Estimation of the sexual transmission of HIV in Kenya and Uganda on the trans-Africa highway: the continuing role for prevention in high risk groups.

OBJECTIVE: To explore the effect of transactional sex on the trans-Africa highway from Mombasa-Kampala in contributing to the HIV epidemic and the impact that an effective prevention intervention could have. METHODS: Variables for input into a simple model of HIV prevention, AVERT, were derived from a study of hot spots of transactional sex on the trans-Africa highway. Diaries were completed by a sample of sex workers at selected sites of transactional sex for a period of 28 consecutive days. Key information elicited included numbers, types and occupations of clients, numbers of liaisons, sexual acts in each liaison, and condom use. 857 diaries were distributed and 578 received and usable in 30 sites. A sexual patterning matrix was completed by 202 truckers at the Malaba border point as part of a health seeking behaviour survey. Two methods were employed to estimate female sex worker (FSW) numbers on the highway. FSW focus group discussions (FGDs) at 15 sites were carried out and included questioning on the number of sex workers at the site. As most transactional sex on the highway is centred on bars and lodgings, a patron census and survey of 1007 bars and lodgings was carried out which included questions on the presence and proportions of FSWs among the clientele. RESULTS: There are an estimated 8000 FSWs on the trans-Africa highway from Mombasa to Kampala. Annual numbers of different sexual partners per FSW were 129, annual numbers of sexual acts per FSW were 634, percentage of sexual acts protected by condom use was 77.7%. Using these input data an estimated 3200-4148 new HIV infections occur on this portion of the trans-Africa highway in 1 year. Having a 90% condom use programme in place could prevent almost two thirds of these infections and cumulative incidence would decline from 1.29% to 0.42%. CONCLUSIONS: In generalised epidemics there has been a debate as to the place of targeted interventions. In the current east African epidemic we show that a targeted intervention could have significant impact in averting HIV infections related to the trans-Africa highway.

A multi-sectorial committee in directing HIV/AIDS-specific interventions in the occupational setting: an example from South Africa.

We present a descriptive analysis of a mechanism to coordinate and implement human immunodeficiency virus (HIV) prevention and care in the occupational setting. The mechanism we describe is a multidisciplinary committee composed of stakeholders in the occupational health environment including unions, management, medical researchers, and medical personnel. The site chosen for the analysis was a South African sugar mill in rural KwaZulu-Natal. The factory is situated in an area of high HIV seroprevalence and has a workforce of 400 employees. The committee was initiated to coordinate a combined prevention-care initiative. The issues that were important in the formation of the committee included confidentiality, trust, and the traditional roles of the stakeholder relationships. When these points were addressed through the focus on a common goal, the committee was able to function in its role as a coordinating body. Central to this success was the inclusion of all stakeholders in the process, including those with traditionally opposing interests and legitimacy conferred by the stakeholders. This committee was functionally effective and demonstrated the benefit of a freestanding committee dedicated to addressing HIV/acquired immune deficiency syndrome (AIDS) issues. We describe the implementation and feasibility of a multisectoral committee in directing HIV/AIDS initiatives in the occupational setting in rural South Africa.

A package of care for HIV in the occupational setting in Africa: results of a pilot intervention.

We describe a package of care including prevention, education, and therapeutics for human immunodeficiency virus (HIV) infection in the occupational setting in sub-Saharan Africa and evaluate the outcomes of this package over 1 year. A prospective cohort study was done between 1999 and 2000 in a sugar mill employing 386 men in Kwa-Zulu Natal in South Africa. A package of care for HIV in the occupational setting was developed and implemented in 1999. This response included prevention, education, and therapeutic components. Outcomes measured included condoms distributed, sexually transmitted infections treated, numbers of HIV-infected individuals entering into the therapeutic pathway developed, and numbers of individuals counselled and tested for HIV. HIV prevalence in this population was 27.15% in January 1999. Between 1999-2000 in this workforce of 386, 58 of 102 (54%) individuals with HIV were identified through voluntary counselling and testing. Of these, 48 (82.8%) voluntarily entered the HIV treatment pathway. Condom distribution in the sugar mill increased 400% and the number of sexually transmitted infections treated at the mill decreased by 88% during this time period. Using AVERT software to model HIV infection over time a decrease in incidence of 91.67% from that expected in this population was calculated. 11 HIV infections were averted in a single year of this program. HIV/acquired immune deficiency syndrome (AIDS) is prevalent in the occupational setting in South Africa. This setting can provide a venue for HIV care and prevention. A package of care for HIV including prevention, education, and therapeutics can be effective in both providing care for HIV-infected individuals and preventing new infections.

Medical profiling: improving standards and risk adjustments using hierarchical models.

The conclusions from a profile analysis to identify performance extremes can be affected substantially by the standards and statistical methods used and by the adequacy of risk adjustment. Medically meaningful standards are proposed to replace common statistical standards. Hierarchical regression methods can handle several levels of random variation, make risk adjustments for the providers' case-mix differences, and address the proposed standards. These methods determine probabilities needed to make meaningful profiles of medical units based on standards set by all appropriate parties.

The direct costs of HIV / AIDS in a South African sugar mill.

PIP: This article assesses the impact of HIV on a retrospective cohort of HIV-infected sugar mill employees and the cost incurred by their employers in the province of KwaZulu-Natal, South Africa. In a single occupational health clinic that provides the primary care needs of a sugar mill workforce with approximately 400 employees (96% males), records of 23 workers who took ill-health retirement due to HIV during 1991-98 were inspected. Direct cost estimation associated with HIV infections were obtained from the occupational health clinic, hospital and insurance sources. In the preliminary study, the cost of HIV treatment increased in the last 2 years of the employee's tenure. Using the human resource data and employee job description, the cost of lost productivity was approximately R100 for each day lost, while the total cost per worker annually for the period of the analysis is R9543.73. These costs could be divided equally into replacement worker costs, productivity losses and absenteeism. Similar findings were also obtained in separate studies conducted in Zimbabwe and Kenya. This article confirms the significant amount of lost economic activity due HIV infection and the increasing burden on the economic industry as the epidemic matures.^ieng

Amiodarone-induced hyperthyroidism and a thyroid nodule.

OBJECTIVE: To report two cases of thyrotoxicosis associated with amiodarone therapy and to discuss how the presence of a thyroid nodule alters management. METHODS: We describe two patients with amiodarone-induced hyperthyroidism, review the mechanisms of disease, and outline a strategy for decision making relative to treatment in the presence of a thyroid nodule. RESULTS: Amiodarone-induced thyrotoxicosis occurs by two mechanisms: a direct toxic effect and iodine loading. This condition may be treated medically or surgically, but when discontinuation of amiodarone therapy is not possible and medical management is ineffective, surgical therapy is often necessary. The optimal presurgical management in the cases described required the use of thyroid scanning to determine whether the disease process was attributable to a hyperfunctioning nodule or generalized. The findings were helpful in planning the extent of surgical excision. CONCLUSION: When surgical treatment is planned for patients with a solitary thyroid nodule and amiodarone-induced hyperthyroidism, preoperative thyroid scanning will direct the surgeon to perform either subtotal thyroidectomy for diffuse disease or lobectomy for a hyperfunctioning nodule.

Improving the statistical approach to health care provider profiling.

This paper reviews and compares existing statistical methods for profiling health care providers. It recommends improvements that are based on the use of better statistical models and the adoption of more realistic, medically based criteria for judging the performance of health care providers. Unlike most profiling methods, the proposed hierarchical models allow the probability of acceptable provider performance to be calculated; thus, they can answer such questions as, "What is the probability that a given hospital's true mortality rate for cardiac surgery patients exceeded 3.33% last year?" The commonly encountered problems of regression-to-the-mean bias and small caseloads can be handled by using hierarchical models to extract more information from profiling data.

Development and validation of a claims based index for adjusting for risk of mortality: the case of acute myocardial infarction.

We developed a comorbidity index on a cohort of 162,699 Medicare beneficiaries who had an acute myocardial infarction (AMI) in 1987 and validate it on two national cohorts: (1) a cohort of 164,427 Medicare beneficiaries who had an AMI in 1988 and (2) a cohort of 10,466 patients admitted to Veterans Administration Hospitals (VAH) for AMI in 1988-1991. The impact of each sensitivity was expressed as; (1) the risk of mortality for those with the comorbidity, (2) the adjustment to the log odds for 2 year mortality and (3) the age-based likelihood of 2 year mortality. Models were validated by calculated the area under an ROC curve obtained by fitting a logistic regression model to each validation population. The two year mortality rate for 30-day survivors was approximately 30% in each of the 3 cohorts. The 5 most prevlent comorbidities coded in the developmental cohort were heart failure (34%), chronic angina (27%), minor arrythmias (25%) and uncomplicated hypertension (18%). Cancer was the most powerful predictor of 2 year mortality, impacting mortality the same as a 18.3 year age increase. Saturation (having all secondary diagnoses in the discharge summary filled) resulted in a 9.2 year age increase. Validation in the 1988 Medicare and in the Veterans Administration Hospitals cohorts resulted in areas of 73% and 72% under the respective ROC curves. Our methods can serve as a prototype for others wishing to assess comorbidity in other targeted subgroups.

The effect of providing health coverage to poor uninsured pregnant women in Massachusetts.

OBJECTIVES: There has been substantial policy interest in whether the provision of health coverage to poor uninsured pregnant women affects access to prenatal care and birth outcomes. We therefore examined whether the statewide provision of health coverage to uninsured low-income pregnant women affects access to prenatal care and infant birth outcomes. DESIGN: Natural experiment. PATIENTS: All in-hospital, single-gestation live births in 1984 (N = 57,257) and 1987 (N = 64,346). INTERVENTION: In 1985, Massachusetts instituted Healthy Start, a program providing health coverage to uninsured pregnant women with incomes below 185% of the federal poverty level. MAIN OUTCOME MEASURES: Rates of satisfactory prenatal care, care initiated before the third trimester, and adverse infant outcome for uninsured women and for two concurrent control groups, women with Medicaid, and women with private insurance. We calculated the difference in rates between the uninsured and each concurrent control. To assess the effect of the program, we examined the change in these interpayer differences in rates between 1984 and 1987. MAIN RESULTS: Between 1984 and 1987, the rate of satisfactory prenatal care declined from 96.4% to 93.8% for all women in Massachusetts (P < .001). There was no statewide change in the overall incidence of adverse birth outcome (6.6% in both years). In 1984, uninsured women were less likely than privately insured women to receive satisfactory prenatal care (90.5% and 98.1%, respectively; interpayer difference, -7.6%) and to initiate care before the third trimester (94.2% and 99.1%; interpayer difference, -4.9%), and were more likely to suffer an adverse birth outcome (7.1% and 5.8%; interpayer difference, 1.3%). Between 1984 and 1987, there were no statistically significant changes in the interpayer differences in rates for any of the outcome measures relative to either control group. CONCLUSIONS: Our findings suggest that access to prenatal care may have declined for all women in Massachusetts between 1984 and 1987. In the setting of this statewide decline in access, the expansion of health coverage to uninsured low-income pregnant women was not associated with an improvement in access to prenatal care or birth outcomes.

The regulatory properties of yeast pyruvate kinase. Effect of fructose 1,6-bisphosphate.

The kinetics of pyruvate kinase from Saccharomyces cerevisiae were studied in assays at pH 6.2 at 25 degrees C as a function of the concentrations of the substrates ADP, phosphoenolpyruvate and Mg2+ and the concentration of the effector fructose 1,6-bisphosphate. The enzyme was activated by 100 mM-K+ and 32 mM-NH4+ throughout. It was found that an increase in the fructose bisphosphate concentration from 24 microM to 1.2 mM brings about a transition from a sigmoidal to a non-inflected form in the relationships v = f([phosphoenolpyruvate]) and v = f([Mg2+]) together with a large increase in the affinity of these substrates for the enzyme. The binding behaviour of ADP is barely affected by the same change in effector concentration. By contrast, increase in fructose bisphosphate concentration below 24 microM increases the affinity of the enzyme for all its substrates and the sigmoidicity of the corresponding velocity-substrate-concentration relationships. As a result of this change in behaviour it has been found impossible to represent all the data by the exponential model for a regulatory enzyme, and it is suggested (supported by comparisons with previous work) that the failure may reflect a secondary action of the effector upon the enzyme.

The regulatory properties of yeast pyruvate kinase. Effect of pH.

The kinetics of pyruvate kinase from Saccharomyces cerevisiae were studied at 25 degrees C as a function of the concentrations of the substrates ADP, phosphoenolpyruvate and Mg2+ and the effector H+ in the pH range 5-6.6. The enzyme was activated by 100 mM-K+ and 32 mM-NH4+ throughout. It was found that the data could be described by the exponential model for a regulatory enzyme. On that basis, it was concluded that the binding of H+ is positively interactive and that the protonated enzyme is catalytically inactive. It was also found that H+ interacts positively with phosphoenolpyruvate but negatively with both ADP and Mg2+.

The regulatory properties of yeast pyruvate kinase. Effects of NH4+ and K+ concentrations.

The kinetics of pyruvate kinase from Saccharomyces cerevisiae were studied at 25 degrees C and pH 6.2 as a function of the concentrations of ADP, phosphoenolpyruvate, Mg2+ and either NH4+ or K+. The data were analysed by the exponential model for four substrates, obtained by extension of the model described by Ainsworth, Kinderlerer & Gregory [(1983) Biochem. J. 209, 401-411]. On that basis, it was concluded that NH4+ binding is almost non-interactive but leads to the appearance of positive interaction in the velocity response to increase in its concentration because of positive interactions with phosphoenolpyruvate and Mg2+. The data obtained with K+ lead to the same conclusions and differ only in suggesting that NH4+ is bound more strongly to the enzyme than is K+. Both data sets are used as the basis for a discussion of the substrate interactions of pyruvate kinase and it appears therefrom that the heterotropic interactions accord with what is known of the events that take place at the active site during catalysis. The paper also reports a determination of the dissociation constants for the NH4+ complexes with ADP and phosphoenolpyruvate and an examination of the simultaneous activation of pyruvate kinase by K+ and NH4+ ions.

The regulatory properties of yeast pyruvate kinase.

The kinetics of pyruvate kinase from Saccharomyces cerevisiae were studied in assays at pH 6.2 where the relationships between the initial velocities of the catalysed reaction and the concentrations of the substrates ADP, phosphoenolpyruvate and Mg2+ are non-hyperbolic. The findings were represented empirically by the exponential model for a regulatory enzyme. The analysis shows that ADP, phosphoenolpyruvate and Mg2+ display positive homotropic interaction in their binding behaviour with (calculated) Hill slopes at half-saturation equal to 1.06, 2.35 and 3.11 respectively [Ainsworth (1977) J. Theor. Biol. 68, 391-413]. The direct heterotropic interaction between ADP and phosphoenolpyruvate is small and negative, but the overall interaction between these substrates becomes positive when their positive interactions with Mg2+ are taken into account. The heterotropic interactions of the substrates, though smaller in magnitude, are comparable with those revealed by the rabbit muscle enzyme [Ainsworth, Kinderlerer & Gregory (1983) Biochem. J. 209, 401-411], and it is suggested that they have a common origin in charge interactions within the active site.

Some interim results from a controlled trial of cost sharing in health insurance.

A total of 7706 persons are participating in a controlled trial of alternative health-insurance policies. Interim results indicate that persons fully covered for medical services spend about 50 per cent more than do similar persons with income-related catastrophe insurance. Full coverage leads to more people using services and to more services per user. Both ambulatory services and hospital admissions increase. Once patients are admitted to the hospital, however, expenditures per admission do not differ significantly among the experimental insurance plans. In addition, hospital admissions for children do not vary by plan. The income-related cost sharing in the experimental plans affects expenditure by different income groups similarly, but adults' total expenditure varies more than children's. Sufficient data are not available on whether higher use by persons with free care reflects overuse, or whether lower use by those with income-related catastrophe coverage reflects underuse. Both may well be true.