The potential epidemiological impact of a genital herpes vaccine for women

BACKGROUND: In two phase III vaccine trials immunisation of women previously uninfected by herpes simplex virus provided protection against genital herpes disease. In deciding policy, an evaluation of the epidemiological impact of the partial protection provided by the vaccine should be considered. METHODS: A sex and sexual activity stratified deterministic differential and partial differential equation model of the natural history of herpes simplex virus type 2 (HSV-2) and the impact of vaccination is developed and analysed. To explore the role of vaccination, the pattern of viral shedding and the transmission of infection during sexual acts within sexual partnerships are described. RESULTS: Using literature derived estimates of parameter values and assuming efficacy in only 40% of women the impact of the vaccine depends on assumptions made about its action. The vaccine has a limited impact if it only prevents disease but a more substantial impact if it reduces asymptomatic viral shedding, which it could do indirectly by preventing infection or directly by modifying the biology of the infection. Concern over the implications of a vaccine that prevents disease but has no impact on viral shedding was addressed in a worst case scenario. Here there is a modest increase in the incidence of infection in both men and women but an increase in disease prevalence in men alone, since the virus directly protects some women from disease. CONCLUSIONS: Results suggest that a herpes vaccine should be used universally and that a vaccine that only protects HSV-1-/2- women can paradoxically have a significant epidemiological impact, the scale of which depends upon changes in patterns of viral shedding.     

Multi-modal MRI in normal pressure hydrocephalus identifies pre-operative haemodynamic and diffusion coefficient changes in normal appearing white matter correlating with surgical outcome

Magnetic resonance techniques were used to investigate haemodynamic abnormalities and their consequences in normal pressure hydrocephalus (NPH) and to assess changes in these parameters following surgery. Eleven patients with NPH were studied pre- and post-operatively using perfusion and diffusion weighted imaging and compared with ten age-matched controls. Pre-operative periventricular relative cerebral blood volume (rCBV) was reduced in patients (0.76+/-0.11) compared with control (1.16+/-0.16, P<0.01). There was no difference between outcome groups and no change in haemodynamic parameters following surgery. The periventricular apparent diffusion coefficient (ADC) was elevated in the poor outcome group (1.67+/-0.3 x 10(-3) mm(2) s(-1)) compared with both controls (1.04+/-0.4 x 10(-3) mm(2) s(-1), P<0.05) and the good outcome group (0.99+/-0.3 x 10(-3) mm(2) s(-1), P<0.05) despite appearing normal on conventional imaging. In white matter hyperintensities (WMH), rCBV was reduced (0.70+/-0.12 vs. 1.00+/-0.10, P<0.01), and the ADC was increased (1.98+/-0.6 vs. 1.04+/-0.4 x 10(-3) mm(2) s(-1), P<0.05) compared with the same anatomical location in controls. As low rCBV and high ADC is characteristic of chronic infarction, the findings in WMH regions suggest they are irreversibly damaged. Normal appearing periventricular tissue rCBV was reduced, implying that significant haemodynamic consequences contribute to symptoms in NPH. The elevated pre-operative ADC of the same region, was correlated with poor outcome, and may, therefore, be useful in selecting patients for surgery.     

Mortality among children residing near the American Smelting and Refining Company (ASARCO) copper smelter in Ruston, Washington

A retrospective cohort study was undertaken to determine whether childhood exposure to ambient arsenic was associated with increased mortality rates. Cohort members comprised children who had lived within 4.0 km (2.5 mi) of the American Smelting and Refining Company (ASARCO) copper smelter and arsenic refinery in Ruston, Washington, for at least 2 yr during the time period from 1907 to 1932. The cohort included 1,827 boys and 1,305 girls identified from school census records. Exposure intensity was computed as the total number of years a child had lived at a residence less than 1.6 km (1.0 mi) from the smelter stack during the study period. In only one exposure intensity group (i.e., residence > or = 10.0 yr less than 1.6 km [1.0 mi] from the smelter) for boys were Cox proportional hazards ratios significantly higher than 1.00: for all causes of death (1.52), ischemic heart disease (1.77), and external causes (1.93). For girls, hazard ratios were not elevated significantly for any cause of death in any exposure intensity group.     

Effect of over-the-counter cimetidine on phenytoin concentrations in patients with seizures.

OBJECTIVE: To determine the effects of the maximum recommended over-the-counter (OTC) cimetidine dosage on phenytoin concentrations in ambulatory seizure patients on long-term phenytoin therapy. METHODS: Adults with seizure disorders requiring phenytoin therapy were recruited. Trough total phenytoin concentrations were measured initially and once weekly for six weeks. All assays were performed using Biotrack patient-side cartridges. After a two-week baseline period, patients took cimetidine 200 mg twice daily for two weeks. Toxicity was monitored via weekly neurologic examinations and midweek telephone surveys. Patients were asked to return to clinic weekly during a two-week cimetidine washout period. RESULTS: Nine patients entered and completed the study. All but two patients took other anticonvulsants known to interact with phenytoin (carbamazepine, n = 5; phenobarbital, n = 2). No adverse effects or changes in seizure frequency were reported. Paired Student's t-tests revealed no significant difference between serum phenytoin concentrations before (12.3+/-3.2 mg/L [mean +/- SD]) and after (12.8+/-4.0 mg/L) two weeks on the OTC cimetidine regimen. No differences were noted in estimated pharmacokinetic parameters (maximum metabolic rate, Michaelis-Menten constant) for the same time periods (paired Student's t-test, p > 0.05). The Biotrack assay had an r2 = 0.7311 (p < 0.001, two-sided) when compared with TDx. CONCLUSIONS: It is possible that the lack of change in phenytoin concentrations was a result of the low daily dosage of cimetidine used or other factors related to the "real world" setting of the study. However, the potential for a serious drug interaction occurring in patients taking long-term oral phenytoin and OTC cimetidine appears to be small.     

The effect of everyday exercise on steady state digoxin concentrations

The purpose of this study was to evaluate the effect of 1 hour of everyday exercise (walking at patient's own pace) on serum digoxin concentrations. Nine white male subjects (ages 58-74) who had been taking the same digoxin dose for greater than 1 month participated. There were three continuous phases: 1 hour of rest, 1 hour of exercise, and a final hour of rest. Serum digoxin concentrations were drawn every 20 minutes. During the first rest period, serum digoxin concentrations rose 30% from the first concentration drawn in the study. After 1 hour of exercise, serum digoxin concentrations fell 26.8% from the last concentration of the first rest period. At the end of the second hour of rest, serum digoxin concentrations increased by 36.6% from the last concentration. Repeated measures analysis of variance demonstrated a significant (P less than .01) change in serum digoxin concentrations. Significant (P less than .01) differences were found between sampling times 0 and 60, 60 and 80, 60 and 100, 60 and 120 and 180 minutes using a paired t-test with Bonferroni correction. A weak correlation (r = 0.74, r2 = 0.55) between percent change in concentrations and age during the exercise phase was found, but there was no correlation between the percent change in concentrations and age during the two immobilization phases. Because significant changes in concentrations occurred during each phase of the study, we conclude that the influence of everyday exercise should be taken into account when interpreting serum digoxin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)