The addition of the sFlt-1/PlGF ratio to the protein/creatinine ratio in multiple pregnancy: Post-hoc analysis of the PREPARE cohort study.

OBJECTIVE: To assess the predictive accuracy of the sFlt-1/PlGF ratio cut-off 38 in addition to the standard-of-care spot urine protein/creatinine ratio (PCr) for multiple pregnancies in women with suspected pre-eclampsia. STUDY DESIGN: Post-hoc analysis of a prospective cohort study. MAIN OUTCOME MEASURES: Primary outcome was the occurrence of pre-eclampsia in one and four weeks after presentation with suspected pre-eclampsia. Test characteristics with 95% confidence intervals (CI) were calculated on pre-eclampsia development in one and four weeks. RESULTS: Twenty-three multiple pregnancies with suspected pre-eclampsia between 20 and 37 weeks gestation were included for analysis. Women who eventually developed pre-eclampsia had a significantly higher PCr (34.0 vs. 16.5, p = 0.015), sFlt-1 (17033 vs. 5270 pg/ml, p = 0.047) and sFlt-1/PlGF ratio (99 vs. 25, p = 0.033) at baseline. Furthermore, PCr ≥ 30 and sFlt-1/PlGF ratio > 38 was respectively seen in 1/16 (6.3 %) and 3/16 (18.8 %) of the women who did not develop pre-eclampsia. For predicting pre-eclampsia within one week the sFlt-1/PlGF ratio sensitivity was 75.0 % [95 % CI 19.4-99.4] and the negative predictive value 93.8 % [73.0-98.8], while no pre-eclampsia developed when PCr was < 30. Consequently, the combination of these tests did not lead to an improvement in test characteristics, with non-significant differences in positive predictive value (50.0 % [29.5-70.5] versus 80.0 % [37.3-96.4]) compared to PCr alone for pre-eclampsia development in one week. CONCLUSIONS: In addition to standard-of-care spot urine PCr measurements, this study has not been able to demonstrate that the sFlt-1/PlGF ratio cut-off 38 is of added value in the prediction of pre-eclampsia in multiple pregnancy. TRIAL REGISTRATION: Netherlands Trial Register (NL8308).

Clinical value and cost analysis of the sFlt-1/PlGF ratio in addition to the spot urine protein/creatinine ratio in women with suspected pre-eclampsia: PREPARE cohort study.

BACKGROUND: This study investigated the clinical value of adding the sFlt-1/PlGF ratio to the spot urine protein/creatinine ratio (PCr) in women with suspected pre-eclampsia. METHODS: This was a prospective cohort study performed in a tertiary referral centre. Based on the combination of PCr (< 30) and sFlt-1/PlGF (≤38) results, four groups were described: a double negative result, group A-/-; a negative PCr and positive sFlt-1/PlGF, group B-/+; a positive PCr and negative sFlt-1/PlGF, group C+/-; and a double positive result, group D+/+. The primary outcome was the proportion of false negatives of the combined tests in comparison with PCr alone in the first week after baseline. Secondary, a cost analysis comparing the costs and savings of adding the sFlt-1/PlGF ratio was performed for different follow-up scenarios. RESULTS: A total of 199 women were included. Pre-eclampsia in the first week was observed in 2 women (2%) in group A-/-, 12 (26%) in group B-/+, 4 (27%) in group C+/-, and 12 (92%) in group D+/+. The proportion of false negatives of 8.2% [95% CI 4.9-13.3] with the PCr alone was significantly reduced to 1.6% [0.4-5.7] by adding a negative sFlt-1/PlGF ratio. Furthermore, the addition of the sFlt-1/PlGF ratio to the spot urine PCr, with telemonitoring of women at risk, could result in a reduction of 41% admissions and 36% outpatient visits, leading to a cost reduction of €46,- per patient. CONCLUSIONS: Implementation of the sFlt-1/PlGF ratio in addition to the spot urine PCr, may lead to improved selection of women at low risk and a reduction of hospital care for women with suspected pre-eclampsia. TRIAL REGISTRATION: Netherlands Trial Register (NL8308).

A tailored intervention does not reduce low value MRI's and arthroscopies in degenerative knee disease when the secular time trend is taken into account: a difference-in-difference analysis.

PURPOSE: To evaluate the effectiveness of a tailored intervention to reduce low value MRIs and arthroscopies among patients ≥ 50 years with degenerative knee disease in 13 Dutch orthopaedic centers (intervention group) compared with all other Dutch orthopaedic centers (control group). METHODS: All patients with degenerative knee disease ≥ 50 years admitted to Dutch orthopaedic centers from January 2016 to December 2018 were included. The tailored intervention included participation of clinical champions, education on the Dutch Choosing Wisely recommendation for MRI's and arthroscopies in degenerative knee disease, training of orthopaedic surgeons to manage patient expectations, performance feedback, and provision of a patient brochure. A difference-in-difference analysis was used to compare the time trend before (admitted January 2016-June 2017) and after introduction of the intervention (July 2017-December 2018) between intervention and control hospitals. Primary outcome was the monthly percentage of patients receiving a MRI or knee arthroscopy, weighted by type of hospital. RESULTS: 136,446 patients were included, of whom 32,163 were treated in the intervention hospitals. The weighted percentage of patients receiving a MRI on average declined by 0.15% per month (ß = - 0.15, P < 0.001) and by 0.19% per month for arthroscopy (ß = - 0.19, P < 0.001). However, these changes over time did not differ between intervention and control hospitals, neither for MRI (ß = - 0.74, P = 0.228) nor arthroscopy (ß = 0.13, P = 0.688). CONCLUSIONS: The extent to which patients ≥ 50 years with degenerative knee disease received a MRI or arthroscopy declined significantly over time, but could not be attributed to the tailored intervention. This secular downward time trend may reflect anoverall focus of reducing low value care in The Netherlands. LEVEL OF EVIDENCE: III.

Challenges in economic evaluations in obstetric care: a scoping review and expert opinion.

OBJECTIVE: The aim of this study is to identify items of economic evaluation guidelines that are frequently not complied within obstetric economic evaluations and to search for reasons for non-adherence. DESIGN: Scoping review and qualitative study. SETTING: Literature on economic evaluations in obstetric care and interviews with experts. POPULATION OR SAMPLE: The sample included 229 scientific articles and five experts. METHODS: A systematic literature search was performed. All types of literature about economic evaluations in obstetric care were included. The adherence to guidelines was assessed and articles were qualitatively analysed on additional information about reasons for non-adherence. Issues that arose from the scoping review were discussed with experts. MAIN OUTCOME MEASURES: Adherence to guideline items of the included economic evaluations studies. Analytical themes describing reasons for non-adherence, resulting from qualitative analysis of articles and interviews with experts. RESULTS: A total of 184 economic evaluations and 45 other type of articles were included. Guideline items frequently not complied with were time horizon, type of economic evaluation and effect measure. Reasons for non-adherence had to do with paucity of long-term health data and assessing and combining outcomes for mother and child resulting from obstetric interventions. CONCLUSIONS: This study identified items of guidelines that are frequently not complied with and the reasons behind this. The results are a starting point for a broad consensus building on how to deal with these challenges that can result in special guidance for the conduct of economic evaluations in obstetric care. TWEETABLE ABSTRACT: Non-adherence to guidelines in obstetric economic evaluation studies: the difficulties in detail.

Study protocol for the DEFENDD trial: an RCT on the Dynamic Locking Blade Plate (DLBP) versus the Dynamic Hip Screw (DHS) for displaced femoral neck fractures in patients 65 years and younger.

BACKGROUND: The Dynamic Locking Blade Plate (DLBP) was recently introduced for fixation of displaced femoral neck fractures (FNF) and has been well received. Although the results of this implant in young patients are promising, the DLBP has not yet been compared to a standard device such as the Dynamic Hip Screw (DHS). The aim of this study is to compare the clinical outcome and costs of displaced FNF treated with internal fixation by means of either the DLBP or the DHS in patients up to 65 years of age. We hypothesize that the DLBP is superior compared to the DHS in terms of revision surgery rate, union rate, incidence of avascular necrosis and implant related failure. METHODS: The DEFENDD (DisplacEd Femoral Neck fractures Dlbp versus Dhs) trial is a multicentre randomized controlled trial that will include 266 patients of 18-65 years with a displaced FNF. Patients will be randomized to receive either a DLBP or a DHS with a 1:1 allocation using a random block size, stratified for centre. Clinical follow up will last 1 year and questionnaires will be obtained up to 2 years. The main outcome parameter is the incidence of revision surgery within 1 year, due to either non-union, avascular necrosis (AVN) or cut out of the implant. Secondary study parameters are the incidence of avascular necrosis, non-union, (implant related) complications, functional outcome, elective removal of the implant and health-related quality of life and costs. DISCUSSION: The outcome of the DEFENDD trial will provide high-level evidence of which implant is favourable for the treatment of femoral neck fractures in young patients (≤65 years). TRIAL REGISTRATION: Netherlands Trial Register, NL7300 Registration date 25-09-2018.

Preferences and beliefs of Dutch orthopaedic surgeons and patients reduce the implementation of "Choosing Wisely" recommendations in degenerative knee disease.

PURPOSE: The purpose of this study was to assess which factors were associated with the implementation of "Choosing Wisely" recommendations to refrain from routine MRI and arthroscopy use in degenerative knee disease. METHODS: Cross-sectional surveys were sent to 123 patients (response rate 95%) and 413 orthopaedic surgeons (response rate 62%) fulfilling the inclusion criteria. Univariate and multivariate logistic regression analyses were used to identify factors associated with implementation of "Choosing Wisely" recommendations. RESULTS: Factors reducing implementation of the MRI recommendation among patients included explanation of added value by an orthopaedic surgeon [OR 0.18 (95% CI 0.07-0.47)] and patient preference for MRI [OR 0.27 (95% CI 0.08-0.92)]. Factors reducing implementation among orthopaedic surgeons were higher valuation of own MRI experience than existing evidence [OR 0.41 (95% CI 0.19-0.88)] and higher estimated patients' knowledge to participate in shared decision-making [OR 0.38 (95% CI 0.17-0.88)]. Factors reducing implementation of the arthroscopy recommendation among patients were orthopaedic surgeons' preferences for an arthroscopy [OR 0.03 (95% CI 0.00-0.22)] and positive experiences with arthroscopy of friends/family [OR 0.03 (95% CI 0.00-0.39)]. Factors reducing implementation among orthopaedic surgeons were higher valuation of own arthroscopy experience than existing evidence [OR 0.17 (95% CI 0.07-0.46)] and belief in the added value [OR 0.28 (95% CI 0.10-0.81)]. CONCLUSIONS: Implementation of "Choosing Wisely" recommendations in degenerative knee disease can be improved by strategies to change clinician beliefs about the added value of MRIs and arthroscopies, and by patient-directed strategies addressing patient preferences and underlying beliefs for added value of MRI and arthroscopies resulting from experiences of people in their environment. LEVEL OF EVIDENCE: IV.

Typology of birth centres in the Netherlands using the Rainbow model of integrated care: results of the Dutch Birth Centre Study.

BACKGROUND: The goal of integrated care is to offer a continuum of care that crosses the boundaries of public health, primary, secondary, and tertiary care. Integrated care is increasingly promoted for people with complex needs and has also recently been promoted in maternity care systems to improve the quality of care. Especially when located near an obstetric unit, birth centres are considered to be ideal settings for the realization of integrated care. At present, however, we know very little about the degree of integration in these centres and we do not know if increased levels of integration improve the quality of the care delivered. The Dutch Birth Centre Study is designed to evaluate birth centres and their contribution to the Dutch maternity care system. The aim of this particular sub-study is to classify birth centres in clusters with similar characteristics based on integration profiles, to support the evaluation of birth centre care. METHODS: This study is based on the Rainbow Model of Integrated Care. We used a survey followed by qualitative interviews in 23 birth centres in the Netherlands to determine which integration profiles can be distinguished and to describe their discriminating characteristics. Cluster analysis was used to classify the birth centres. RESULTS: Birth centres were classified into three clusters: 1)"Mono-disciplinary-oriented birth centres" (n = 10): which are mainly owned by primary care organizations and established as physical facilities to provide an alternative birthplace for low risk births; 2) "Multi-disciplinary-oriented birth centres" (n = 6): which are mainly multi-disciplinary oriented and can be regarded as facilities to give birth, with a focus on integrated birth care; 3) "Mixed Cluster of birth centres" (n = 7): which have a range of organizational forms that differentiate them from centres in the other clusters. CONCLUSION: We identified a recognizable classification, with similar characteristics between birth centres in the clusters. The results of this study can be used to relate integration profiles of birth centres to quality of care, costs, and perinatal outcomes. This assessment makes it possible to develop recommendations with regard to the type and degree of integration of Dutch birth centres in the future.

Cost-utility of an internet-based intervention with or without therapist support in comparison with a waiting list for individuals with eating disorder symptoms: a randomized controlled trial.

OBJECTIVE: To investigate the cost-utility of the internet-based intervention "Featback" provided with different levels of therapist support, in comparison to a waiting list. METHOD: This economic evaluation was conducted from a societal perspective and was part of a randomized controlled trial in which participants (N = 354) with self-reported ED symptoms were randomized to: (1) 8 weeks of Featback, consisting of psychoeducation and a fully automated monitoring- and feedback system, (2) Featback with low-intensity (weekly) therapist support, (3) Featback with high-intensity (three times a week) therapist support, and (4) a waiting list. Participants were assessed at baseline, postintervention, and 3-month follow-up. Cost-utility acceptability curves were constructed. RESULTS: No significant differences between the study conditions were found regarding quality-adjusted life-years (P = 0.55) and societal costs (P = 0.45), although the mean costs per participant were lowest in the Featback condition with low-intensity therapist support (€1951), followed by Featback with high-intensity therapist support (€2032), Featback without therapist support (€2102), and the waiting list (€2582). Featback seemed to be cost-effective as compared to the waiting list. No clear preference was found for Featback with or without therapist support. DISCUSSION: A fully automated Internet-based intervention for ED symptoms with no, low-, or high-intensity therapist support represented good value for money when compared to a waiting list. This finding may have important implications for clinical practice, as both the unguided- and guided intervention could allow for more efficient care and widespread dissemination, potentially increasing the accessibility and availability of mental health care services for individuals with ED symptoms. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:1068-1076).

Erythropoietin to reduce allogeneic red blood cell transfusion in patients undergoing total hip or knee arthroplasty.

BACKGROUND AND OBJECTIVES: To determine the value of erythropoietin in reducing allogeneic transfusions, it is important to assess the effects, safety and costs for individual indications. Previous studies neither compared the effects of erythropoietin between total hip and total knee arthroplasty, nor evaluated the safety or costs. We performed a meta-analysis to assess the effects of erythropoietin in total hip and knee arthroplasty separately. Safety and costs were evaluated as secondary outcomes. MATERIALS AND METHODS: A systematic literature search was performed to identify randomized controlled trials evaluating the effect of erythropoietin in total hip and knee arthroplasty until April 2014. Study data were extracted using standardized forms and pooled using a random-effects model. Strength of the evidence was evaluated using Cochrane's Collaboration's tool for risk of bias assessment. RESULTS: Seven studies were included (2439 patients). Erythropoietin significantly reduced exposure to allogeneic transfusion in both hip (RR 0·45; 95%CI 0·33-0·61) and knee (RR 0·38; 95%CI 0·27-0·53) arthroplasty, without differences between indications (P = 0·44). Mean number of transfused red blood cell units was significantly decreased in erythropoietin-treated patients (mean difference -0·57; 95%CI -0·86 to -0·29)(unable to split). No differences in thromboembolic or adverse events were found. Only one study evaluated costs, so that no pooled cost-effectiveness estimates could be given. CONCLUSION: Erythropoietin is effective in both hip and knee arthroplasty and can be considered as safe. However, the decision to use erythropoietin on a routine base should be balanced against its costs, which may be relatively high.

Cost-effectiveness of newborn screening for cystic fibrosis determined with real-life data.

BACKGROUND: Previous cost-effectiveness studies using data from the literature showed that newborn screening for cystic fibrosis (NBSCF) is a good economic option with positive health effects and longer survival. METHODS: We used primary data to compare cost-effectiveness of four screening strategies for NBSCF, i.e. immunoreactive trypsinogen-testing followed by pancreatitis-associated protein-testing (IRT-PAP), IRT-DNA, IRT-DNA-sequencing, and IRT-PAP-DNA-sequencing, each compared to no-screening. A previously developed decision analysis model for NBSCF was fed with model parameters mainly based on a study evaluating two novel screening strategies among 145,499 newborns in The Netherlands. RESULTS: The four screening strategies had cost-effectiveness ratios varying from €23,600 to €29,200 per life-year gained. IRT-PAP had the most favourable cost-effectiveness ratio. Additional life-years can be gained by IRT-DNA but against higher costs. When treatment costs reduce with 5% due to early diagnosis, screening will lead to financial savings. CONCLUSION: NBSCF is as an economically justifiable public health initiative. Of the four strategies tested IRT-PAP is the most economic and this finding should be included in any decision making model, when considering implementation of newborn screening for CF.

Impact of scalp cooling on chemotherapy-induced alopecia, wig use and hair growth of patients with cancer.

INTRODUCTION: Cytotoxic therapy for patients with cancer frequently induces reversible, but long-lasting alopecia which might be prevented by scalp cooling. This study evaluates the effectiveness of scalp cooling with respect to the severity of chemotherapy-induced alopecia (CIA) and the purchase and use of wigs and head covers. MATERIALS AND METHODS: In this observational study, scalp-cooled patients (n = 160) were compared with non scalp-cooled patients (n = 86) with several types of cancer. Patients were enrolled in 15, mostly general hospitals prior to taxane and/or anthracycline-based chemotherapy. Patients completed four questionnaires between the start and one year after the last chemotherapy. RESULTS: Severity of CIA, and purchasing and actually wearing wigs and head covers were significantly lower among scalp-cooled than non scalp-cooled patients. Overall, scalp cooling reduced the use of wigs and head covers by 40%. Among 84 scalp-cooled patients who purchased a wig (53%), only 52 patients actually wore it (62%), and they just wore it intensively (86% daily) for less than six months (80%). Especially young patients camouflaged CIA with a head cover instead of a wig. DISCUSSION: The relatively long duration of CIA, the wish of many patients to camouflage or rather prevent it and the 40% reduction for head covering by scalp cooling, makes it a worthwhile supportive intervention. However, (cost-) effectiveness can be improved. Many scalp-cooled patients purchased a wig unnecessarily.

Costs associated with persistent allergic rhinitis are reduced by levocetirizine.

BACKGROUND: Allergic rhinitis was recently classified by the ARIA guidelines as persistent or intermittent. Levocetirizine was shown to improve symptoms and health-related quality of life of patients with persistent allergic rhinitis in the XPERT study, a 6-month randomized double blind placebo-controlled trial. OBJECTIVE: To assess the total costs of persistent allergic rhinitis, and the effect of long-term treatment with levocetirizine on these costs from several perspectives (societal, social security system, and employers). METHODS: Direct medical cost parameters (medications, physician visits and hospitalizations) and time lost parameters (workdays and Usual Daily Activities (UDA) lost) related to persistent allergic rhinitis and its comorbidities (asthma, sinusitis, otitis and upper respiratory infection) were measured. A cost analysis was performed using 2002 French costing data. RESULTS: From a societal perspective, the total cost of persistent allergic rhinitis without long-term treatment was estimated at 355.06/patient/month. From a social security perspective, levocetirizine treatment yielded an additional cost of 2.78/patient/month, compared to no-treatment. However, levocetirizine reduced the total cost of persistent allergic rhinitis and its comorbidities by 152.93/patient/month from a societal perspective and by 64.70/patient/month from an employer perspective. Most gains resulted from a decrease in the lost workdays and UDA in the levocetirizine group. CONCLUSION: The cost of persistent allergic rhinitis is substantial. Treatment with levocetirizine reduces the cost of persistent allergic rhinitis and its comorbidities to the society by 152.93/patient/month while improving symptoms and health-related quality of life.

Cost-effectiveness of stereotactic large-core needle biopsy for nonpalpable breast lesions compared to open-breast biopsy.

This paper demonstrates that the introduction of large-core needle biopsy (LCNB) replacing needle-localised breast biopsy (NLBB) for nonpalpable (screen-detected) breast lesions could result in substantial cost savings at the expense of a possible slight increase in breast cancer mortality. The cost-effectiveness of LCNB and NLBB was estimated using a microsimulation model. The sensitivity of LCNB (0.97) and resource use and costs of LCNB and NLBB were derived from a multicentre consecutive cohort study among 973 women who consented in getting LCNB and NLBB, if LCNB was negative. Sensitivity analyses were performed. Replacing NLBB with LCNB would result in approximately six more breast cancer deaths per year (in a target population of 2.1 million women), or in 1000 extra life-years lost from breast cancer (effect over 100 years). The total costs of management of breast cancer (3% discounted) are estimated at pound 4676 million with NLBB; introducing LCNB would save pound 13 million. The incremental cost-effectiveness ratio of continued NLBB vs LCNB would be pound 12 482 per additional life-year gained (3% discounted); incremental costs range from pound -21 687 (low threshold for breast biopsy) to pound 74 378 (high sensitivity of LCNB).

Low risk of cervical cancer during a long period after negative screening in the Netherlands.

A condition for effective cervical cancer screening is a low incidence of cervical cancer after negative screening compared to that in the absence of screening. This relative risk was studied for the period 1994-1997 in the Netherlands and compared with previous studies. All cases of invasive cervical cancer diagnosed from 1994 to 1997 in the Netherlands were related to woman-years at risk, stratified by age, number of preceding negative screenings and time since the preceding negative screening. These incidence rates were compared with that before screening started in the Netherlands. The relative risk increases from 0.13 in the first year after screening to 0.24 after more than 6 years after screening for women with one previous negative screening. These figures reduce to 0.06 and 0.18, respectively, for women with two or more previous screenings. However, these estimates are less favourable when account is taken of the likely decrease in risk for cervical cancer in the period studied. Our data show a low relative risk of cervical cancer for several years following the last negative Pap smear. However, the denominator of the relative risk, that is, the incidence without screening, may have been overestimated. This applies also to the IARC multicountry study, and may have caused too optimistic expectations about the effectiveness of cervical cancer screening.

[Less pap-2 results ('minor abnormalities') in the population screening for cervical cancer since the introduction of new guidelines in 1996]. / Minder Pap-2-uitslagen ('lichte afwijkingen') in het bevolkingsonderzoek naar baarmoederhalskanker sinds de invoering van nieuwe richtlijnen in 1996.

OBJECTIVE: To determine whether the 1996 implementation of new guidelines for the classification and management of cervical smears in the Dutch population screening programme for cervical cancer (i.e. inflammatory symptoms are no longer classified as moderate dysplasia and women with two smears with moderate dysplasia are referred directly to the gynaecologist) was followed by a reduction in both the number of women with repeat smears and the length of follow-up. METHODS: The results of all smears of women aged 35-54 years from 1990 onwards, were retrieved from the Dutch Network and National Database for Pathology (PALGA). The percentage of smears with moderate dysplasia was analysed with respect to time. The percentage of women with a histological examination during the follow-up phase of the population screening programme (1990 and 1991) was compared with that for the new screening programme (1996). RESULTS: Following the implementation of the new guidelines, the percentage of smears with moderate dysplasia was reduced from 10% to 2%. The percentage of women with a histological examination during the follow up of two smears with moderate dysplasia remained the same. The new recommendations for additional smears were not followed: for 28% no repeat smear was available after 2.25 years versus 10% in 1992. There were indications that the referral of women with two cases of moderate dysplasia to a gynaecologist was not strictly adhered to either. Since the introduction of the new guidelines, the estimated percentage of women that should be referred to the gynaecologist following smears with moderate dysplasia has not changed. CONCLUSION: The new recommendations have lead to fewer smears being classified as moderate dysplasia. The long-term effects, such as a reduction in the length of the follow-up period, can only be analysed in a few years time.

Endocervical status is not predictive of the incidence of cervical cancer in the years after negative smears.

The clinical relevance of the lack of endocervical cells was never well established in a longitudinal study with histologically proven cervical cancer as an end point. From the Dutch Network and National Database for Pathology, results for all negative smears obtained in 1990 and 1991 in the Netherlands were retrieved, as were data for all cytologic and histologic examinations performed after the negative smears before April 1998. There were no significant differences between the proportion of preinvasive lesions (cervical intraepithelial neoplasia 1, 2, and 3) detected after negative smears without endocervical cells compared with negative smears with endocervical cells. The proportion of women in whom invasive cancer developed was the same in both groups. These data suggest there is no reason to advise women with negative smears without endocervical cells to undergo an additional smear.

Breast cancer screening in Navarra: interpretation of a high detection rate at the first screening round and a low rate at the second round.

Our objective was to evaluate the on-going European pilot project for breast cancer screening in Navarra, Spain, and to predict the effects and costs of the programme in the long run. Observed results in Navarra, consisting of more than 100,000 screens, were compared with expected results. A microsimulation screening analysis model was used that included demographical, epidemiological and screening characteristics of Navarra. Alternative assumptions on epidemiological and screening characteristics were also addressed. The observed detection rate (5.9 per 1,000 screened women) in the first round was 18% higher than expected; the observed rate in the subsequent round (2.9) was 17% lower than expected. Longer pre-clinical durations, lower sensitivity or the existence of a high-risk group in Navarra could not satisfactorily explain the first and second round results together. Nevertheless, the programme will have an important health benefit for the women involved, due to an important trend in incidence in recent years and the relatively unfavourable clinical stage distribution in Navarra. The proportion T2+ cancers that will be prevented after 10 years of screening amounts to 36%. The annual mortality reduction in steady state is expected to range between 17% (if the observed rates in the second round indicate real screening performance) to 23% (if the first round indicates real performance). Our results demonstrate that a high detection rate in the first round is insufficient to evaluate the quality of a programme. Interval cancer rates, results of the subsequent round and size distributions are also crucial indicators of the quality of the screening programme and should be analysed in their specific context.

Present evidence on the value of HPV testing for cervical cancer screening: a model-based exploration of the (cost-)effectiveness.

Human papillomavirus (HPV) is the main risk factor for invasive cervical cancer. High risk ratios are found in cross-sectional data on HPV prevalence. The question raised is whether this present evidence is sufficient for making firm recommendations on HPV screening. A validated cervical cancer screening model was extended by adding HPV infection as a possible precursor of cervical intraepithelial neoplasia (CIN). Two widely different model quantifications were constructed so that both were compatible with the observed HPV risk ratios. One model assumed a much longer duration of HPV infection before progressing to CIN and a higher sensitivity of the HPV test than the other. In one version of the model, the calculated mortality reduction from HPV screening was higher and the (cost-)effectiveness was much better than for Pap smear screening. In the other version, outcomes were the opposite, although the cost-effectiveness of the combined HPV + cytology test was close to that of Pap smear screening. Although small follow-up studies and studies with limited strength of design suggest that HPV testing may well improve cervical cancer screening, only large longitudinal screening studies on the association between HPV infection and the development of neoplasias can give outcomes that would enable a firm conclusion to be made on the (cost-)effectiveness of HPV screening. Prospective studies should address women aged 30-60 years.