Childhood atopic dermatitis is associated with a decreased chance of completing education later in life: a register-based cohort study.

BACKGROUND: Atopic dermatitis (AD) has far-reaching consequences in childhood and later in working life, but information on how it affects completion of education is sparse. OBJECTIVES: To compare the educational achievement of individuals with AD in childhood/adolescence and individuals without a history of AD. METHODS: The study population included patients diagnosed with AD prior to the age of 16 registered in the Danish National Patient Register (DNPR) born in the period 1977-1993 and a 23-fold matched control group from the background population. Cross-linkage of five different Danish registers from 1977 to 2015 allowed comparison of AD patients with controls regarding completion of education. RESULTS: In total, 10 173 individuals were registered with AD in the DNPR, while 234 683 individuals served as control group. Mild/moderate AD was associated with a decreased chance of completing basic compulsory education [hazard ratios (HR): 0.92, 95% CI: 0.90-0.95] and further academic education (HR: 0.96, 95% CI: 0.93-0.98). Severe AD was associated with a decreased chance of completing further academic education (HR: 0.86, 95% CI: 0.80-0.92), further vocational education (HR: 0.90, 95% CI: 0.84-0.97) and higher education: master's level (HR: 0.66, 95% CI: 0.53-0.81). CONCLUSION: Atopic dermatitis in childhood/adolescence is associated with a decreased chance of completing an education.

Activity studies of sesquiterpene oxides and sulfides from the plant Hyptis suaveolens (Lamiaceae) and its repellency on Ixodes ricinus (Acari: Ixodidae).

Hyptis suaveolens (Lamiaceae), a plant traditionally used as a mosquito repellent, has been investigated for repellent properties against nymphs of the tick Ixodes ricinus. Essential oils and volatile compounds of fresh and dried leaves, from plants originating from Laos and Guinea-Bissau, were identified by GC-MS and tested in a tick repellency bioassay. All the essential oils were strongly repellent against the ticks, even though the main volatile constituents differed in their proportions of potentially tick repellent chemicals. (+)/(-)-sabinene were present in high amounts in all preparations, and dominated the emission from dry and fresh leaves together with 1,8-cineol and α-phellandrene. 1,8-Cineol and sabinene were major compounds in the essential oils from H. suaveolens from Laos. Main compounds in H. suaveolens from Guinea-Bissau were (-)-sabinene, limonene and terpinolene. Among the sesquiterpene hydrocarbons identified, α-humulene exhibited strong tick repellency (96.8 %). Structure activity studies of oxidation or sulfidation products of germacrene D, α-humulene and ß-caryophyllene, showed increased tick repellent activity: of mint sulfide (59.4 %), humulene-6,7-oxide (94.5 %) and caryophyllene-6,7-oxide (96.9 %). The substitution of oxygen with sulfur slightly lowered the repellency. The effects of the constituents in the oils can then be regarded as a trade off between the subsequently lower volatility of the sesquiterpene derivatives compared to the monoterpenes and may thus increase their potential usefulness as tick repellents.

Tick repellent properties of three Libyan plants.

Specimens of Salvadora persica Wallich (Salvadoraceae), Pistacia atlantica Desfontaines (Anacardiaceae), and Juniperus phoenicea L. (Cupressaceae) were collected at The Green Mountain in northeastern Libya. The tick-repellent effects of the essential oils from the plants were evaluated using host-seeking nymphs of Ixodes ricinus L. (Acari: Ixodidae) in the laboratory. Significant tick repellent effects were observed for the oils of all three species, but the duration of action was short. The oils were obtained by steam distillation. Volatile compounds of the essential oils were collected by solid phase microextraction and the constituents were identified by gas chromatographymass spectrometry.

High levels of hybridization between molecular forms of Anopheles gambiae from Guinea Bissau.

In the malaria vector Anopheles gambiae Giles sensu stricto, two molecular forms denoted M and S are considered units of incipient speciation within this species. Very low hybrid frequencies and significant genetic differentiation have been found in sympatric M- and S-form populations. We studied the molecular form composition and the degree of genetic differentiation at 15 microsatellites in two samples of An. gambiae collected in two consecutive years from Bissau, Guinea Bissau. High frequencies of M/S hybrids (19-24%) were found in this area. Coincidently, very low levels of genetic differentiation were detected between forms when analysis involved microsatellites mapped at chromosome-3 (mean Fst, 0.000-0.002). The single exception was the X-linked AGXH678, for which high differentiation was measured (Fst, 0.158-0.301). This locus maps near the centromere of chromosome X, a low recombination region in which selection is likely to promote divergence between M and S forms. These results strongly suggest that the degree of isolation between M and S forms, considered the units of incipient speciation within An. gambiae, is not homogenous throughout the species distribution range.

Repellency of MyggA Natural spray (para-menthane-3,8-diol) and RB86 (neem oil) against the tick Ixodes ricinus (Acari: Ixodidae) in the field in east-central Sweden.

In the field in south-central Sweden, we tested by randomised, standardised methodology the potential anti-tick repellent activity of two concentrations of MyggA Natural spray (containing PMD) (4.2 and 3.2 g/m2) and one of RB86 (with 70% neem oil containing azadirachtin) (3 g/m2) to host seeking nymphs of Ixodes ricinus. Each substance was applied separately to 1 m2 cotton flannel cloths. Nymphal ticks on the cloths, pulled over the vegetation, were recorded at 10-m stops. Nymphal numbers recorded differed significantly between treated cloths [4.2 or 3.2 g MyggA Natural spray/m2 and 3 g RB86/m2] and the untreated control (df = 3, chi2 = 112.74, P < 0.0001). Nymphal numbers also differed significantly among collectors (df = 3, chi2 = 15.80, P < 0.001). Repellency of treated cloths, i.e., 4.2 or 3.2 g MyggA Natural spray/m2 and 3 g RB 86/m2 declined from day 0 (i.e. the day of impregnation) to day 3 after impregnation from 77 to 24%, 58 to 16% and 47 to 0.5%, respectively. This study suggests that all three treatments have significant repellent activities against I. ricinus nymphs.

High HIV seroprevalence and increased HIV-associated mortality among hospitalized patients with deep bacterial infections in Dar es Salaam, Tanzania.

OBJECTIVES: To correlate deep bacterial infections with HIV infection and evaluate the influence of HIV on clinical picture and outcome in patients with meningitis, pneumonia or pyomyositis. DESIGN: Case-control comparison of HIV seroprevalence between patients and an age- and sex-matched control group in a prospective cross-sectional study of hospitalized patients. PARTICIPANTS: One hundred and sixty-five patients admitted to hospital with either purulent meningitis, pneumonia or pyomyositis and 165 age- and sex-matched controls from orthopaedic/trauma wards. SETTING: University Hospital, Dar es Salaam, Tanzania. OUTCOME MEASURES: Differences in HIV seroprevalence and mortality. RESULTS: Of 78 patients with purulent meningitis, 19 (24%) were HIV-seropositive, compared with 13 (17%) in the control group (P = 0.345). Of 36 patients with meningitis seen before a meningococcal epidemic affected Dar es Salaam, there was a statistically significant association with HIV infection (P = 0.013). Ten out of 19 (53%) HIV-seropositives died, compared with nine out of 59 (15%) seronegatives (P = 0.028). Of patients with pneumococcal meningitis, five out of six (83%) seropositives died, compared with two out of 12 (17%) seronegatives (P = 0.013). Fifteen out of 45 (33%) patients with pneumonia were HIV-seropositive, compared with four (9%) in the control group (P = 0.001). There was no difference in mortality between seropositive and seronegative patients with pneumonia. HIV seroprevalence was 62% among 42 patients with pyomyositis and 12% among 42 controls (P less than 0.0001). Eighteen out of 25 (72%) seropositive patients with pyomyositis fulfilled the World Health Organization (WHO) clinical case definition for AIDS. Response to recommended antibiotic treatment was satisfactory among patients with pneumonia and pyomyositis. CONCLUSIONS: These results show a strong association between pyomyositis, pneumonia and HIV infection. They also indicate an increased mortality associated with HIV infection in patients with pyogenic meningitis, especially pneumococcal meningitis. Pyomyositis should be considered an indicator of stage III HIV disease in the proposed WHO clinical staging system.

PIP: This study sought to correlate deep bacterial infection with HIV infection and evaluate the influence of HIV on clinical practice and outcome in patients with meningitis, pneumonia, or pyomyositis. At University Hospital, Dar es Salaam, Tanzania, 165 patients were admitted to the hospital with purulent meningitis, pneumonia, or pyomyositis and were evaluated in a prospective, cross-sectional study along with 165 age- and sex-matched controls from orthopedic/trauma wards to determine HIV seroprevalence. Of the 78 patients with purulent meningitis, 19 (24%) were HIV-seropositive, as compared with 13 (17%) in the control group (p=0.345). Of 36 patients with meningitis seen before a meningococcal epidemic affected Dar es Salaam, there was a statistically significant association with HIV infection (p=0.013). 10 of 19 (53%) HIV-seropositives died, compared with 9 of 59 (15%) seronegatives (p=0.028). Of patients with pneumococcal meningitis, 5 of 6 (83%) seropositives died, compared with 2 of 12 (17%) seronegatives (p=0.013). 15 of 45 (33%) patients with pneumonia were HIV-seropositive compared with 4 (9%) in the control group (p=0.001). There was no difference in mortality between seropositive and seronegative patients with pneumonia. HIV seroprevalence was 62% among 42 patients with pyomyositis and 12% among 42 controls (p0.0001). 18 of 25 (72%) seropositive patients with pyomyositis fulfilled the WHO clinical case definition of AIDS. Response to recommended antibiotic treatment was satisfactory among patients with pneumonia and pyomyositis. These results show a strong association between pyomyositis, pneumonia, and HIV infection. They also indicate an increased mortality associated with HIV infection in those patients with pyogenic meningitis, especially pneumococcal meningitis. Pyomyositis should be considered an indicator of stage III HIV disease in the proposed WHO clinical staging system.

Alternative confirmatory strategies in HIV-1 antibody testing.

Alternatives to confirmation of human immunodeficiency virus (HIV)-1 seropositivity by Western blot analysis were evaluated retrospectively using combinations of six anti-HIV-1 screening assays, including four enzyme-linked immunosorbent assays (ELISA) and two simple tests (a rapid dot immunoassay and an agglutination assay), according to an algorithm where sera are first screened by one assay and those repeatedly reactive on this assay are tested repeatedly by a second assay. Two panels of sera collected in Dar es Salaam, Tanzania, were used. Panel 1 was composed of 1,465 consecutive blood donor sera of which 99 (6.8%) were confirmed HIV-1 antibody positive, and panel 2 was composed of sera from 396 consecutively admitted patients at two medical wards of which 116 (29.3%) were confirmed HIV-1 antibody positive. Sera reactive on any of the six screening assays were also tested by a confirmatory Western blot assay. The sensitivity of the assays at the initial valid testing were as follows: Abbott 99.5%, Behring 99.5%, Organon 97.7%, Wellcozyme 100%, HIV CHEK-1 95.8%, and Serodia 95.8%. After repeat testing of sera that initially gave false-negative results all assays showed 100% sensitivity except HIV CHEK-1 (98.6%). The specificities after repeat testing were between 99.6 and 99.9% for all assays except for the Behring ELISA (98.1%). Several combinations of screening assays were found to give the same diagnostic accuracy as the screening assay followed by Western blot analysis. We conclude that an alternative confirmatory strategy can be fully satisfactory for some testing purposes.

An amplification technology for improving sensitivity when measuring components in biological samples.

A new technology for improving the sensitivity in measuring components in biological samples is described. The method is based on the use of spherical microbeads (detection beads) which contain a large amount of immobilized enzyme and a reagent with biospecific affinity for the component to be detected. These microbeads have been used in a 'sandwich reaction' for visualization of P-fimbriated Escherichia coli which has a known receptor structure (Gal(alpha 1-4)Gal(beta)). In the initial step the bacteria were enriched on a solid support (e.g., a plastic film or beads (greater than 150 microns)) to which the receptor structure had been covalently bound. In the next step detection beads coupled with enzyme and receptor structure were added and finally a chromogenic substrate for the enzyme was used for visualization. A sensitivity of 10(5) bacteria/ml was reached. The detection beads are of general utility and might be useful for the detection of lectins on other pathogens.

Performance of prothrombin-proconvertin time as a monitoring test of oral anticoagulation therapy.

Outcome and anticoagulation intensity was evaluated during 121 patient years of oral anticoagulant therapy monitored with the prothrombin-proconvertin clotting time (PP, also known as P&P). The PP-based international normalized ratio (INR; PP-INR) correlated well with the INR calculated from the prothrombin clotting time (PT; r = 0.92), and results were almost identical over a wide range after linear conversion (1/INR). When the PP-INR was 4.5 or less, the risk of major bleeding was 1 for every 118 treatment years, but it was 1 for every 73 days when the INR was 6 or more. The 1/PP-INR correlated better with factor II coagulant activity (r = 0.85) than did the 1/PT-INR (r = 0.78). The 1/PP-INR also correlated better with the native prothrombin antigen (r = 0.76) than did the 1/PT-INR (r = 0.68). The PP and PT results correlated better with factor II coagulant activity than with native prothrombin antigen. Thus, the PP clotting time results can be accurately converted to INR. The results also suggest that the PP may have advantages over the PT as an indicator of anticoagulation intensity during oral anticoagulation.

Traditional use of mosquito-repellent plants in western Kenya and their evaluation in semi-field experimental huts against Anopheles gambiae: ethnobotanical studies and application by thermal expulsion and direct burning.

Ethnobotanical survey in 2 communities in western Kenya revealed that the most commonly known repellent plants were Ocimum americanum L. (64.1%), Lantana camara L. (17.9%), Tagetes minuta L. (11.3%) and Azadirachta indica A. Juss (8.7%) on Rusinga Island, and Hyptis suaveolens Poit. (49.2%), L. camara (30.9%) and O. basilicum L. (30.4%) in Rambira. Direct burning of plants is the most common method of application for O. americanum (68.8%), L. camara (100%) and O. basilicum (58.8%). Placing branches or whole plants inside houses is most common for H. suaveolens (33.3 and 57.8% for the respective locations), A. indica (66.7 and 100%), and T. minuta (54.8 and 56.0%). The repellency of plants suggested by the ethnobotanical survey and other empirical information was evaluated against the malaria vector Anopheles gambiae s.s. Giles in experimental huts within a screenwalled greenhouse. Thermal expulsion and direct burning were tested as alternative application methods for the selected plants O. americanum, O. kilimandscharicum Guerke, O. suave Willd., L. camara, A. indica, H. suaveolens, Lippia uckambensis Spreng and Corymbia citriodora Hook. When thermally expelled, only H. suaveolens failed to repel mosquitoes, whereas the leaves of C. citriodora (74.5%, P < 0.0001), leaves and seeds of O. suave (53.1%, P < 0.0001) and O. kilimandscharicum (52.0%, P < 0.0001) were the most effective. Leaves of C. citriodora also exhibited the highest repellency (51.3%, P < 0.0001) by direct burning, followed by leaves of L. uckambensis (33.4%, P = 0.0004) and leaves and seeds of O. suave (28.0%, P = 0.0255). The combination of O. kilimandscharicum with L. uckambensis repelled 54.8% of mosquitoes (P < 0.0001) by thermal expulsion. No combination of plants increased repellency by either method. The semi-field system described appears a promising alternative to full-field trials for screening large numbers of candidate repellents without risk of malaria exposure.

Plant products used as mosquito repellents in Guinea Bissau, West Africa.

By standardized interviews of people in 23 rural villages, in the Oio region of Guinea Bissau, we collected data on which plant species and plant derived products or methods people use to reduce mosquito biting activity. The following plants were used to reduce numbers of mosquitoes indoors at night: fresh or smouldering Hyptis suaveolens Poit. (Lamiaceae), smoke of the bark of Daniellia oliveri Rolfe (Caesalpiniaceae), smoke of the infructescence of Elaeis guineensis Jacq. (Arecaceae), smoke of the seed capsules of Parkia biglobosa (Jacq.) Benth. (Mimosaceae), smoke of the leaves of Azadirachta indica A.Juss. (Meliaceae) and Eucalyptus sp. (Myrtaceae), fresh Ocimum canum Sims (Lamiaceae), and fresh Senna occidentalis (L.) Link (Caesalpiniaceae). In two field experiments we estimated the 'repellent activity' of certain of these plants and compared their efficacies with those of two commercially available mosquito repellents, i.e. 'positive' controls. In the first experiment we tested: smouldering H. suaveolens (85.4% repellency); fresh H. suaveolens (73.2%); burning of the bark of D. oliveri (74.7%); and smoke of the leaves of Eucalyptus (72.2%). In the second experiment we tested: smouldering H. suaveolens (83.6% repellency); fresh H. suaveolens (66.5%); burning of the bark of D. oliveri (77.9%); smoke of the leaves of A. indica (76.0%); smoke of the infructescence of E. guineensis (69.0%); fresh O. canum (63.6%); and fresh S. occidentalis; (29.4%). All the products tested, except S. occidentalis were significantly more effective than the negative control.

The palpal ratio method compared with PCR to distinguish between Anopheles gambiae s.s. and A. melas from Guinea Bissau, West Africa.

We compared the palpal ratio method with the polymerase chain reaction (PCR) to distinguish between Anopheles gambiae s.s. and A. melas. At the end of the rainy season of 1995, female mosquitoes were collected indoors in the Antula area of Bissau, Guinea Bissau. A subsample of 354 mosquitoes were identified first with PCR and then with the palpal ratio method (study A). Subsequently, another 195 mosquitoes were identified first with the palpal ratio method and then with PCR (study B). The highest percentage (100%, n = 16) of correctly identified A. melas was obtained at the palpal ratio cut-off point of 0.83. However, at this point 4.0% (14/347) and 11.3% (21/186) of the A. gambiae were erroneously identified as A. melas in study A and B, respectively. This suggests that the palpal ratio method is not sufficiently reliable to distinguish between A. gambiae and A. melas from the Bissau area.

Comparison of plant products and pyrethroid-treated bed nets for protection against mosquitoes (Diptera: Culicidae) in Guinea Bissau, West Africa.

In Guinea Bissau, West Africa, the shrub Hyptis suaveolens Poit. (Lamiaceae) and smoke of the bark of the tree Daniellia oliveri Rolfe (Caesalpiniaceae) traditionally are used to reduce numbers of mosquitoes indoors at night. We recorded the numbers of mosquitoes in the bedrooms of 30 households in a rural village, Mandinka-Rá in central Guinea Bissau. Each household was provided with bed nets and allocated randomly to 1 of 6 treatments as follows: (1) lambda-cyhalothrin-treated bed nets (10 mg/m2), (2) permethrin-treated bed nets (500 mg/m2), (3) burning of H. suaveolens, (4) burning of the bark of D. oliveri, (5) fresh H. suaveolens, and (6) control group using untreated bed nets and no plant products. In treatment groups 1-4, the mean number of mosquitoes was significantly less than the mean of the control. These results indicated that the use of burning H. suaveolens or D. oliveri indoors at night repelled endophagic mosquitoes and may contribute significantly to reducing the prevalence of diseases caused by pathogens transmitted by house-frequenting, nocturnally blood-feeding arthropods.

Transmission of mixed malaria species and strains by mosquitoes, as detected by PCR, in a study area in Guinea-Bissau.

Parasites present in blood samples of asymptomatic carriers and in the midgut of mosquitoes collected within a few days from the same households, have been analysed by PCR. A high prevalence (32%) of infected mosquitoes was observed and, in half of these, two parasite species were found simultaneously. The distribution of parasite species in the mosquito correlated with that found in the infected persons. Genotype patterns of Plasmodium falciparum populations were however found to be different in the two sets of samples. These results and the potential of PCR are discussed with reference to investigations of the dynamics of malaria transmission.

Evaluation of extracts and oils of tick-repellent plants from Sweden.

Abstract. Leaves of Myrica gale Linnaeus (Myricaceae), Rhododendron tomentosum (Stokes) H. Harmaja (formerly Ledum palustre Linnaeus: Ericaceae) and Artemisia absinthium Linnaeus (Asteraceae) were extracted with organic solvents of different polarities and the essential oils of leaves were obtained by steam distillation. The extracts or oils were tested in the laboratory for repellency against host-seeking nymphs of Ixodes ricinus Linnaeus (Acari: Ixodidae). Rhododendron tomentosum oil, 10%, diluted in acetone, exhibited 95% repellency; R. tomentosum and A. absinthium extracts in ethyl acetate, > 70% repellency; A. absinthium extract in hexane, approximately 62% repellency; and M. gale oil, 10%, approximately 50% repellency on I. ricinus nymphs. Compounds in the leaf extracts or in the oils were collected by solid phase microextraction (SPME) and identified by gas chromatography-mass spectrometry (GC-MS) and/or MS. Characteristic volatiles detected from oil or extract of M. gale were the monoterpenes 1,8-cineole, alpha-terpineol, 4-terpineol and thujenol; and of R. tomentosum myrcene and palustrol. Characteristic volatiles from leaf extracts of A. absinthium were sabinene, oxygenated monoterpenes, e.g. thujenol and linalool, and geranyl acetate. Each plant species synthesized numerous volatiles known to exhibit acaricidal, insecticidal, 'pesticidal' and/or arthropod repellent properties. These plants may be useful sources of chemicals for the control of arthropods of medical, veterinary or agricultural importance.

Additive effects of moderate dietary salt reduction and captopril in hypertension.

In a randomized, cross-over study 27 patients had diastolic blood pressure of greater than or equal to 96 mmHg during four visits without treatment. Following captopril 25 mg b.i.d. nine patients' blood pressure was less than or equal to 90 mmHg. The remaining 18 were randomized into two treatment modalities, captopril and moderate dietary salt reduction, and captopril and hydrochlorothiazide 25 mg daily. Following a wash-out period the groups crossed over to the alternative treatment. At the end of the control period the average blood pressure was 151/100 +/- 12/6 mmHg recumbent and 140/91 +/- 11/7 standing, following captopril 144/94 +/- 13/5 and 132/92 +/- 12/6, respectively, with low salt diet added to captopril 140/91 +/- 12/6 and 128/89 +/- 11/6 and with hydrochlorothiazide and captopril 133/86 +/- 12/7 and 120/84 +/- 11/7 mmHg supine and erect, respectively. It is concluded that moderate dietary salt reduction, which is easily advised, will significantly potentiate the blood pressure fall following captopril treatment in moderate arterial hypertension.

Left bundle branch block: prevalence, incidence, follow-up and outcome.

In a randomly selected population screening study of 8450 men and 9039 women 33 to 71 years of age conducted in Iceland in 1967-1977, 27 men and 17 women were found to have left bundle branch bock (LBBB). The prevalence of LBBB at that time was 0.43% for men and 0.28% for women. The incidence of LBBB was 3.2 per 10,000 per year for men and 3.7 per 10,000 per year for women. All except one of 37 alive patients with LBBB were examined in 1984 including chest X-ray, echocardiography and exercise testing (Bruce protocol). Eight men had had myocardial infarction (P less than 0.05), 12 had angina pectoris, 15 had hypertension, 7 had cardiomyopathy, 13 had primary conduction disease, and 3 had pacemakers. Five men and two women had died in comparison with 18 men and 1 woman in an age-matched control group of 176 people (P : ns). Three of 5 decreased LBBB men had cardiomyopathy at autopsy. Three men died suddenly. The two women died of noncardiac causes. Only one patient in the control group had cardiomyopathy (P less than 0.01). There was no significant difference in other cardiac diagnoses between the groups. Eleven LBBB women out of thirteen had a normal exercise duration (greater than or equal to 6 min) and 11/17 men exercised normally (less than or equal to 7 min). In comparison with the control group, the LBBB patients had an increased LV diameter 2.85 +/- 0.38 vs 2.58 +/- 0.38 cm m-2 body surface area (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[A prospective study of oral anticoagulation therapy monitored with the P&P-test.].

OBJECTIVE: To analyze the outcome of patients on oral anticoagulation therapy who are monitored with the prothrombin proconvertin time (P&P-test, PP). MATERIAL AND METHODS: The prothrombin-proconvertin time was used to adjust anticoagulant intensity in a prospective study of 326 patients treated with oral anticoagulants for a study period of 121 patient years. The goal intensity INR was 2.0-3.0 for all patients. The main indications were: artificial heart valves 26%, venousthromboembolism 25%, atrial fibrillation 23%, atherosclerotic disease 14% and systemic arterial embolism of uncertain etiology 7%. RESULTS: INR calculated directly from the PP correlated well with INR calculated from the PT. The mean time adjusted anticoagulant intensity was 2.3 and did not differ significantly according to indication. Six major bleedings, including one fatal, occurred in five patients during the study period. The INR was 1.8 in one patient who bled from a duodenal ulcer, but 6.8,7.9,8.6,11.6 (died) and 15.5 at five other events. The INR was <4.5 during 97% of the treatment time of the whole group and 1% of treat notment time were at an INR>6.0. The bleeders had a different pattern with 18% of the treatment time at INR>6.0. The risk of bleeding was one for every 73 days at that intensity or an almost 600 fold risk increase compared to an INR<4.5. One patient anticoagulated for systemic embolism had cerebral infarction with an event related INR of 2.0. Two patients with atrial fibrillation died from acute myocardial infarction but event related INR's were not available. One patient anticoagulated for venous thromboembolism died suddenly but was not autopsied. No embolic events occurred in patients with artificial heart valves in spite of the low intensity anticoagulation. CONCLUSION: Despite a relatively low intensity in all patient groups in this study thromboembolic events were rare. The risk of bleeding increased markedly at INR>6.0. The mortality rate of the ariticoagulated population was comparable to the expected age adjusted Icelandic mortality rate.