle exchange (NSP) and antiretroviral therapy (ARV) suggests that NSP be given the highest priority. Future HIV prevention programming should continue to provide Harm Reduction programs for PWID coupled with interventions aimed at reducing sexual transmission. As HIV continues to spread in low- and middle-income countries, it is important to achieve and maintain high coverage of Harm Reduction programs in these locations. As PWID almost always experience multiple health problems, it will be important to address these multiple problems within a comprehensive approach grounded in a human rights perspective.

Epigenetic influences may explain dental differences in monozygotic twin pairs.

BACKGROUND: Comparisons between monozygotic (MZ) co-twins have tended to focus on the similarities between their dentitions rather than differences. The aim of this study was to determine the prevalence of discordant expression for simple hypodontia and supernumerary teeth in MZ twin pairs and to explain how phenotypic differences might occur despite their similar genotypes. METHODS: Records of 278 pairs of MZ twins, including dental casts and radiographs, were examined and the prevalences of discordant expression for missing upper lateral incisors (ULI) or second premolars (PM2), and of mesiodentes, were determined. Zygosities were confirmed by comparisons of blood markers and DNA. RESULTS: There was evidence of at least one missing ULI or PM2 in 24 of the 278 MZ pairs (8.6 per cent), with 21 of these 24 pairs (87.5 per cent) showing discordant expression. Nine of the 278 MZ pairs (3.2 per cent) displayed evidence of mesiodentes, with eight of these nine pairs (88.9 per cent) being discordant. CONCLUSION: Our findings show that differences in the expression of missing or extra teeth occur often between MZ co-twins whose genetic make-up predisposes them to simple hypodontia or mesiodentes. We postulate that minor variations in epigenetic events during odontogenesis may account for these distinct differences.

Drug use and sexual risk behaviours among female Russian IDUs who exchange sex for money or drugs.

Countries of the former Soviet Union are experiencing the steepest increases in annual HIV incidence in the world. Over 80% of registered HIV cases in Russia have occurred among intravenous drug users (IDUs), but current conditions set the stage for a heterosexually-transmitted epidemic. IDUs who also trade sex for money or drugs may serve as a conduit, or 'bridge' group, through which HIV could make inroads into the general Russian population. The present study examined the prevalence of sex trading among female Russian IDUs, and further examined drug use, sexual behaviour, and perceived vulnerability in this group. Female IDUs (n=100) in St Petersburg, Russia participated; 37% reported a history of sex trading. This group reported a mean of 49.5 male sexual partners in the previous month and an average of 15.4 unprotected vaginal intercourse acts in the previous 30 days. A significant minority (44%) also reported sharing injection equipment with others. Mathematical models to calculate risk estimates for HIV seroconversion indicated that participants were at significant risk of contracting HIV and infecting sexual partners. Despite significant rates of risk behaviours, most participants perceived themselves to be at little risk of contracting HIV. Effective HIV prevention programmes targeted at this group are urgently needed and are likely to be a cost-effective step in curtailing the spread of HIV in the region.

The value of twins in dental research.

Due to recent advances in molecular genetics, studies of twins will continue to provide important insights into how genetic and environmental factors contribute to variation in human physical and behavioural traits and disorders. This review emphasizes that biometrical genetic studies of twins are particularly valuable in complementing and directing molecular approaches to facilitate the detection of quantitative trait loci. It also describes several other research models involving twins, apart from the traditional comparison of similarities in monozygotic (identical) and dizygotic (non-identical) pairs, that have the potential to provide new information in the future. Current knowledge about the genetic bases of common dental problems is summarized and future directions in dental research involving twins are outlined.

All STDs are not created equal: an analysis of the differential effects of sexual behaviour changes on different STDs.

The same sexual behaviours that transmit HIV are implicated in the transmission of certain other STDs, including chlamydia, gonorrhoea, and syphilis. Consequently, it is often assumed that preventive methods that are effective against HIV should be equally effective against other STDs. The purpose of this study was to examine this assumption. We applied a mathematical model of HIV/STD transmission to empirical data from a large HIV prevention intervention that stressed sexual behaviour change. We modelled the effects of two behavioural strategies - reducing the number of sex partners and increasing condom use-on the proportionate change in intervention participants' cumulative risk of acquiring HIV or a highly-infectious STD, such as gonorrhoea. The results of this modelling exercise indicate that decreasing the number of partners is a more effective strategy for reducing STD risk than it is for HIV risk. In contrast, condoms are somewhat more effective at reducing the cumulative transmission risk for HIV than for highly infectious STDs. The protection provided by condoms for multiple acts of intercourse critically depends on the infectiousness of the STD. The results of this study suggest caution in extrapolating from one STD to another, or from one behavioural risk reduction strategy to another.

Influence of a partner's HIV serostatus, use of highly active antiretroviral therapy, and viral load on perceptions of sexual risk behavior in a community sample of men who have sex with men.

OBJECTIVE: To assess the perceptions of gay and bisexual men concerning the risk of HIV transmission through various sexual practices with a new sex partner depending on that partner's disclosed HIV status, antiretroviral treatment status, and viral load. METHODS: Study participants read four different scenarios describing sexual situations with a new partner and rated each scenario for risk of HIV transmission. HIV status and antiretroviral treatment status disclosed by the new sex partner were varied across four scenarios: unknown HIV status; HIV-negative; HIV-positive and not taking highly active antiretroviral therapy (HAART); and HIV-positive and taking HAART with an undetectable viral load. RESULTS: Study participants were 472 men attending a gay pride festival who reported that they were HIV-negative. Eighty-nine percent of the men were white, and the mean age of the study participants was 35.8 years. Of the four scenarios, sex with an HIV-positive partner not taking HAART was rated as posing the greatest risk. Sex with an HIV-positive partner taking HAART who had an undetectable viral load was not consistently viewed as riskier than sex with an HIV-negative partner or a man with an unknown HIV status. CONCLUSIONS: The current study provides preliminary evidence for the effect of disclosure of HIV serostatus, use of HAART, and the presence of an undetectable viral load on the perceptions of sexual risk for HIV-negative men. The findings suggest that some gay and bisexual men judge risk based on the perceived HIV status of their sex partners and not on the general assumption that all sex partners entail equal risk, as many prevention campaigns have emphasized.

Sexual risk compensation and HIV/STD transmission: empirical evidence and theoretical considerations.

This study was conducted to answer the question, "Are sexual risk behaviors subject to compensation?" For example, do people who increase their use of condoms compensate for this reduction in human immunodeficiency virus and sexually transmitted disease (HIV/STD) risk by engaging in more overall acts of intercourse or by having sex with more partners than before? Utilizing the HIV prevention literature, studies in which participants demonstrated sexual risk compensation were identified. A simple HIV/STD transmission model was applied to these data to determine whether compensation produced a net increase in HIV/STD risk, despite positive changes in one or more aspects of sexual behavior. Although a number of studies were found in which there were simultaneous increases in condom use and the overall number of acts of intercourse, in none of these instances was there an overall increase in HIV/STD risk. Moreover, none of these studies reported concomitant increases in the number of sex partners. Extensive modeling exercises also were conducted to determine the theoretical conditions under which compensation would produce a net increase in risk. The results of the modeling exercise indicated that relatively small increases in overall sexual activity could be sufficient to offset risk-reduction gains due to increased condom use in populations in which baseline condom use is very low. In sum, although sexual risk compensation occurs, no empirical evidence was found that this compensation is sufficient to offset reductions in risk due to greater condom use, despite the theoretical plausibility of this scenario.

Probabilistic cost-effectiveness analysis of HIV prevention. Comparing a Bayesian approach with traditional deterministic sensitivity analysis.

In cost-effectiveness analysis, the incremental cost-effectiveness ratio is used to measure economic efficiency of a new intervention, relative to an existing one. However, costs and effects are seldom known with certainty. Uncertainty arises from two main sources: uncertainty regarding correct values of intervention-related parameters and uncertainty associated with sampling variation. Recently, attention has focused on Bayesian techniques for quantifying uncertainty. We computed the Bayesian-based 95% credible interval estimates of the incremental cost-effectiveness ratio of several related HIV prevention interventions and compared these results with univariate sensitivity analyses. The conclusions were comparable, even though the probabilistic technique provided additional information.

Cost-effectiveness of an HIV prevention intervention for mentally ill adults.

Adults with severe mental illness are at high risk for human immunodeficiency virus (HIV) infection and transmission. Small-group interventions that focus on sexual communication, condom use skills, and motivation to practice safer sex have been shown to be effective at helping mentally ill persons reduce their risk for HIV. However, the cost-effectiveness of these interventions has not been established. We evaluated the cost-effectiveness of a 9-session small-group intervention for women with mental illness recruited from community mental health clinics in Milwaukee, Wisconsin. We used standard techniques of cost-utility analysis to determine the cost per quality-adjusted life year (QALY) saved by the intervention. This analysis indicated that the intervention cost $679 per person, and over $136,000 per QALY saved. When the analysis was restricted to the subset of women who reported having engaged in vaginal or anal intercourse in the 3 months prior to the baseline assessment, the cost per QALY saved dropped to approximately $71,000. These estimates suggest that this intervention is marginally cost-effective in comparison with other health promotion interventions, especially if high-risk, sexual-active women are preferentially recruited.

Effectiveness of an intervention to reduce HIV transmission risks in HIV-positive people.

BACKGROUND: As many as one in three HIV-positive people continue unprotected sexual practices after learning that they are HIV infected. This article reports the outcomes of a theory-based intervention to reduce risk of HIV transmission for people living with HIV infection. METHODS: Men (n=233) and women (n=99) living with HIV-AIDS were randomly assigned to receive either (1) a five-session group intervention focused on strategies for practicing safer sexual behavior, or (2) a five-session, contact-matched, health-maintenance support group (standard-of-care comparison). Participants were followed for 6 months post-intervention. RESULTS: The intervention to reduce risk of HIV transmission resulted in significantly less unprotected intercourse and greater condom use at follow-up. Transmission-risk behaviors with non-HIV-positive sexual partners and estimated HIV transmission rates over a 1-year horizon were also significantly lower for the behavioral risk-reduction intervention group. CONCLUSIONS: This study is among the first to demonstrate successful HIV-transmission risk reduction resulting from a behavioral intervention tailored for HIV-positive men and women.

Using cost-effectiveness league tables to compare interventions to prevent sexual transmission of HIV.

Cost-effectiveness information is needed to help public health decision makers choose between competing HIV prevention programs. One way to organize this information is in a 'league table' that lists cost-effectiveness ratios for different interventions and which facilitates comparisons across interventions. Herein we propose a common outcome measure for use in HIV prevention league tables and present a preliminary league table of interventions to reduce sexual transmission of HIV in the US. Fifteen studies encompassing 29 intervention for different population groups are included in the table. Approximately half of the interventions are cost-saving (i.e. save society money, in the long run), and three-quarters are cost-effective by conventional standards. We discuss the utility of such a table for informing the HIV prevention resource allocation process and delineate some of the difficulties associated with the league table approach, especially as applied to HIV prevention cost-effectiveness analysis.

A relative risk-based, disease-specific definition of sexual abstinence failure rates.

Sexual abstinence programs have the potential to reduce the incidence of unplanned pregnancies and sexually transmitted diseases (STDs) among adolescents. Effectiveness measures are needed to help researchers assess the impact of sexual abstinence promotion programs on STD and pregnancy rates and to enable comparisons of abstinence effectiveness with other contraception and STD prevention methods. Abstinence "failure rates" have been proposed as one measure of program effectiveness. However, the concept of abstinence failure rates has not been adequately operationalized. The present study examines a novel mathematical framework for estimating abstinence failure rates, both theoretically and empirically. Examples are provided, and the advantages and disadvantages associated with the mathematical model-based approach are discussed.

Economic evaluation of HIV risk reduction intervention in African-American male adolescents.

PURPOSE: To evaluate the cost-effectiveness of a cognitive-behavioral HIV risk reduction intervention for African-American male adolescents that has previously been shown to be effective at reducing sexual risk taking. METHODS: Standard techniques of cost-utility analysis were employed. A societal perspective and a 3% discount rate were used in the main analysis. Program costs were ascertained retrospectively. A mathematical model of HIV transmission was used to translate observed changes in sexual behavior into an estimate of the number of HIV infections the intervention averted. Intervention effects were assumed to last for 1 year. For each infection averted, the corresponding savings in future HIV-related medical care costs and quality-adjusted life years (QALYs) were estimated. The overall net cost per QALY saved (cost-utility ratio) was then calculated. Sensitivity analyses were performed to assess the robustness of the main results. RESULTS: The cost-utility ratio was approximately $57,000 U.S. per QALY saved when training costs were included, and $41,000 U.S. per QALY saved when they were excluded. The intervention appeared substantially more cost-effective when the analysis was restricted to the subgroup of participants who reported being sexually active at baseline. Assumptions about the prevalence of HIV infection and the duration of intervention effectiveness also greatly affected the cost-utility ratio. CONCLUSIONS: The HIV prevention intervention was moderately cost-effective in comparison with other health care programs. Selectively implementing the intervention in high-HIV prevalence communities and with sexually active youth can enhance cost-effectiveness.

Consequences of HIV prevention interventions and programs: spectrum, selection, and quality of outcome measures.

The outcome measures employed in an HIV prevention intervention study should match the research and policy questions at hand. If the question is 'did the intervention work to prevent HIV infection?', then seroincidence data may be insufficient. However, if the question is 'why did the intervention work?', then more detailed behavioral data are necessary (and sometimes behavior change itself is the real goal of an intervention study). Given the wide range of questions asked by HIV prevention policy makers, funders and researchers, a spectrum of outcome measures is needed across HIV prevention intervention studies. These include measures of behavioral determinants, HIV-related risk behaviors, HIV incidence (and other biologic markers), morbidity, mortality, and cost-effectiveness factors (such as cost per quality-adjusted life year saved). In this paper, we review the range of outcome measures used and needed in these intervention studies. Particular attention is paid to the psychometric properties of self-reported behavior change measures of sexual behavior and substance use. Additional emphasis is placed on the role of cost-effectiveness measures in intervention studies. A general framework is proposed for conceptualizing the array of outcome measure possible for any given HIV prevention intervention study.

Prioritization methods for HIV community planning.

Since 1994, community planning groups (CPGs) have played an important role in shaping local HIV prevention efforts. The community planning process requires CPGs to prioritize HIV prevention interventions and unmet needs among at-risk populations. This article describes and compares four prioritization methods: (1) the ranking method, (2) Holtgrave's method, (3) Kaplan's method, and (4) a novel utility-based prioritization method. These methods are compared in terms of effectiveness, efficiency, equity, and political feasibility. The methods described here are meant to assist CPGs in the difficult prioritization task by helping CPG members organize their thoughts in the prioritization process.

Cost-effectiveness of an HIV risk reduction intervention for adults with severe mental illness.

Small-group HIV prevention interventions that focus on individual behavioural change have been shown to be especially effective in reducing HIV risk among persons with severe mental illness. Because economic resources to fund HIV prevention efforts are limited, health departments, community planning groups and other key decision-makers need reliable information on the cost and cost-effectiveness (not solely on effectiveness) of different HIV prevention interventions. This study used an economic evaluation technique known as cost-utility analysis to assess the cost-effectiveness of three related cognitive-behavioural HIV risk reduction interventions: a single-session, one-on-one intervention; a multi-session small-group intervention; and a multi-session small-group intervention that taught participants to act as safer sex advocates to their peers. For men, all three interventions were cost-effective, but advocacy training was the most cost-effective of the three. For women, only the single-session intervention was cost-effective. The gender differences observed here highlight the importance of focusing on gender issues when delivering HIV prevention interventions to men and women who are severely mentally ill.