Imprisonment: a risk factor for HIV infection counteracting education and prevention programmes for intravenous drug users.

OBJECTIVES: To examine changes of risk behaviour and its determinants as well as risk factors for HIV infection in intravenous drug users (IVDU) with particular attention to imprisonment and its risk patterns. SETTING: In 1993 a multisite cross-sectional study was carried out by standardized questionnaires and blood/saliva samples in which 612 IVDU from Berlin were enrolled. RESULTS: Multifactorial analysis revealed that the most important risk factor for HIV infection was needle-sharing in prison. In total, 353 IVDU (58%) reported reduced risk behaviour; changes related more to injection behaviour than sexual practices (91 versus 68%). Important determinants for needle-sharing during the last 6 months were intravenous drug use in prison, duration of drug-taking history, and knowledge of a negative HIV test. The most frequently reported reasons for current needle-sharing were having shared needles with only one regular partner (45%) and imprisonment (26%). CONCLUSION: Information campaigns and other prevention measures appear to have produced risk awareness in IVDU, and as a consequence, a reduction in risk behaviour. The situation in prisons (no sterile injecting equipment, no effective disinfectants), however, is counteractive to prevention measures implemented outside prisons. An important task for future strategies should be to enable IVDU to avoid HIV transmission while in prisons.

Frontloading: a risk factor for HIV and hepatitis C virus infection among injecting drug users in Berlin.

OBJECTIVE: To determine whether frontloading (i.e., syringe-mediated drug-sharing) is a risk factor for HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection among injecting drug users (IDU). DESIGN: Cross-sectional study. Data on sociodemographic and behavioural characteristics were obtained by a standardized questionnaire. Serum samples were tested for seromarkers for HIV, HBV and HCV. SETTING AND PARTICIPANTS: IDU were recruited at 'low-threshold' storefront agencies (out-of-treatment sample), and at a centre for long-term drug use treatment (in-treatment sample). Individuals were included in the study if they had injected drugs within the previous 3 months. MAIN OUTCOME MEASURES: Serological evidence for HIV, HBV, HCV exposure. RESULTS: Of all IDU (n = 324), 84% had ever practised frontloading with non-sterile injecting equipment, and 46% had done so more than 100 times; 32% had front-loaded during the 6 months prior to the interview. The crude seroprevalence rates for HIV, HBV and HCV increased with the overall frequency of frontloading, and reached 22, 71 and 94%, respectively, among IDU who had frontloaded more than 100 times. After controlling for confounding effects by logistic regression, having practised frontloading more than 100 times was significantly associated with HIV infection [adjusted prevalence odds ratio (POR) 3.5; 95% confidence interval (CI), 1.4-9], and HCV infection (adjusted POR, 5.4; 95% CI, 2.3-12), but not with HBV infection. Another independent risk factor for all three virus infections was needle-sharing in prison. CONCLUSIONS: In communities where sterile injection equipment is readily available, and IDU have substantially reduced their overall levels of needle-sharing, the practice of frontloading appears to be a major risk factor for infections by blood-borne viruses among IDU. Prevention activities should specifically address this risk behaviour.

Cell density of human lens epithelium in women higher than in men.

Flat preparations of the central lens epithelium in 181 human donor eyes, 120 male, 61 female, were used to determine epithelial cell density. Donor age ranged from 13 to 91 years. A similar linear age-dependent decrease of cell density was found in both sexes. In addition, the epithelial cell density was significantly higher in females. The age-adjusted mean cell density in males was 5008.6 cells/mm2, in females 5780.6 cells/mm2. A similar sex difference had been found before in lens epithelium of human cataracts. The cause and significance of this observation are unknown.

Quantitative assessment of the polysome profile of the livers of mice treated with tetracycline or doxycycline.

The influence of tetracycline and doxycycline (10-100 micrograms/g i.v.) on the aggregational state of ribosomes from mouse liver was tested. Both drugs caused a disaggregation of the ribosomes as evidenced by a rise of the monosomes + disomes/polysomes ratio. Tetracycline was much more potent than doxycycline, the minimum effective doses for tetracycline being 10 micrograms/g i.v. as compared to 100 micrograms/g for doxycycline. The results show that tetracycline but not doxycycline at therapeutic dose range may interfere with the protein synthesis of the liver.

The immunocytochemical demonstration of human placental lactogenic hormone (hPL): a parameter for the functional capacity of the trophoblast.

Forty-two placentae from pregnancies of 36 to 42 weeks' gestation were examined: the maternal serum human placental lactogen (hPL) values of the mothers during the last week of gestation ranged between 3 and 12 micrograms/ml. hPL was demonstrated by the indirect immunofluorescence technique and was present in all placentae. A significant regional difference in hPL concentration was not found, but within individual sections focal differences in intensity were apparent. Of intensity group I (weakly positive) 92 per cent correlated with maternal serum hPL values of 3 to 6 micrograms/ml; 78 per cent of group II/III (very strongly positive) with values above 6 micrograms/ml. In the four-field Chi-square test the probability of error was at 5%. In 32 cases trophoblast islands (Islands of Ortmann) were present, of which 20 were hPL positive. Their degree of intensity corresponded to group I of the syncytiotrophoblast. Of the placentae showing hPL-positive Islands of Ortmann, 95 per cent correlated with maternal serum hPL values below 6 micrograms/ml whilst 70 per cent of the hPL-negative trophoblast islands correlated with serum values above 8 micrograms/ml. It is suggested that maternal serum hPL values are determined by the rate of synthesis of hPL by the placenta and not by the rate of secretion. The focal differences in intensity indicates that the serum level does not only depend on the absolute surface area of the trophoblast, but that there also exist qualitative and functional differences between different areas of the syncytiotrophoblast. Heterotopic hPL synthesis in the Islands of Ortmann is considered to be independent of hPL synthesis by the syncytiotrophoblast.

The meaning of kappa: probabilistic concepts of reliability and validity revisited.

A framework--the "agreement concept"--is developed to study the use of Cohen's kappa as well as alternative measures of chance-corrected agreement in a unified manner. Focusing on intrarater consistency it is demonstrated that for 2 x 2 tables an adequate choice between different measures of chance-corrected agreement can be made only if the characteristics of the observational setting are taken into account. In particular, a naive use of Cohen's kappa may lead to strikingly overoptimistic estimates of chance-corrected agreement. Such bias can be overcome by more elaborate study designs that allow for an unrestricted estimation of the probabilities at issue. When Cohen's kappa is appropriately applied as a measure of chance-corrected agreement, its values prove to be a linear--and not a parabolic--function of true prevalence. It is further shown how the validity of ratings is influenced by lack of consistency. Depending on the design of a validity study, this may lead, on purely formal grounds, to prevalence-dependent estimates of sensitivity and specificity. Proposed formulas for "chance-corrected" validity indexes fail to adjust for this phenomenon.

Problems in defining cutoff points of continuous prognostic factors: example of tumor thickness in primary cutaneous melanoma.

Continuous prognostic factors are often categorized by defining optimized cutoff points. One component of criticism of this approach is the problem of multiple testing that leads to an overestimation of the true prognostic impact of the variable. The present study focuses on another crucial point by investigating the dependence of optimized cutoff points on the observed distribution of the continuous variable. The continuous variable investigated was the vertical tumor thickness according to Breslow, which is known to be the most important prognostic factor in primary melanoma. Based on the data of 5093 patients, stratified random samples were drawn out of six artificially created distributions of tumor thickness. For each of these samples, Cox models were calculated to explore optimized cutoff points for tumor thickness together with other prognostic variables. The optimized cutoff points for tumour thickness varied considerably with the underlying distribution. Even in samples from the same distribution, the range of cutoff points was amazingly broad and, for some of the distributions, covered the whole region of possible values. The results of the present study demonstrate that optimized cutoff points are extremely data dependent and vary notably even if prerequisites are constant. Therefore, if the classification of a continuous prognostic factor is necessary, it should not be based on the results of one single study, but on consensus discussions including the findings of several investigations.

Plasmodium falciparum malaria and human red cells. II. Red cell genetic traits and resistance against malaria.

In 702 Nigerian children under 6 years of age the incidence and the severity of malarial infection was studied with respect to haemoglobin types and red cell glucose-6-phosphate dehydrogenase variants. The results suggest that Hb AS as well as the female genotype GdA-/GdB offer selective advantage against the disease. Parasite densities in carriers of these genotypes were significantly lower than in other subjects. Whereas protection by Hb AS was found mainly in children between 2 and 4 years of age, the advantage afforded by GdA-/GdB was similar in all age groups. Possible mechanisms are discussed.

Plasmodium falciparum malaria and human red cells. I. A genetic and clinical study in children.

In a holoendemic malaria region of Nigeria children of both sexes aged from 9 months to 6 years with an acute febrile illness were examined for malaria. In 461 children with malaria, predominantly P. falciparum, and in 241 children without malaria, haemoglobin levels, haemoglobin types, red cell glucose-6-phosphate dehydrogenase variants and parasite densities were recorded. The G6PD status was determined by a combination of spectrophotometric enzyme quantitation, electrophoresis and the cytochemical methaemoglobin elution technique. Malaria morbidity and parasitaemia decreased with increasing age. Frequencies of haemoglobin types and G6PD variants were not significantly different in the malaria and the non-malaria series. Haemoglobin values were significantly lower in children with malaria to about the same extent in HbAA and HbAS subjects, but no close correlation existed between haemoglobin level and parasite density. Details of the G6PD classification and the effect of malaria on enzyme activity are discussed.

History of syringe sharing in prison and risk of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infection among injecting drug users in Berlin.

BACKGROUND: Injecting drug users (IDU) are at risk of parenterally transmitted diseases such as hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infection. We investigated whether a history of syringe sharing in prison is a risk factor for these infections. In the longitudinal part of the study, HBV, HCV, and HIV seroincidence rates were determined. METHODS: The participants were recruited by multisite-sampling at different agencies for IDU. Data on risk behaviour were obtained by a standardized questionnaire. Serological markers for HBV, HCV, and HIV were determined. Logistic regression analysis was performed to adjust for confounding effects. RESULTS: A history of syringe sharing in prison was significantly associated with HBV (adjusted prevalence odds ratio [POR] = 3.9, 95% confidence interval [CI]: 2-10), HCV (POR = 9.7, 95% CI: 3-33), and HIV infection (POR = 10.4, 95% CI: 4-29). The HIV seroincidence rate was 5.9 per 100 person-years. None of the IDU receiving methadone maintenance treatment (MMT) seroconverted whereas the HIV incidence was 8.5 among IDU not in MMT (P = 0.01). CONCLUSIONS: The increased risk of HBV, HCV, and HIV infection among IDU who had shared syringes in prison warrants specific preventive action. The longitudinal data suggest that IDU in MMT have a lower risk of HIV infection.

Classification and regression trees (CART) for estimation of prognosis in patients with gastric carcinoma.

A total of 961 patients who had received resective surgery for gastric carcinoma were grouped according to prognosis by classification and regression trees (CART). This grouping was compared to the present UICC stage grouping. For patients resected for cure (R0) the CART approach allows a better discrimination of patients with poor prognosis (5-year survival rates 15%-30%) from patients with a 5-year survival of 50%, on the one hand, and from patients with extremely poor prognosis (5-year survival rates below 5%) on the other. In the present investigation CART grouping was not influenced by the differentiation between pT1 and pT2 or between pT3 and pT4.

Malaria and erythrocyte glucose-6-phosphate dehydrogenase variants in West Africa.

In a clinical study, 702 Nigerian children aged 1-6 years were examined for malaria. Comparison of morbidity rates and parasitemia of patients with different glucose-6-phosphate dehydrogenase (G6PD) status provided evidence that in heterozygous females the gene for G6PD deficiency (GdA-/GdB) confers an advantage against malaria.

Determinants of HIV infection and recent risk behaviour among injecting drug users in Berlin by site of recruitment.

This study investigated differences in prevalence and determinants of HIV infection, and in recent risk behaviour (previous 6 months) among injecting drug users (IDUs) who are in contact with different types of services for IDUs in Berlin. Participants (n = 557) were recruited from drug-free long-term treatment centres, a storefront agency and a syringe exchange bus. HIV seroprevalence was lowest (3.9%) at the treatment centres, and highest among IDUs at the storefront agency (20.7%). In logistic regression, independent risk factors for HIV infection were duration of injecting drug use, borrowing syringes in prison, sex with HIV-positive partners, and prostitution. Syringe sharing in prison was the most important independent determinant of HIV infection among all three subpopulations of IDUs. Participants entering long-term treatment were most likely, and IDUs at the syringe exchange bus were least likely to have borrowed and passed on syringes in the previous 6 months. In logistic regression, site of recruitment was independently associated with recent borrowing of syringes, but not with condom use. Injection of drugs other than heroin only, and injecting in prisons, were also independent predictors of recent borrowing. The results indicate that IDUs entering treatment form an important target group for health education. There is a need for AIDS prevention measures in prisons. The comparatively low levels of recent injection risk behaviour among IDUs at the syringe exchange bus suggest that this type of intervention may be effective in harm reduction.

Methadone maintenance treatment and HIV risk-taking behaviour among injecting drug users in Berlin.

STUDY OBJECTIVE: To determine whether methadone maintenance treatment (MMT) is effective in reducing the levels of HIV risk-taking behaviour (borrowing and lending of injection equipment, irregular condom use) among injecting drug users (IDUs), and to identify independent predictors of the borrowing of used syringes. DESIGN: Cross sectional study of IDUs in MMT and not in MMT, using standardised interviews for collection of sociodemographic and behavioural data, and laboratory tests for detecting HIV antibodies. SETTING AND PARTICIPANTS: The 612 IDUs were recruited at different services for drug users such as treatment centres, walk in agencies, a hospital, and on the streets. MAIN RESULTS: Of all IDUs, 41% had borrowed and 34% had passed on used injection equipment in the previous six months. In univariate analysis, IDUs receiving MMT had injected less frequently and were significantly less likely to borrow and lend syringes. In logistic regression analysis, MMT was protective against the borrowing of syringes (adjusted odds ratio 0.36, 95% confidence interval 0.2, 0.8), but not against syringe lending nor against sexual risk behaviour (i.e., numbers of sex partners, lack of condom use). Important independent predictors of the borrowing of syringes were injecting drug use in prison, use of sedatives, and sex with another IDU in the previous six months. CONCLUSIONS: MMT may play a significant role in reducing the levels of borrowing of syringes among IDUs. However, additional prevention measures are needed which should specifically address sexual risk behaviour and target subgroups of IDUs with high levels of needle sharing, such as IDUs who have been in prison and and those who are sedative users.

Detection of Dirofilaria immitis microfilariae in peripheral blood. A quantitative comparison of the efficiency and sensitivity of four techniques.

Four techniques for the detection and quantification of Dirofilaria immitis microfilariae in peripheral blood were compared, namely the conventional thick smear, thick films prepared by cytocentrifugation, filtration of blood through polycarbonate membranes, and density gradient centrifugation followed by membrane filtration. The efficiency of the methods and their sensitivity was assessed by determining quantitatively the recovery of known numbers of microfilariae from defined volumes of blood. Polycarbonate membrane filtration either alone or in combination with density gradient centrifugation showed an efficiency of 0.9 and 0.8, respectively, and reached 100% sensitivity with microfilariae densities of greater than or equal to 10 microfilariae per ml of blood. Conventional thick smears and cytocentrifugation were of considerably lower efficiency (0.02 and 0.03, respectively) and reached 100% sensitivity with more than 200 microfilariae per ml.

Thromboembolic stroke in young women. A European case-control study on oral contraceptives. Transnational Research Group on Oral Contraceptives and the Health of Young Women.

A matched case-control study was performed between 1993 and 1996 in 16 centers in the United Kingdom, Germany, France, Switzerland, and Austria. The objective was to determine the influence of oral contraceptives (OC), particularly those containing modern progestins, on the risk for ischemic stroke in women aged 16-44 years. A total of 220 women who had had an incident ischemic stroke and were compared with 775 control subjects who were unaffected by stroke. At least one hospital and one community control subject per patient was matched and interviewed with the corresponding patient for 5-year age band and for area of residence. Crude odds ratios (95% confidence intervals [CI]) for ischemic stroke were as follows. For current use of any OC versus no use 2.3 (1.7-3.2), the adjusted odds ratio (OR) 3.6 (2.4-5.4). The OC associated risk was higher for first generation than for second or third generation OC. The risk estimates for patients versus community control subjects were always lower than for hospital control subjects. No major regional difference of the risk estimates was found. Compared with nonusers of OC without hypertension, women with hypertension who used OC had an almost 10-fold increased risk. However, OC users who had had a blood pressure check before OC prescription had a lower risk than did those without such a check. Smoking > 10 cigarettes/day is associated with higher risk of stroke, particularly for OC users. No significant effect was found for duration of OC use. We conclude that although there is a small relative risk of occlusive stroke for healthy women currently using OC, the attributable risk is very small because the incidence in this age group is very low. The small increase in risk of OC use may be further reduced by preventive efforts for cardiovascular risk factors, particularly hypertension and smoking.

Case-control study of oral contraceptives and risk of thromboembolic stroke: results from International Study on Oral Contraceptives and Health of Young Women.

OBJECTIVE: To determine the influence of oral contraceptives (particularly those containing modern progestins) on the risk for ischaemic stroke in women aged 16-44 years. DESIGN: Matched case-control study. SETTING: 16 Centres in the United Kingdom, Germany, France, Switzerland, and Austria. SUBJECTS: Cases were 220 women aged 16-44 who had an incident ischaemic stroke. Controls were 775 women (at least one hospital and one community control per case) unaffected by stroke who were matched with the corresponding case for 5 year age band and for hospital or community setting. Information on exposure and confounding variables were collected in a face to face interview. MAIN OUTCOME MEASURES: Odds ratios derived with stratified analysis and unconditional logistic regression to adjust for potential confounding. RESULTS: Adjusted odds ratios (95% confidence intervals) for ischaemic stroke (unmatched analysis) were 4.4 (2.0 to 9.9), 3.4 (2.1 to 5.5), and 3.9 (2.3 to 6.6) for current use of first, second, and third generation oral contraceptives, respectively. The risk ratio for third versus second generation was 1.1 (0.7 to 2.0) and was similar in the United Kingdom and other European countries. The risk estimates were lower if blood pressure was checked before prescription. CONCLUSION: Although there is a small relative risk of occlusive stroke for women of reproductive age who currently use oral contraceptives, the attributable risk is very small because the incidence in this age range is very low. There is no difference between the risk of oral contraceptives of the third and second generation; only first generation oral contraceptives seem to be associated with a higher risk. This small increase in risk may be further reduced by efforts to control cardiovascular risk factors, particularly high blood pressure.

PIP: A matched case-control study conducted at 16 centers in the UK, Germany, France, Switzerland, and Austria in 1993-96 investigated the influence of combined oral contraceptives (OCs) on ischemic stroke risk in women 16-44 years of age. Enrolled were 220 women who experienced an incident ischemic stroke and 775 controls matched on age, hospital, and community. The adjusted odds ratios for current use of first-, second-, and third-generation OCs were 4.4 (95% confidence interval (CI), 2.0-9.9), 3.4 (95% CI, 2.1-5.5), and 3.9 (95% CI, 2.3-6.6), respectively. High-dose estrogen OCs were associated with a greater ischemic stroke risk, regardless of the type of progestin. The risk ratio for third- vs. second-generation OCs was 1.1 (95% CI, 0.7-2.0). Compared with current non-users, the odds ratios for stroke were 4.5 (95% CI, 2.1-9.6) for second-generation OCs and 2.5 (95% CI, 1.4-4.4) for third-generation OCs. Risk estimates were lower if blood pressure had been screened before OCs were prescribed. Although these findings indicate current OC use--especially of first-generation formulations--is associated with a slightly increased risk of thromboembolic stroke, the absolute risk is very small in this age group and can be reduced by avoiding prescription of OCs to women with cardiovascular risk factors such as high blood pressure.