Geen basis voor verlaging onderste leeftijdsgrens van bevolkingsonderzoek op baarmoederhalskanker

Doel:\ud Nagaan of de onderste leeftijdsgrens van het bevolkingsonderzoek op baarmoederhalskanker verlaagd moet worden.\ud \ud Opzet:\ud Retrospectieve data-analyse.\ud \ud Methode:\ud Uit de Nederlandse Kankerregistratie werden alle gevallen geselecteerd van invasieve baarmoederhalskanker, gediagnosticeerd in de periode 1989-2003. Voor de leeftijdsgroep van 25-39 jaar waren ook gegevens beschikbaar over 2004 en 2005. Gegevens over sterfte werden verkregen via het Centraal Bureau voor de Statistiek. Trends werden beschreven met behulp van de geschatte jaarlijkse procentuele verandering en ‘joinpoint’-analyse.\ud \ud Resultaten:\ud Bij de 25-29-jarigen varieerde het aantal gevallen van baarmoederhalskanker van 0 tot 9 per jaar. De incidentie van baarmoederhalskanker daalde in de leeftijdsgroepen van 35-39 en 45-49 jaar (respectievelijk p < 0,001 en p = 0,012). Het aantal vrouwen dat stierf aan baarmoederhalskanker fluctueerde per jaar en daalde in de leeftijdsgroepen van 30-34 en 35-39 jaar (respectievelijk p = 0,01 en p = 0,03).\ud \ud Conclusie:\ud De incidentie- en sterftecijfers van baarmoederhalskanker onder vrouwen jonger dan 30 jaar zijn heel laag en stijgen niet. Met het verlagen van de onderste leeftijdsgrens van het bevolkingsonderzoek zouden veel afwijkingen worden opgespoord die normaliter in regressie zouden gaan. Omdat de voordelen van het verlagen van de leeftijdsgrens niet opwegen tegen de nadelen in termen van overbehandeling en angst heeft deze verlaging volgens ons op dit moment geen zin

Rapid elimination of cervical cancer while maintaining the harms and benefits ratio of cervical cancer screening: a modelling study

Background: Human papillomavirus (HPV) vaccination and intensifying screening expedite cervical cancer (CC) elimination, yet also deteriorate the balance between harms and benefits of screening. We aimed to find screening strategies that eliminate CC rapidly but maintain an acceptable harms-benefits ratio of screening. Methods: Two microsimulation models (STDSIM and MISCAN) were applied to simulate HPV transmission and CC screening for the Dutch female population between 2022 and 2100. We estimated the CC elimination year and harms-benefits ratios of screening for 228 unique scenarios varying in vaccination (coverage and vaccine type) and screening (coverage and number of lifetime invitations in vaccinated cohorts). The acceptable harms-benefits ratio was defined as the number of women needed to refer (NNR) to prevent one CC death under the current programme for unvaccinated cohorts (82.17). Results: Under current vaccination conditions (bivalent vaccine, 55% coverage in girls, 27.5% coverage in boys), maintaining current screening conditions is projected to eliminate CC by 2042, but increases the present NNR with 41%. Reducing the number of lifetime screens from presently five to three and increasing screening coverage (61% to 70%) would prevent an increase in harms and only delay elimination by 1 year. Scaling vaccination coverage to 90% in boys and girls with the nonavalent vaccine is estimated to eliminate CC by 2040 under current screening conditions, but exceeds the acceptable NNR with 23%. Here, changing from five to two lifetime screens would keep the NNR acceptable without delaying CC elimination. Conclusions: De-intensifying CC screening in vaccinated cohorts leads to little or no delay in CC elimination while it substantially reduces the harms of screening. Therefore, de-intensifying CC screening in vaccinated cohorts should be considered to ensure acceptable harms-benefits ratios on the road to CC elimination

The Natural Disease Course of Pancreatic Cyst–Associated Neoplasia, Dysplasia, and Ductal Adenocarcinoma:Results of a Microsimulation Model

Background &amp; Aims: Estimates on the progression of precursor lesions to pancreatic cancer (PC) are scarce. We used microsimulation modeling to gain insight into the natural disease course of PC and its precursors. This information is pivotal to explore the efficacy of PC screening. Methods: A Microsimulation Screening Analysis model was developed in which pancreatic intraepithelial neoplasms and cysts can evolve from low-grade dysplasia (LGD) to high-grade dysplasia (HGD) to PC. The model was calibrated to Dutch PC incidence data and Japanese precursor prevalence data (autopsy cases without PC) and provides estimates of PC progression (precursor lesion onset and stage duration).Results: Mean LGD state durations of cysts and pancreatic intraepithelial neoplasms were 15.8 years and 17.1 years, respectively. Mean HGD state duration was 5.8 years. For lesions that progress to PC, the mean duration was 4.8–4.9 years for LGD lesions and 4.0–4.1 years for HGD lesions. In 13.7% of individuals who developed PC, the HGD state lasted less than 1 year. The probability that an individual at age 50 years developed PC in the next 20 years was estimated to be 1.8% in the presence of any cyst and 6.1% in case of an LGD mucinous cyst. This 20-year PC risk was estimated to be 5.1% for individuals with an LGD pancreatic intraepithelial neoplasm. Conclusions: Mean duration of HGD lesions before development of PC was estimated to be 4.0 years. This implies a window of opportunity for screening, presuming the availability of a reliable diagnostic test. The probability that an LGD cyst will progress to cancer was predicted to be low.</p

Identifying key factors for the effectiveness of pancreatic cancer screening:A model-based analysis

Pancreatic cancer (PC) survival is poor, as detection usually occurs late, when treatment options are limited. Screening of high-risk individuals may enable early detection and a more favorable prognosis. Knowledge gaps prohibit establishing the effectiveness of screening. We developed a Microsimulation Screening Analysis model to analyze the impact of relevant uncertainties on the effect of PC screening in high-risk individuals. The model simulates two base cases: one in which lesions always progress to PC and one in which indolent and faster progressive lesions coexist. For each base case, the effect of annual and 5-yearly screening with endoscopic ultrasonography/magnetic resonance imaging was evaluated. The impact of variance in PC risk, screening test characteristics and surgery-related mortality was evaluated using sensitivity analyses. Screening resulted in a reduction of PC mortality by at least 16% in all simulated scenarios. This reduction depended strongly on the natural disease course (annual screening: −57% for “Progressive-only” vs −41% for “Indolent Included”). The number of screen and surveillance tests needed to prevent one cancer death was impacted most by PC risk. A 10% increase in test sensitivity reduced mortality by 1.9% at most. Test specificity is important for the number of surveillance tests. In conclusion, screening reduces PC mortality in all modeled scenarios. The natural disease course and PC risk strongly determines the effectiveness of screening. Test sensitivity seems of lesser influence than specificity. Future research should gain more insight in PC pathobiology to establish the true value of PC screening in high-risk individuals.</p

Ongelijke discontering van zorgkosten en -effecten: verwarrend

Discounting is a widely accepted practice in cost-effectiveness analysis to weigh future costs and effects for their timing. In 2006, the Dutch Health Care Insurance Board revised its recommended rates for discounting. They recommended differential discounting of costs and effects, whereby effects are discounted at a lower rate relative to the costs. The question is whether this guideline is to be generally used for decision-making in the Netherlands. We show how the use of unequal discount rates leads to confusing cost-effectiveness results and why further implementation guidelines are essential

Shift in harms and benefits of cervical cancer screening in the era of HPV screening and vaccination: a modelling study

Objective: To calculate the changes in harms and benefits of cervical cancer screening over the first three screening rounds of the Dutch high-risk human papillomavirus (hrHPV) screening programme. Design: Microsimulation study. Setting: Dutch hrHPV screening programme; women are invited for screening every 5 or 10 years (depending on age and screening history) from age 30 to 65. Population: Partly vaccinated population of 100 million Dutch women. Methods: Microsimulation model MISCAN was used to estimate screening effects. Sensitivity analyses were performed on test characteristics and attendance. Main outcome measures: Harms (screening tests, unnecessary referrals, treatment-related health problems), benefits (CIN2 + diagnoses) and programme efficiency (number needed to screen [NNS]) over the first (period 2017–2021), second (period 2022–2026) and third (period 2027–2031) rounds of hrHPV-based screening. Results: The number of screening tests and CIN2 + diagnoses decreased from the first to the second round (−25.8% and −23.6%, respectively). In the third screening round, these numbers decreased further, albeit only slightly (−2.7% and −5.3%, respectively). NNS to detect a CIN2 + remained constant over the rounds; however, it increased in younger age groups while decreasing in older age groups. Conclusion: Both harms and benefits of hrHPV screening decreased over the first screening rounds. For younger women, the efficiency would decrease, whereas longer screening intervals would lead to increased efficiency in older women. Programme efficiency overall remained stable, showing the importance of longer intervals for low-risk women. Tweetable abstract:: Cervical cancer screening: both harms and benefits of hrHPV screening will decrease in the future

Heterogeneity in Reports of Dementia Disease Duration and Severity: A Review of the Literature

Background: The burden of dementia is changing due to population aging and changes in incidence and risk factor profiles. Reliable projections of future disease burden require accurate estimates of disease duration across different stages of dementia severity. Objective: To provide an overview of current evidence on severity stage and disease duration in patients with dementia. Methods: We reviewed the literature on duration of mild cognitive impairment (MCI), dementia, and various dementia severity stages. Data on study setting, country, sample size, severity stages, dementia type, and definition of disease duration was collected. Weighted averages and Q-statistics were calculated within severity stages and duration definitions. Results: Of 732 screened articles, 15 reported the duration of one or more severity stages and only half of those reported severity stage onset to conversion to the following stage. In those studies, MCI, very mild dementia, and mild dementia stages lasted 3-4 years and moderate and severe dementia stages lasted 1-2 years. Information on the disease duration was reported in 93 (13%) of screened articles and varied from 1 to 17 years. Reporting of dementia severity stage and disease duration in the literature was highly heterogeneous, which was accounted for only in part by dementia type, study setting, or continent of data collection. Conclusion: The duration of dementia disease stages shortens with advancing stage. However, reliable modelling of future dementia burden and informing of intervention strategies will require more consistently reported duration estimates from studies that follow individuals longitudinally throughout their entire disease course

Projected prevalence and incidence of dementia accounting for secular trends and birth cohort effects: a population-based microsimulation study

There is need for accurate projections of the future dementia burden to prepare healthcare systems and policymakers. Existing projections only account for population ageing, not for observed declines in age-specific dementia incidence of 13% per decade. We developed a dementia microsimulation model that synthesizes population-based data from the Rotterdam Study with changes in demographics between birth cohorts from the early 1900s onwards. We determined dementia prevalence and incidence until 2050 for three different dementia incidence trend scenarios: (1) stable age-specific incidence, (2) linear decline by 13% per decade, (3) nonlinear declines averaging 13% per decade. Assuming a stable age-specific incidence resulted in a 130% increase in incidence and 118% in prevalence between 2020 and 2050. By contrast, the linearly declining trend resulted in substantially smaller increases of 58% in incidence (95%CI: 29–87%), and 43% in prevalence (95%CI: 13–66%), corresponding to 39% lower incidence and 36% lower prevalence by 2050 than in the stable-incidence scenario. Results for various non-linear declines fell between the stable and linear trend. The future burden of dementia is highly susceptible to achievable changes in age-specific incidence. Extension of previously established secular trends globally would reduce widely upheld projections of new dementia cases until 2050 by 39%