Voluntary contraceptive use by HIV-positive women currently prevents more HIV-positive births, at a lower cost, than anti-retroviral drug (ARV) regimens. Despite this evidence, most prevention of mother-to-child transmission (PMTCT) programs focus solely on providing ARV prophylaxis to pregnant women and rarely include the prevention of unintended pregnancies among HIV-positive women.To strengthen support for family planning as HIV prevention, we systematically identified key individuals in the field of international HIV/AIDS—those who could potentially influence the issue—and sought to determine their perceptions of barriers to and facilitators for implementing this PMTCT strategy. We used a criteria-based approach to determine which HIV/AIDS stakeholders have the most significant impact on HIV/AIDS research, programs, funding and policy and stratified purposive sampling to conduct interviews with a subset of these individuals. The interview findings pointed to obstacles to strengthening linkages between family planning and HIV/AIDS, including the need for: resources to integrate family planning and HIV services, infrastructure or capacity to provide integrated services at the facility level, national leadership and coordination, and targeted advocacy to key decision-makers.The individuals we identified as having regional or international influence in the field of HIV/AIDS have the ability to leverage an increasingly conducive funding environment and a growing evidence base to address the policy, programmatic and operational challenges to integrating family planning with HIV/AIDS. Fostering greater support for implementing contraception for HIV prevention will require the dedication, collaboration and coordination of many such actors. Our findings can inform a targeted advocacy campaign. Ninety percent of new HIV infections among children under age 15 are a result of mother-to-child transmission current contraceptive use may already be preventing more than 220,000 HIV-positive births per year in countries hardest hit by the HIV epidemic Although linking family planning and HIV services is generally considered feasible and effective We implemented a project based on the theory that support from key influential individuals is critical to widespread adoption of a new or underused idea or practice This paper focuses on the first two goals. We used criteria-based searches to identify key opinion leaders in HIV/AIDS, and through key informant interviews we explored their knowledge of contraception as an effective PMCT strategy, and their perceived facilitators and barriers to implementing element 2 of a comprehensive PMTCT program.most direct impact on HIV/AIDS research, programs, funding and policy: researchers, program managers, donors, policy makers, advocates, and other public figures.To identify opinion leaders in HIV/AIDS we adapted a stakeholder analysis methodology that focused on identifying influential individuals We searched online information products–published research, conference presentations, grants, media digests, and lists of key staff/directors of major HIV and AIDS organizations–to identify and create a list of key HIV/AIDS stakeholders. To ensure that developing country stakeholders were included, we supplemented our global searches with additional searches in six countries: Kenya, Nigeria, Uganda, South Africa, Tanzania, and India.To identify key researchers, we searched online journals (via PubMed and Popline databases), conference presentations, and NIH grants. Due to the high volume of HIV researchers listed in PubMed, we chose to add individuals to the list only if they had published research on PMTCT.To find key HIV program planners and managers, we searched for organizations implementing work funded by the Bill & Melinda Gates Foundation, the President's Emergency Plan for AIDS Relief (PEPFAR), the World Bank, and the Global Fund for AIDS, Tuberculosis and Malaria (GFATM). We added principal grant recipients, team leaders, and others in leadership positions to the list.Kaiser Daily HIV/AIDS Reports (an email newsletter and online digest). To narrow down the list of individuals included in these news reports, we only added individuals to the list if they were mentioned or quoted in a news summary about PMTCT, and we excluded current heads of state.To identify public figures in HIV/AIDS that may not have been found in our other searches, we reviewed two years of Finally, we conducted internet searches to find lists of managers, directors, and other high-level staff at major global HIV/AIDS donor organizations and normative bodies , and the leaders and members of major international HIV and AIDS task forces, working groups, research organizations, and advocacy organizations . We included all of these global leaders in our list.and deciding whom to target with individualized messages about contraception for HIV prevention , we sought to narrow down the larger list to identify the most influential leaders. To select these individuals, we used stratified purposive sampling For the process of both identifying interviewees To ensure that key informants represented the views of the larger group that we identified, we based our selections on the overall geographic distribution of individuals, choosing from both the global and country-level lists. Furthermore, we wanted the interview responses to reflect the range of individual characteristics and societal roles of these opinion leaders, so we selected individuals who represented a variety of organizations and institutions (maximum variation sampling). Finally, individuals who appeared in more than one data search were included in our list of interviewees (intensity sampling). We hypothesized that these individuals would be “information-rich,” and would have detailed knowledge of the topic We selected forty-eight individuals for interviews based on these maximum variation and intensity sampling techniques. However, due to the high-profile–and thus hard-to-reach–status of some of the individuals on our list, we narrowed this list down further to 24 individuals on the list who were known by colleagues, were easily reachable, or otherwise the most likely to respond (opportunistic sampling) We conducted semi-structured qualitative interviews in English, either in person or by phone. Interviews ranged from 10 minutes to 30 minutes in length. All interviews were tape recorded and then transcribed verbatim. Participants were not reimbursed or given any incentives for participating in interviews.Each interview explored the following topics:The participant's general opinion about contraception for PMTCTAny professional work he/she was currently doing that supported contraception for PMTCTWhat resources his/her organization might need to more actively support implementation of such activitiesWhat factors he/she believed could facilitate or provide a more prominent place for contraception among PMTCT effortsnot support integrating contraceptive services into HIV prevention and PMTCT effortsWhat objections he/she has perceived among those who do Who he/she thought could have a strong influence over others if they were to promote contraception for the prevention of HIVWhere he/she accesses information about HIV and/or contraception, and which communication channels most influence his/her decisionsAll parts of the interviews were reviewed, but we focused our coding and analysis on: opinions about contraception for PMTCT; opinions about barriers/facilitators of implementing integrated family planning/HIV services; and communication channels.Two analysts read through several transcripts and independently identified a list of emerging ideas, which they grouped into 12 broad themes. The two individuals worked together to develop a codebook. Each theme was given a code. They independently coded each transcript. Due to the small data set, the analysts coded the data by hand and no software was used. Using an iterative process, they altered the codebook as new themes emerged.The two individuals met to compare how they coded each transcript. Any discrepancies between the two coders were resolved through discussion. Since all discrepancies were resolved, no inter-reliability metrics were needed. The analysts calculated the total number of interviews in which each theme was mentioned (for the entire sample), and then compiled separate totals for country-level and global-level interviews. They also performed a thematic analysis of the interviews, examining the major themes and ideas that arose in each interview Through our searches we generated a list of 467 HIV stakeholders. All of our target groups for the future communications intervention were represented in this list: researchers, program managers, policymakers, donors, advocates, and other public figures. Forty-eight percent were based in Africa, 28% in North America, 13% in Europe, 10% in Asia, 0.6% in Latin America and the Caribbean, and 0.4% in Australia.The number of stakeholders identified by each of our data search methods is shown in Global HIV Prevention Working Group.After applying stratified purposive sampling, forty-eight individuals were eligible to be interviewed. The 22 interviewees chosen were the most accessible and available. The geographic distribution of the 22 key informants  and the male to female ratio  were similar to the broader group of stakeholders. The group of interviewees included 11 researchers and scientists, 5 national-level health officials, 3 international donors, 2 advocates, and 1 program manager. Five of the key informants sit on the high-level Although we asked about participants' perceptions of contraception as a PMTCT strategy, respondents often talked about family planning and HIV/AIDS integration more broadly since strengthening linkages between the two is how contraception for HIV prevention is typically operationalized  Overall, the most common theme in the interviews was a ‘lack of resources to link family planning and HIV/AIDS services’, which was mentioned as a barrier to implementing integrated family planning and HIV/AIDS services by 20 participants. Interviewees usually used the term “resources” to refer to funding for services generally (either family planning or HIV/AIDS); however, human resources, contraceptive commodities, and clinic supplies were also discussed.[A]lthough we want to incorporate it [family planning] into a [HIV/AIDS] clinic we would need…additional staff to help in the clinics where they don't have enough resources for anything.” One HIV researcher said, “Organizations follow the money,” so the most effective way to strengthen linkages between family planning and HIV is to “encourage funding organizations to make this a priority.”Many participants mentioned that while HIV programs may benefit from integrating family planning with other clinical services, the overall lack of funding for existing services makes implementation difficult. As the director of one infectious disease institute in Africa explained, ““We need support in training health workers to give them skills, but also for supervision to make sure that integration is properly done, especially maintaining the quality of care.” This lack of training and support for health workers was mentioned often as an obstacle to implementing integrated family planning/HIV programming. An interviewee from Uganda said, “Capacity building and training the service providers to be able to handle these services [is needed]…if it is the same health worker who is providing counseling and services for HIV prevention, and he or she is trained in family planning services, then integration becomes easy.”The second most common theme, discussed by 18 participants, was the ‘lack of infrastructure or capacity to provide integrated services at the facility level’. Each of these interviewees appreciated the need for the provision of both HIV and family planning services within the same physical structure. Most participants listed specific constraints that prevent this from being a norm. One senior AIDS official from a ministry of health in East Africa said, “There is need for leadership to be able to guide the integration process so that if you mobilize resources for–say–HIV/AIDS, then the leadership should be on board in terms of guiding this money… to advance the cause of family planning.” Some informants proposed that more national coordination or “ownership” of the issue from ministries of health and other national officials could improve implementation by providing a platform on which to build bridges between family planning and HIV programs and carry out existing supportive policies. Another interviewee from Uganda noted, “Advocacy [is needed] within the Ministry of Health itself ultimately. It is the Ministry of Health who are responsible for health care.”Sixteen participants discussed the ‘lack of national-level leadership or coordination’ as a barrier. A participant from Uganda said, “What it is going to take is some advocacy to make it happen. I'm always optimistic that funding organizations can be encouraged to do quite a bit. They are quite open to it, so I think it is probably a matter of advocates getting them interested in it.”A ‘lack of targeted advocacy to key decision-makers’ was also mentioned by sixteen participants. They noted the need for advocacy aimed at stakeholders across the spectrum, including global policymakers, national program managers, and individual service providers. Many participants recommended that advocacy be targeted at international donors, including a senior official from an international foundation who said, Fifteen participants mentioned ‘lack of knowledge and/or understanding’ of contraception's contributions to HIV prevention and the benefits of family planning/HIV integration among all levels of stakeholders as a barrier. Most interviewees who mentioned this linked it with the need for advocacy to remedy the lack of understanding.“Often what happens, because the funding streams are somewhat artificially divided, is health care personnel are trained in HIV/AIDS prevention care or treatment and then they are trained, perhaps separately, around family planning. … The training cycles are not integrated,” said the top official at an international HIV/AIDS foundation. This challenge was often described as a reason why program planners are not able to design comprehensive services, and also as a contributor to overlapping efforts and inefficient use of resources. With regard to strict HIV programming, an HIV researcher explained that the prevailing thinking is “This is an HIV initiative, not a family planning initiative, and we are not going to use HIV money for these other things. This does not make any sense because if [family planning] has an HIV impact then it should be required of an HIV program.”The separate funding streams for family planning and HIV/AIDS programming and services, from donors and within national governments, were also mentioned by fifteen participants as a barrier to integrated service provision. “There is a tendency… [in] some parts of the HIV community to see their primary area of work as being rather more narrowly defined HIV services, and saying, ‘Family planning is important, sure, but that's not our responsibility.’ …you'll find that reproductive health people are struggling with family planning service generally and they kind of feel like they don't have the means [to offer HIV services] …if a woman has HIV, programs are available and they are so well resourced so surely they [HIV providers] should be doing it.”Further, some participants suggested that this separation of resources may be the cause of competition or tension between the reproductive health and HIV/AIDS fields over which programs are responsible for what services, especially when resources are not available to create bi-directional integrated programs. This was illustrated when a staffer at WHO stated, Overall, similar themes were mentioned by both country-level and global stakeholders see . Howeverand HIV/AIDS professionals to avoid responsibility for implementing integrated programs (the theme ‘family planning or HIV/AIDS program managers and service providers see the responsibility as lying elsewhere’).Those working at the global level focused more on macro-level funding, global policy and overall trends than did interviewees working at the country level. The theme ‘separation of family planning and HIV/AIDS programming’ was more common in these interviews than among the country-level participants. Global stakeholders also pointed out the tendency of both family planning Compared to global level participants, country-level interviewees focused more on the specifics of implementing family planning and HIV integration. The most common theme among this group was the ‘lack of national leadership or coordination’, which was mentioned by all country-level informants. Additionally, more participants at the country-level than the global-level mentioned the ‘lack of infrastructure or capacity to provide integrated services at the facility level’ as a barrier to integrating family planning and HIV programs.most influences their decisions, 15 of the 22 interviewees said either print or online publications; 7 individuals stated that conferences/meetings were the most important source of information for them.Regarding which communications channels the participants use to make decisions about HIV/AIDS research, funding, policy, or programming, all 22 key informants said that they take into account information received at meetings and conferences; 18 of the 22 responded that they use information from print publications, online publications, and other colleagues; 17 informants said that they use information found in emails; and 10 said the same for listservs . Television and radio were not seen as important sources of information for the majority of the participants. In response to a question about which information source Funding for HIV/AIDS continues to increase The results of our key informant interviews with opinion leaders in HIV/AIDS substantiated these barriers and constraints. Regardless of their professional affiliation, most of the stakeholder informants told us the biggest challenges to implementing element 2 of WHO's PMTCT strategy were restricted or siloed funding and the need to improve health infrastructure and human capacity to provide better services. It is worth noting that our interviews took place in 2008, before the U.S. presidential election and subsequent administration change. Since that time, a growing number of USAID bilateral agreements are encouraging integration by combining funding for HIV/AIDS and family planning into single health programs, and global HIV/AIDS funding mechanisms like PEPFAR and the Global Fund are becoming increasingly supportive of family planning services as essential components of HIV/AIDS programs.During our interviews, participants recommended directing more advocacy at international donors to counter the lack of and parallel nature of family planning and HIV/AIDS funding, As the funding environment continues to improve, however, advocacy and communication campaigns will eventually need to shift toward national decision-makers and program planners to improve their ability to leverage these new and less restrictive funding opportunities. To strengthen national-level coordination, participants suggested that countries take more ownership over the issue of harmonizing planning for funding, programming and training structures between the two fields. The importance of establishing close partnerships between the family planning and HIV/AIDS sectors was mentioned by several interviewees as a way to overcome the challenges of parallel programming.Few participants mentioned the ‘lack of visibility in published literature or technical conferences’ as a main reason why this HIV prevention strategy has not been more prominent. At the same time, the theme of ‘lack of knowledge and understanding’ came up frequently, suggesting that the evidence regarding family planning's contribution to HIV prevention does in fact need to be disseminated more broadly. Furthermore, as the evidence base for effective models of family planning and HIV/AIDS integration continues to grow, research findings should be accompanied by guidance documents Interestingly, both global-level and country-level participants tended to defer accountability to others, electing not to assume responsibility themselves for promoting access to contraception as a core element of PMTCT. All of the participants acknowledged the role of family planning in HIV prevention, yet most simultaneously asserted that their professional focus lay elsewhere and that taking action to increase access to contraception for PMTCT was not within their current purview. At the same time, many interviewees mentioned the potential impact of having notable individuals–presumably people like themselves–champion the issue, serving as catalysts for an organized and multi-sector response.general population may better contribute to meeting the contraceptive needs of HIV-positive women (and by extension reducing MTCT) than will integrating a poor quality family planning program with HIV services.It is also worth mentioning that although, perhaps surprisingly, none of the key informants highlighted this issue as a barrier, there is a critical need to improve the access to and quality of current national family planning programs (integrated or otherwise) in low- and middle-income countries. Particularly for low HIV prevalence areas, and in light of the fact that many women remain unaware of their HIV status in both low and high prevalence areas, we would argue that making improvements in family planning services for the On a final note, the systematic stakeholder mapping approach we used filtered substantial amounts of information to arrive at a relatively small but comprehensive list  of professionally and geographically diverse individuals who play key roles in HIV/AIDS research, funding, policy and programming. Even the rigorous, systematic approach we used to identify individual stakeholders, however, has limitations and likely still missed “key players.” Others using this approach might consider supplementing their searches opportunistically–for example, by incorporating the tacit knowledge available through staff or from key informants, or by identifying a cohort via existing pre-vetted coalitions or working groups.Preventing unintended pregnancies in HIV-infected women is a proven PMTCT approach and therefore an essential component of a comprehensive PMTCT program. A diverse set of individuals have regional or international influence in the field of HIV, and the challenge of strengthening the implementation of contraception for HIV prevention is complex. Our findings affirm the existence of a multi-layered set of barriers and offer recommendations for addressing several of the primary challenges. Harnessing the influence of key individuals–to launch strengthened education, advocacy, and research efforts, as well as to support evolving funding mechanisms and policy structures–will be a necessary first step toward affecting measurable change.


Methionine (MET) is required for cell metabolism. MET endogenously synthesized from homocysteine (HCY) supports the proliferation of normal cells, but not that of numerous malignant cells, as shown previously. MET starvation should have an anti-tumour effect, and its deleterious effects on the hosts might be prevented by HCY. Anti-tumour effects of MET starvation must be reinforced by ethionine (ETH), a MET analogue. MET dependency of PC-3, a human prostate cancer cell line, was studied in vitro. Proliferation of PC-3 cells, cultivated in MET-free medium, was 29% compared with growth in MET+HCY- medium. Addition of HCY to MET-free medium increased the proliferation rate to 56%. The concentration of ETH required to decrease the PC-3 cell proliferation rate to 50% (IC50) was 0.5 mg ml(-1) in MET-HCY- medium. ETH-induced inhibition was abolished by MET addition and was reinforced by HCY. PC-3 cell cycle was blocked in the S-G2-phase after 30 h culture in the absence of MET; this blockage was not reversed by addition of HCY. ETH at the IC50 in MET-HCY+ medium blocked DNA replication. Apoptotic cells appeared after 30 h incubation in MET-HCY+ medium only when ETH was added. ATP pools were decreased after 15 h of culture in MET-free medium. In vivo, MET starvation was obtained by feeding tumour-bearing mice a diet containing a synthetic amino acid mixture as the protein supply, in which HCY replaced MET. Given to nude mice bearing xenografted PC-3, from day 1 after grafting and for 3 weeks, this diet inhibited tumour growth ; this effect was potentiated by ETH (200 mg kg(-1) day(-1) i.p.) ). The differences between the effects of these two treatments were significant (P < 0.017) and optimal on day 20. These data showed that combination of ETH and HCY slowed the proliferation of prostate cancer cells in vitro and in vivo, decreased ATP synthesis and caused cell cycle arrest and apoptosis. Experimental therapy based on cancer cell MET metabolism deficiency could be efficient for treating advanced prostate cancers refractory to current therapies.


Most of the literature that does exist present HRQL measured by disease specific instruments, but such data is of little use as input to economic evaluations.While health outcomes of HIV/AIDS treatments in terms of increased A systematic review of the literature on HRQL weights for people living with HIV/AIDS in Africa was performed, and the findings are presented and interpreted. We also use focus group discussions in panels of clinical AIDS experts to test the preference based on a generic descriptive system EQ-5D. We contrast quality of life with and without antiretroviral treatment (ART), and with and without treatment failure.In only four papers were the HRQL weights for HIV/AIDS in sub-Saharan Africa estimated with generic preference based methodologies that can be directly applied in economic evaluation. A total of eight studies were based on generic health profiles. While such 'health profiles' are not preference based, the scores could potentially be transformed into health state utilities. Most of the available literature (20 papers) utilized disease specific instrument, which are not applicable for economic evaluation.The focus group discussions revealed that HRQL weights are strongly correlated to disease stage. Furthermore, clinical experts consistently report that ART has a strong positive impact on the HRQL of patients, although this effect appears to rebound in cases of drug resistance.EQ-5D appears to be an appropriate tool for measuring and valuing HRQL of HIV/AIDS in Africa. More empirical research is needed on various methodological aspects in order to obtain valid and reliable HRQL weights in economic evaluations of HIV/AIDS prevention and treatment interventions. There is high international pressure to allocate more resources on treatment programmes for people living with HIV/AIDS , which iEconomic evaluations of HIV/AIDS interventions can largely be divided into two groups; studies that ignore improvement in health related quality of life and those that seek to capture such improvements. While the former group of studies focus on simple clinical outcomes such as mortality or averted cases of HIV, the latter attempt to capture effect changes both in terms of life expectancy and improvements in health states. This is typically being done either by estimating quality adjusted life year (QALY) or disability adjusted life year (DALY). A basic premise for QALY analyses is that they depend on HRQL weights that should reflect peoples preferences . Cost pePatients with HIV/AIDS are routinely categorized into one of four clinical disease stages of the WHO staging system (CS I - IV). The clinical stages involve different degrees of impaired health related to different dimensions of health that are affected, e.g. anxiety, pain and functioning. Given that medications may improve the different dimensions of health to varying extents, it becomes important to compare the improvements on a commensurable scale. Suitable methodologies for cost-utility analysis (CUA) would mean using generic descriptive instruments or a generic health scale . FurtherTengs and colleagues performed a meta analysis of utility estimates for HIV/AIDS. Based on studies from high income settings, they calculated pooled utility weights of 0.70 for AIDS, 0.82 for symptomatic HIV and 0.94 for asymptomatic HIV -13. WhilThis lack of studies from SSA is a paradox as roughly two-thirds of all people with HIV/AIDS are living and dying in this region . Hence, The main objectives of this paper are twofold. First, we present a review of the existing evidence on health related quality of life in HIV/AIDS patients in sub-Saharan Africa and consider how this information is used in the economic evaluation literature. The larger body of research using instruments that are not directly applicable in economic evaluation, will also be reviewed, though in less detail. Given the limited availability of studies that have been based on preferences for HRQL as experienced in the specific disease stages, and in the relevant cultural settings, our second objective reflects a recent research initiative: To test the appropriateness of an instrument designed to estimate HRQL in all four stages of HIV/AIDS. In this instrument, a direct Visual Analogue Scale (VAS) approach and an indirect descriptive system (EQ-5D) is applied with a panel of clinical AIDS experts. This instrument specifically seeks to contribute to better quality of life information on: patients in the different disease stages; patients who do or do not receive antiretroviral treatment (ART), and; patients who are or are not experiencing treatment failure.commensurable - or generic - unit, only QALYs claim to be preference based.Estimating HRQL-weights for disease is important for several reasons, such as monitoring the health status of individual patients and establishing levels of health for patient groups . PerhapsWe searched for literature in the databases PubMed, EmBase and ISI using the key words "HIV OR AIDS", "Africa south of the Sahara" AND "health related quality of life". A few abstracts based on expert input were also included. The total number of different hits of this process was 288. Detailed search strategies varied slightly with the different databases and are available from authors upon request together with the complete list of hits. The abstracts were screened for eligibility, using the following exclusion criteria: studies that clearly did not present HRQL data n = 199); studies which were not about HIV/AIDS (n = 33); applied economic evaluations that were not primary sources of HRQL data (n = 12), and; studies not related to sub-Saharan Africa (n = 1). For the remaining abstracts (n = 43), the full articles were obtained and evaluated. After full article evaluation we excluded studies that turned out not to present data on HIV/AIDS (n = 6), did not present HRQL data (n = 4), that were not original research articles (n = 3) or turned out not to address sub-Saharan Africa (n = 1). A detailed description of this process is presented in Figure 99; studidisease specific descriptive systems. Such instruments may provide important information for clinical considerations and for monitoring treatment and development of individual patients. For economic evaluation, however, the outcome units used are of limited value because they are incommensurable across disease areas, and incommensurable with the valuation of the duration of the quality improvement, i.e. quality and quantity of life cannot be measured on the same metric. Eight of the studies assessed HRQL using generic instruments and health profiles, and several of these instruments can potentially be combined with value sets to present health state utilities. Preference based HRQL weights - or utility estimations - were not done for five of these studies, and the evidence is therefore not directly applicable in economic evaluations. Only four papers present preference based HRQL weights that can be directly applied in economic evaluations. Brief summaries of this evidence are provided below.The remaining 29 research articles contain various types of health related quality of life evidence for people living with HIV/AIDS in sub-Saharan Africa. The majority of these studies (n = 20) assess quality of life using various The papers by Hughes et al.  and Jelshttp://www.euroqol.org.While Hughes focused on baseline quality of life, the effect of antiretroviral treatment (ART) in the same patient population is reported by Jelsma and colleagues . Their mIn a large study from Free State province in South Africa, Louwagie estimate HRQL in a wide-scale roll out of ART in South Africa . Like thThe fourth and most recent publication presenting HRQL weights of AIDS in SSA is from a Ugandan setting. This study by Lara and colleagues is the only evidence available from outside South Africa that is appropriate for application in economic evaluation of ART in SSA. While the South African studies present estimates for the patients' real-time perceived health, the Lara study in addition ask people living with HIV/AIDS about their preferences for a set of predefined health states representing WHO clinical stages 2, 3 and 4, respectively . In thisThe VAS scores for people waiting to start ART treatment is very similar in the three South African studies, ranging from 0.60 to 0.62 ,11,13. Iquality of life to be measured in the same metric as quantity of life, the next class of studies present so-called 'health profiles'. These profiles represent generic measures of health, but they are not preference based, and, furthermore, the HRQL scores are incommensurable with quantity of life.While the studies referred to above present preference based HRQL weights on a [0-1] scale that enables A total of eight studies apply generic HRQL profiles, three of which had also used utility estimates (the South African papers referred to above). An overview of this literature is given in Table Two studies address the quality of life of pregnant HIV positive women. In a study from Tanzania, Kaaya et al. evaluate screening of depression in antenatal care by using the generic SF-36 instrument together with the disease specific Hopkins Symptoms Checklist-25 (HSCL-25) to . The HSCSeveral recent studies report quality of life profiles of patients with access to antiretroviral treatment. The quality of life findings from a clinical trial in Cape Town are reported in two publications. A main finding presented by Hughes and colleagues was that people with HIV had significantly more limitations across all the five health dimensions of the EQ-5D instrument , while JThe most recent publication included in this review is from KwaZulu-Natal, also in South Africa. McInerney and colleagues assessed how physical functioning for adults receiving ART is related to different medical and social variables. To assess HRQL they used the SF-36 instrument and found evidence that treatment duration, less co-morbidity, and better social support improved physical functioning .generic descriptive systems to measure HRQL, the studies below have applied disease specific descriptive systems.While the above studies used The largest amount of HRQL evidence on HIV/AIDS is based on descriptive instruments that address issues of specific relevance to the disease, with social stigma as a typical example. Such disease specific information can be useful for clinical purposes but is not very useful for economic evaluation, because the measures of outcome are not comparable across disease and patient groups. Some of the instruments are not even comparable within the same disease.The 20 studies included utilized a total of 18 different AIDS specific instruments, with MOS HIV being the most commonly applied (three publications). The WHOQOL BREF, WHOQOL HIV and HAT-QOL instruments were also used in at least two different studies each. The 20 different studies focused on a wide range of different areas, including various types of mental health, oral health and alternative medicine. This list of references is available from the authors upon request.Our review of the economic evaluation literature on HIV/AIDS interventions in SSA confirms that the weights assigned to QALYs in most of the cases are more or less arbitrary. We argue that the DALY weights used in many influential economic evaluation studies on HIV/AIDS have an insufficient evidence basis as well. DALYs were used to calculate health effects in two influential review papers on the cost-effectiveness of HIV/AIDS interventions in Africa ,24, as wThe disability weights used in the DALY calculations are all taken from the Global Burden of Disease study, in which the values 0.123 and 0.505 are applied for HIV and AIDS, respectively . Note thA couple of recent economic evaluations use QALYs as the outcome measure for ART. In a study addressing early versus late provision of ART in southern African adults, Bachman used the HRQL weights estimated in Khayelitsha by Hughes and colleagues ,28. CleaThis review reveals several knowledge gaps on health related quality of life for people with HIV/AIDS in SSA, and particularly so for evidence that can be applied in economic evaluations: i) no studies combine generic descriptive systems, such as the EQ-5D, with locally developed value sets; ii) except for one study  little iWe wanted to explore how clinical expert working in low income settings in sub-Saharan Africa judge the health related quality of life for different categories of people living with HIV/AIDS. Our study applied the EQ-5D questionnaire which consists of two parts; the generic descriptive system and the EQ-VAS  . Typicalhttp://www.euroqol.org provides more than 1,800 references). By applying an existing tariff, the EQ-5D model produce HRQL-indices for the various health combinations in the descriptive system. While the EQ-5D descriptive system is an indirect approach to eliciting health state preferences, the VAS directly asks the respondent to assign a quality of life score on a vertical 0-100 thermometer.The EQ-5D system was chosen because it is simple to use, and has been demonstrated to produce valid results for a wide range of health conditions  and patients will be explored based on data from a newly initiated research project at a hospital in Tanzania.The EQ-5D indices were calculated using the most commonly applied UK tariff  as well The participating experts had no problems responding to the EQ-5D exercise. The results of the nominal group discussions are illustrated in Figure Figure The associated EQ-5D indices as well as the VAS scores are presented in Figure It may be noted that even for clinical stage I, the HRQL weight is 0.8, which may not appear intuitive given the fact that this is non-symptomatic HIV. The major reason for this finding is that we stressed that the HIV-status was known to the patients, and the clinical experts therefore judged anxiety and depression to be a problem. For the most severe health states, clinical stage IV without treatment or with treatment failure, the expert opinions resulted in worse-than-death levels for the EQ-5D index when using the UK tariff.The expert panel in this pilot study reported much lower quality of life weights for advanced and severe AIDS than has typically been found in studies in high income countries ,33. A poAmartya Sen has suggested that people growing up in a community with much disease burden and few health facilities may be inclined to perceive certain symptoms as more "normal" than people living in well developed communities would do. Hence, he warns that using patients' own perception to evaluate states can be "extremely misleading" . It is tOur findings suggest that EQ-5D is a good candidate tool for eliciting health related quality of life weights for HIV/AIDS, since both the VAS and the descriptive parts of the tool were relatively easily assessed, produced similar results and were sensitive to differences in health states and availability of treatment. The results suggest that quality of life, as perceived by clinical experts, is strongly correlated to disease stage. Experts also indicate that ART has a strong positive impact on patients' HRQL, although it seems that this treatment effect rebounds dramatically with the occurrence of drug resistance. More research into these areas in clinical settings in sub-Saharan Africa is needed to qualify future economic evaluations on HIV/AIDS treatment and prevention interventions.The authors declare that they have no competing interests.Both authors made equal contributions to conception and design, acquisition, analysis and interpretation of data. Both were involved in drafting the manuscript and both gave final approval of the version to be published.


In 2007, the Mozambican Ministry of Health (MOH) conducted a nationwide evaluation of the quality of care delivered by non-physician clinicians . Correct management of all 5 main aspects of patient care  was observed in 10.6% of encounters.The observed clinical errors were heterogeneous. Common errors included assignment of clinical stage before completing the relevant patient evaluation, and initiation or continuation of co-trimoxazole or ART without indications or when contraindicated.In Mozambique, the in-service ART training was suspended. MOH subsequently revised the TMs' scope of work in HIV/AIDS care, defined new clinical guidelines, and initiated a nationwide re-training and clinical mentoring program for these health professionals. Further research is required to define clinically effective methods of health-worker training to support HIV/AIDS care in Mozambique and similarly resource-constrained environments. In sub-Saharan Africa, the human immunodeficiency virus (HIV) epidemic has expanded rapidly, access to antiretroviral therapy (ART) is often inadequate, and shortages of health workers and infrastructure are often critical . Task-shtécnicos de medicina' (TMs).In 2004, when the Mozambican Ministry of Health (MOH) first contemplated task-shifting, Mozambique estimated that nationwide adult HIV seroprevalence was 16.2%, 1.5 million citizens were infected with HIV, and the health workforce included only 662 physicians (0.35/10 000 population) and 2698 non-physician clinicians (1.43/10 000 population) [th grade) did not yet include HIV/AIDS content, MOH developed a new in-service training course. Its curriculum emphasized ART and co-trimoxazole prophylaxis, with lesser attention given to clinical staging of HIV/AIDS [Because pre-service training for TMs  and opportunistic infections (OIs). Secondary objectives included qualitative descriptions of the TMs' clinical environment , and of health workers' attitudes toward HIV/AIDS training.This cross-sectional evaluation used direct observation of the clinical practice of randomly selected TMs, supplemented by semi-structured interviews with key informants. Two trained clinical observers (COs) observed each TM as he or she cared for HIV-infected ambulatory adults > = 18 years)   or the y3, and no known allergy to sulfonamides; or discontinuation of co-trimoxazole in a patient who had had an adverse drug reaction (ADR) or whose CD4 count was > = 200 cells/mm3 on the 2 most recent measurements.Correct management of co-trimoxazole was defined as initiation or continuation of co-trimoxazole prophylaxis in patients with confirmed HIV infection, WHO clinical stages 3 or 4 or CD4+ T-lymphocyte (CD4) count <200 cells/mm3, and no contra-indications to first-line therapy , ADR, laboratory abnormalities, or unstabilized OI); or discontinuation or modification of ART in a patient who had experienced a significant ADR or developed another contra-indication to first-line therapy.Correct management of ART was defined as initiation or continuation of the first-line regimen  in a patient with confirmed HIV infection, WHO clinical stage 4 or CD4 <200 cells/mm3, and ART eligibility criteria were expanded to include patients in clinical stage 3 with CD4 < 350 cells/mm3), TMs whose clinical decisions conformed to the new but not to the old norms were also given credit for correct performance.Because Mozambican national norms for co-trimoxazole and ART initiation were modified between the development of the in-service course and the initiation of the study  program ,10 and aDescriptions of TM demographic and professional characteristics and of health unit characteristics were based on semi-structured interviews with key informants.We attempted to minimize observer bias by using 2 COs for each patient observation. In each 2-observer team, there was no more than 1 clinician who had served as an instructor in the ART course for TMs, and COs were not permitted to evaluate TMs whom they supervised directly. We also used each patient's clinical data as recorded on the observation instrument to validate COs' conclusions. For example, we reviewed the patient's clinical stage, medication allergies, and CD4 count in order to confirm that the TM's management of co-trimoxazole was consistent with Mozambican norms, the patient's clinical presentation, and the CO's assessment. We attempted to minimize sampling bias by constructing the TM sampling frame from multiple, frequently updated sources.For this descriptive study, we sought a randomized sample of 44 TMs and their respective health units. This was estimated to be a 21% sample of all MOH health units with ART capacity. We estimated that a clinical observation team could visit a maximum of 4 health units in a single week of field work. We did not prepare a formal power calculation because no prior data described the frequency of clinical errors in this setting. Random-number tables were used to guide selection of TMs from each province's list of trained, practicing TMs.Quantitative analyses described the proportion of patient encounters in which each primary clinical domain  was managed correctly by the TM, as recorded by COs. Sampling weights  were used to reflect the probability of selection of each TM, and robust confidence intervals were calculated to reflect likely correlation of results for patients attended by the same TM . It was We also constructed a dichotomized composite variable representing TM and CO concordance in all 3 of the following domains: clinical staging, co-trimoxazole management, and ART management. Using logistic regression, we calculated odds ratios (ORs) and their 95% confidence intervals (CIs) for association of TM, health unit, and patient characteristics and this indicator of correct diagnosis and management in both bivariate and multivariate analyses. To account for correlation between patients seen by the same TM, we used the robust sandwich estimate of standard error around odds ratios reported.The study protocol was approved by the Mozambican National Bioethics Committee. Secondary data analysis was authorized by the University of Washington Human Subjects Division. This study also underwent review at the Centers for Disease Control and Prevention, where it was deemed to be a non-research program evaluation. Participating MOH staff  gave written informed consent. Patients gave oral consent. TM and patient data were confidential.Clinical mentoring by the COs was incorporated into the protocol based on the ethical principle of beneficence, and allowed patients to benefit directly from clinical observer correction of clinical omissions or mistakes. Immediate clinical feedback was also of benefit to the TMs themselves.técnicos were initially reported to have received ART training. After inspection of training lists and consultation with provincial HIV/AIDS coordinators, 53% of these names were discarded . We were often unable to ascertain the status of TMs stationed in remote rural districts.Six hundred and sixty-nine No eligible and available TM refused to participate. The characteristics of the observed TMs and the health units at which they practiced are described in Tables We observed 127 patient consultations . The characteristics of the observed patients are given in Table We observed a broad range of clinical practice quality. Table Differences of opinion between COs and TMs were of three main types: Understaging (miscategorizing a patient as having less advanced disease), overstaging (miscategorizing a patient as having more advanced disease), and premature staging . Correct staging is predicated on correct identification of OIs, which was difficult in this resource-constrained setting. In particular, Stage IV OIs could be diagnosed only infrequently. Examples of staging difficulties are described in Additional file Disagreements were of 2 main types: initiation or continuation of medications when not indicated, and failure to initiate or continue when co-trimoxazole and/or ART were indicated. Examples are given in Additional files ADRs were confirmed by the CO in 20 patients 15.7%), and were often under-diagnosed or under-treated by the TMs. Examples are given in Additional file %, and weBivariate and multivariate analyses revealed three principal correlates of correct patient management . In multivariate analyses, increasing ART caseloads at the TM's home health unit were positively correlated with correct performance in all 3 domains , while increasing TM age and the presence of any sign or symptom of TB or of confirmed TB were both negatively associated with correct performance . No other observed characteristic of patients, TMs, or health units was significantly associated with 'correct' performance.We found that, in the majority of observed patient encounters, Mozambican non-physician clinicians who had received brief in-service HIV/AIDS training did not adhere to Mozambican national clinical standards as taught in their course. These assessments were based on direct observation of patient care by experienced clinicians familiar with the Mozambican clinical environment. Although some errors were unlikely to have had adverse effects on patient outcomes, others were more serious, and even life-threatening. However, we also observed TMs who provided excellent patient care.Better TM performance was correlated with younger TM age, the absence of confirmed TB or TB symptoms in the observed patients, and higher ART caseloads at the TMs' home health facilities. The younger TMs may have performed better because they began their pre-service training after pre-service faculty had begun to acquire expertise of their own in HIV/AIDS care. Worse TM performance when faced with TB patients or TB suspects may be the result of Mozambican policy restricting TB/HIV co-infection care to physicians; or may be a marker for worse performance in the presence of symptomatic patients in general. Better performance in health facilities with larger numbers of patients on ART may reflect the impact of better-evolved systems for support of HIV/AIDS care. However, because our data were cross-sectional and our patient numbers small, we are not able to draw firm conclusions from the observed associations.To the best of our knowledge, this study is the first to use direct observation of patient care to describe the quality of HIV/AIDS care in the context of task-shifting in a highly resource-constrained environment, using a randomized national sample of providers.Because we were unable to follow patients longitudinally, we cannot link observed clinical practice to patient outcomes. However, the process indicators we examined are significantly linked to patient outcomes in multiple published studies -16.The cross-sectional design and the paucity of laboratory and imaging support also resulted in a high proportion of encounters in which available patient data were insufficient to justify specific diagnostic, staging, and/or management decisions. However, had we conducted the study in a better-resourced environment, the results would not have reflected actual clinical practice in the TMs' worksites.Because we did not use standardized patients , some diWe were not able to describe the TMs' level of exposure to other HIV/AIDS training (in addition to the ART course). For example, we were unable to obtain data on the quantity or quality of post-course hours of expert clinical mentoring, or provincial-level variations in ART course design and implementation. Some of the observed variation in clinical performance may have been caused by these unmeasured differences. Our subjective impression was that the most proficient TMs had served long apprenticeships with expert HIV/AIDS clinicians.Exclusion of TMs based in the most remote rural sites may have resulted in overestimation of the quality of HIV/AIDS care as delivered by TMs, because medications, medical equipment, and clinical supervisors were all less likely to reach these health units. If so, this constraint to generalizability actually strengthens our conclusions.Faced with a widespread HIV/AIDS epidemic and extreme constraints in human and material resources, Mozambique shifted day-to-day responsibility for HIV/AIDS-related patient care, including care of critically ill patients, from physicians to non-physician clinicians. Our findings suggest that Mozambique's 2-week in-service ART training strategy did not result in creation of adequate TM capacity to provide high-quality clinical HIV/AIDS services.There are two likely explanations - not mutually exclusive - for these findings. First, the content and methods of the 2-week in-service course were not adequate to provide the TMs with the skills and knowledge needed to attend a high-volume, symptomatic, and challenging patient population. Course duration was almost certainly too short, and many assumptions that drove curriculum development  proved to be incorrect. Course content had significant lacunae; for example, the TMs were not taught standard guidelines for differential diagnosis, diagnosis and management of most OIs, and they were not taught to diagnose or manage most severe ADRs.Second, newly trained TMs were often deployed to health units that lacked both clinical mentoring and material resources; these constraints often prohibited both the use and further development of the TMs' knowledge and skills. The excellent clinical practice that we observed on some occasions suggests that properly supported, more experienced TMs are able to perform at a substantially higher clinical level than what was observed in the overall sample.Although there is only sparse published literature on health worker performance following HIV/AIDS training, the quality of care difficulties that we observed are consistent with those described after the introduction of other health initiatives -20. PartHowever, evaluations of other programs have demonstrated that the combination of health worker training and focused, sustained systems support can indeed result in substantial improvements in patient outcomes ,26.These findings were not intended to be generalizable to other cadres of health workers (e.g. physicians or nurses), or to settings other than the Mozambican public sector. However, the synergistic problems of high HIV seroprevalence, extreme resource constraints, and ineffectual health worker training in HIV/AIDS treatment are not unique to Mozambique, and other programs may find these results relevant ,27,28. TImmediately upon dissemination of preliminary study findings, MOH recognized that the study results had important implications for Mozambican policy, particularly with regard to health-worker training and the definition and promulgation of cadre-specific standards for clinical care. In consequence, MOH suspended the in-service ART training, re-evaluated the TMs' HIV/AIDS-related scope of work, and began drafting new guidelines for diagnosis and management of OIs and other complications of AIDS and AIDS treatment. In November 2008, MOH initiated a new program to re-train TMs in HIV/AIDS care; this program includes both didactic sessions and long-term, workplace-based clinical mentoring. The new interventions will also undergo rigorous evaluation, in order to create a Mozambique-specific evidence base to support future approaches to clinically effective health-worker training and health policy. Finally, MOH is currently integrating HIV/AIDS content into the pre-service curriculum for TMs to ensure that these providers possess the necessary competencies when they enter the workforce.técnicos de medicina (Mozambican mid-level non-physician clinicians); WHO: World Health Organization; 3TC: lamivudine.The following abbreviations, listed in alphabetical order, were used in this paper: ADR: adverse drug reaction; AIDS: acquired immune deficiency syndrome; ART: antiretroviral therapy; AZT: zidovudine; CD4: CD4+ T-lymphocyte; CI: confidence interval; CSF: cerebrospinal fluid; CO: clinical observer; d4T: stavudine; EFV: efavirenz; HIV: human immunodeficiency virus; IMCI: Integrated Management of Childhood Illness; MOH: Mozambican Ministry of Health; NVP: nevirapine; OI: opportunistic infection; OR: odds ratio; TB: tuberculosis; TMs: Three of this paper's co-authors  serve as technical advisors to the funder in Mozambique. The authors have no other conflicts of interest or competing interests to declare.AA, PEB, CM, LJN, and LRL designed the study. PEB, AEG, PMM, and JVT participated in both data collection and data coding; OB also participated in data collection. PEB and AEG conducted the data analysis. All authors participated in data interpretation. PEB drafted this paper; all authors participated in critical revision of the manuscript, and all approved the final version.Selection and training of clinical observers.Click here for filetécnicos de medicinaSampling frame for .Click here for fileThe clinical observation instrument.Click here for filetécnicos de medicinaClinical staging and opportunistic infection diagnosis: examples of concordance and disagreement between clinical observers and .Click here for filetécnicos de medicinaCo-trimoxazole prophylaxis: examples of concordance and disagreement between clinical observers and .Click here for filetécnicos de medicinaAntiretroviral therapy: examples of concordance and disagreement between clinical observers and .Click here for filetécnicos de medicinaAdverse drug reactions: examples of concordance and disagreement between clinical observers and .Click here for file


Medical Emergency Teams (METs), also known as Rapid Response Teams, are recommended as a patient safety measure. A potential benefit of implementing an MET is the capacity to systematically assess preventable adverse events, which are defined as poor outcomes caused by errors or system design flaws. We describe how we used MET calls to systematically identify preventable adverse events in an academic tertiary care hospital, and describe our surveillance results.For four weeks we collected standard information on consecutive MET calls. Within a week of the MET call, a multi-disciplinary team reviewed the information and rated the cause of the outcome using a previously developed rating scale. We classified the type and severity of the preventable adverse event.We captured information on all 65 MET calls occurring during the study period. Of these, 16  were felt to be preventable adverse events. The most common cause of the preventable adverse events was error in providing appropriate therapy despite an accurate diagnosis. One service accounted for a disproportionate number of preventable adverse events .Our method of reviewing MET calls was easy to implement and yielded important results. Hospitals maintaining an MET can use our method as a preventable adverse event detection system at little additional cost. Medical Emergency Teams (METs), alternatively known as Rapid Response Teams, have recently been implemented in many hospitals worldwide . The priIn this study, we report on our experience with expanding the role of our institution's MET to support the detection of preventable adverse events, which are defined as poor outcomes caused by medical error. We felt a systematic evaluation of patient care immediately prior to MET notification might provide useful information for system improvement because the MET is responding to critical situations in which there is at least some likelihood of prior inappropriate treatment -16. Our The study was approved by the Ottawa Hospital Research Ethics Board. The Ottawa Hospital General Campus is a 487-bed tertiary care teaching hospital. It implemented an MET in January 2005. The team is composed of a physician , a critical care nurse, and a critical care-trained respiratory therapist. The MET can be activated by any hospital staff and is active 24 hours a day. Providers in our hospital use standard criteria for activating the MET. The MET has over 40 calls per 1,000 hospital admissions, and more than 70% of intensive care unit admissions are preceded by an MET call.For a 4-week period in 2007, we used a standard form to collect information on each MET call , an anesthetist/intensivist (AB), and a PGY2 (post-graduate year two) internal medicine resident (AI) – within 1 week of each MET call. The group of three physicians achieved consensus on whether the outcome was a result of medical management using a previously derived and widely accepted review process -24. If sWe did not obtain patient or provider consent as part of the protocol. We argued successfully to our Research Ethics Board that the protocol posed minimal risk to patients or providers. The principal ethical concern was the potential of an inappropriate disclosure of personal health information. We created a case report form that did not contain usual patient or provider identifiers. Individuals could be identified only if someone obtained our case report forms and used our hospital information systems inappropriately.We created descriptive statistics for all studied factors. We compared the distribution of these factors by preventable adverse event status using the chi-square statistic for categorical variables and the Wilcoxon rank-sum test for continuous variables. As only one variable was significantly associated with adverse event status, we did not perform a multi-variable analysis. We used SAS version 9.1  for all analyses.Sixty-five MET calls occurred during the study period Table . Patient'Therapeutic errors', defined as a failure to apply the appropriate treatment regimen, contributed to the outcome in 14 of the 16 patients with preventable adverse events . The other two preventable adverse events were considered adverse drug events.We assessed factors associated with preventable adverse event classifications Table . The onlWe found our MET-based approach for preventable adverse event detection to be simple to implement, easy to maintain, and informative for quality improvement efforts. One quarter of MET calls were associated with preventable adverse events. We found one service responsible for a disproportionate number of preventable adverse events. We also found inappropriate responses to critical patients as the most common cause of preventable adverse events. Our hospital is using this information to guide quality improvement strategies.Our program cost very little to implement. Although we collected data specifically for the study, it is possible for the care providers present at the MET call to incorporate information collected at each call directly into the routine. The program required weekly meetings, which lasted less than an hour and could be performed remotely using telephone conferencing. This task was not onerous for the physicians participating in the program and was seen as part of their professional obligations of monitoring the effectiveness of the hospital system.Although we believe our methodology is easily replicable, our surveillance results should not be generalized. Our study was performed in a single site for a limited period of time. Despite the relatively short observation period, we did identify a statistically significant and clinically plausible pattern of factors associated with preventable adverse events. Prior research has suggested that, even in acute care hospitals, there is often an inadequate response to critically ill patients -16. FurtSimilarly, it is important to consider specific biases inherent in this approach to finding care-related problems in a hospital. The physician review process is biased by knowledge of outcome severity and by our natural and variable inclinations to find fault ,26. ThesGiven the widespread implementation of METs, our proposed approach could immediately offer many hospitals an efficient method for monitoring preventable adverse events. This is an important advance given the apparent widespread patient safety problems in hospitals ,20,28-30• Medical emergency teams (METs) provide care to critically ill ward-based inpatients. METs have been implemented in many hospitals worldwide.• METs often respond to clinical events in which there has been inappropriate antecedent care. Therefore, METs could form the basis of a preventable adverse event detection system.• We have adopted a structured method of data collection and peer review to be used by METs to assist institutional learning regarding the avoidance of preventable adverse events.• We have determined our method to be feasible.• We have demonstrated the method's capacity to document important quality issues in the care of critically ill patients.CI: confidence interval; MET: Medical Emergency Team.The authors declare that they have no competing interests.AJF conceived of the idea of the study and helped to facilitate data collection and provide important intellectual contributions during preparation of the manuscript. AI and AB helped to facilitate data collection and provide important intellectual contributions during preparation of the manuscript. All authors read and approved the final manuscript.Appendix 1 containing our case review form.Click here for fileA text box with several examples of adverse events identified during the study.Click here for fileAppendix 2 with descriptions of all adverse events identified during the study.Click here for file


Objective: The aim of this study was to prospectively evaluate the efficacy of a therapeutic courseof intravenous antibiotics followed by oral antibiotics vs. intravenous antibiotics alone to preventrecurrent urinary tract infection.            Methods: Pyelonephritis was documented by strict criteria in 67 pregnant women who were thentreated with appropriate intravenous antibiotics until afebrile and asymptomatic for 48 h. Womenwere then randomized to completion of a 10-day course of oral nitrofurantoin 100 mg qid or nofurther antibiotic therapy. Urine cultures (UC) were obtained 2 and 6 weeks after discharge, andat delivery. A positive UC or readmission for pyelonephritis was considered endpoints for participationin the study. Antibiotic suppression was not used.            Results: Readmission for pyelonephritis prior to the 2-week follow-up visit occurred in 2/36(5.6%) women randomized to the oral therapy group compared to 4/31 (12.9%) in the no oraltreatment group (P = 0.29). At the 2-week follow-up visit, 6/31 (19.4%) women had a positive UCin the oral therapy compared to 8/26 (30.1%) in the no oral treatment group but this difference wasnot statistically significant (P = 0.31).            Conclusions: Completion of 10 days of antibiotic therapy with oral medication does not significantlyreduce the risk of recurrent pyelonephritis immediately post-parenteral treatment. Women inthe no oral treatment group had a non-significant increase in positive UC at the 2-week follow-upvisit. The high rates of recurrent urinary tract infection during pregnancy in both groups underscorethe need for regular UC and for the possible role of oral antibiotic suppression.


PLoS Medicine Editors call for continued efforts to develop definitive methods of HIV prevention.Introducing the World AIDS Day 2007 issue, The World AIDS Day, the annual December 1 commemoration, first took place in 1988 under the auspices of the Joint United Nations Programme on HIV/AIDS .Twenty years later, HIV treatment has the potential to become one of medicine's success stories. Combination anti-HIV therapies, referred to generically as highly active antiretroviral therapy (HAART), began to appear around 1996. Although costly and not without adverse effects, these “cocktails” have proved so effective that many who narrowly escaped death from AIDS in the mid-1990s are now facing the usual health concerns of advancing age. Although emergence of drug-resistant virus creates ongoing challenges, HIV treatment has continued to advance, as evidenced by the development of more convenient treatment regimens, and by FDA approval in 2007 of drugs from two new mechanistic classes: the first integrase inhibitor and the first chemokine receptor blocker.On the global scale, 2007 has seen further progress in the impressive effort to address financial and logistical barriers to providing HIV treatment in low-resource settings. Although some 5 million people remain in need of HAART, and a recent systematic review found that many who begin HAART in developing countries do not continue zreatment , the facIn this context of global progress toward HIV treatment, the official theme of World AIDS Day 2007 appropriately calls on “Leadership” to “Keep the Promise” of universal access to HIV care and services.Pounds of much-needed treatment, however, should not obscure the fact that precious ounces of prevention remain elusive: interrupting HIV transmission remains one of the world's greatest scientific challenges. Indeed, in contrast to the progress made in treatment, World AIDS Day 2007 marks the end of a particularly sobering year in HIV prevention science, particularly in the area of female-controlled methods, which have long been recognized as key to interrupting HIV transmission when social and economic disempowerment prevent women from insisting on condoms. January brought the announcement that two developing country trials of the vaginal microbicide cellulose sulfate had to be stopped because of an increased risk of HIV infection in women using the product ,5. The rIn the area of behavioral prevention, a 2007 systematic review of available reports  found thIn perhaps the year's most convincing results regarding HIV prevention, clinical trials in Uganda and Kenya, confirming an earlier trial from South Africa , showed In terms of short-term benefit, then, it could be argued that basic research funding should instead be redirected toward condom education programs. In the long term, however, more definitive prevention methods are desperately needed to bring the AIDS crisis to an end, and we must not give up working toward a breakthrough in prevention comparable to the treatment advances of the past decade. New microbicides and vaccines are being developed and tested, trials of pre-exposure prophylaxis are under way, and more basic research in HIV epidemiology and pathogenesis continues to advance.PLoS Medicine has published many papers on HIV/AIDS, is featuring several new papers [PLoS Medicine as well as papers on HIV/AIDS in PLoS ONE, we invite our readers to check, and comment via, the PLoS Medicine blog (http://www.plos.org/cms/plosmedicine/).The essential need for global dissemination and discussion of research reports is nowhere better illustrated than in the response to the vast complexity of the AIDS pandemic. w papers  in this


As part of a partnership arrangement with the Joint United Nations Programme on HIV/AIDS and the Public Health Agency of Canada, Health Canada hosted an International Policy Dialogue on HIV/AIDS and Disability from 11 to 13 March 2009 in Ottawa, Canada. The dialogue provided a forum for stakeholders from governments, academia, and non-governmental and multilateral organizations to explore the issues and evidence related to HIV/AIDS and disability, and to chart a way forward in terms of policy and programme development. This meeting report outlines the participants, objectives and high-level outcomes. Health Canada, as part of a partnership arrangement with the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the Public Health Agency of Canada, hosted an International Policy Dialogue on HIV/AIDS and Disability from 11 to 13 March 2009 in Ottawa, Canada. The objectives of the dialogue were: to explore the place of disability in the changing nature of the global HIV/AIDS epidemic and the required response; to share and learn from participants' experiences; and to build and reinforce the partnerships needed to sustain a comprehensive global response to HIV/AIDS, which includes issues related to disability.Approximately 50 participants from around the world took part in the dialogue, including persons with disabilities and people living with HIV/AIDS, as well as other policy makers, representatives of civil society, and academics. Stephen Lewis, the former United Nations Special Envoy for HIV/AIDS in Africa and co-founder of AIDS-Free World, provided the keynote address during the dialogue's opening session.The dialogue took place through a combination of expert presentations, panels and small breakout group sessions. The detailed results of the dialogue have been outlined in a final report and disseminated via existing national and international networks on HIV/AIDS and disability. The final report is available from Health Canada.The three-day dialogue began with a discussion on the shared experiences and barriers to full and equitable participation in all aspects by society of persons with disabilities (PWD) and people living with HIV/AIDS (PLHIV). This included discussion of the definition of "disability", namely how inclusive a term it can be, and when it is strategic to define HIV/AIDS as a disability.With this foundational understanding of the commonalities and differences of the experiences of PWD and PLHIV, the second day allowed for more in-depth discussion on some of the specific challenges associated with HIV/AIDS and disability. The final day of the dialogue was then used to discuss the next steps and opportunities to ensure that policy and programming agendas worldwide integrate HIV/AIDS and disability.A number of themes emerged over the course of the dialogue, including various ways to use the Convention on the Rights of Persons with Disabilities (CRPD) as a tool for change. Although HIV/AIDS is not explicitly mentioned within the convention, Article 25 (a) may be interpreted to include HIV/AIDS as a disability. Article 25 (a) states that state parties shall: "Provide persons with disabilities with the same range, quality and standard of free or affordable health care and programmes as provided to other persons, including in the area of sexual and reproductive health and population-based public health programmes." The CRPD offers the prospect of a binding treaty and viable legal instrument that could be used to protect and promote equal rights of PWD and PLHIV, complementing (but not replacing) other human rights instruments. Dialogue participants suggested that in addition to advocating for the implementation of the CRPD and the Optional Protocol, the CRPD Committee of Experts should also be lobbied to include HIV/AIDS in guidelines for implementation, monitoring and reporting on the convention. The importance of raising awareness on the potential of the CRPD for advancing the rights of PWD and PLHIV was also highlighted.Discussions on the intersectionality of HIV/AIDS and disability were also a major theme at the dialogue. This intersectionality manifests itself in the experiences of PWD and PLHIV:1. PWD experience all of the risk factors associated with HIV infection and are, in fact, often at increased risk of infection because of such factors as poverty, limited access to education and increased risk of violence, including sexual assault.2. PLHIV often develop disabilities as a result of HIV, either as a result of the disease progression or as side effects of antiretroviral treatment.In addition to these key themes, a number of emerging issues in HIV/AIDS and disability were also discussed, identifying the challenges and gaps in policy development, programming, research, and education and/or awareness. These discussions included the basic, but fundamental, acknowledgement that PLHIV and issues related to HIV/AIDS are not adequately integrated into disability policies or programmes, and vice versa, at the international, national, or sub-national levels.Overarching gaps were also identified regarding the availability of funding, both for programming and for research. The need for a substantial increase in the amount of research, both quantitative baseline statistics and qualitative data, was also highlighted throughout the dialogue.Other key issues that were discussed included:The importance of disability support programmes. In countries where social and/or disability support programmes are available, the level of support is often inadequate, resulting in PWD living in poverty or exacerbating their impoverishment. In addition, PLHIV may be excluded from benefits because of the episodic nature of their impairment.1) Misperceptions regarding HIV/AIDS and PWD. There is a common misperception that PWD are sexually inactive and are unlikely to use drugs or alcohol. As a result, AIDS service organizations and health practitioners have tended to overlook the needs and risks experienced by PWD in HIV/AIDS prevention campaigns and service delivery. Even disability rights groups have tended to place a low priority on providing sexual health information and support to PWD.2) Mental health and HIV/AIDS. A large proportion of PLHIV experience depression as a result of the psychosocial aspects of HIV infection. Front-line health professionals and AIDS service providers often have limited knowledge and skills related to: identifying the unique mental health problems of PLHIV; recognizing the disabling effects of these problems; and providing appropriate support and referrals.3) Development disabilities and HIV/AIDS. Many people fear that providing information about sex to persons with development disabilities will increase their vulnerability, which creates barriers to access to information about sexual health and HIV/AIDS prevention. More research is needed to increase understanding of effective means for sharing sexual health information with these groups.4) In response to these challenges a number of opportunities and recommended next steps emerged. These recommendations included:• Sustaining dialogue between disability and HIV/AIDS networks, and implementing mechanisms for the exchange of research and promising practices• Applying a disability lens to HIV/AIDS policies and programmes and, likewise, assessing disability policies and programmes to better meet the needs of PLHIV• Building the capacity of PWD and disabled persons' organizations to facilitate meaningful involvement in HIV/AIDS activities• Identifying regular events and meetings on either HIV/AIDS or disabilities, where the intersectionality of disability and HIV/AIDS could be profiled• Removing barriers to full participation of PWD in HIV/AIDS prevention, treatment, care and support activities, including the promotion of healthy sexuality among PWD• Studying the lessons learned through joint programming for HIV and tuberculosis at the international, country and grassroots level• Promoting the inclusion of disability issues in the formal education of medical and other health care providers• Advocating for the inclusion of PWD in national HIV/AIDS strategic plans, and inclusion of HIV/AIDS in CRPD guidelines, monitoring and reporting processes• Developing a standard process for monitoring and reporting in order to establish baseline data and a consistent evidence base on disability and HIV/AIDS.The issue of HIV/AIDS and disability is one that has been inadequately recognized and addressed at all levels; it is an issue that requires concrete concerted action in order to respond to the needs of PWD and PLHIV. The International Policy Dialogue on HIV/AIDS and Disability, held in Ottawa in March 2009, made important headway in identifying the key gaps and some of the opportunities and next steps for action.The dialogue also strengthened and expanded the network of people working on issues related to HIV/AIDS and disability, and enabled them to share resources, best practices, challenges and experiences. By raising the profile of these important issues and further mobilizing key partners, the dialogue provided a strengthened foundation for future action.The author declares that they have no competing interests.


We face a unique, transitory opportunity in the history of the HIV/AIDS epidemic, because we have collectively pooled money faster than the epidemic has grown . Can we The OptAIDS project was conceived as a means to address this issue. Its implementation thus far has been twofold: a workshop held in July 2008 and this supplement on the eradication of AIDS. The aims of the project are to address two questions:1. Can we optimally spend our way out of the HIV/AIDS epidemic?2. Can we work together to build a World Halting AIDS Model (WHAM) that would permit us to estimate the quickest way to halt HIV/AIDS, monitor our success, and adjust our strategy as we go?The OptAIDS project grew out of a frustration with existing attempts to tackle the disease. AIDS exceptionalism means that HIV/AIDS is handled differently from other public-health epidemics, which has likely been detrimental ,5. ConseAlthough fund accumulation has recently outpaced the epidemic, we argue that plans to spend donor money are too long range in the face of a growing epidemic . Long-raThe OptAIDS project was an outgrowth of the Stop Afghan AIDS project . This prSo too, epidemics are quantitative creatures with predictable thresholds. Models that can be adapted to new results and to changes in control policy have been identified as an integral part of disease-control programs . ModelliThe West African Onchocerciasis (river blindness) Control Program successfully used modeling to supplement intervention programs . By usinWeather prediction models provide a workable analogy. Such models consist of continually updatable inputs, that must adapt to an enormous array of incoming data . Short-tExisting scenarios for HIV control have typically been spread out over two or more decades , which m® http://secondlife.com, a virtual landscape that allows real-time communication. The broad topic was the eradication of AIDS using optimal spending models, but this encompasses an enormous number of issues surrounding the AIDS epidemic. Topics covered included the impact of circumcision, the effect of traditional medicine, prevention strategies for countries with nascent epidemics and the difficulties of developing an HIV vaccine.The OptAIDS workshop was the first of its kind: a scientific meeting held simultaneously in both a real world location and also Second Lifehttp://www.mitacs.ca gave us a Can$10,000 workshop grant for this meeting, which was held on July 29, 2008. Given that this amount would only cover a few airfares, we decided to allow people to participate via Second Life®. Second Life® allows the creation of avatars [MITACS  avatars , so that®, four of whom were presenters. The workshop was advertised to pertinent groups in Second Life® and open to the avatar public. The Second Life® building includes a location where the original slide presentations can be viewed , and faced questions from Toronto and other Second Life® participants. The size of the turnout in Second Life® demonstrated the effectiveness of virtual conferencing; many more people were able to attend the conference than would have been feasible otherwise.The four speakers presenting via Second LifeNational Post, which reported on the innovative use of Second Life® in an academic setting. All the presentations remain in Second Life®  http://slurl.com/secondlife/Silver Bog/21/27/22 as posters that can be clicked on by anyone interested. Speakers can be asked to show up personally as avatars to go over the slides.The event was covered by the The aim of this supplement is to discuss AIDS as a global phenomenon and address issues surrounding its eradication. Due to the scale of the epidemic, a great number of sub-issues arise. In thinking of AIDS as a global pandemic, we need to tackle the disease from as many directions as possible. Some of the articles involve mathematical models, others involve a thorough examination of the state of resources, or an understanding of the effect of the disease on society.This supplement comprises fifteen articles (including this introduction), divided into six themes:1. History2. Resources3. Demographics4. In-host models5. Computation6. Spending our way out of the epidemicTheme 1 comprises an introduction and overview of mathematical modeling , as wellTheme 3 looks at the effects of demographic changes in China on HIV  and the Theme 5 looks at using virtual epidemics to understand real ones  and deveThe collection of articles in this supplement run the gamut of topics related to HIV/AIDS. They examine the disease from a global perspective, in an attempt to untangle many of the problems associated with the epidemic. However, we view this as a starting point: the next step is for policymakers and the donor community to embrace the idea of global eradication. Only by working together can we combat this disease.AIDS is the fourth worst infectious disease of all time, resulting in more deaths per day over the past 25 years than occurred on 9/11/2001 . Over 33However, this special issue demonstrates that, despite the immensity of the epidemic, eradication is not only possible, it is feasible. The time has come to stop thinking locally and to start acting globally.The authors declare that they have no competing interests.RJS wrote the introduction, overview of the supplement and the conclusion. RG set the theme in the first draft and wrote the start of the introduction and the section on the workshop. Both authors proofread and approved the final manuscript.