Prevalence and estimation of hepatitis B and C infections in the WHO European Region: a review of data focusing on the countries outside the European Union and the European Free Trade Association.

Knowledge of hepatitis B and C prevalence, and numbers infected, are important for planning responses. Published HBsAg and anti-HCV prevalences for the 20 WHO European Region countries outside the EU/EFTA were extracted, to complement published data for the EU/EFTA. The general population prevalence of HBsAg (median 3·8%, mean 5·0%, seven countries) ranged from 1·3% (Ukraine) to 13% (Uzbekistan), and anti-HCV (median 2·3%, mean 3·8%, 10 countries) from 0·5% (Serbia, Tajikistan) to 13% (Uzbekistan). People who inject drugs had the highest prevalence of both infections (HBsAg: median 6·8%, mean 8·2%, 13 countries; anti-HCV: median 46%, mean 46%, 17 countries), and prevalence was also elevated in men who have sex with men and sex workers. Simple estimates indicated 13·3 million (1·8%) adults have HBsAg and 15·0 million (2·0%) HCV RNA in the WHO European Region; prevalences were higher outside the EU/EFTA countries. Efforts to prevent, diagnose, and treat these infections need to be maintained and improved. This article may not be reprinted or reused in any way in order to promote any commercial products or services.

Plasma total bilirubin levels predict amputation events in type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

AIMS/HYPOTHESIS: Bilirubin has antioxidant and anti-inflammatory activities. Previous studies demonstrated that higher bilirubin levels were associated with reduced prevalence of peripheral arterial disease (PAD). However, the relationship between bilirubin and lower-limb amputation, a consequence of PAD, is currently unknown. We hypothesised that, in patients with type 2 diabetes, bilirubin concentrations may inversely associate with lower-limb amputation. METHODS: The relationship between baseline plasma total bilirubin levels and amputation events was analysed in 9,795 type 2 diabetic patients from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. The analysis plan was pre-specified. Lower-limb amputation was adjudicated blinded to treatment allocation. Relevant clinical and biochemical data were available for analyses. Amputation was a pre-specified tertiary endpoint. RESULTS: Bilirubin concentrations were significantly inversely associated with lower-limb amputation, with a greater than threefold risk gradient across levels. Individuals with lower bilirubin concentrations had a higher risk for first amputation (HR 1.38 per 5 µmol/l decrease in bilirubin concentration, 95% CI 1.07, 1.79, p = 0.013). The same association persisted after adjustment for baseline variables, including age, height, smoking status, γ-glutamyltransferase level, HbA1c, trial treatment allocation (placebo vs fenofibrate), as well as previous PAD, non-PAD cardiovascular disease, amputation or diabetic skin ulcer, neuropathy, nephropathy and diabetic retinopathy (HR 1.38 per 5 µmol/l decrease in bilirubin concentration, 95% CI 1.05, 1.81, p = 0.019). CONCLUSIONS/INTERPRETATION: Our results identify a significant inverse relationship between bilirubin levels and total lower-limb amputation, driven by major amputation. Our data raise the hypothesis that bilirubin may protect against amputation in type 2 diabetes.

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.

Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study.

AIMS/HYPOTHESIS: Fenofibrate caused an acute, sustained plasma creatinine increase in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) studies. We assessed fenofibrate's renal effects overall and in a FIELD washout sub-study. METHODS: Type 2 diabetic patients (n = 9,795) aged 50 to 75 years were randomly assigned to fenofibrate (n = 4,895) or placebo (n = 4,900) for 5 years, after 6 weeks fenofibrate run-in. Albuminuria (urinary albumin/creatinine ratio measured at baseline, year 2 and close-out) and estimated GFR, measured four to six monthly according to the Modification of Diet in Renal Disease Study, were pre-specified endpoints. Plasma creatinine was re-measured 8 weeks after treatment cessation at close-out (washout sub-study, n = 661). Analysis was by intention-to-treat. RESULTS: During fenofibrate run-in, plasma creatinine increased by 10.0 µmol/l (p < 0.001), but quickly reversed on placebo assignment. It remained higher on fenofibrate than on placebo, but the chronic rise was slower (1.62 vs 1.89 µmol/l annually, p = 0.01), with less estimated GFR loss (1.19 vs 2.03 ml min(-1) 1.73 m(-2) annually, p < 0.001). After washout, estimated GFR had fallen less from baseline on fenofibrate (1.9 ml min(-1) 1.73 m(-2), p = 0.065) than on placebo (6.9 ml min(-1) 1.73 m(-2), p < 0.001), sparing 5.0 ml min(-1) 1.73 m(-2) (95% CI 2.3-7.7, p < 0.001). Greater preservation of estimated GFR with fenofibrate was observed with baseline hypertriacylglycerolaemia (n = 169 vs 491 without) alone, or combined with low HDL-cholesterol (n = 140 vs 520 without) and reductions of ≥ 0.48 mmol/l in triacylglycerol over the active run-in period (pre-randomisation) (n = 356 vs 303 without). Fenofibrate reduced urine albumin concentrations and hence albumin/creatinine ratio by 24% vs 11% (p < 0.001; mean difference 14% [95% CI 9-18]; p < 0.001), with 14% less progression and 18% more albuminuria regression (p < 0.001) than in participants on placebo. End-stage renal event frequency was similar (n = 21 vs 26, p = 0.48). CONCLUSIONS/INTERPRETATION: Fenofibrate reduced albuminuria and slowed estimated GFR loss over 5 years, despite initially and reversibly increasing plasma creatinine. Fenofibrate may delay albuminuria and GFR impairment in type 2 diabetes patients. Confirmatory studies are merited. TRIAL REGISTRATION: ISRCTN64783481.

Perceived cancer-related pain and fatigue, information needs, and fear of cancer recurrence among adult survivors of childhood cancer.

OBJECTIVE: Pain and fatigue are under-researched late effects of childhood cancer and its treatment, and may be interpreted by survivors as indicating cancer recurrence. Moreover, unmet information needs for managing pain and fatigue may be related to fear of cancer recurrence. We investigated the complex relationships between perceived cancer-related pain and fatigue, unmet information needs for managing pain and fatigue, and fear of cancer recurrence. METHODS: We surveyed 404 adult survivors of any form of childhood cancer (M = 16.82 years since treatment completion). RESULTS: Many survivors reported perceived cancer-related pain (28.7%) and fatigue (40.3%), and anticipated future pain (19.3%) and fatigue (26.2%). These symptomologies were all related to unmet information needs for managing pain (18.8%) and fatigue (32.2%; all p's<.001). Survivors reporting unmet information needs for managing pain (B = .48, 95% CI = 0.19-0.76, p = .001) and fatigue (B = .32, 95% CI = 0.06-0.52, p = .015) reported higher fear of cancer recurrence than survivors reporting no information needs. CONCLUSION: Survivors often have unmet information needs for managing pain and fatigue, and these unmet needs are related to fear of cancer recurrence. PRACTICE IMPLICATIONS: Long-term follow-up clinics should assess pain and fatigue. Information provision about pain and fatigue may be an important tool to help manage fear of cancer recurrence.

HIV/AIDS surveillance in Europe: update 2007.

Human immunodeficiency virus (HIV) infection remains of major public health importance in Europe, with evidence of increasing transmission of HIV in several countries. This article provides an overview of HIV and acquired immunodeficiency syndrome (AIDS) surveillance data, and indicates that since 2000 the rate of newly reported cases of HIV per million population has almost doubled in Europe. In 2007, a total of 48,892 cases of HIV infection were reported from 49 of 53 countries in the Region, with the highest rates in Estonia, Ukraine, Portugal and the Republic of Moldova. In the European Union (EU) and European Free Trade Association (EFTA) countries, the predominant mode of transmission for HIV infection is sex between men followed by heterosexual contact. Injecting drug use is still the main mode of transmission in the eastern part of the WHO European region, while in the central part heterosexual contact is the predominant mode of transmission. In 2007, the reported number of AIDS cases diagnosed decreased in the Region overall, except in the eastern part. HIV/AIDS surveillance data are vital to monitor the trends of the HIV epidemic and evaluate public health responses.

HIV among injecting drug users in Europe: increasing trends in the East.

The human immunodeficiency virus (HIV) epidemic among injecting drug users (IDUs) shows different developments in different parts of the European region. In the countries of the European Union (EU) and the European Free Trade Association (EFTA), the rates of reported newly diagnosed cases of HIV infection in IDUs are mostly at stable and low levels or in decline. In contrast, those rates increased in 2007 in many of the other (eastern) countries in the World Health Organization (WHO) European Region, suggesting that the HIV epidemic among IDUs in Europe is still growing. In countries or regions where indicators of HIV incidence show upward trends, existing prevention measures may be insufficient and in need of strengthening. In the EU/EFTA region the larger availability of harm reduction measures such as opioid substitution treatment and needle and syringe programmes may have played a key role in containing the epidemic among IDUs.

Changes in HIV risk behaviour in clients of syringe-exchange schemes in England and Scotland.

The impact of syringe-exchange schemes on the behaviour of injecting drug users was investigated through self-reported behaviour change. Fifteen syringe-exchange schemes in England and Scotland participated in a government-sponsored pilot programme from April 1987. Clients were provided with sterile injecting equipment and condoms, and with knowledge of HIV risks. One hundred and forty-two injecting drug users who first attended between April 1987 and March 1988 participated in a prospective interview-based survey with questions at two points in time. Measurements were self-reported attitudinal, knowledge and behavioural changes relevant to HIV infection and transmission. Many clients maintained or adopted low-risk behaviours: 79% sustained or adopted low or lower levels of syringe sharing. Trends identified include decreases in syringe-sharing, from 34 to 27%; using others' syringes (risk of infection) from 25 to 19%; passing on syringes (risk of transmission) from 30 to 25%. Many clients reported changes in sexual behaviour; those with sexual partners decreased from 77 to 69% and those with two or more sexual partners from 26 to 21%. However, non-use of condoms increased from 62 to 79%. Comparison groups of non-attenders showed higher levels of risk behaviour (59-62% sharing syringes, 86-88% with sexual partners). Overall, changes in HIV risk behaviour show small but encouraging trends and support arguments that injectors can be helped to change their behaviour, which could be of cumulative importance in reducing the spread of HIV.

HIV testing and unreported HIV positivity among injecting drug users in London.

OBJECTIVE: To assess the importance of community-recruited drug injectors with no treatment experience and no previous testing history when estimating HIV prevalence among drug injectors. DESIGN: HIV testing behaviour and prevalence were measured in a serial point prevalence study of drug injectors recruited in community-based non-treatment and treatment settings. METHODS: Pearson's chi 2 and Fisher's exact tests were used to measure differences between treatment groups and non-treatment groups in demographic characteristics, including age and length of injecting career, recent drug use, recent syringe sharing, uptake of previous HIV testing, confirmed HIV-antibody status by saliva and self-reported HIV status. RESULTS: Rates of HIV-antibody testing were significantly lower in community-recruited drug injectors with no experience of treatment than those previously or currently in treatment. Confirmed HIV prevalence by saliva was highest in drug injectors with no experience of treatment. HIV-antibody-positive drug injectors with no treatment experience were less likely to be aware of their antibody status than injectors who were, or who had been, in treatment. CONCLUSIONS: Previous studies of HIV prevalence among drug injectors may be biased by drawing on samples primarily from treatment settings. Drug injectors with no treatment experience and no previous history of HIV testing should be included in HIV prevalence studies. Regular and repeat HIV testing in low-threshold community-based programmes should be considered a necessary part of interventions which seek to provide better access to treatment and other HIV prevention services.

Changes in the injecting risk behaviour of injecting drug users in London, 1990-1993.

OBJECTIVE: To describe changes in the injecting risk behaviour of injecting drug users (IDU) in London between 1990 and 1993. DESIGN: Injecting risk behaviour was measured over 4 years (1990-1993) in a serial point HIV prevalence study of 2062 IDU recruited in both drug treatment and non-treatment community-based settings within greater London. The study used a structured questionnaire and common sampling and interview strategy developed by a World Health Organization technical group and implemented in 13 cities. METHODS: Log-linear models were used to assess patterns of change over years and of differences in injecting risk behaviour, including syringe sharing and syringe hygiene between 1990 and 1993. The log likelihood chi 2 statistic, G2, was used to test statistical significance. Changes in the mean values were assessed first using parametric tests assuming normality and the results were compared with Kruskal-Wallis (non-parametric) tests. Pearsons chi 2 was used to measure differences in frequency of sharing occasions and partner selectivity. RESULTS: An overall reduction in injecting risk behaviour was observed during the first 2 years of this study, including a decline in syringe sharing (both accepting and passing on used syringes), the number of sharing partners and the frequency of sharing occasions. Most sharers restricted sharing to sexual partners and close friends. The majority of sharers reported always cleaning injecting equipment. Main source of sterile equipment was pharmacies and syringe exchanges. Indirect sharing (of spoons, filters, and by front- or backloading) was reported. Since 1991 there has been a stabilization in risk behaviour. CONCLUSIONS: The data indicate that IDU in London have made positive reductions in risk behaviour. Levels of syringe sharing were substantially lower than those reported up to 1987 before AIDS awareness and the introduction of HIV prevention measures. The majority did not share syringes or confined their sharing to close friends and sexual partners, and if shared, cleaned their syringes. Continuation of indirect sharing indicates the need for more detailed prevention messages. While the initial decline in syringe-sharing rates may be attributed to the wide availability of sterile injecting equipment and other preventive measures, it may now be necessary to look beyond current intervention initiatives to develop interventions which seek to change the social etiquette of sharing and move towards the long-term maintenance of low levels of injecting risk behaviour.

HIV-1 prevalence in community-wide samples of injecting drug users in London, 1990-1993.

OBJECTIVE: To provide time-trend estimates of HIV-1 prevalence among injecting drug users (IDU) in London. DESIGN: HIV-1 prevalence and HIV testing behaviour were measured in four serial point prevalence surveys of IDU recruited at multiple sites in community-based non-treatment and drug treatment settings between 1990 and 1993. METHODS: Community subjects were recruited through social network sampling by trained indigenous interviewers; treatment subjects were interviewed at agencies. With informed consent, subjects responded to a structured questionnaire covering risk behaviour. Volunteered saliva samples were tested anonymously for anti-HIV-1. Statistical comparisons across years were examined using mixed binomial logistic and log-linear models. Pearson's chi 2 and Fisher's exact tests were also used for some two-group comparisons. RESULTS: Similar samples were recruited each year. HIV-1 prevalence rate declined from 12.8% in 1990, 9.8% in 1991, 7.0% in 1992, to 6.9% in 1993. The statistical modelling suggested that the overall trend in prevalence rates was one of decelerating decline. There was no difference in prevalence rate by gender and length of injecting. Less than one-half (46%) had received a named HIV test. Over one-half of the HIV-positive IDU were unaware of their status. CONCLUSIONS: The pattern of decline in HIV prevalence rate is attributed to changes in risk behaviour following HIV prevention interventions.

Crack use and injection on the increase among injecting drug users in London.

Fears of a crack 'epidemic' in the United Kingdom of the kind experienced in the United States remain unfounded. However, findings from an ongoing serial point HIV prevalence study indicate that the use and injection of crack cocaine among injecting drug users (IDUs) in London is on the increase. Data on patterns of drug use and drug injection were collected over 4 years (1990-93), from IDUs recruited from both drug treatment and community-based settings. All respondents were asked about their drug use in the 6-month period prior to interview. The use of crack cocaine increased significantly from 16% in 1990 to 59% in 1993 and the injection of crack cocaine from 1% to 27%, respectively. The findings suggest that crack cocaine is being injected more regularly, with increases over the 4-year period in those who reported injecting the drug at least once per week. In response this paper considers both the health implications of, and the treatment response to, the increasing use and injection of crack cocaine among IDUs in London.

Sexual behaviour of drug injectors in London: implications for HIV transmission and HIV prevention.

The importance of sharing injecting equipment in the transmission dynamics of HIV is well established. Comparatively less is known about the sexual behaviour of drug injectors and the risks posed to themselves and their sexual partners through the sexual transmission of HIV. Findings are reported from survey-based interviews undertaken in 1991 which investigated the sexual behaviour of 516 drug injectors, both in and out of treatment in London. The majority of respondents (80%) were sexually active in the 6 months preceding interview. During this time, respondents had a mean of 2.1 non-commercial opposite sex partners. Most (66%) had vaginal intercourse at least once a week, although 68% never used condoms with primary partners and 34% never used condoms with casual partners. Those having sexual intercourse most often were less likely to use condoms. Many had non-injecting sexual partners, and 62% of respondents' primary and casual partners did not inject drugs. Confirmed saliva HIV test results show 10% of respondents to be antibody positive, with a higher rate of prevalence (14% positive) among those with no experience of treatment. This group were also more likely to report casual sexual intercourse. The average rate of partner change, the high proportion of drug injectors with non-injecting partners and the infrequency of condom use within primary and causal relationships indicates the potential for HIV transmission between injectors and their non-injecting sexual partners. The paper concludes by emphasizing the importance of outreach and community-based intervention in safer sex health promotion.

Continued risk behaviour among HIV positive drug injectors in London: implications for intervention.

Findings are reported on the risk behaviour of 104 confirmed HIV-1 antibody positive drug injectors in London. Findings indicate that 41.3% of respondents had never received treatment or help for their drug use, and that 52.0% had never received a named test for HIV antibodies. The majority of confirmed HIV positive respondents (70.1%) were unaware of their HIV positive status. Respondents unaware of their HIV positive status were less likely to use condoms with primary sexual partners than respondents aware of their HIV status, and were marginally (though not significantly) more likely to report borrowing and lending used injecting equipment. Overall levels of risk-taking were similar to those reported in UK studies of injecting drug use as a whole. The paper concludes by emphasising the high potential for HIV transmission among the equipment sharing and sexual partners of HIV positive drug injectors and by stressing the importance of low-threshold HIV testing, education and treatment interventions in the community. If significant proportions of HIV positive drug injectors remain unaware of their antibody status, and if they also continue to engage in behaviours of risk to others, the spread of HIV among drug injectors and their partners may escape current efforts of prevention and prevalence control.

Prevalence of markers for hepatitis B virus and HIV-1 among drug injectors in London: injecting careers, positivity and risk behaviour.

Concerns about the risks of HIV infection among drug injectors have eclipsed concerns about the prevalence and transmission of hepatitis, and in particular hepatitis B virus infection. Findings are reported from surveys undertaken with two separate community-recruited samples of drug injectors in London collected in 1992 (n = 505) and in 1993 (n = 507). Anonymized confirmed testing of saliva shows 51.5% of drug injectors in 1992 and 47.9% in 1993 to be antibody positive to the core antigen of hepatitis B virus (anti-HBc). Approximately half of the drug injectors confirmed as anti-HBc positive were unaware that they had been infected with hepatitis. Anti-HIV-1 prevalence was considerably lower at 7.0% in 1992 and 6.9% in 1993. Multivariate analyses showed anti-HBc positivity to be most likely among older injectors with longer injecting careers who had a history of having shared used needles and syringes. HIV-1 positivity was also associated with a history of having shared injecting equipment as well as with recent sharing (i.e. in the last 6 months). Unlike anti-HBc positivity, there were no associations between HIV-1 positivity and age or length of injecting career. Younger injectors with shorter injecting careers were more likely to report recent sharing of used injecting equipment than older injectors with longer injecting careers. We note the potential for continued transmission of HBV and HIV-1, particularly among younger injectors. We recommend an integrated strategy to maximize the health of drug injectors, of which HIV and HBV prevention is a part. There is a need to widen the availability of HBV vaccinations for HBV negative drug injectors and their sexual partners and for clear guidelines to drug injectors about the relative efficacy of bleach to disinfect injecting equipment of HBV and HIV.

Reductions in HIV risk behaviour and stable HIV prevalence in syringe-exchange clients and other injectors in England.

Syringe-exchange attenders (n = 86) and a comparison group of injectors not attending exchanges (n = 121) were recruited and interviewed in 1989 to examine HIV risk behaviour and HIV antibody status. In 1990, 59% of attenders and 50% of non-attenders were re-contacted and re-interviewed to examine changes over time. Re-interviewed subjects did not differ demographically or in drug use from those not re-interviewed. At first interview, all were injecting, and 35% of attenders and 42% of non-attenders reported recent syringe-sharing. One year later, levels of HIV-risk were similar for both groups, but risk reduction had been achieved by different routes. At Time 2, 16% of attenders were injecting and sharing (IS), 70% injecting and not sharing (INS), and 14% not injecting (NI), compared to non-attenders, 22% IS, 47% INS and 31% NI. Attenders were more likely to continue injecting (86%) with low sharing (18% of those still injecting). Non-attenders were less likely to continue injecting (69%), but continuing injectors had higher sharing rates (32% of those still injecting). More non-attenders than attenders stopped injecting, but non-attenders who continued to inject were at a higher risk of HIV infection than attenders who continued to inject. Baseline HIV prevalence was 2.5% and there were no sero conversions. The levels of sharing for both groups were lower than levels in the UK before HIV prevention programmes commenced and are lower than 1990 sharing rates in the USA. The study indicates the importance of tracking individual change over time, and of measuring outcomes additional to changes in sharing.