No abstract

Objective To estimate the cost effectiveness of alternative methods of managing low grade cervical cytological abnormalities detected at routine screening. Design Cost analysis within multicentre individually randomised controlled trial. Setting Grampian, Tayside, and Nottingham. Participants 4201 women with low grade abnormalities. Interventions Cytological surveillance or referral to colposcopy for biopsy and recall if necessary or referral to colposcopy with immediate treatment based on colposcopic appearance. Main outcome measures Data on resource use collected from participants throughout the duration of the trial (36 months), enabling the estimation of both the direct (health care) and indirect (time and travel) costs of management. Quality of life assessed at recruitment and at 12, 18, 24, and 30 months, using the EQ-5D instrument. Economic outcomes expressed as costs per case of cervical intraepithelial neoplasia (grade II or worse) detected, by trial arm, as confirmed at exit, and cost utility ratios (cost per quality adjusted life year (QALY) gained) for the three pairwise comparisons of trial arms. Results The mean three year discounted costs of surveillance, immediate treatment, and biopsy and recall were £150.20 (€177, $249), £240.30 (€283, $415), and £241.10 (€284, $4000), respectively, viewed from the health service perspective. From the social perspective, mean discounted costs were £204.40 (€241, $339), £339.90 (€440, $563), and £327.50 (€386, $543), respectively. Estimated at the means, the incremental cost effectiveness ratios indicated that immediate treatment was dominated by the other two management methods, although it did offer the lowest cost per case of cervical intraepithelial neoplasia detected and treated. The pronounced skews in the distributions indicated that probabilistic uncertainty analysis would offer more meaningful estimates of cost effectiveness. The observed differences in the cost effectiveness ratios between trial arms were not significant. Conclusion Judged within the time frame of the TOMBOLA evaluation, there is no compelling economic reason to favour any one follow-up method over either of the others. Trial Registration ISRCTN 34841617.

An enzyme-linked immunosorbent assay was developed for the titration of antibodies in human sera to influenza virus neuraminidase, employing partially purified N1 neuraminidase. Specificity of the test was demonstrated, and the test was more sensitive than either the conventional neuraminidase inhibition or plaque size reduction tests in detecting anti-neuraminidase antibody.

Neuraminidases were purified from reassortant viruses (H6N1 and H6N2) containing the two antigenic subtypes (Nl and N2) found in human influenza viruses. Surface glycoproteins were solubilized with octylglucoside, and the neuraminidase was isolated by chromatography on DEAE-Sephadex. Neuraminidase isolated by this technique coeluted with viral lipids and spontaneously formed liposomes on dialysis. The purified neuraminidase was immunogenic in rabbits, producing a significant antibody response at dose levels as low as 1 ,ug.

Studies of cell-mediated immunity (CMI) to measles were carried out in patients with natural measles infection, in recipients of live measles vaccine, and in umbilical cord blood specimens from infants of mothers who were seropositive for measles. Evidence of CMI to measles was found in 100% of patients with natural infection but in only 62% of vaccine recipients and, interestingly, in 40% of umbilical cord blood specimens. Eight of these infants were subsequently studied at 4 to 5 months of age, at which time evidence of measles CMI was still detectable in three. Sufficient stimulation of cell-mediated immune mechanisms may be a prerequisite for the development of life-long immunity to measles. The effect of congenitally acquired CMI to measles on the outcome of immunization or of exposure to natural measles during the first year of life remains to be determined.