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IntroductionComparable indicators on complete cancer prevalence are increasingly needed in Europe to support survivorship care planning. Direct measures can be biased by limited registration time and estimates are needed to recover long term survivors. The completeness index method, based on incidence and survival modelling, is the standard most validated approach.MethodsWithin this framework, we consider two alternative approaches that do not require any direct modelling activity: i) empirical indices derived from long established European registries; ii) pre-calculated indices derived from US-SEER cancer registries. Relying on the EUROCARE-6 study dataset we compare standard vs alternative complete prevalence estimates using data from 62 registries in 27 countries by sex, cancer type and registration time.ResultsFor tumours mostly diagnosed in the elderly the empirical estimates differ little from standard estimates (on average less than 5% after 10-15 years of registration), especially for low prognosis cancers. For early-onset cancers (bone, brain, cervix uteri, testis, Hodgkin disease, soft tissues) the empirical method may produce substantial underestimations of complete prevalence (up to 20%) even when based on 35-year observations. SEER estimates are comparable to the standard ones for most cancers, including many early-onset tumours, even when derived from short time series (10-15 years). Longer observations are however needed when cancer-specific incidence and prognosis differ remarkably between US and European populations (endometrium, thyroid or stomach).DiscussionThese results may facilitate the dissemination of complete prevalence estimates across Europe and help bridge the current information gaps.

Tyrosine kinase inhibitors (TKIs) have been improving the prognosis of patients with chronic myeloid leukemia (CML), but there are still large differences in survival among European countries. This raises questions on the added value of results from population-based studies, which use real-world data, compared to results of randomized controlled trials (RCTs) involving patients with CML. There are also questions about the extent of the findings on RCTs effectiveness for patients in the general population. We compare survival data extracted from our previous systematic review and meta-analysis of CML RCTs with the latest updated population-based survival data of EUROCARE-6, the widest collaborative study on cancer survival in Europe. The EUROCARE-6 CML survival estimated in patients (15–64 years) diagnosed in 2000–2006 vs. 2007–2013 revealed that the prognostic improvement highlighted by RCTs was confirmed in real-world settings, too. The study shows, evaluating for the first time all European regions, that the optimal outcome figures obtained in controlled settings for CML are also achievable (and indeed achieved) in real-world settings with prompt introduction of TKIs in daily clinical practice. However, some differences still persist, particularly in Eastern European countries, where overall survival values are lower than elsewhere, probably due to a delayed introduction of TKIs. Our results suggest an insufficient adoption of adequate protocols in daily clinical practice in those countries where CML survival values remain lower in real life than the values obtained in RCTs. New high-resolution population-based studies may help to identify failures in the clinical pathways followed there.

Background: The impact of geographical accessibility on cancer survival has been investigated in few studies, with most research focusing on access to reference care centers, using overall mortality and limited to specific cancer sites. This study aims to examine the association of access to primary care with mortality in excess of patients with the 10 most frequent cancers in France, while controlling for socioeconomic deprivation., Methods: This study included a total of 151,984 cases diagnosed with the 10 most common cancer sites in 21 French cancer registries between 2013 and 2015. Access to primary care was estimated using two indexes: the Accessibilité Potentielle Localisée index (access to general practitioners) and the Scale index (access to a range of primary care clinicians). Mortality in excess was modelized using an additive framework based on expected mortality based on lifetables and observed mortality., Findings: Patients living in areas with less access to primary care had a greater mortality in excess for some very common cancer sites like breast (women), lung (men), liver (men and women), and colorectal cancer (men), representing 46% of patients diagnosed in our sample. The maximum effect was found for breast cancer; the excess hazard ratio was estimated to be 1.69 (95% CI, 1.20-2.38) 1 year after diagnosis and 2.26 (95% CI, 1.07-4.80) 5 years after diagnosis., Interpretation: This study revealed that this differential access to primary care was associated with mortality in excess for patients with cancer and should become a priority for health policymakers to reduce these inequalities in health care accessibility., (© 2024 American Cancer Society.)

Background: Basal cell carcinoma (BCC) is the most frequent malignancy reported in populations with fair skin. In most countries, BCCs are only partially or not at all recorded, and incidence data are lacking., Objectives: This study assessed the current incidence rates and trends in the only two French départements where BCCs have been recorded for several decades., Methods: This regional population-based study thus used data from two French cancer registries (Doubs and Haut-Rhin) where first-time BCC diagnoses were recorded. The European age-standardized incidence rates (EASR) were calculated per 100 000 person-years (PY). The trends and the annual percentages of change were assessed using joinpoint analysis., Results: In all, 48 989 patients were diagnosed with a first BCC in the study period. The median age at diagnosis was 69 years and the BCCs were mainly located on the head and neck (68.8%). In the Doubs area between 1980 and 2016, the EASR of BCC increased from 59.9 to 183.1 per 100 000 PY. The annual increase for men was 5.73% before 1999 and 1.49% thereafter, and among women 4.56% before 2001 and 1.31% thereafter. In the Haut-Rhin area, the EASR increased from 139.2 in 1991 to 182.8 per 100 000 PY in 2019. Among men, the EASR increased annually by 2.31% before 2000, and by 0.29% after 2000; among women, it increased by 0.95% over the entire period (1991-2019). In the most recent period and for these two départements, the age-specific incidence rates of BCC for men and women were close before the age of 60 years, except for the 40-49-year age group, where the rates were significantly higher among women. For patients aged 60 years and over, men had much higher rates of BCC., Conclusions: BCC incidence has increased since 1980 and is still rising, particularly among men and the elderly. A slowing was observed from 2000, which could be explained by a shift in the management of BCCs and by the possible efficacy of prevention actions. This study provides insight into the BCC burden in France and highlights the need to maintain effective prevention strategies, as incidence is still increasing., Competing Interests: Conflicts of interest None to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Data on post-colonoscopy colorectal cancers (PCCRCs) after fecal occult blood test (FOBT)-positive colonoscopies is scarce (guaiac-based (gFOBT) or fecal immunochemical test (FIT))., Aims: Evaluate the prevalence and characteristics of PCCRCs in the French gFOBT CRC screening program., Methods: Retrospective population-based cohort study of all gFOBT-positive colonoscopies performed among individuals aged 50-74 between 2003 and 2014 within the CRC screening program organized in the Haut-Rhin (Alsace, France). The main outcome was PCCRC-3y rate. Adenoma detection rates (ADRs) calculated on gFOBT-positive colonoscopies were compared to those calculated on FIT-positive colonoscopies performed by the same gastroenterologists., Results: Overall, 9106 gFOBT-positive colonoscopies performed by 36 gastroenterologists were included. Sixteen PCCRC-3y and 31 PCCRC-5y were diagnosed (68.8 % and 58.1 % were true interval PCCRCs respectively). The unadjusted PCCRC-3y rate was 2.4 % [95 % confidence interval (CI) 1.4 %-3.9 %]. The risk for PCCRC-5y was significantly higher when the gastroenterologist's ADR was <35 % compared to ≥35 % (HR 2.17 [95 %CI 1.19-3.93]). The mean absolute difference for ADR between gFOBT- and FIT-positive colonoscopies was 16.3 % in favor of FIT-positive colonoscopies., Conclusion: PCCRC-3y prevalence was low, estimated at 2.4 %. We suggest that the minimum standard for ADR in gFOBT- and FIT-positive colonoscopies should be set at 35 % and 50 % to 55 % respectively, in the French screening program., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Objective: Imipenem is recommended in patients with chemotherapy-induced febrile neutropenia. Although alterations of antibiotic pharmacokinetic parameters have been reported in such patients, little data is available on imipenem., Methods: Prospective, single-center, non-interventional pharmacokinetic cohort study in adults with chemotherapy-induced febrile neutropenia. Critically ill patients were excluded. Imipenem was administered as a 30-min infusion of 1000 mg/8h. Total imipenem plasma concentrations were assayed by high-performance liquid chromatography during neutropenia and just after neutrophil recovery. We estimated population pharmacokinetic parameters of imipenem by non-linear mixed-effect modelling using the SAEM algorithm., Results: Sixteen patients were included in the study, including nine women (56.3%), median age 37 years (range, 18.3; 78.3). Eight patients had an hematological malignancy (50.0%) and seven had a solid tumor (43.8%). Imipenem pharmacokinetics were best described by a one-compartment model with first-order elimination. Mean values for imipenem were: clearance 14.3L/h and 10.9L/h and volume of distribution 20.7L and 14.5 L during neutropenia and after recovery, respectively. Imipenem plasma area under the curve at steady state was reduced by 23% during neutropenia. However, all patients achieved a pharmacodynamic target of %fT >MIC  ≥ 40% with a regimen of 1000 mg/8 h or 500 mg/6 h, for MICs up to 2 mg/L. The pharmacodynamics profile for a target of %fT > MIC = 100% was however less favorable with 500 mg/6 h or 1000 mg/8 h either during or after neutropenia., Conclusion: Pharmacokinetic/pharmacodynamic goals for imipenem were similar in patients during and after neutropenia, despite reduced plasma exposure., (Copyright © 2022. Published by Elsevier Masson SAS.)

Purpose: In an attempt to understand why cervical cancer (CC) survival is decreasing with diagnosis period among older women in France, this study aimed to estimate the effects of main prognostic factors on net survival in CC according to age., Methods: French cancer registries databases were used to retrospectively analyze women diagnosed with CC in 2011-2012. Net survival was estimated with the Pohar-Perme method and prognostic factors (socio-demographic, clinical variables, stage at diagnosis, therapeutic management) were analyzed with Lambert and Royston's flexible parametric model., Results: One thousand one hundred fifty three women with CC were identified. 30.4% were < 45, 41.4% 45-64, and 28.3% ≥ 65 years. Older women were diagnosed at a more advanced stage than younger women: 54.8% regional (FIGO IB2-IVA), 33.0% distant (IVB) in women ≥ 65 years vs 33.7% and 8.0%, respectively in women < 45 years. Half of women with regional stage of CC received recommended treatment; this rate decreased with increasing age (< 45: 66.1%, 45-64: 62.7%, ≥ 65: 29.2%). Older age was significantly associated with increased risk of death: hazard ratio 1.89 for age ≥ 65, as were regional stage (2.81), distant stage (15.99), and not receiving recommended treatment (2.26)., Conclusion: Older women with CC diagnosed at advanced stage who do not receive standard of care are at markedly increased risk of death. Special attention to the management of older women is warranted in France, not only to diagnose cancer at an earlier stage (via gynecological follow-up in these menopaused women who remain at risk of CC), but also to ensure they receive standard of care, taking into account their overall state of health., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Research Question: What is the prevalence of embryo abnormal early cleavage (ACL) identified by time lapse and factors related to patients and treatment that explain ACL occurrence?, Design: A single-centre, retrospective cohort study. Data were collected on all IVF cycles for which embryos were observed in the EmbryoScope® between December 2015 and August 2017. Only diploid zygotes cleaved on day 2 were included. The study included 318 cycles (250 couples and 1343 embryos). Embryo videos were retrospectively analysed for ACL. The prevalence of each type of ACL was recorded. The influence of clinical factors (whether they were intrinsic to patients or specific to IVF treatment) on ACL occurrence was analysed in multivariate multilevel mixed-effect logistic regression analysis., Results: A high prevalence of ACL was observed: 37.6% (505/1343) of embryos presented at least one ACL, 22.8% (306/1343) a trichotomous mitosis, 25.8% (347/1343) a rapid cleavage, 6.7% (90/1343) a cell fusion and two or more ACL (16.1%). Part of the variation (12-25%) in ACL occurrence could be explained by embryo origin. Trichotomous mitosis and two or more ACL phenotypes were less likely to occur in women with endometriosis or tubal pathology and tubal pathology alone, respectively. No factor related to IVF cycles was found to be statistically associated with ACL occurrence., Conclusions: Our findings emphasize the importance of considering embryo origin when interpreting studies focusing on embryo characteristics and factors that could affect their quality. The present study is limited by a small sample size of known embryo implantations and monocentric criterion., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

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Purpose: This study was undertaken to determine cancer survival and describe the spectrum of cancers diagnosed among French adolescent and young adult (AYA) population. Methods: All cases of cancer diagnosed in 15-24 years, recorded by all French population-based registries (18% of the French population), over the 2000-2016 period, were included. Age-standardized incidence rates, conventional annual percentage change (cAPC) of incidence over time, and 5-year overall survival (5yOS) were calculated. Results: We analyzed 2734 cancer diagnoses in adolescents and 4199 in young adults. Overall incidence rates were 231.9/10 6 in 15-19 year olds and 354.0/10 6 in 20-24 year olds. The most frequently diagnosed cancers in male AYA were malignant gonadal germ-cell tumors (GCT), Hodgkin lymphoma (HL), and malignant melanoma and were HL, thyroid carcinoma, and malignant melanoma in females. Cancer incidence was stable over time with a cAPC of 0.8% ( p  = 0.72). For all cancers combined, 5yOS was 86.6% (95% CI: 85.8-87.4), >85% for HL, non-Hodgkin lymphomas (NHL), GCT, thyroid carcinomas, and malignant melanomas, and around 60% and lower for osteosarcomas, Ewing tumors, hepatic carcinomas, and rhabdomyosarcomas. The 5yOS has significantly improved from 2000-2007 to 2008-2015 for all cancers pooled, with a substantial gain of 4% for 15-19 year olds and 3% for 20-24 year olds. Conclusion: Notwithstanding the encouraging results for some cancers, and overall, persistent poorer survivals in AYA were shown compared to children for acute lymphoblastic leukemia, osteosarcoma, Ewing tumor, rhabdomyosarcoma, and malignant hepatic tumors. These disparities require further investigation to identify and address the causes of these inferior outcomes.

In order to investigate patients' experience of healthcare, repeated assessments of patient-reported outcomes (PRO) are increasingly performed in observational studies and clinical trials. Changes in PRO can however be difficult to interpret in longitudinal settings as patients' perception of the concept being measured may change over time, leading to response shift (longitudinal measurement non-invariance) and possibly to erroneous interpretation of the observed changes in PRO. Several statistical methods for response shift analysis have been proposed, but they usually assume that response shift occurs in the same way in all individuals within the sample regardless of their characteristics. Many studies aim at comparing the longitudinal change of PRO into two groups of patients (treatment arm, different pathologies, …). The group variable could have an effect on PRO change but also on response shift effect and the perception of the questionnaire at baseline. In this paper, we propose to enhance the ROSALI algorithm based on Rasch Measurement Theory for the analysis of longitudinal PRO data to simultaneously investigate the effects of group on item functioning at the first measurement occasion, on response shift and on changes in PRO over time. ROSALI is subsequently applied to a longitudinal dataset on change in emotional functioning in patients with breast cancer or melanoma during the year following diagnosis. The use of ROSALI provides new insights in the analysis of longitudinal PRO data., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Hammas, Sébille, Brisson, Hardouin and Blanchin.)

Background: Different methodological choices such as inclusion/exclusion criteria and analytical models can yield different results and inferences when meta-analyses are performed. We explored the range of such differences, using several methodological choices for indirect comparison meta-analyses to compare nalmefene and naltrexone in the reduction of alcohol consumption as a case study., Methods: All double-blind randomized controlled trials (RCTs) comparing nalmefene to naltrexone or one of these compounds to a placebo in the treatment of alcohol dependence or alcohol use disorders were considered. Two reviewers searched for published and unpublished studies in MEDLINE (August 2017), the Cochrane Library, Embase, and ClinicalTrials.gov and contacted pharmaceutical companies, the European Medicines Agency, and the Food and Drug Administration. The indirect comparison meta-analyses were performed according to different inclusion/exclusion criteria (based on medical condition, abstinence of patients before inclusion, gender, somatic and psychiatric comorbidity, psychological support, treatment administered and dose, treatment duration, outcome reported, publication status, and risk of bias) and different analytical models (fixed and random effects). The primary outcome was the vibration of effects (VoE), i.e. the range of different results of the indirect comparison between nalmefene and naltrexone. The presence of a "Janus effect" was investigated, i.e. whether the 1st and 99th percentiles in the distribution of effect sizes were in opposite directions., Results: Nine nalmefene and 51 naltrexone RCTs were included. No study provided a direct comparison between the drugs. We performed 9216 meta-analyses for the indirect comparison with a median of 16 RCTs (interquartile range = 12-21) included in each meta-analysis. The standardized effect size was negative at the 1st percentile (- 0.29, favouring nalmefene) and positive at the 99th percentile (0.29, favouring naltrexone). A total of 7.1% (425/5961) of the meta-analyses with a negative effect size and 18.9% (616/3255) of those with a positive effect size were statistically significant (p < 0.05)., Conclusions: The choice of inclusion/exclusion criteria and analytical models for meta-analysis can result in entirely opposite results. VoE evaluations could be performed when overlapping meta-analyses on the same topic yield contradictory result., Trial Registration: This study was registered on October 19, 2016, in the Open Science Framework (OSF, protocol available at https://osf.io/7bq4y/ ).

Background: Despite intensive research over several decades, the etiology of multiple sclerosis (MS) remains poorly understood, although environmental factors are supposedly implicated. Our goal was to identify spatial clusters of MS incident cases at the small-area level to provide clues to local environmental risk factors that might cause or trigger the disease., Methods: A population-based and multi-stage study was performed in the French Brittany region to accurately ascertain the clinical onset of disease during the 2000-2004 period. The municipality of residence at the time of clinical onset was geocoded. To test for the presence of MS incidence clusters and to identify their approximate locations, we used a spatial scan statistic. We adjusted for socioeconomic deprivation, known to be strongly associated with increased MS incident rates, and scanned simultaneously for areas with either high or low rates. Sensitivity analyses (focusing on relapsing-remitting forms and/or places of residence available within the year following clinical onset) were performed., Results: A total of 848 incident cases of MS were registered in Brittany, corresponding to a crude annual incidence rate of 5.8 per 100,000 inhabitants. The spatial scan statistic did not find a significant cluster of MS incidence in either the primary analysis (p value ≥ 0.56) or in the sensitivity analyses (p value ≥ 0.16)., Conclusion: The findings of this study indicate that MS incidence is not markedly affected across space, suggesting that in the years preceding the first clinical expression of the disease, no environmental trigger is operative at the small-area population level in the French Brittany region.