Quality of life assumptions determine which cervical cancer screening strategies are cost-effective.

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.

A revised prediction model for natural conception.

One of the aims in reproductive medicine is to differentiate between couples that have favourable chances of conceiving naturally and those that do not. Since the development of the prediction model of Hunault, characteristics of the subfertile population have changed. The objective of this analysis was to assess whether additional predictors can refine the Hunault model and extend its applicability. Consecutive subfertile couples with unexplained and mild male subfertility presenting in fertility clinics were asked to participate in a prospective cohort study. We constructed a multivariable prediction model with the predictors from the Hunault model and new potential predictors. The primary outcome, natural conception leading to an ongoing pregnancy, was observed in 1053 women of the 5184 included couples (20%). All predictors of the Hunault model were selected into the revised model plus an additional seven (woman's body mass index, cycle length, basal FSH levels, tubal status,history of previous pregnancies in the current relationship (ongoing pregnancies after natural conception, fertility treatment or miscarriages), semen volume, and semen morphology. Predictions from the revised model seem to concur better with observed pregnancy rates compared with the Hunault model; c-statistic of 0.71 (95% CI 0.69 to 0.73) compared with 0.59 (95% CI 0.57 to 0.61).

Realizing a desired family size: when should couples start?

STUDY QUESTION: Until what age can couples wait to start a family without compromising their chances of realizing the desired number of children? SUMMARY ANSWER: The latest female age at which a couple should start trying to become pregnant strongly depends on the importance attached to achieving a desired family size and on whether or not IVF is an acceptable option in case no natural pregnancy occurs. WHAT IS KNOWN ALREADY: It is well established that the treatment-independent and treatment-dependent chances of pregnancy decline with female age. However, research on the effect of age has focused on the chance of a first pregnancy and not on realizing more than one child. STUDY DESIGN, SIZE, DURATION: An established computer simulation model of fertility, updated with recent IVF success rates, was used to simulate a cohort of 10 000 couples in order to assess the chances of realizing a one-, two- or three-child family, for different female ages at which the couple starts trying to conceive. PARTICIPANTS/MATERIALS, SETTING, METHODS: The model uses treatment-independent pregnancy chances and pregnancy chances after IVF/ICSI. In order to focus the discussion, we single out three levels of importance that couples could attach to realizing a desired family size: (i) Very important (equated with aiming for at least a 90% success chance). (ii) Important but not at all costs (equated with a 75% success chance) (iii) Good to have children, but a life without children is also fine (equated with a 50% success chance). MAIN RESULTS AND THE ROLE OF CHANCE: In order to have a chance of at least 90% to realize a one-child family, couples should start trying to conceive when the female partner is 35 years of age or younger, in case IVF is an acceptable option. For two children, the latest starting age is 31 years, and for three children 28 years. Without IVF, couples should start no later than age 32 years for a one-child family, at 27 years for a two-child family, and at 23 years for three children. When couples accept 75% or lower chances of family completion, they can start 4-11 years later. The results appeared to be robust for plausible changes in model assumptions. LIMITATIONS, REASONS FOR CAUTION: Our conclusions would have been more persuasive if derived directly from large-scale prospective studies. An evidence-based simulation study (as we did) is the next best option. We recommend that the simulations should be updated every 5-10 years with new evidence because, owing to improvements in IVF technology, the assumptions on IVF success chances in particular run the risk of becoming outdated. WIDER IMPLICATIONS OF THE FINDINGS: Information on the chance of family completion at different starting ages is important for prospective parents in planning their family, for preconception counselling, for inclusion in educational courses in human biology, and for increasing public awareness on human reproductive possibilities and limitations. STUDY FUNDING/COMPETING INTERESTS: No external funding was either sought or obtained for this study. There are no conflicts of interest to be declared.

Should colorectal cancer screening be considered in elderly persons without previous screening? A cost-effectiveness analysis.

BACKGROUND: The U.S. Preventive Services Task Force recommends against routine screening for colorectal cancer (CRC) in adequately screened persons older than 75 years but does not address the appropriateness of screening in elderly persons without previous screening. OBJECTIVE: To determine at what ages CRC screening should be considered in unscreened elderly persons and to determine which test is indicated at each age. DESIGN: Microsimulation modeling study. DATA SOURCES: Observational and experimental studies. TARGET POPULATION: Unscreened persons aged 76 to 90 years with no, moderate, and severe comorbid conditions. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: One-time colonoscopy, sigmoidoscopy, or fecal immunochemical test (FIT) screening. OUTCOME MEASURES: Quality-adjusted life-years gained, costs, and costs per quality-adjusted life-year gained. RESULTS OF BASE-CASE ANALYSIS: In unscreened elderly persons with no comorbid conditions, CRC screening was cost-effective up to age 86 years. Screening with colonoscopy was indicated up to age 83 years, sigmoidoscopy was indicated at age 84 years, and FIT was indicated at ages 85 and 86 years. In unscreened persons with moderate comorbid conditions, screening was cost-effective up to age 83 years (colonoscopy indicated up to age 80 years, sigmoidoscopy at age 81 years, and FIT at ages 82 and 83 years). In unscreened persons with severe comorbid conditions, screening was cost-effective up to age 80 years (colonoscopy indicated up to age 77 years, sigmoidoscopy at age 78 years, and FIT at ages 79 and 80 years). RESULTS OF SENSITIVITY ANALYSES: Results were most sensitive to assuming a lower willingness to pay per quality-adjusted life-year gained. LIMITATION: Only persons at average risk for CRC were considered. CONCLUSION: In unscreened elderly persons CRC screening should be considered well beyond age 75 years. A colonoscopy is indicated at most ages. PRIMARY FUNDING SOURCE: National Cancer Institute.

Models in the development of clinical practice guidelines.

Clinical practice guidelines should be based on the best scientific evidence derived from systematic reviews of primary research. However, these studies often do not provide evidence needed by guideline development groups to evaluate the tradeoffs between benefits and harms. In this article, the authors identify 4 areas where models can bridge the gaps between published evidence and the information needed for guideline development applying new or updated information on disease risk, diagnostic test properties, and treatment efficacy; exploring a more complete array of alternative intervention strategies; assessing benefits and harms over a lifetime horizon; and projecting outcomes for the conditions for which the guideline is intended. The use of modeling as an approach to bridge these gaps (provided that the models are high-quality and adequately validated) is considered. Colorectal and breast cancer screening are used as examples to show the utility of models for these purposes. The authors propose that a modeling study is most useful when strong primary evidence is available to inform the model but critical gaps remain between the evidence and the questions that the guideline group must address. In these cases, model results have a place alongside the findings of systematic reviews to inform health care practice and policy.

How distressing is referral to colposcopy in cervical cancer screening?: a prospective quality of life study.

OBJECTIVE: Referral for colposcopy because of abnormal Pap test results is likely to be distressing, but the extent and duration of these effects are unknown. We aimed to fill this gap. METHODS: We conducted a prospective observational study at two departments of Obstetrics and Gynecology (an academic and a non-academic setting). Women referred for colposcopy completed questionnaires before colposcopy, and at 1, 3, and 6 months afterwards. A reference group of 706 screen participants, aged 29-60 years old, was included and completed questionnaires once. Main outcome measures were generic health-related quality of life (HRQoL), assessed through the EQ-5D and the SF-12 physical and mental scores (PCS-12 and MCS-12); anxiety as assessed by STAI-6, and screen-specific anxiety as assessed by the psychological consequences questionnaire (PCQ). RESULTS: 154 women responded to the questionnaire, of whom 132 were included in the analyses. Histological results were CIN 1 in 17/115 women (15%) and CIN 2+ in 62 (54%). In 36 women (31%) there was no histologically confirmed neoplasia. Before colposcopy physical HRQoL scores were similar or slightly better than in the reference group, while mental HRQoL (MSC-12) and (screen-specific) anxiety were worse (p<0.001). Irrespective of CIN-grades, anxiety washed out during follow-up (p<0.001), with changes being clinically relevant. CONCLUSIONS: Referral for gynecological evaluation because of abnormal PAP-test results was distressing. Anxiety--and not the physical burden of management--seemed to be the most bothersome to women. For all CIN-grades, distress disappeared over six months following colposcopy, suggesting a reassuring effect of gynecological management.

Cost-effectiveness of one versus two sample faecal immunochemical testing for colorectal cancer screening.

OBJECTIVE: The sensitivity and specificity of a single faecal immunochemical test (FIT) are limited. The performance of FIT screening can be improved by increasing the screening frequency or by providing more than one sample in each screening round. This study aimed to evaluate if two-sample FIT screening is cost-effective compared with one-sample FIT. DESIGN: The MISCAN-colon microsimulation model was used to estimate costs and benefits of strategies with either one or two-sample FIT screening. The FIT cut-off level varied between 50 and 200 ng haemoglobin/ml, and the screening schedule was varied with respect to age range and interval. In addition, different definitions for positivity of the two-sample FIT were considered: at least one positive sample, two positive samples, or the mean of both samples being positive. RESULTS: Within an exemplary screening strategy, biennial FIT from the age of 55-75 years, one-sample FIT provided 76.0-97.0 life-years gained (LYG) per 1000 individuals, at a cost of € 259,000-264,000 (range reflects different FIT cut-off levels). Two-sample FIT screening with at least one sample being positive provided 7.3-12.4 additional LYG compared with one-sample FIT at an extra cost of € 50,000-59,000. However, when all screening intervals and age ranges were considered, intensifying screening with one-sample FIT provided equal or more LYG at lower costs compared with two-sample FIT. CONCLUSION: If attendance to screening does not differ between strategies it is recommended to increase the number of screening rounds with one-sample FIT screening, before considering increasing the number of FIT samples provided per screening round.

Random comparison of repeated faecal immunochemical testing at different intervals for population-based colorectal cancer screening.

OBJECTIVE: Colorectal cancer screening by means of faecal immunochemical tests (FITs) requires successive screening rounds for an optimal preventive effect. However, data on the influence of the length of the screening interval on participation and diagnostic yield are lacking. Repeated FIT screening was therefore performed in a population-based trial comparing various repeat intervals. DESIGN: 7501 Dutch individuals aged 50-74 years were randomly selected and invited for two 1-sample FIT screening rounds (haemoglobin (Hb) concentration ≥ 50 ng/ml, corresponding to 10 µg Hb/g faeces) with intervals of 1 (group I), 2 (group II) or 3 years (group III). RESULTS: In group I, participation was 64.7% in the first screening round and 63.2% in the second. The corresponding percentages for groups II and III were 61.0% vs 62.5% and 62.0% vs 64.0%. Triennial screening resulted in a higher participation rate in the second screening round compared with annual screening (p=0.04). The overall positivity rate in the second screening round was significantly lower compared with the first round (6.0% vs 8.4%; OR 0.69, 95% CI 0.58 to 0.82) and did not depend on interval length (p=0.23). Similarly, the overall detection rate of advanced neoplasia was significantly lower in the second round compared with the first screening round (1.9% vs 3.3%; OR 0.57, 95% CI 0.43 to 0.76) and also did not depend on interval length (p=0.62). The positive predictive value of the FIT did not significantly change over time (41% vs 33%; p=0.07). CONCLUSION: The total number of advanced neoplasia found at repeat FIT screening is not influenced by the interval length within a range of 1-3 years. Furthermore, there is a stable and acceptably high participation in the second screening round. This implies that screening intervals can be tailored to local resources.

Cost-effectiveness analysis of a quantitative immunochemical test for colorectal cancer screening.

BACKGROUND & AIMS: Two European randomized trials (N = 30,000) compared guaiac fecal occult blood testing with quantitative fecal immunochemical testing (FIT) and showed better attendance rates and test characteristics for FIT. We aimed to identify the most cost-effective FIT cutoff level for referral to colonoscopy based on data from these trials and allowing for differences in screening ages. METHODS: We used the validated MIcrosimulation SCreening ANalysis (MISCAN)-Colon microsimulation model to estimate costs and effects of different screening strategies for FIT cutoff levels of 50, 75, 100, 150, and 200 ng/mL hemoglobin. For each cutoff level, screening strategies were assessed with various age ranges and screening intervals. We assumed sufficient colonoscopy capacity for all strategies. RESULTS: At all cost levels, FIT screening was most effective with the 50 ng/mL cutoff level. The incremental cost-effectiveness ratio of biennial screening between ages 55 and 75 years using FIT at 50 ng/mL, for example, was 3900 euro per life year gained. Annual screening had an incremental cost-effectiveness ratio of 14,900 euro per life year gained, in combination with a wider age range (between ages 45 and 80 years). In the sensitivity analysis, 50 ng/mL remained the preferred cutoff level. CONCLUSIONS: FIT screening is more cost-effective at a cutoff level of 50 ng/mL than at higher cutoff levels. This supports the recommendation to use FIT at a cutoff level of 50 ng/mL, which is considerably lower than the values used in current practice.

How much colonoscopy screening should be recommended to individuals with various degrees of family history of colorectal cancer?

BACKGROUND: Individuals with a family history of colorectal cancer (CRC) are at increased risk for CRC. Current screening recommendations for these individuals are based on expert opinion. The authors investigated optimal screening strategies for individuals with various degrees of family history of CRC based on a cost-effectiveness analysis. METHODS: The MISCAN-Colon microsimulation model was used to estimate costs and effects of CRC screening strategies, varying by the age at which screening was started and stopped and by screening interval. The authors defined 4 risk groups, characterized by the number of affected first-degree relatives and their age at CRC diagnosis. For all risk groups, the optimal screening strategy had an incremental cost-effectiveness ratio of approximately $50,000 per life-year gained. RESULTS: The optimal screening strategy for individuals with 1 first-degree relative diagnosed after age 50 years was 6 colonoscopies every 5 years starting at age 50 years, compared with 4 colonoscopies every 7 years starting at age 50 years for average risk individuals. The optimal strategy had 10 colonoscopies every 4 years for individuals with 1 first-degree relative diagnosed before age 50 years, 13 colonoscopies every 3 years for individuals with 2 or more first-degree relatives diagnosed after age 50 years, and 15 colonoscopies every 3 years for individuals with 2 or more first-degree relatives of whom at least 1 was diagnosed before age 50 years. CONCLUSIONS: The optimal screening strategy varies considerably with the number of affected first-degree relatives and their age of diagnosis. Shorter screening intervals than the currently recommended 5 years may be appropriate for the highest risk individuals.

Attempting to explain heterogeneous HIV epidemics in sub-Saharan Africa: potential role of historical changes in risk behaviour and male circumcision.

BACKGROUND: A key conclusion of the Four Cities Study, carried out to explore reasons for heterogeneity in the HIV epidemic between two cities in sub-Saharan Africa with relatively low prevalence (Cotonou and Yaoundé) and two with high prevalence (Kisumu and Ndola), was that differences in biological cofactors outweighed differences in sexual risk behaviours. The authors explore an alternative hypothesis, that risk behaviours were historically higher in the high-prevalence cities. They also investigate the effects of different prevalence of male circumcision on the HIV epidemics in the four cities. METHODS: A transmission model was fitted to data from the Four Cities Study. Default scenarios included biological cofactor effects on HIV transmission. Counter-factual scenarios were simulated without biological cofactors, with and without higher historical sexual behaviours, and with various rates of male circumcision. RESULTS: Simulated adult HIV prevalence in 1997 for the default scenarios was 3.1%, 7.8%, 28.9% and 27.1% in Cotonou, Yaoundé, Kisumu and Ndola, respectively, in line with data. Without biological cofactors, even implausibly high historical levels of risk behaviour in East Africa could not reproduce the observed heterogeneity in the late 1990s. Increasing the proportion of men circumcised in Ndola from 10% to 100% reduced HIV prevalence in 1997 to 7%. Decreasing the proportion circumcised in Yaoundé from 100% to 10% increased HIV prevalence to 26%. CONCLUSIONS: Differences in male circumcision rates are likely to have played a key role in the heterogeneous spread of HIV across Africa. The effect of circumcision interventions can vary depending on the epidemic setting, with a larger effect in more generalised epidemics.

Practical implications of differential discounting in cost-effectiveness analyses with varying numbers of cohorts.

OBJECTIVE: To call attention to the influence of the number of birth-cohorts used in cost-effectiveness analysis (CEA) models on incremental cost-effectiveness ratios (ICERs) under differential discounting. METHODS: The consequences of increasing the number of birth-cohorts are demonstrated using a CEA of cervical cancer prevention as an example. The cost-effectiveness of vaccinating 12-year-old girls against the human papillomavirus is estimated with the MISCAN microsimulation screening analysis model for 1, 10, 20, and 30 birth-cohorts. Costs and health effects are discounted with equal rates of 4% and alternatively with differential rates of 4% and 1.5% respectively. The effects of increasing the number of cohorts are shown by comparing the ICERs under equal and differential discounting. RESULTS: The ICER decreases as the number of cohorts increases under differential discounting, but not under equal discounting. CONCLUSIONS: The variation of ICERs with the number of cohorts under differential discounting prompts questions regarding the appropriate specification of CEA models and interpretation of their results. In particular, it raises concerns that arbitrary variation in study specification leads to arbitrary variation in results. Such variations could lead to erroneous policy decisions. These findings are relevant to CEA guidance authorities, CEA practitioners, and decision makers. Our results do not imply a problem with differential discounting per se, yet they highlight the need for practical guidance for its use.

Anaplasma phagocytophilum from Rodents and Sheep, China.

To characterize the strains of Anaplasma phagocytophilum in wild and domestic animals in China, we isolated the organism from rodents and sheep in northeastern China. We isolated 3 strains (2 from rodents and 1 from sick sheep) through propagation in BALB/c mice and then cell culture in HL60 cells. The 3 isolates were identified by Wright-Giemsa staining, immunofluorescence, and electronic microscopy and were characterized by sequence analyses of the 16S rRNA gene, partial citrate synthase gene, major surface protein 4 gene, and heat shock protein gene. The multiple sequences of the 3 isolates were identical to each other but different from all known strains from other countries. The public health and veterinary relevance of the isolates deserves further investigation.

Increased risk of adenomas in individuals with a family history of colorectal cancer: results of a meta-analysis.

OBJECTIVE: It is unclear to what extent the increased risk of colorectal cancer in individuals with a family history of colorectal cancer and no known genetic disorders is associated with a higher adenoma prevalence. Our aim is to estimate the relative difference in adenoma prevalence and its age-pattern in individuals with a family history of colorectal cancer compared to those without. METHODS: We performed a literature search to identify colonoscopy studies reporting the adenoma prevalence by age. Using multilevel logistic regression, we examined how the adenoma prevalence by age differed between individuals with and without a family history of colorectal cancer. We excluded members of families with a known genetic disorder. RESULTS: Thirteen colonoscopy studies were identified. The adenoma prevalence was significantly higher in individuals with a family history than in those without (OR 1.7, 95% CI 1.4-3.5). The adenoma prevalence increased with age (OR per year of age 1.06, 95% CI 1.05-1.07). The age trend did not differ significantly between the two groups. CONCLUSION: Individuals with a family history of colorectal cancer have a considerably higher prevalence of adenomas compared to individuals without a family history. This is consistent with their increased risk of colorectal cancer.

Strong association between in-migration and HIV prevalence in urban sub-Saharan Africa.

BACKGROUND: Enormous variation exists in HIV prevalence between countries in sub-Saharan Africa. The contribution of migration to the spread of HIV has long been recognized, but its effect at the population level has never been assessed. In this ecological analysis, we explore how much variation in HIV prevalence in urban sub-Saharan Africa is explained by in-migration. METHODS: We performed a linear regression to analyze the association between the proportion of recent in-migrants and HIV prevalence for men and women in urban areas, using 60 data points from 28 sub-Saharan African countries between 1987 and 2005. RESULTS: We found a strong association between recent in-migration and HIV prevalence for women (Pearson R = 57%, P < 0.001) and men (R = 24%, P = 0.016), taking the earliest data point for each country. For women, the association was also strong within east/southern Africa (R = 50%, P = 0.003). For both genders, the association was strongest between 1985 and 1994, slightly weaker between 1995 and 1999, and nonexistent as from 2000. The overall association for both men and women was not confounded by the developmental indicators GNI per capita, income inequalities, or adult literacy. CONCLUSIONS: Migration explains much of the variation in HIV spread in urban areas of sub-Saharan Africa, especially before the year 2000, after which HIV prevalences started to level off in many countries. Our findings suggest that migration is an important factor in the spread of HIV, especially in rapidly increasing epidemics. This may be of relevance to the current HIV epidemics in China and India.

Probiotic yogurt consumption is associated with an increase of CD4 count among people living with HIV/AIDS.

AIM: To evaluate the long term effect of yogurt supplemented with Lactobacillus rhamnosus Fiti on the immune function (CD4 count) of people living with HIV/AIDS. BACKGROUND: Gastrointestinal infections and the leakage of microbial products from the gut have a profound impact on the deterioration of the immune system among people living with HIV/AIDS. Among persons not infected with the virus, probiotics can prevent gastrointestinal infections and restore an effective gut barrier, suggesting they might have a beneficial effect on the immune function of people living with HIV/AIDS. STUDY: We carried out an observational retrospective study over a period of 3 years, with longitudinal comparison of the CD4 count within participants (n=68) before and during probiotic yogurt consumption, and compared with a control group of participants not consuming the yogurt (n=82). RESULTS: Among the yogurt consumers before use and the nonconsumers, an average increase in CD4 count was seen of 0.13 cells/µL/day (95% CI; 0.07-0.20, P=<0.001). After commencing consumption, yogurt consumers experienced an additional increase of 0.28 cells/µL/day (95% CI; 0.10-0.46, P=0.003). When adjusting for length of time using antiretroviral medication, the additional increase explained by yogurt consumption remained 0.17 cells/µL/day (95% CI; 0.01-0.34, P=0.04). Treatment with antiretroviral medication was associated with an increase of 0.27 cells/µL/day (95% CI; 0.17-0.38, P=<0.001). CONCLUSION: The introduction of probiotic yogurt, made by local women in a low-income community in Tanzania, was significantly associated with an increase in CD4 count among consumers living with HIV.

Labeled versus unlabeled discrete choice experiments in health economics: an application to colorectal cancer screening.

OBJECTIVES: Discrete choice experiments (DCEs) in health economics commonly present choice sets in an unlabeled form. Labeled choice sets are less abstract and may increase the validity of the results. We empirically compared the feasibility, respondents' trading behavior, and convergent validity between a labeled and an unlabeled DCE for colorectal cancer (CRC) screening programs in The Netherlands. METHODS: A labeled DCE version presented CRC screening test alternatives as "fecal occult blood test,""sigmoidoscopy," and "colonoscopy," whereas the unlabeled DCE version presented them as "screening test A" and "screening test B." Questionnaires were sent to participants and nonparticipants in CRC screening. RESULTS: Total response rate was 276 (39%) out of 712 and 1033 (46%) out of 2267 for unlabeled and labeled DCEs, respectively (P<0.001). The labels played a significant role in individual choices; approximately 22% of subjects had dominant preferences for screening test labels. The convergent validity was modest to low (participants in CRC screening: r=0.54; P=0.01; nonparticipants: r=0.17; P=0.45) largely because of different preferences for screening frequency. CONCLUSION: This study provides important insights in the feasibility and difference in results from labeled and unlabeled DCEs. The inclusion of labels appeared to play a significant role in individual choices but reduced the attention respondents give to the attributes. As a result, unlabeled DCEs may be more suitable to investigate trade-offs between attributes and for respondents who do not have familiarity with the alternative labels, whereas labeled DCEs may be more suitable to explain real-life choices such as uptake of cancer screening.

A randomised controlled trial on the effectiveness of bracing patients with idiopathic scoliosis: failure to include patients and lessons to be learnt.

Trials often do not succeed in including as many patients as anticipated beforehand. The aim of this paper was to describe why we were not able to include more than a few patients in our randomized controlled treatment trial on the effectiveness of bracing patients with idiopathic scoliosis, and to describe which lessons can be learnt. A pilot study on the willingness to participate in such a trial was conducted amongst 21 patients and their parents. A description of how we prepared and designed this trial, the problems we faced and how we tried to improve the inclusion are given. A total of four patients were included, and 14 refused to participate in an 18-month period. There were a lot less eligible patients than anticipated (40 instead of 100 per year), and the patients' participation rate was much lower than we had found in our pilot study (21% instead of 70%). The trial failed to include more than a few patients because of an overestimation of the number of eligible patients and because a lot less eligible patients were willing to participate compared to our pilot study. One reason for a low participation rate could be that this trial evaluated a frequently used existing treatment instead of a new treatment, and patients and parents might be afraid of not being treated (despite an intensive secure system for the control arm).

Tick-borne agents in rodents, China, 2004-2006.

A total of 705 rodents from 6 provinces and autonomous regions of mainland People's Republic of China were tested by PCRs for tick-borne agents (Anaplasma phagocytophilum, Borrelia burgdorferi sensu lato, spotted fever group rickettsiae, and Francisella tularensis). Infection rates were 5.5%, 6.7%, 9.1% and 5.0%, respectively. Eighteen (2.6%) rodents of 10 species were positive for 2 or 3 agents. Sequence analysis of PCR products confirmed the presence and genotypes of detected agents. These findings demonstrate that these tick-borne agents cocirculate and that a variety of rodent species may be involved in their enzootic maintenance.