Stanley D. Musgrave

Leukotriene Antagonists as First-Line or Add-on Asthma-Controller Therapy

BACKGROUND Most randomized trials of treatment for asthma study highly selected patients under idealized conditions. METHODS We conducted two parallel, multicenter, pragmatic trials to evaluate the real-world effectiveness of a leukotriene-receptor antagonist (LTRA) as compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta(2)-agonist (LABA) as add-on therapy in patients already receiving inhaled glucocorticoid therapy. Eligible primary care patients 12 to 80 years of age had impaired asthma-related quality of life (Mini Asthma Quality of Life Questionnaire [MiniAQLQ] score ≤6) or inadequate asthma control (Asthma Control Questionnaire [ACQ] score ≥1). We randomly assigned patients to 2 years of open-label therapy, under the care of their usual physician, with LTRA (148 patients) or an inhaled glucocorticoid (158 patients) in the first-line controller therapy trial and LTRA (170 patients) or LABA (182 patients) added to an inhaled glucocorticoid in the add-on therapy trial. RESULTS Mean MiniAQLQ scores increased by 0.8 to 1.0 point over a period of 2 years in both trials. At 2 months, differences in the MiniAQLQ scores between the two treatment groups met our definition of equivalence (95% confidence interval [CI] for an adjusted mean difference, -0.3 to 0.3). At 2 years, mean MiniAQLQ scores approached equivalence, with an adjusted mean difference between treatment groups of -0.11 (95% CI, -0.35 to 0.13) in the first-line controller therapy trial and of -0.11 (95% CI, -0.32 to 0.11) in the add-on therapy trial. Exacerbation rates and ACQ scores did not differ significantly between the two groups. CONCLUSIONS Study results at 2 months suggest that LTRA was equivalent to an inhaled glucocorticoid as first-line controller therapy and to LABA as add-on therapy for diverse primary care patients. Equivalence was not proved at 2 years. The interpretation of results of pragmatic research may be limited by the crossover between treatment groups and lack of a placebo group. (Funded by the National Coordinating Centre for Health Technology Assessment U.K. and others; Controlled Clinical Trials number, ISRCTN99132811.).

HIV risk factors in three geographic strata of rural Rakai District, Uganda

ObjectivesTo examine risk factors for HIV-1 infection in three geographic strata (main road trading centers that service local and international traffic, small trading villages on secondary dirt roads that serve as foci for local communications, and agricultural villages off main and secondary roads) in Rakai District, Uganda. Design and methodsSerological, sociodemographic, knowledge/hehaviors and health survey conducted in 21 randomly selected community clusters; complete data were collected for 1292 consenting adults. ResultsFifteen per cent of the men and 24% of the women were HIV-1-positive. On univariate analysis, several sociodemographic and behavioral factors were significantly associated with risk of HIV infection, including age, place of residence, travel, occupation, marital status, number of sex partners, sex for money or gifts, history of sexually transmitted disease (STD), and history of injections. On multivariate analysis, age, residence and number of sex partners remained significantly associated with HIV infection in both sexes; a history of STD and not having been circumcised were significant in men. There was a significant interaction between place of residence and reported number of sex partners: for any given level of sexual activity, the risk of HIV infection was markedly increased if the background community prevalence was high. ConclusionSexual transmission appears to be the primary behavioral risk factor for infection, but the risks associated with this factor vary substantially between the three geographic strata. These data can be used to design targeted interventions.

Demographic impact of HIV infection in rural Rakai district, Uganda: Results of a population-based cohort study

ObjectivesTo examine HIV-1-related mortality and demographic impact in a high HIV prevalence rural district of Uganda. DesignOne-year follow-up (1990–1991) in a population-based rural cohort. Setting and participantsAnnual enumeration of all consenting residents of 1945 households in 31 randomly selected community clusters in Rakai District. Subjects provided yearly HIV serological samples, behavioral and health information. Main outcome measureMortality in HIV-infected and uninfected persons. ResultsMortality among HIV-seropositive adults aged ≥15 years of 118.4 per 1000 person-years (PY) was substantially higher than in HIV-seronegative adults [12.4 per 1000 PY; relative risk (RR), 9.5; 95% confidence interval (CD, 6.0–14.9]. Infant mortality among offspring of HIV-infected mothers was almost double that for uninfected women (210 compared with 111 per 1000 live births; RR, 1.9; 95% Cl, 1.0–3.5). Adult HIV-related mortality was associated with HIV prevalence and, in this cohort, with higher education, non-agricultural occupation and residence in roadside trading centers. We estimate that adult HIV prevalence in the district is 13% and adult HIV attributable mortality 52%. For all ages combined, district HIV attributable mortality is 28%. ConclusionHIV is the leading cause of adult death in Rakai. Its effects on mortality are particularly marked in the most economically active sectors. However, the overall crude birth rate in the district (45.7 per 1000 population) remains higher than the crude death rate (28.1 per 1000 population), resulting in continued rapid population growth.

Dynamics of spread of HIV-I infection in a rural district of Uganda.

OBJECTIVE--To define the geographical distribution of HIV infection and the community characteristics associated with HIV prevalence in a rural population of Uganda. DESIGN--Seroprevalence survey and interviews of the population aged 13 years and older in 21 randomly selected clusters. SETTING--Rural population of Rakai district, south west Uganda. SUBJECTS--1292 adults, of whom 594 men and 698 women gave a blood sample and answered the questionnaire. MAIN OUTCOME MEASURES--HIV status determined by ELISA and western blotting in relation to community characteristics. RESULTS--The weighted seroprevalence of HIV for the district was 12.6% with prevalence by cluster varying from 1.2% to 52.8%. Seroprevalence was highest in main road trading centres (men 26%, women 47%), intermediate in rural trading villages on secondary roads (men 22%, women 29%), and lowest in rural agricultural villages (men 8%, women 9%). For both men and women, multiple regression showed a strong negative association between cluster seroprevalence and the proportion of the population employed in agriculture (beta = -0.677 for men, -0.807 for women). Among women, cluster seroprevalence increased with a higher proportion of the population reporting multiple sex partners (beta = 0.814), external travel (beta = 0.579), and injections (beta = 0.483). CONCLUSIONS--Community characteristics, particularly the proportion of the population in agriculture, are associated with HIV prevalence and can be used for targeting interventions. The seroprevalences of HIV suggest spread of infection from main road trading centres, through intermediate trading villages, to rural agricultural villages.

Fisherfolk are among groups most at risk of HIV: cross-country analysis of prevalence and numbers infected.

HIV prevalence in some fishing communities in low and middle-income countries is known to be high relative to national average seroprevalence rates. Most of the studies supporting this claim refer to the men involved in fish-catching operations (fishermen). However they acknowledge that the men and women who work in associated occupations such as fish trading and processing are also vulnerable in part because they are often within the fishermen’s sexual networks. This vulnerability stems from the nature and dynamics of the fish trade and fishing lifestyle in which a number of known or hypothesized ‘risk factors’ converge. (excerpt)

Incidence of HIV-1 infection in a rural region of Uganda

Abstract Objective : To determine the incidence of infection with HIV-1 and the risk factors associated with seroconversion in three geographical strata of a rural Ugandan district. Design : Serological, sociodemographic, and behavioural surveys of everyone aged 13 or more in 21 randomly selected communities at baseline and 20 one year later. Setting : Rural population of Rakai district, south-western Uganda, residing in main road trading centres, secondary trading villages, and agricultural villages. Subjects : In 1989, 1292 adults provided a blood sample and interview data; one year later, 778 survivors (77%) who had been seronegative at baseline provided follow up data. Main outcome measures : Incidence of HIV infection in relation to individual characteristics and risk factors, including place of residence. Results : Incidence of HIV infection in all adults was 2.1/100 person years of observation (SE 0.5 (95% confidence interval 1.1 to 3.1)); in people aged 15-39 the incidence was 3.2/100 person years. Incidence was highest in men and women aged 20-24 (9.2/100 person years (3.9) and 6.8/100 person years (2.9) respectively). Risk factors significantly associated with seroconversion were age 24 and under and two or more sexual partners. Between the surveys the proportion of all respondents reporting high risk behaviour (two or more partners) significantly increased from 8.9% to 12.3%. Conclusions : Despite preventive programmes and substantial knowledge about AIDS the incidence of HIV infection remains high in this rural population. Prevention aimed at vulnerable rural communities is urgently needed to contain the HIV epidemic.

AIDS and HIV infection in Uganda - Are more women infected than men?

In countries in sub-Saharan Africa, HIV is transmitted primarily heterosexually. HIV infection and AIDS in women not only affects womens health but also has implications for the other members of society. Maternal infection is the source of most childhood HIV infection in Africa and maternal health is a strong predictor of child survival. In Uganda, a review of passive AIDS surveillance has shown almost equal numbers of clinical cases reported in men and women. However, in three population-based HIV serosurveys, women were consistently found to have a higher infection rate (approximately 1.4 times) than men. In addition, both AIDS case surveillance and seroprevalence studies demonstrate an earlier age of presentation and mean age of infection in women. The higher rate of HIV infection in women suggests either differential rates of transmission between women and men, higher rates of female sexual exposure to infected men, or longer survival among HIV-infected women compared with men. Although further studies are required to illuminate both the biology and the epidemiology of heterosexual HIV transmission in Africa, these findings of earlier and higher infection rates in women have important implications for womens health and child survival in Uganda and indicate the need for specially targeted interventions to reduce transmission in this group.

Focus group interviews about AIDS in Rakai district of Uganda

Focus group interviews about AIDS were held in Rakai district, Uganda during early 1990 with groups from various sections of the community. It was found that the knowledge of AIDS symptoms and its transmission were widespread. Attitudes regarding many aspects of sexual behavior, AIDS patients, condoms, injections, hospital treatment, sexually transmitted diseases and an AIDS cure were investigated. We found that most people no longer fear casual contact with AIDS patients but they blame spouses of people with AIDS for spreading the infection. Condoms are generally not trusted. Many people feel that condoms cannot prevent transmission of the AIDS virus and some fear that they may get torn and cause complications in women. Most people now do not like injections for treatment and when necessary, prefer disposable needles and syringes. Hospital treatment for AIDS patients is not trusted very much, and many people believe that AIDS patients are intentionally killed off by doctors. Sexual behavior was extensively discussed and it was found that there is generally a reduced level of multiple sexual partners. The reduction is more marked in rural areas but the urban areas are still having higher levels of multiple sexual partners.

Congenital Oral Tumor Associated with Neurofibromatosis Detected by Prenatal Ultrasound

utes. No respiratory distress was noted. One lobe of the tumor broke off as the infant was delivered, with an estimated blood loss of 5 to 10 cc. On physical examination the patient was noted to have an irregular hypopigmented patch on the right flank and a 0.5 cm X 0.5 cm cafe au lait spot on the midabdomen. No subcutaneous masses were noted on physical examination. Multiple tumors (Fig. 1) extruded from the patient’s mouth. The palate was intact. The remainder of the physical examination was unremarkable. The patient was transported to a tertiary care center for futher management. Prior to scheduled surgery on day 2 of life, the patient was noted to be lethargic, irritable, and febrile. Blood, urine, and CSF cultures were obtained, and the patient was given ampicillin and gentamicin. The presumed diagnosis was sepsis. Cultures were negative at 72 hours, and all antibiotics were discon-

A pragmatic single-blind randomised controlled trial and economic evaluation of the use of leukotriene receptor antagonists in primary care at steps 2 and 3 of the national asthma guidelines (ELEVATE study).

This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 15, No. 21. See the HTA programme website for further project information.