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Quality-adjusted life years are used in cost-effectiveness analyses (CEAs). To calculate QALYs, a "utility" (0-1) is used for each health state induced or prevented by the intervention. We aimed to estimate the impact of quality of life (QoL) assumptions (utilities and durations of health states) on CEAs of cervical cancer screening. To do so, 12 alternative sets of utility assumptions were retrieved from published cervical cancer screening CEAs. Two additional sets were based on empirical QoL data that were integrally obtained through two different measures (SF-6D and EQ-5D) from eight groups of women (total n = 3,087), from invitation for screening to diagnosis with cervical cancer. Per utility set we calculated the number of quality-adjusted days lost (QADL) for each relevant health state in cervical cancer screening, by multiplying the study-specific assumed disutilities (i.e., 1-utility) with study-specific durations of the loss in QoL, resulting in 14 "QADL-sets." With microsimulation model MISCAN we calculated cost-effectiveness of 342 alternative screening programs (varying in primary screening test [Human Papillomavirus (HPV) vs. cytology], starting ages, and screening interval) for each of the 14 QADL-sets. Utilities used in CEAs appeared to differ largely. We found that ten QADL-sets from the literature resulted in HPV and two in cytology as preferred primary test. The SF-6D empirical QADL-set resulted in cytology and the EQ-5D one in HPV as preferred primary test. In conclusion, assumed utilities and health state durations determine cost-effectiveness of cervical cancer screening. Also, the measure used to empirically assess utilities can be crucial for CEA conclusions.

The costs of computed tomographic colonography (CTC) are not yet established for screening use. In our study, we estimated the threshold costs for which CTC screening would be a cost-effective alternative to colonoscopy for colorectal cancer (CRC) screening in the general population. We used the MISCAN-colon microsimulation model to estimate the costs and life-years gained of screening persons aged 50-80 years for 4 screening strategies: (i) optical colonoscopy; and CTC with referral to optical colonoscopy of (ii) any suspected polyp; (iii) a suspected polyp >= 6 mm and (iv) a suspected polyp 10 mm. For each of the 4 strategies, screen intervals of 5, 10, 15 and 20 years were considered. Subsequently, for each CTC strategy and interval, the threshold costs of CTC were calculated. We performed a sensitivity analysis to assess the effect of uncertain model parameters on the threshold costs. With equal costs ($662), optical colonoscopy dominated CTC screening. For CTC to gain similar life-years as colonoscopy screening every 10 years, it should be offered every 5 years with referral of polyps >= 6 mm. For this strategy to be as cost-effective as colonoscopy screening, the costs must not exceed $285 or 43% of colonoscopy costs (range in sensitivity analysis: 39-47%). With 25% higher adherence than colonoscopy, CTC threshold costs could be 71% of colonoscopy costs. Our estimate of 43% is considerably lower than previous estimates in literature, because previous studies only compared CTC screening to 10-yearly colonoscopy, where we compared to different intervals of colonoscopy screening. (c) 2008 Wiley-Liss, Inc.

BACKGROUND. Although colorectal cancer (CRC) is the second leading cause of cancer death in the U.S., available interventions to reduce CRC mortality are disseminated only partially throughout the population. This study assessed the potential reduction in CRC mortality that may be achieved through further dissemination of current interventions for risk-factor modification, screening, and treatment. METHODS. The MISCAN-COLON microsimulation model was used to simulate the 2000 U.S. population with respect to CRC risk-factor prevalence, screening use, and treatment use. The model was used to project age-standardized CRC mortality from 2000 to 2020 for 3 intervention scenarios. RESULTS. Without changes in risk-factor prevalence, screening use, and treatment use after 2000, CRC mortality would decrease by 17% by the Year 2020. If the 1995 to 2000 trends continue, then the projected reduction in mortality would be 36%. However, if trends in the prevalence of risk-factors could be improved above continued trends, if screening use increased to 70% of the target population, and if the use of chemotherapy increased among all age groups, then a 49% reduction would be possible. Screening drove most (23%) of the projected mortality reduction with these optimistic trends; however, decreasing risk-factors (16%) and increasing use of chemotherapy (10%) also contributed substantially. The contribution of risk-factors may have been overestimated, because effect estimates could not be obtained from randomized controlled trials. CONCLUSIONS. Currently available interventions for risk-factor modification, screening, and treatment have the potential to reduce CRC mortality by almost 50% by the Year 2020. However, without action now to further increase the uptake of current effective interventions, the reduction in CRC mortality may be only 17%. Cancer 2006. © American Cancer Society.

A logistic regression model may be used to provide predictions of outcome for individual patients at another centre than where the model was developed. When empirical data are available from this centre, the validity of predictions can be assessed by comparing observed outcomes and predicted probabilities. Subsequently, the model may be updated to improve predictions for future patients. As an example, we analysed 30-day mortality after acute myocardial infarction in a large data set (GUSTO-I, n = 40 830). We validated and updated a previously published model from another study (TIMI-II, n = 3339) in validation samples ranging from small (200 patients, 14 deaths) to large (10,000 patients, 700 deaths). Updated models were tested on independent patients. Updating methods included re-calibration (re-estimation of the intercept or slope of the linear predictor) and more structural model revisions (re-estimation of some or all regression coefficients, model extension with more predictors). We applied heuristic shrinkage approaches in the model revision methods, such that regression coefficients were shrunken towards their re-calibrated values. Parsimonious updating methods were found preferable to more extensive model revisions, which should only be attempted with relatively large validation samples in combination with shrinkage.

After chemotherapy for metastatic non-seminomatous testicular cancer, surgical resection is a generally accepted treatment to remove remnants of the initial metastases, since residual tumour may still be present (mature teratoma or viable cancer cells). In this paper, we review the development and external validation of a logistic regression model to predict the absence of residual tumour. Three sources of information were used. A quantitative review identified six relevant predictors from 19 published studies (996 resections). Second, a development data set included individual data of 544 patients from six centres. This data set was used to assess the predictive relationships of five continuous predictors, which resulted in dichotomization for two, and a log, square root, and linear transformation for three other predictors. The multiple logistic regression coefficients were reduced with a shrinkage factor (0.95) to improve calibration, based on a bootstrapping procedure. Third, a validation data set included 172 more recently treated patients. The model showed adequate calibration and good discrimination in the development and in the validation sample (areas under the ROC curve 0.83 and 0.82). This study illustrates that a careful modelling strategy may result in an adequate predictive model. Further study of model validity may stimulate application in clinical practice.

Objective To estimate the potential preventive effect of antipyretic drugs on the recurrence of febrile seizures (FS). Design An experimental and a descriptive patient series, both prospectively followed, were combined in this study. Setting/participants Children who visited the outpatient department of the Sophia Children’s Hospital because of a FS experienced between the age of 10 and 36 months. Intervention A treatment group of 109 children was offered treatment with ibuprofen or acetaminophen syrup during fever, a control group of 103 children was not offered antipyretic treatment. This was not a randomized trial. In an intention-to-treat analysis, the risk of any recurrence and the number of recurrences per fever were compared between both groups. In an additional on-treatment analysis, we compared the number of recurrences per fever between the control group and the children in the treatment group who actually received the study medication during fever. Effect measures were odds ratio (OR) as estimated by the Mantel–Haenszel procedure and hazard ratios (HR) as estimated by Cox regression. Results According to the intention-to-treat analysis, the hazard ratio of any recurrence in the treatment group compared with the control group was 1.1 [95% confidence interval (CI), 0.7–1.8]. The recurrence risk per fever was 15% in the treatment group and 12% in the control group (OR, 1.2; 95% CI, 0.7–2.3). In the exploratory on-treatment analysis, the recurrence risk in the treatment group was estimated 6.9% in the treatment group versus 12% in the control group (OR, 0.5; 95% CI, 0.2–1.3). Conclusions/implications for practice We conclude that antipyretic treatment may have little or no preventive effect on the recurrence of febrile seizures in common practice. Some reduction of the risk of a recurrence may be acquired under optimal circumstances, namely that fever is noticed at once and that antipyretic drugs can be administered on time.

BACKGROUND After chemotherapy for metastatic, nonseminomatous testicular cancer, small, retroperitoneal lymph nodes still harbor mature teratoma or viable cancer cells in less than half of patients with normal tumor markers. Surgical resection is an effective treatment to remove residual masses, but observation may also be considered. METHODS Using a decision analysis model, the authors estimated the survival achieved with either resection or observation for patients with residual masses measuring 0–20 mm. Prognostic estimates were obtained from an international data set containing 362 patients with masses ≤20 mm and from 10 clinical experts. RESULTS According to the model, resection prolonged life expectancy by more than 2 years for masses 11–20 mm and by more than 1 year for masses 0–10 mm. The estimated gains in 5-year survival were 4.3% and 2.7%, respectively. In a sensitivity analysis, these results appeared rather robust for changes in the estimates of the experts. The magnitude of the gain in survival, however, depended on the probabilities of the residual histologies, which could be estimated with several well-known predictors, and the assumed benefit of resection for residual mature teratoma or cancer. CONCLUSIONS Resection may on average be beneficial for patients with small, residual masses. The expected benefit depends on the probability and risks of residual malignancy, regarding which further research is required. For decision-making regarding individual patients, the morbidity and costs of resection and a patient's individual preferences should be considered in addition to any assumed gain in survival. Cancer 1999;85:1331–41. © 1999 American Cancer Society.

markdownabstractObjective. To quantify potential risk factors for septic arthritis, in order to identify a basis for prevention. Methods. The occurrence of potential risk factors for septic arthritis in patients with joint diseases attending a rheumatic disease clinic was prospectively monitored at 3-m onth intervals over a period of 3 years. Potential risk factors investigated were type of joint disease, comorbidity, medication, joint prosthesis, infections, and invasive procedures. The frequencies of risk factors in patients with and those without septic arthritis were compared using multiple logistic regression analysis. Results. There were 37 patients with and 4,870 without septic arthritis. Risk factors for developing septic arthritis were age ≥80 years (odds ratio [OR] = 3.5, 95% confidence interval [95% CI] 1.4–8.6), diabetes mellitus (OR = 3.3, 95% CI 1.1–10.1), rheumatoid arthritis (OR = 4.0, 95% CI 1.9–8.3), hip and/or knee prosthesis (OR = 15, 95% CI 4.1–54.3), joint surgery (OR = 5.1, 95% CI 2.2–11.9), and skin infection (OR = 27.2, 95% CI 7.6–97.1) Conclusion. These findings indicate that preventive measures against septic arthritis in patients with joint diseases should mainly be directed at those with joint prostheses and/or skin infection.

The evidence on survival in dementia is summarized. There are no reliable data on survival after onset of dementia or after first contact with medical services. People with dementia in outpatient clinics and nursing homes have 2-year survival rates of 75% (range 60%-95%) and 50% (range 30%-65%), respectively. Differences in survival between patients with senile dementia of the Alzheimer's type (SDAT) and multi infarct dementia (MID) are small. Women in nursing homes have a better prognosis than men (2-year survival rates, 60% vs 40%). Dementia patients have a considerable excess mortality when compared to the vital statistics. There is no evidence for improvement of survival rates during recent decades. Recommendations for future studies are made.

The influence of attendance on the health effects and cost-effectiveness of cervical-cancer screening was studied, both for organized screening programmes and for spontaneous screening. The asymmetric distribution of smears among the female population and the higher risk incurred by women who never or only occasionally attend screening appear crucial in determining the health effects of screening. An increase in attendance rate induces a substantial rise in health effects and a less than proportionate rise in costs, thus improving cost-effectiveness. Wider screening coverage, in order to increase the number of life-years saved, is achieved more efficiently by encouraging a greater number of women to attend than by inviting the same number of women to attend more often, i.e., with a shorter interval between successive screens. Spontaneous screening is characterized by high coverage for younger women and low coverage for middle-aged and older women. This leads to a small amount of health effects and poor cost-effectiveness as compared with organized screening.