The state of hepatitis B and C in the Mediterranean and Balkan countries: report from a summit conference.

The burden of disease due to chronic viral hepatitis constitutes a global threat. In many Balkan and Mediterranean countries, the disease burden due to viral hepatitis remains largely unrecognized, including in high-risk groups and migrants, because of a lack of reliable epidemiological data, suggesting the need for better and targeted surveillance for public health gains. In many countries, the burden of chronic liver disease due to hepatitis B and C is increasing due to ageing of unvaccinated populations and migration, and a probable increase in drug injecting. Targeted vaccination strategies for hepatitis B virus (HBV) among risk groups and harm reduction interventions at adequate scale and coverage for injecting drug users are needed. Transmission of HBV and hepatitis C virus (HCV) in healthcare settings and a higher prevalence of HBV and HCV among recipients of blood and blood products in the Balkan and North African countries highlight the need to implement and monitor universal precautions in these settings and use voluntary, nonremunerated, repeat donors. Progress in drug discovery has improved outcomes of treatment for both HBV and HCV, although access is limited by the high costs of these drugs and resources available for health care. Egypt, with the highest burden of hepatitis C in the world, provides treatment through its National Control Strategy. Addressing the burden of viral hepatitis in the Balkan and Mediterranean regions will require national commitments in the form of strategic plans, financial and human resources, normative guidance and technical support from regional agencies and research.

A prospective longitudinal study of the prevalence of post-traumatic stress disorder resulting from childbirth events.

BACKGROUND: Childbirth has been linked to postpartum impairment. However, controversy exists regarding the onset and prevalence of post-traumatic stress disorder (PTSD) after childbirth, with seminal studies being limited by methodological issues. This longitudinal prospective study examined the prevalence of PTSD following childbirth in a large sample while controlling for pre-existing PTSD and affective symptomatology. METHOD: Pregnant women in their third trimester were recruited over a 12-month period and interviewed to identify PTSD and anxiety and depressive symptoms during the last trimester of pregnancy, 4-6 weeks postpartum, 12 weeks postpartum and 24 weeks postpartum. RESULTS: Of the 1067 women approached, 933 were recruited into the study. In total, 866 (93%) were retained to 4-6 weeks, 826 (89%) were retained to 12 weeks and 776 (83%) were retained to 24 weeks. Results indicated that, uncontrolled, 3.6% of women met PTSD criteria at 4-6 weeks postpartum, 6.3% at 12 weeks postpartum and 5.8% at 24 weeks postpartum. When controlling for PTSD and partial PTSD due to previous traumatic events as well as clinically significant anxiety and depression during pregnancy, PTSD rates were less at 1.2% at 4-6 weeks, 3.1% at 12 weeks and 3.1% at 24 weeks postpartum. CONCLUSIONS: This is the first study to demonstrate the occurrence of full criteria PTSD resulting from childbirth after controlling for pre-existing PTSD and partial PTSD and clinically significant depression and anxiety in pregnancy. The findings indicate that PTSD can result from a traumatic birth experience, though this is not the normative response.

How to improve transfusion medicine. A treating physician's perspective.

As transfusion medicine becomes more complex, cooperative strategies are gaining increasing importance in relaying information to the treating physician and in incorporating the treating physician into the education and quality control processes. The broad domain of transfusion medicine is illustrated by the variety of disciplines involved in defining the use of products such as fresh frozen plasma and the newly released solvent-detergent-treated plasma, fibrin glue and highly purified fibrin sealant, and leukoreduced and irradiated blood products. Cooperative efforts among physicians and other personnel of multiple disciplines are essential to ensure appropriate use and continuous evaluation of blood products.

Can Europe afford combination therapy?

AIDS: Mounting drug costs for AIDS patients in Europe are becoming problematic. An urgent need is being expressed in the UK to prove that combination therapy makes financial sense in terms of reducing patient stays, outpatient visits, and concomitant medication costs. France is currently meeting the extra costs of this therapy but the future cost escalation is worrisome. Germany will also experience problems in paying for combination therapy, as will other European countries which also face the financial burden of a steadily aging population. European governments, in a response to this problem, have pursued a policy of maximizing the rewards of employed citizens at the expense of people on the margins of society. Drug companies need to carefully consider their pricing policies before they make AIDS an unprofitable area.^ieng

Slow progress against HIV.

PIP: Treatment for people with HIV attempts to prevent HIV from reproducing, boost the immune system, or cure opportunistic infections. The chemical structure of anti-viral drugs is similar to that of DNA. Since HIV bonds with the drugs rather than DNA, it cannot replicate itself. The most widely used anti-viral drug is zidovudine or AZT (brand name, Retrovir), but it does not help HIV infected persons who are still healthy. A recent trial shows that a combination of anti-viral drugs is more likely to delay opportunistic infections and death than AZT alone. When pregnant women use AZT before and during delivery and when their newborns receive AZT therapy, the likelihood of HIV transmission to the newborn is reduced by about 66%. Follow-up studies are needed, however, since AZT is toxic. Disadvantages of anti-viral drugs include resistance, toxicity, side effects (e.g., nausea and anemia), which are particularly severe at high doses, and accessibility of regular and expensive monitoring tests. Protease inhibitors are in the early stages of development. They deactivate the HIV enzyme which allows HIV to attach to white blood cells. Imuthiol (DTC) aims to increase the number of white blood cells so the body can fight HIV longer, but it appears that it has no benefit and may even facilitate development of opportunistic infections. Interleuken 2 may increase the number of CD4 cells. Alternative approaches to strengthening the immune system are lifestyle changes, improved diet, reduced stress, Chinese medicine and acupuncture, herbal medicines, and relaxation exercises. HIV/AIDS therapies are very expensive and often induce side effects. Many HIV positive people in developed countries are opting out of these treatments, even though they have access to them. Prevention and treatment of opportunistic infection remain the best strategies for most HIV-infected persons.^ieng

Europe out of step with the US.

AIDS: The disparity in the availability of AIDS drugs between the United States and Europe is frustrating to members of the European AIDS Treatment Group, among others. It is hoped that the newly-created European Medicines Evaluation Agency (EMEA) will streamline drug approval for the European Union overall, since previous approvals were done on a country-by-country basis. Although alternative methods of drug approval in Europe cause apprehension, it is hoped that a system will be created that will deliver drugs quickly without sacrificing the physician and patient guideline requirements.^ieng

Europe's drug lottery.

AIDS: Europeans regard American drug lotteries as unethical, but their own programs for experimental drugs demonstrate the difficulty of designing programs that are fair, consistent, and timely. Although many of the European countries present themselves as a unified market, there are marked differences in how each handles the issue of experimental drugs. Examples from Germany's saquinivir program and France's 3TC and oral ganciclovir programs are cited.^ieng

Europe learns from US drug mistakes.

AIDS: The European Medicines Evaluation Agency (EMEA) has a role in drug approval similar to the Food and Drug Administration (FDA). One of EMEA's biggest challenges is to resolve the differences in opinion over the use of surrogate markers to approve anti-HIV drugs. The EMEA's document, Points to Consider in the Assessment of Anti-HIV Medicinal Products, specifies its policies related to clinical trials and risk/benefit analyses. Because U.S. regulations are open to interpretation, experimental drugs are often approved. The European criterion has tighter controls on experimental drugs, although they allow rapid approval of drugs to immediately benefit very sick patients.^ieng

Europe looks to strategy trials.

AIDS: In Europe, as in other countries, a great deal of attention is being paid to HIV treatment strategies, such as when to begin treatment, what to begin with, when to switch treatments, and what to switch to. These questions were addressed at a meeting of the European AIDS Treatment Group and the European Medicines Evaluation Agency. There is concern in Europe about approving drugs too rapidly. Europe is learning from the United States' mistake of rapidly approving drugs with no clear guidelines for their use. Drugs should be conditionally approved based on surrogate marker data, giving full approval after efficacy data is collected. These trials will be costly, and lobbying efforts will be needed to encourage the national governments to subsidize the trials. Various groups and researchers are attempting to design large treatment strategy trials, although not all advocates think these are necessary.^ieng

It's the bureaucracy, stupid.

AIDS: Drug licensing in Europe is proving to be a slow and tedious process that requires many weeks to complete, due to bureaucratic red tape. Activists have fought this delay with little progress, with the exception of a case in the Netherlands. Netherlands activists' letters to the Dutch Health Minister resulted in the government reimbursing the cost of all drugs upon their approval by the CPMP, the scientific committee of the European Medicines Evaluation Authority in London. The Netherlands will also be collecting data on various protease inhibitor-containing triple combinations, with viral load measured on a regular basis, thus supplying a real-life strategy trial funded by the Dutch health service.^ieng

Epidemiology and public health.

AIDS: There has been much concern over whether women are treated equally to men with respect to HIV/AIDS research. At the Vancouver Conference, it was evident that progress toward this goal has been shamefully slow. Whether protease inhibitors work as well in women with liver disease as they do in men has not been studied. In most parts of the developed world, a high proportion of HIV-infected women have histories of drug use, and possibly serious liver damage. When potential problem areas are brought to light, such as increased risk for genital cancers in women, suggestions for treatment are not made. In some areas, self help groups and advocacy organizations exist, but more need to be developed to help women cope with HIV infection, and to help them become educated to maintain their own health and prevent infection. Methods giving women some control over HIV prevention include the female condom and microbiocides, with the former being potentially effective but less accepted by male partners in some countries. Attention was also given to the female aspect of HIV transmission, such as viral shedding in genital secretions. Finally, the known effect of AZT on preventing perinatal transmission of HIV was discussed.^ieng

Who will pay for patient education?

AIDS: Large differences between European countries exist on how HIV-infected patients get educated on available therapies. In Southern European countries and Eastern Europe, treatment education is still underdeveloped, with Spain being the furthest advanced in this area. In the United Kingdom, the AIDS Treatment Project provides telephone counseling and advocacy, and community organizations have recently launched a campaign encouraging compliance with treatment regimens. Other organizations offering education include ACT UP Paris, Info SIDA, Action Traitements, and Arcat SIDA. A European network, the European AIDS Treatment Group, links treatment activists and educators. Community organizations are looking to the pharmaceutical industry to support their work, but financial support for treatment education is a problem, partly because of the suspicion people with HIV have of any messages emanating from pharmaceutical companies.^ieng

EU consensus lacking on needle exchange.

AIDS: Although Europe has already addressed the needle exchange issue that is currently being debated in the United States, there is no consensus among the members of the European Commission. Some countries favor a harm reduction approach to drug use by promoting needle exchanges and the decriminalization of drug possession laws, and as a result, have the lowest rates of HIV prevalence in Europe. England, Holland, and Denmark are pioneers among this group. In other countries, such as Italy, France, and Portugal, needle exchange programs face great political resistance, and Sweden has pursued a policy of a drug-free society for 20 years, with compulsory drug treatment. The European debate has also focused on the social exclusion that affects drug users. There continues to be much disparity in drug policy and attitudes across Europe.^ieng

Rift over viral load data and clinical guidelines.

AIDS: European and United States doctors differ in their opinions on approaches to treatment. The debate over viral load data and its use in directing treatment of HIV-infected patients is discussed. Issues include viral load thresholds for beginning HIV therapy, the appropriate regimen, and the potential of developing triple-resistant mutants and viral load undetectability as a measure of disease progression.^ieng

Europe far from united in treatment standards.

AIDS: A survey of AIDS treatment guidelines shows a wide variation in treatment practices between countries. At present, there are no mechanisms to enforce a standard of care. In some cases, clinical practice diverges widely from the standard set in national guidelines. In one example, Italian guidelines explicitly reject monotherapy, yet twenty percent of people living in Italy are still using ZDV or ddI monotherapy. Some activists are urging that a Europe-wide guideline be developed; however, others say that such international guidelines do not take into account the realities of the standard of care in Second World countries, including Spain, Portugal and Italy. A chart summarizes European antiretroviral treatment guidelines and practices for nine European countries.^ieng

Euro debate offers a preview of health policy.

AIDS: As Europe struggles to unite under one currency, the criteria for admission to the European Monetary Union (EMU) is causing some governments to short change their AIDS research and treatment plans. The EMU is being considered by some as a potential disaster as a deflationary pact that drives up unemployment and drains funds for public services in the name of fiscal stability. Others fear the opposite, in which an inflationary pact develops where fiscal management is sacrificed in order to bail out bankrupt welfare States with State pension commitments far greater than the national GDP. More solvent States are suspicious of any unifying moves that have to do with taxation, welfare, or healthcare spending.^ieng

Productive partnerships: European treatment activism.

AIDS: As the countries in Europe grow economically and politically closer, AIDS activism efforts are also moving together. The European AIDS Treatment Group comprises 60 activists from 17 European countries. The group currently focuses on approving anti-HIV agents more quickly and devises strategies for clinical trial development. Their other efforts include developing a minimum standard of care for HIV infection, making viral load testing more available, and improving access to new treatments. Dutch AIDS organizations were successful in obtaining access to and reimbursement for protease inhibitors.^ieng

Europe's treatment roulette.

AIDS: Access to new combination drug therapies for the treatment of AIDS is varied across the European Union, where some countries have agreed to reimburse patients for the costly drugs but others are reluctant to do so. The drugs are provided in France, Germany, the Netherlands, and Scandinavia, but not in Spain, Italy, Belgium, or the United Kingdom. At a press conference organized to highlight the need for government action, Philippo von Schloesser of the European AIDS Treatment Group estimated that 11,830 deaths could be prevented in these countries if the treatments were used. Dr. Joep Lange stressed the importance of treating HIV with the most powerful drugs available to curb drug resistance. Reimbursement for the drugs is now being negotiated in Spain, while hospitals in the United Kingdom are being told to cut costs in other areas if they want to prescribe the costly therapies. Even with a 7 percent increase in funding, however, Britain's AIDS treatment budget is inadequate to provide an updated level of care. Italian patients, meanwhile, are likely to continue to face limited treatment options due to the lack of funding for small local hospitals. At the EATG press conference, University of North Carolina researcher Kit Simpson reported that in some European countries, the impact of triple-combination therapy on morbidity and mortality could offset drug costs by 50 percent to 60 percent.^ieng

A French lesson. French experience shows full funding of treatment advances saves money.

AIDS: France's HIV treatment expenditures, the highest in Europe and second only to the United States, have created evidence of the real-life cost-effectiveness of triple combination antiretroviral therapy. The French have demonstrated that savings in treatment costs can be obtained with early and intensive antiretroviral therapy. Based on such findings, the French Ministry of Health projects a 20 percent reduction in hospitalization, a 30 percent reduction in deaths, and a reduction in new AIDS cases in 1997. Italy and England are, by comparison, having problems developing a standard of HIV care and finding funding to support antiretroviral therapy.^ieng

The HIV-infected physician.

AIDS: The United Kingdom's policies regarding HIV infection and the medical community are the most explicit in Europe. The guidelines have had two inevitable consequences: physician paranoia and public panic. France has no official guidelines on the obligations or rights of physicians with HIV infection. Currently, in Europe, HIV has primarily affected physicians who are either gay men or African, and who face professional discrimination. Guidelines on practice and disclosure that recognize the facts without exacerbating public anxiety are needed.^ieng