Evaluation of the relative cost-effectiveness of treatments for infertility in the UK

This paper aims to complement existing clinical guidelines byproviding evidence of the relative cost-effectiveness of treatmentsfor infertility in the UK. A series of decision–analyticalmodels have been developed to reflect current diagnostic andtreatment pathways for the five main causes of infertility.Data to populate the models are derived from a systematic reviewand routine National Health Service activity data, and are augmentedwith expert opinion. Costs are derived from an analysis of extra-contractualreferral tariffs and private sector data. Sensitivity analysishas been carried out to take account of the uncertainty of modelparameters and to allow results to be interpreted in the lightof local circumstances. Results of the modelling exercise suggestin-vitro fertilization is the most cost-effective treatmentoption for severe tubal factors and endometriosis, with surgerythe most cost-effective in the case of mild or moderate disease.Ovulatory factors should be treated medically with the additionof laparoscopic ovarian diathermy in the presence of polycysticovarian syndrome. For other causes, stimulated intrauterineinsemination (unexplained and moderate male factor) and stimulateddonor intrauterine insemination (severe male) are cost-effective.     

Recommended amikacin doses in newborns often produce excessive serum levels

Emergence of a multiply drug resistant Enterobacter cloacae during a seven-week period in 1980 caused amikacin to become the aminoglycoside of choice in the initial management of suspected sepsis in a neonatal intensive care unit. Recommended doses (7.5-10 mg/kg loading; 15 mg/kg in two divided doses IV) were given to 5 infants < or = 1,000 gm and to 13 larger babies. Trough levels 11.5 hours after a dose were 16.6 +/- 11.9 microg/ml in infants < or = 1,000 gm and 6.5 +/- 4.3 microg/ml in the larger infants (P < 0.02). Peak levels one hour postinfusion exceeded 40 microg/ml in 3 of 5 < or = 1,000-gm babies and 4 of 12 > 1,000-gm infants (P = NS). Overall, 7 of 10 peak and/or trough levels in < or = 1,000-gm infants were in the range considered toxic in adults, versus 7 of 24 in larger babies (P = 0.03). These data show that surprisingly excessive blood levels of amikacin are likely in infants < or = 1,000 gm and may also occur in larger infants using currently recommended dosage schedules. These unexpected findings emphasize the need to monitor drug levels and individualize therapy in very low birthweight infants.     

Uptake, initial effects, and chemotherapeutic efficacy of harringtonine in murine leukemic cells sensitive and resistant to vincristine and other chemotherapeutic agents

[3H]Harringtonine was shown to be taken up rapidly by L1210/0 cells using a fast-mixing, fast-separating technique and was retained with a slow rate of limited release to the medium. Cells resistant to vincristine (L1210/VCR) showed impaired capability to take up the drug at 20 degrees. Its initial uptake in L1210 sublines in vitro was: L1210/0 greater than L1210/cyclophosphamide, L1210/1-beta-D-arabinofuranosylcytosine, L1210/6-mercaptopurine greater than L1210/5-fluorouracil, L1210/Adriamycin greater than L1210/VCR. In [3H]harringtonine-preloaded cells, L1210/0 retained significantly more radioactivity than did L1210/VCR cells after repeated washing with fresh medium at 37 degrees. The radioactivity appeared to be predominantly bound to the microsomal fractions. [3H]Leucine incorporation into protein in L1210/0 cells was inhibited 90% within 15 min by harringtonine (0.5 micrograms/ml); incorporation of [3H]thymidine into DNA and [3H]cytidine into RNA was much less inhibited and showed an apparent lag of onset for 5 and 10 min, respectively. The relative potency of harringtonine to inhibit [3H]leucine incorporation in the above sublines in vitro follows an order similar to their rates of uptake of harringtonine by these sublines of cells. The efficacy of harringtonine, 2.4 or 3.6 mg/kg i.p., in increasing the life span of C57BL/6 X DBA/2 F1 mice bearing the sublines of leukemic cells, on the average, was: L1210/0 greater than L1210/cyclophosphamide, L1210/6-mercaptopurine greater than L1210/1-beta-D-arabinofuranosylcytosine, L1210/5-fluorouracil greater than L1210/Adriamycin, L1210/VCR. These results suggest that: (a) protein synthesis is the major initial target for the effect of harringtonine; (b) harringtonine bound more tightly to the cellular components of VCR-sensitive leukemic cells than to VCR-resistant cells; and (c) cellular uptake of harringtonine and the relative potency of inhibiting protein synthesis in sublines have a rank order similar to the chemotherapeutic efficacy of harringtonine in these cells.     

Return of fertility following discontinuation of an injectable contraceptive — Norethisterone oenanthate (NET EN) 200mg dose

The return of fertility following discontinuation of norethisterone oenanthate (NET EN) 200 mg injectable contraceptive after use for a minimum period of six months or more was studied in 69 women who discontinued the method for planning pregnancy. Former users of copper intra-uterine device (CuT 200) were enrolled as a control group. Another 161 women who had discontinued NET EN due to other reasons (e.g. amenorrhoea, excessive bleeding or personal reasons) were also studied for return of fertility after ensuring that they were not using any other method of contraception and were exposed to the risk of pregnancy. The subjects from both groups were followed for a period of one year. The cumulative conception rates at one year were 72.5 and 83.6 per 100 subjects for ex-NET EN and ex-CuT 200 users who had discontinued the method for planning pregnancy and this difference was not statistically significant (P > 0.05). The median time for conception for ex-NET EN users was 7.8 months as compared to 3.7 months in ex-CuT 200 users but the cumulative conception rates at the end of one year show that future return of fertility in NET EN users does not appear to be adversely affected.

In 51 subjects who had discontinued NET EN due to amenorrhoea, the return of fertility was predictably slower and less. The return of fertility in subjects who discontinued NET EN for other reasons (e.g. excessive bleeding and other personal reasons) was similar to ex-NET EN and ex-CuT 200 users.     

The half-life of truth: what are appropriate time horizons for research decisions?

PURPOSE: To evaluate alternative approaches taken to estimate the population that could benefit from research and to demonstrate that explicitly modeling future change leads to more appropriate estimates of the expected value of information (EVI). METHODS: Existing approaches to estimating the population typically focus on the time horizon for decisions, employing seemingly arbitrary estimates of the appropriate horizon. These approaches implicitly use the time horizon as a proxy for future changes in technologies, prices, and information. Different approaches to quantifying the time horizon are explored, in the context of a stylized model, to demonstrate the impact of uncertainty in this estimate on EVI. An alternative approach is developed that explicitly models future changes in technologies, prices, and information and that demonstrates the impact on EVI estimates. RESULTS: Explicitly modeling future changes means that the EVI for the decision problem may increase or decrease over time, but the EVI for the group of parameters that can be evaluated by current research tends to decline. The finite and infinite time horizons for the decision problem represent special cases (e.g., price shock or no changes, respectively). This type of analysis can be used to inform policy decisions relating to the timing of research. CONCLUSIONS: The value of information depends on future changes in technologies, prices, and evidence. Finite time horizons for decision problems can be seen as a proxy for the complex and uncertain process of future change. A more explicit approach to modeling these changes could provide a more appropriate basis for calculating EVI, but this raises a number of significant methodological and technical challenges.     

The radiology of cystic liver tumours

Six patients with cystic liver tumours are presented. The definitive diagnosis of such cystic lesions may be difficult and needle aspiration or biopsy or even operation may be necessary. Clinical and biochemical features may be helpful and in five of the six patients presented, the liver function tests were abnormal. In two patients, diagnostic imaging could not distinguish the tumour from a benign cyst. The differential diagnosis of such cystic liver tumours includes simple cyst, polycystic liver disease, hydatid, liver abscess, haematoma and biloma.