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Objective: To determine trends in asthma mortality by age group in England and Wales during 1983-95. Design: Observational study. Setting: England and Wales. Subjects: All deaths classified as having an underlying cause of asthma registered from 1 January 1983 to 31 December 1995. Main outcome measure: Time trends for age specific asthma deaths. Results: Deaths in the age group 5-14 years showed an irregular downward trend during 1983-95; deaths in the age groups 15-44, 45-64, and 65-74 years peaked before 1989 and then showed a downward trend; and deaths in the age group 75-84 years peaked between 1988 and 1993 and subsequently dropped. Trends were: age group 5-14 years, 6% (95% confidence interval 3% to 9%); 15-44 years, 6% (5% to 7%); 45-64 years, 5% (4% to 6%); 65-74 years, 2% (1% to 3%). Deaths in the 75-84 and 85 and over categories plateaued. Conclusions: There are downward trends in asthma mortality in Britain, which may be due to increased use of prophylactic treatment.

Human immunodeficiency virus (HIV) type 1 sequences obtained from HIV-infected persons in different risk groups in Edinburgh were studied to determine the number and origin of virus variants and patterns of virus transmission. Phylogenetic analysis revealed that 12 of 14 hemophiliac patients who had been exposed to a single common batch of factor VIII had closely related gag gene sequences. Sequences from intravenous drug users and patients infected through heterosexual contact formed another distinct group, and 2 other hemophiliacs formed a third group. However, epidemiologic relationships inferred from analysis of the V3 region of the env gene were less conclusive, especially when the V3 loop was taken in isolation. This appears to be due to the length of time since infection and the action of selection, which has favored the independent appearance of similar V3 loop variants.

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Substantial differences have been described in the response of individual patients to zidovudine (ZDV) therapy, both in the clinical impact and in virus load. Genotypic changes associated with the appearance of drug resistance may also be different or occur at different rates. We have obtained the nucleotide sequence of the RT domain of individual HIV-1 genomes extracted from 10 plasma and peripheral blood mononuclear cell (PBMC) samples donated by two haemophiliac patients before, during, and after long-term ZDV therapy. Although the plasma virus load was similar throughout, the order and timing of appearance of resistance-associated substitutions differed in the two patients. In patient p74, K70R appeared after 4 months, T215Y at 5.5 months, and M41L at 13 months. In p87, K70R also appeared at 4 months, but T215Y and K219Q were not observed until 18 months and M41L not at all. Much greater sequence change overall occurred in p74. The evolution of the viral population in that patient was dominated by the unique appearance of T215Y and subsequently M41L, with all sequences from the last time point being descended by a single path from the pretreatment samples. However, in p87, several different lineages of RT sequences were found to persist throughout treatment. We propose that these differences in outcome may be determined by differences in genetic background at sites other than the five generally considered to be associated with ZDV sensitivity.