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Guiling Zhou,1 Stijn de Vos,1 Catharina CM Schuiling-Veninga,1 Jens Bos,1 Katrien Oude Rengerink,2 Anna Maria Gerdina Pasmooij,2 Peter GM Mol,2,3 Geertruida H de Bock,4 Eelko Hak1 1Unit of Pharmaco-Therapy, -Epidemiology and -Economics (PTEE), Department of Pharmacy, University of Groningen, Groningen, the Netherlands; 2Medicines Evaluation Board, Utrecht, the Netherlands; 3Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 4Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the NetherlandsCorrespondence: Guiling Zhou, Unit of Pharmaco-Therapy, -Epidemiology and -Economics (PTEE), Department of Pharmacy, University of Groningen, Antonius Deusinglaan 1, Groningen, 9713 AV, the Netherlands, Tel +31 503638707, Fax +31 503632772, Email g.zhou@rug.nlBackground: Repurposing registered drugs could reduce coronavirus disease (COVID-19) burden before novel drugs are authorized. Little is known about how the pandemic and imposed restrictions changed their dispensing. We aimed to investigate the impact of COVID-19 pandemic on repurposed drugs dispensing in the Netherlands.Methods: We performed interrupted time-series study using University of Groningen prescription database IADB.nl to evaluate dispensing trends of 24 repurposed drugs before (2017-February 2020) and after (March 2020– 2021) the pandemic’ start. Primary outcomes were monthly prevalence and incidence rates. An autoregressive integrated moving average model assessed the effect of pandemic and stringency index (measuring strictness of government’s restriction policies).Results: Annual number of IADB.nl population ranged from 919,697 to 952,400. Generally, dispensing of common long-term-used drugs was not significantly affected by pandemic. The prevalence of antibacterials (− 4.20 users per 1000 people), antivirals (− 0.04), corticosteroids (− 1.29), prednisolone (− 1.32), calcium channel blocker (− 0.41), and diuretics (− 1.29) was lower than expected after the pandemic’s start, while the prevalence of ivermectin (0.07), sulfonylureas (0.15), sodium-glucose co-transporter-2 (SGLT2) inhibitor (0.17), and anticoagulants (1.95) was higher than expected. The pandemic was associated with statistically significant decreases in the incidence of antibacterials (− 1.21), corticosteroids (− 0.60), prednisolone (− 0.64) and anticoagulants (− 0.02), and increases in ivermectin (0.02), aggregated antidiabetic drugs (0.13), and SGLT2 inhibitors (0.06). These trends were positively associated with pandemic and negatively associated with stringency index.Conclusion: Dispensing of most drugs was not significantly associated with pandemic and government’s response. Despite some statistically significant disruptions, these were not necessarily clinically relevant due to small absolute differences observed.Keywords: COVID-19, drug utilization, repurposed drug, stringency index

Fan Zhang,1– 3 Geertruida H de Bock,1 Petra Denig,4 Gijs W Landman,5 Qingying Zhang,2 Grigory Sidorenkov1 1Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 2Department of Preventive Medicine, Shantou University Medical College, Shantou, People’s Republic of China; 3Oncology Research Laboratory, Cancer Hospital of Shantou University Medical College, Shantou, People’s Republic of China; 4Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 5Department of Internal Medicine, Gelre Hospital, Apeldoorn, the NetherlandsCorrespondence: Grigory Sidorenkov, Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands, Email g.sidorenkov@umcg.nlPurpose: Women with type 2 diabetes mellitus (T2DM) have an increased risk of breast cancer. We aimed to determine the contribution of lipids, glucose and blood pressure to this risk based on the multifactorial nature of T2DM.Patients and Methods: This population-based cohort study used data from a Dutch database (the Groningen Initiative to Analyse Type 2 Diabetes Treatment) for the period 2004– 2013. The cohort included women diagnosed with T2DM, aged 30– 80 years, with no history of breast cancer and with follow-up data for at least 1 year. We used Cox proportional hazards models to estimate the associations of exposures with breast cancer occurrence, reporting adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Exposures of interest included total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, glycated hemoglobin A (HbA1c) and systolic blood pressure (SBP).Results: During a median of 4.45 years’ follow-up, 183 of 10,183 included women received a breast cancer diagnosis. We observed U-shaped associations with breast cancer incidence for total cholesterol and HDL-C at baseline. Compared with moderate elevations, women had significantly higher breast cancer risks associated with high total cholesterol (aHR, 95% CI: 1.72, 1.15– 2.55) and HDL-C (aHR, 95% CI: 1.74, 1.18– 2.58) levels, while low total cholesterol (aHR, 95% CI: 1.43, 0.94– 2.19) and HDL-C (aHR, 95% CI: 1.44, 0.95– 2.17) levels produced marginal effects without significance. Women with high LDL-C levels more often received a breast cancer diagnosis than those with medium levels (aHR, 95% CI: 1.56, 1.03– 2.35).Conclusion: This real-world dataset highlights the importance of balancing lipid profiles, particularly total cholesterol and HDL-C. Dysregulation of the lipid profile, not the glucose or blood pressure profiles, may increase the risk of breast cancer in women with T2DM.Keywords: cholesterol, triglycerides, glycated hemoglobin A, systolic blood pressure, breast cancer

Yu Pu,1,* Xiuxiu Zhou,1,* Di Zhang,1,* Yu Guan,1,* Yi Xia,1 Wenting Tu,1 Yang Lu,2 Weidong Zhang,2 Chi-Cheng Fu,2 Qu Fang,2 Geertruida H de Bock,3 Shiyuan Liu,1 Li Fan1 1Department of Radiology, Changzheng Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Scientific Research, Shanghai Aitrox Technology Corporation Limited, Shanghai, People’s Republic of China; 3Department of Epidemiology, University Medical Center Groningen, Groningen, the Netherlands*These authors contributed equally to this workCorrespondence: Shiyuan Liu; Li Fan, Department of Radiology, ChangZheng Hospital, Naval Medical University, No. 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel +86 21 81886012 ; Tel +86 21 81886012, Fax +86 21 63587668, Email cjr.liushiyuan@vip.163.com; fanli0930@163.comPurpose: To explore optimal threshold of FEV1% predicted value (FEV1%pre) for high-risk chronic obstructive pulmonary disease (COPD) using the parameter response mapping (PRM) based on machine learning classification model.Patients and Methods: A total of 561 consecutive non-COPD subjects who were screened for chest diseases in our hospital between August and October 2018 and who had complete questionnaire surveys, pulmonary function tests (PFT), and paired respiratory chest CT scans were enrolled retrospectively. The CT quantitative parameter for small airway remodeling was PRM, and 72 parameters were obtained at the levels of whole lung, left and right lung, and five lobes. To identify a more reasonable thresholds of FEV1% predicted value for distinguishing high-risk COPD patients from the normal, 80 thresholds from 50% to 129% were taken with a partition of 1% to establish a random forest classification model under each threshold, such that novel PFT-parameter-based high-risk criteria would be more consistent with the PRM-based machine learning classification model.Results: Machine learning-based PRM showed that consistency between PRM parameters and PFT was better able to distinguish high-risk COPD from the normal, with an AUC of 0.84 when the threshold was 72%. When the threshold was 80%, the AUC was 0.72 and when the threshold was 95%, the AUC was 0.64.Conclusion: Machine learning-based PRM is feasible for redefining high-risk COPD, and setting the optimal FEV1% predicted value lays the foundation for redefining high-risk COPD diagnosis.Keywords: chronic obstructive pulmonary disease, computed tomography, pulmonary function test, quantitative imaging, artificial intelligence

Justine M Briët,1 Marian JE Mourits,1 Barbara L van Leeuwen,2 Edwin R van den Heuvel,3 Monique JA Kenkhuis,1 Henriette JG Arts,1 Geertruida H de Bock3 1Department of Gynecologic Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 2Department of Surgical Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 3Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands Purpose: A prospective, multicenter cohort study was performed on the implementation of laparoscopic hysterectomy (LH) in the Netherlands. The aim of this study was to evaluate the impact of LH on quality of life (QOL) with respect to age up to 6 months postoperatively. Patients and methods: Women with an indication for LH, either for benign conditions or early-stage low-risk endometrial cancer were included. QOL was measured before and 6 weeks and 6 months after surgery, using the 36-item Short Form Health Survey. Mean QOL values were compared to an unselected, female, Dutch reference population. A longitudinal linear mixed model was applied to assess changes in QOL over time after LH and to determine if in patients ≥65 years of age QOL scores were different. Results: Data on 116 patients were available for analysis. The median age was 54 years at time of surgery (range 34–83) with an interquartile range of 43–65 years. Six months after LH, all QOL values were higher than before surgery and were equal to or higher than those of the reference population. Older women tend to score higher on QOL preoperatively, and these scores remain high postoperatively. Conclusion: After LH, QOL improves. Older women report higher QOL values preoperatively and QOL is still high 6 months after the operation. Age does not confer a negative impact on QOL following LH and should not be the reason to refrain from laparoscopic surgery. Keywords: quality of life, laparoscopic surgery, hysterectomy, elderly

The identification of causal BRCA1/2 pathogenic variants (PVs) in epithelial ovarian carcinoma (EOC) aids the selection of patients for genetic counselling and treatment decision‐making. Current recommendations therefore stress sequencing of all EOCs, regardless of histotype. Although it is recognised that BRCA1/2 PVs cluster in high‐grade serous ovarian carcinomas (HGSOC), this view is largely unsubstantiated by detailed analysis. Here, we aimed to analyse the results of BRCA1/2 tumour sequencing in a centrally revised, consecutive, prospective series including all EOC histotypes. Sequencing of n = 946 EOCs revealed BRCA1/2 PVs in 125 samples (13%), only eight of which were found in non‐HGSOC histotypes. Specifically, BRCA1/2 PVs were identified in high‐grade endometrioid (3/20; 15%), low‐grade endometrioid (1/40; 2.5%), low‐grade serous (3/67; 4.5%), and clear cell (1/64; 1.6%) EOCs. No PVs were identified in any mucinous ovarian carcinomas tested. By re‐evaluation and using loss of heterozygosity and homologous recombination deficiency analyses, we then assessed: (1) whether the eight 'anomalous' cases were potentially histologically misclassified and (2) whether the identified variants were likely causal in carcinogenesis. The first 'anomalous' non‐HGSOC with a BRCA1/2 PV proved to be a misdiagnosed HGSOC. Next, germline BRCA2 variants, found in two p53‐abnormal high‐grade endometrioid tumours, showed substantial evidence supporting causality. One additional, likely causal variant, found in a p53‐wildtype low‐grade serous ovarian carcinoma, was of somatic origin. The remaining cases showed retention of the BRCA1/2 wildtype allele, suggestive of non‐causal secondary passenger variants. We conclude that likely causal BRCA1/2 variants are present in high‐grade endometrioid tumours but are absent from the other EOC histotypes tested. Although the findings require validation, these results seem to justify a transition from universal to histotype‐directed sequencing. Furthermore, in‐depth functional analysis of tumours harbouring BRCA1/2 variants combined with detailed revision of cancer histotypes can serve as a model in other BRCA1/2‐related cancers. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Objective: To assess the short- and long-term effects of mindfulness-based stress reduction (MBSR) on the resulting quality of life, sexual functioning, and sexual distress after risk-reducing salpingo-oophorectomy (RRSO).Design: Randomised controlled trial.Setting: A specialised family cancer clinic of the university medical center Groningen.Population: Sixty-six women carriers of the BRCA1/2 mutation who developed at least two moderate-to-severe menopausal symptoms after RRSO.Methods: Women were randomised to an 8-week MBSR training programme or to care as usual (CAU).Main Outcome Measures: Change in the Menopause-Specific Quality of Life Questionnaire (MENQOL), the Female Sexual Function Index, and the Female Sexual Distress Scale, administered from baseline at 3, 6, and 12 months. Linear mixed modelling was applied to compare the effect of MBSR with CAU over time.Results: At 3 and 12 months, there were statistically significant improvements in the MENQOL for the MBSR group compared with the CAU group (both P = 0.04). At 3 months, the mean MENQOL scores were 3.5 (95% confidence interval, 95% CI 3.0-3.9) and 3.8 (95% CI 3.3-4.2) for the MBSR and CAU groups, respectively; at 12 months, the corresponding values were 3.6 (95% CI 3.1-4.0) and 3.9 (95% CI 3.5-4.4). No significant differences were found between the MBSR and CAU groups in the other scores.Conclusion: Mindfulness-based stress reduction was effective at improving quality of life in the short- and long-term for patients with menopausal symptoms after RRSO; however, it was not associated with an improvement in sexual functioning or distress.Tweetable Abstract: Mindfulness improves menopause-related quality of life in women after risk-reducing salpingo-oophorectomy. [ABSTRACT FROM AUTHOR]

Background: During menopause women experience vasomotor and psychosexual symptoms that cannot entirely be alleviated with hormone replacement therapy (HRT). Besides, HRT is contraindicated after breast cancer. Objectives: To review the evidence on the effectiveness of psychological interventions in reducing symptoms associated with menopause in natural or treatment‐induced menopausal women. Search strategy: Medline/Pubmed, PsycINFO, EMBASE and AMED were searched until June 2017. Selection criteria: Randomised controlled trials (RCTs) concerning natural or treatment‐induced menopause, investigating mindfulness or (cognitive‐)behaviour‐based therapy were selected. Main outcomes were frequency of hot flushes, hot flush bother experienced, other menopausal symptoms and sexual functioning. Data collection and analysis: Study selection and data extraction were performed by two independent researchers. A meta‐analysis was performed to calculate the standardised mean difference (SMD). Main results: Twelve RCTs were included. Short‐term (<20 weeks) effects of psychological interventions in comparison to no treatment or control were observed for hot flush bother (SMD −0.54, 95% CI −0.74 to −0.35, P < 0.001, I2 = 18%) and menopausal symptoms (SMD −0.34, 95% CI −0.52 to −0.15, P < 0.001, I2 = 0%). Medium‐term (≥20 weeks) effects were observed for hot flush bother (SMD −0.38, 95% CI −0.58 to −0.18, P < 0.001, I2 = 16%). [Correction added on 9 July 2018, after first online publication: there were miscalculations of the mean end point scores for hot flush bother and these have been corrected in the preceding two sentences.] In the subgroup treatment‐induced menopause, consisting of exclusively breast cancer populations, as well as in the subgroup natural menopause, hot flush bother was reduced by psychological interventions. Too few studies reported on sexual functioning to perform a meta‐analysis. Conclusions: Psychological interventions reduced hot flush bother in the short and medium‐term and menopausal symptoms in the short‐term. These results are especially relevant for breast cancer survivors in whom HRT is contraindicated. There was a lack of studies reporting on the influence on sexual functioning. Systematic review: psychological interventions reduce bother by hot flushes in the short‐ and medium‐term. Systematic review: psychological interventions reduce bother by hot flushes in the short‐ and medium‐term. [ABSTRACT FROM AUTHOR]

Objective: To estimate the cost-effectiveness and cost-utility of actively encouraging older community-dwelling women with urinary incontinence to be diagnosed and treated.Design: The study was designed as cost-effectiveness and cost-utility analyses alongside a cluster randomised controlled trial. Analyses were performed from a societal perspective. Direct medical and nonmedical costs were taken into account and valued according to the standard Dutch guidelines for economic evaluations.Setting: Primary care.Population: Study participants were 350 community-dwelling women 55 years or older with urinary incontinence.Methods: Women in the intervention group were invited for diagnostic testing and treatment. The control group received usual care according to the Dutch guideline on urinary incontinence. Follow-up period was 12 months.Main Outcome Measures: Incontinence Impact Adjusted Life Years (IIALY), Quality Adjusted Life Years (QALY) and incremental costs calculated per IIALY and per QALY gained.Results: Costs per extra life year without impact on daily life from urinary incontinence amounted to €5179 (95% CI -17 323 to 36 260). Costs per QALY amounted to €23 907 (95% CI -124 849 to 121 849). Assuming a ceiling ratio of €20 000, the probability that the intervention was cost-effective based on IIALYs was 91% and 46% based on QALYs.Conclusions: Improvements in severity of incontinence in older community-dwelling women can be achieved against reasonable costs, with an improvement of symptom-specific QALYs. Findings support an active role of primary care physicians towards women who hesitate to ask for help for urinary incontinence.Tweetable Abstract: Encouraging women with urinary incontinence to be treated, improves symptoms and QOL against reasonable costs. [ABSTRACT FROM AUTHOR]

Objective: To assess the sensitivity of detection and accuracy of volumetry by manual and semi-automated quantification of artificial pulmonary nodules in an anthropomorphic thoracic phantom on low-dose CT.Methods: Fifteen artificial spherical nodules (diameter 3, 5, 8, 10 and 12 mm; CT densities -800, -630 and +100 HU) were randomly placed inside an anthropomorphic thoracic phantom. The phantom was examined on 16- and 64-row multidetector CT with a low-dose protocol. Two independent blinded observers screened for pulmonary nodules. Nodule diameter was measured manually, and volume calculated. For solid nodules (+100 HU), diameter and volume were also evaluated by semi-automated software. Differences in observed volumes between the manual and semi-automated method were evaluated by a t-test.Results: Sensitivity was 100 % for all nodules of >5 mm and larger, 60-80 % for solid and 0-20 % for non-solid 3-mm nodules. No false-positive nodules but high inter-observer reliability and inter-technique correlation were found. Volume was underestimated manually by 24.1 ± 14.0 % for nodules of any density, and 26.4 ± 15.5 % for solid nodules, compared with 7.6 ± 8.5 % (P < 0.01) semi-automatically.Conclusion: In an anthropomorphic phantom study, the sensitivity of detection is 100 % for nodules of >5 mm in diameter. Semi-automated volumetry yielded more accurate nodule volumes than manual measurements. [ABSTRACT FROM AUTHOR]

Objectives: A systematic review and meta-analysis to assess sensitivity and specificity of coronary CT angiography (CCTA) for significant stenosis at different degrees of coronary calcification.Methods: A literature search was performed including studies describing test characteristics of CCTA for significant stenosis, performed with at least 16-MDCT and according to calcium score (CS). Invasive coronary angiography was the reference standard. Pooled sensitivity and specificity of CCTA by CS categories and CT equipment were calculated.Results: Of 14,121 articles, 51 studies reported on the impact of calcium scoring on diagnostic performance of CCTA and could be included in the systematic review. Twenty-seven of these studies (5,203 participants) were suitable for meta-analysis. On a patient-basis, sensitivity of CCTA for significant stenosis was 95.8, 95.6, 97.6 and 99.0% for CS 0-100, 101-400, 401-1,000 and >1,000 respectively. Specificity was 91.2, 88.2, 50.6 and 84.0% respectively. Specificity of CCTA was significantly lower for CS 401-1,000 due to lack of patients without significant stenosis. Sensitivity and specificity of 16-MDCT were significantly lower compared to more modern CT systems.Conclusions: Even in cases of severe coronary calcification, sensitivity and specificity of CCTA for significant stenosis are high. With 64-MDCT and newer CT systems, a CS cut-off for performing CCTA no longer seems indicated.Key Points: Decisions about performing coronary CT angiography (CCTA) sometimes depend on calcium scoring. CCTA is highly sensitive for coronary stenosis. With 16-MDCT, however, heavy calcification reduces specificity for significant stenosis. For 64-MDCT (and above), CCTA has high specificity, even with severe coronary calcification. [ABSTRACT FROM AUTHOR]

Objective: To evaluate performance of computer-aided detection (CAD) beyond double reading for pulmonary nodules on low-dose computed tomography (CT) by nodule volume.Methods: A total of 400 low-dose chest CT examinations were randomly selected from the NELSON lung cancer screening trial. CTs were evaluated by two independent readers and processed by CAD. A total of 1,667 findings marked by readers and/or CAD were evaluated by a consensus panel of expert chest radiologists. Performance was evaluated by calculating sensitivity of pulmonary nodule detection and number of false positives, by nodule characteristics and volume.Results: According to the screening protocol, 90.9 % of the findings could be excluded from further evaluation, 49.2 % being small nodules (less than 50 mm(3)). Excluding small nodules reduced false-positive detections by CAD from 3.7 to 1.9 per examination. Of 151 findings that needed further evaluation, 33 (21.9 %) were detected by CAD only, one of them being diagnosed as lung cancer the following year. The sensitivity of nodule detection was 78.1 % for double reading and 96.7 % for CAD. A total of 69.7 % of nodules undetected by readers were attached nodules of which 78.3 % were vessel-attached.Conclusions: CAD is valuable in lung cancer screening to improve sensitivity of pulmonary nodule detection beyond double reading, at a low false-positive rate when excluding small nodules.Key Points: • Computer-aided detection (CAD) has known advantages for computed tomography (CT). • Combined CAD/nodule size cut-off parameters assist CT lung cancer screening. • This combination improves the sensitivity of pulmonary nodule detection by CT. • It increases the positive predictive value for cancer detection. [ABSTRACT FROM AUTHOR]

Objectives: To determine the correlation between CT measurements of emphysema or peripheral airways and airflow obstruction in chronic obstructive pulmonary disease (COPD).Methods: PubMed, Embase and Web of Knowledge were searched from 1976 to 2011. Two reviewers independently screened 1,763 citations to identify articles that correlated CT measurements to airflow obstruction parameters of the pulmonary function test in COPD patients, rated study quality and extracted information. Three CT measurements were accessed: lung attenuation area percentage < -950 Hounsfield units, mean lung density and airway wall area percentage. Two airflow obstruction parameters were accessed: forced expiratory volume in the first second as percentage from predicted (FEV(1) %pred) and FEV(1) divided by the forced volume vital capacity.Results: Seventy-nine articles (9,559 participants) were included in the systematic review, demonstrating different methodologies, measurements and CT airflow obstruction correlations. There were 15 high-quality articles (2,095 participants) in the meta-analysis. The absolute pooled correlation coefficients ranged from 0.48 (95 % CI, 0.40 to 0.54) to 0.65 (0.58 to 0.71) for inspiratory CT and 0.64 (0.53 to 0.72) to 0.73 (0.63 to 0.80) for expiratory CT.Conclusions: CT measurements of emphysema or peripheral airways are significantly related to airflow obstruction in COPD patients. CT provides a morphological method to investigate airway obstruction in COPD.Key Points: • Computed tomography is widely performed in patients with chronic obstructive pulmonary disease (COPD) • CT provides quantitative morphological methods to investigate airflow obstruction in COPD • CT measurements correlate significantly with the degree of airflow obstruction in COPD • Expiratory CT measurements correlate more strongly with airflow obstruction than inspiratory CT • Low-dose CT decreases the radiation dose for diagnosis and quantitative emphysema evaluation. [ABSTRACT FROM AUTHOR]

Background: Women with familial or genetic aggregation of breast cancer are offered screening outside the population screening programme. However, the possible benefit of mammography screening could be reduced due to the risk of radiation-induced tumours. A systematic search was conducted addressing the question of how low-dose radiation exposure affects breast cancer risk among high-risk women.Methods: A systematic search was conducted for articles addressing breast cancer, mammography screening, radiation and high-risk women. Effects of low-dose radiation on breast cancer risk were presented in terms of pooled odds ratios (OR).Results: Of 127 articles found, 7 were selected for the meta-analysis. Pooled OR revealed an increased risk of breast cancer among high-risk women due to low-dose radiation exposure (OR = 1.3, 95% CI: 0.9- 1.8). Exposure before age 20 (OR = 2.0, 95% CI: 1.3-3.1) or a mean of ≥5 exposures (OR = 1.8, 95% CI: 1.1-3.0) was significantly associated with a higher radiation-induced breast cancer risk.Conclusion: Low-dose radiation increases breast cancer risk among high-risk women. When using low-dose radiation among high-risk women, a careful approach is needed, by means of reducing repeated exposure, avoidance of exposure at a younger age and using non-ionising screening techniques. [ABSTRACT FROM AUTHOR]

Objective: To assess volumetric measurement variability in pulmonary nodules detected at low-dose chest CT with three reconstruction settings.Methods: The volume of 200 solid pulmonary nodules was measured three times using commercially available semi-automated software of low-dose chest CT data-sets reconstructed with 1 mm section thickness and a soft kernel (A), 2 mm and a soft kernel (B), and 2 mm and a sharp kernel (C), respectively. Repeatability coefficients of the three measurements within each setting were calculated by the Bland and Altman method. A three-level model was applied to test the impact of reconstruction setting on the measured volume.Results: The repeatability coefficients were 8.9, 22.5 and 37.5% for settings A, B and C. Three-level analysis showed that settings A and C yielded a 1.29 times higher estimate of nodule volume compared with setting B (P = 0.03). The significant interaction among setting, nodule location and morphology demonstrated that the effect of the reconstruction setting was different for different types of nodules. Low-dose CT reconstructed with 1 mm section thickness and a soft kernel provided the most repeatable volume measurement.Conclusion: A wide, nodule-type-dependent range of agreement between volume measurements with different reconstruction settings suggests strict consistency is required for serial CT studies. [ABSTRACT FROM AUTHOR]

The purpose of the study was to assess the reliability of (semi-) automatic left ventricular (LV) function measurements using three different software packages on the same dual-source computed tomography (DSCT) datasets and to compare agreement among the software packages. Forty consecutive patients, undergoing cardiac DSCT were included (31 men, mean age 58±14 years). LV function analysis was performed with all three software packages. ANOVA testing was used to determine the difference among the repeated measurements and the difference among the software packages. Bland-Altman plots were computed to describe the agreement among the software packages. No significant difference was found among the repeated measurements. In the comparison of the three software packages, a significant difference was observed when measurements were used with minimal user interaction. When end-diastolic and end-systolic phases were manually set, there was no overall significant difference, but in 12.5% of patients a large (>10%) difference in LVEF was found. All three software packages have good intraobserver variability, but the results of the three packages were significantly different. For clinical use, one should be aware of the clinical impact of possible segmentation flaws when (semi-)automatic LV function assessment is used. [ABSTRACT FROM AUTHOR]

Background: Assessing a genetic risk for developing breast cancer is not an easy task for a GP. Current expert guidelines for referring and counselling women with a family history positive for breast cancer are complex and difficult to apply in general practice, and have only two strategies (to refer or not to refer for genetic counselling), giving no guidance for the GP on the management of women with a moderately increased risk of familial breast cancer.Objectives: We aimed to develop a set of simple practical guidelines for use in primary care for assessing risk and advising women with a positive family history in general practice and aimed to explore its performance.Methods: Based on a consensus meeting of the Leiden working party of hereditary tumours, the GPs of a university-related health care centre developed a set of GP guidelines to assess risk and advise women with a family history positive for breast cancer in general practice. The GP guidelines include four therapeutic strategies (reassuring, starting surveillance, starting surveillance and contacting a family cancer clinic, referring to a family cancer clinic). Its performance was tested in 67 patients whose pedigrees were available together with the risk assessment of a clinical geneticist using Claus' tables as a gold standard. The gold standard was dichotomized regarding (i) referral to a family cancer clinic and (ii) surveillance. Two existing expert guidelines were similarly compared.Results: Regarding referral to a family cancer clinic, the GP guidelines were very specific, whereas the expert guidelines were more sensitive. Regarding surveillance, the GP guidelines were very sensitive, whereas the expert guidelines were very specific. The total number of misclassified patients was lowest when using the GP guidelines, and higher when using the expert guidelines.Conclusions: The GP guidelines provide a simplification of current guidelines. Before using them on a larger scale, more testing and refining are needed to increase their sensitivity regarding a referral to a family cancer clinic and their specificity regarding surveillance. They incorporate a role for the GP in the care for women with a family history positive for breast cancer with a moderately increased risk. [ABSTRACT FROM AUTHOR]

Aims: To ascertain whether women who consulted their GP because they perceived themselves as at increased risk of familial breast cancer were indeed at increased risk, and to evaluate potential strategies for assessing genetic risk of breast cancer in general practice.Methods: Sixty-seven out of 81 women who had consulted their GP for advice about their possible increased risk of developing breast cancer due to breast cancer in the family were interviewed. Familial breast cancer risk was assessed by a clinical geneticist. This assessment was compared with two recent guidelines for referral for genetic counselling.Results: More than half (52%; n = 35) the women had a relative risk of two and over for developing breast cancer, while another half of these 35 (25%; n = 17) had a relative risk of three and over. All the women (n = 17) with a relative risk of three and over were identified by means of the two current guidelines for referral for genetic counselling, while more than half of the women (61%; n = 11) with a relative risk between two and three were identified.Conclusions: More than half the women concerned about their familial risk of breast cancer are indeed at increased risk of breast cancer. Current guidelines correctly identify women at high risk. However, doubts about the health gain and feasibility of referral warrant caution, and need further investigation. [ABSTRACT FROM AUTHOR]

Background: An increased risk of breast cancer for relatives of breast cancer patients has been demonstrated in many studies, and having a relative diagnosed with breast cancer at an early age is an indication for breast cancer screening. This indication has been derived from estimates based on data from cancer-prone families or from BRCA1/2 mutation families, and might be biased because BRCA1/2 mutations explain only a small proportion of the familial clustering of breast cancer. The aim of the current study was to determine the predictive value of a family history of cancer with regard to early onset of female breast cancer in a population based setting.Methods: An unselected sample of 1,987 women with and without breast cancer was studied with regard to the age of diagnosis of breast cancer.Results: The risk of early-onset breast cancer was increased when there were: (1) at least 2 cases of female breast cancer in first-degree relatives (yes/no; HR at age 30: 3.09; 95% CI: 128-7.44), (2) at least 2 cases of female breast cancer in first or second-degree relatives under the age of 50 (yes/no; HR at age 30: 3.36; 95% CI: 1.12-10.08), (3) at least 1 case of female breast cancer under the age of 40 in a first- or second-degree relative (yes/no; HR at age 30: 2.06; 95% CI: 0.83-5.12) and (4) any case of bilateral breast cancer (yes/no; HR at age 30: 3.47; 95%: 1.33-9.05). The positive predictive value of having 2 or more of these characteristics was 13% for breast cancer before the age of 70, 11% for breast cancer before the age of 50, and 1% for breast cancer before the age of 30.Conclusion: Applying family history related criteria in an unselected population could result in the screening of many women who will not develop breast cancer at an early age. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate prospectively the value of size, shape, margin and density in discriminating between benign and malignant CT screen detected solid non-calcified pulmonary nodules. Material and Methods: This study was institutional review board approved. For this study 405 participants of the NELSON lung cancer screening trial with 469 indeterminate or potentially malignant solid pulmonary nodules (>50mm3) were selected. The nodules were classified based on size, shape (round, polygonal, irregular) and margin (smooth, lobulated, spiculated). Mean nodule density and nodule volume were automatically generated by software. Analyses were performed by univariate and multivariate logistic regression. Results were presented as likelihood ratios (LR) with 95% confidence intervals (CI). Receiver operating characteristic analysis was performed for mean density as predictor for lung cancer. Results: Of the 469 nodules, 387 (83%) were between 50 and 500mm3, 82 (17%) >500mm3, 59 (13%) malignant, 410 (87%) benign. The median size of the nodules was 103mm3 (range 50-5486mm3). In multivariate analysis lobulated nodules had LR of 11 compared to smooth; spiculated nodules a LR of 7 compared to smooth; irregular nodules a LR of 6 compared to round and polygonal; volume a LR of 3. The mean nodule CT density did not predict the presence of lung cancer (AUC 0.37, 95% CI 0.32-0.43). Conclusion: In solid non-calcified nodules larger than 50mm3, size and to a lesser extent a lobulated or spiculated margin and irregular shape increased the likelihood that a nodule was malignant. Nodule density had no discriminative power. [ABSTRACT FROM AUTHOR]

Purpose: To examine the prognostic value of three endogenous hypoxia markers (hypoxia inducible factor 1 alpha subunit [HIF1 alpha], carbonic anhydrase IX [CA-IX], and glucose transporter type 1 [GLUT-1]) on the clinical outcome in patients with early-stage glottic carcinoma primarily treated with radiotherapy (RT) and to determine the predictive hypoxic profile to choose the optimal treatment of early-stage laryngeal carcinoma. Methods and Materials: Immunohistochemistry for HIF1 alpha, CA-IX, and GLUT-1 was performed on formalin-fixed, paraffin-embedded, pretreatment tissue samples of 91 glottic squamous cell carcinoma specimens. The patient group consisted only of those with early-stage (T1-T2) glottic carcinoma, and all patients were treated with RT only. Relative tumor staining was scored on the tissue samples. Receiver operating curve analysis was performed to determine the optimal cutoff value for each tumor marker. Cox regression analyses for the variables HIF1 alpha, CA-IX, GLUT-1, gender, age, hemoglobin level, T category, N category, tobacco use, and alcohol use were performed with local control and overall survival as endpoints. Results: HIF1 alpha overexpression in early-stage glottic carcinoma correlated significantly with worse local control (hazard ratio [HR], 3.05; p = 0.021) and overall survival (HR, 2.92; p = 0.016). CA-IX overexpression correlated significantly with worse local control (HR, 2.93; p = 0.020). GLUT-1 overexpression did not show any correlation with the clinical outcome parameters. Tumors with a nonhypoxic profile (defined as low HIF1 alpha and low CA-IX expression) had significantly better local control (HR, 6.32; p = 0.013). Conclusion: The results of our study have shown that early-stage glottic laryngeal carcinomas with low HIF1 alpha and CA-IX expression are highly curable with RT. For this group, RT is a good treatment option. For tumors with HIF1 alpha or CA-IX overexpression, hypoxic modification before RT or primary surgical treatment should be considered. [ABSTRACT FROM AUTHOR]

Patients with pT1cN0 oral squamous cell carcinomas (OSCC) are generally not treated with a neck dissection (ND). However, in 25% of cN0 patients, nodal metastases become apparent during follow-up. Infiltration depth of the primary tumour has been consistently associated with the presence of nodal metastasis, but proposed cut-off depths for performing a ND vary considerably. The aim of this study was to explore the infiltration depth as predictor for the nodal status and to recommend a cut-off depth for performing a ND. From our database of 351 primary oral carcinomas, we selected all pT1-2 tumours (n=246). Infiltration depth was measured in 212 cases. Neck status was determined by histopathological examination of the dissection specimen, or by at least two years of follow-up. Mean infiltration depth was 5.49mm (95% CI: 4.86-6.12) in the N0 and 8.40mm (95% CI: 7.38-9.43) in the N+ group (p<0.001). cN status, lymphovascular invasion and infiltration depth were the only independent predictors for nodal status in multiple logistic regression. ROC-analysis on pT1cN0 tumours resulted in an optimal cut-off for the prediction of the nodal status at a depth of 4.59mm. This cut-off identified a subgroup of patients at increased risk for nodal metastasis (OR=8.3) and with significantly shorter survival. Tumour infiltration depth is an independent predictor for nodal status in pT1-2 OSCC. In pT1cN0 tumours, a cut-off at 4.59mm results in the best predictive value. We recommend an infiltration depth of 4mm as an indication to perform a neck dissection in pT1cN0 OSCC. [ABSTRACT FROM AUTHOR]

INTRODUCTION: For women with a BRCA1 or BRCA2 mutation or a strong family history of breast cancer, there is no clear estimation of the risk of tumour induction versus the beneficial effects of mammography screening available. This study aims to validate the Simulation Model on Radiation Risk and breast cancer Screening (SiMRiSc) model in these women, which can provide information on the benefits and risks of screening for breast cancer for various screening scenarios. METHODS: The simulation model for breast cancer screening was developed and the values for model parameters including cancer induction due to radiation were derived from the literature. The simulation model was validated by comparing the outcome data of the model with the data from three published screening studies of women with an increased hereditary breast cancer risk. A sensitivity analysis was used to estimate the error margins of the outcome data and to analyse the sensitivity of the simulation model to each parameter. RESULTS: The model predicted 71+/-4% of the reported tumours. When excluding the excess number of incident tumours detected in the first screening round, the model predicted 85+/-6% of the tumours reported. The model was most sensitive to changes in the parameters related to lifetime breast cancer risk and sensitivity of mammography. CONCLUSIONS: We conclude that the simulation model is suitable for the provision of accurate benefits' and risks' estimations necessary for the refinement of the screening guidelines for women at an increased risk of breast cancer. [ABSTRACT FROM AUTHOR]

Objectives: The World Health Organization supports both the screen-and-treat (ST) approach and the screen, triage and treat (STT) approach to cervical cancer screening using high-risk human papillomavirus (hrHPV) testing. For Uganda, the sequence of hrHPV-ST and hrHPV-STT could be similar, with visual inspection with acetic acid (VIA) after positive hrHPV tests in both. To consider potential tradeoffs (overtreatment in ST versus missed cancer cases in STT), we compared hrHPV-STT with VIA triage (STT-VIA), and STT with HPV 16/18 genotyping risk stratification, to hrHPV-ST for Uganda, in terms of overtreatment, cervical cancer incidence, and life years, for the general female population of Uganda., Methods: A microsimulation model of cervical cancer was adapted. Incremental benefit-harm ratios of STT were calculated as ratios of prevented overtreatment to reduced life years, and to increased cancer cases. Additional scenarios with 20% difference in intra- and inter-screening follow-up between ST and STT were modeled., Results: Both STT strategies resulted in life year losses on average compared to ST. STT-VIA prevented more overtreatment but led to increased cervical cancer incidence and life year losses. STT-G-VIA resulted in better harm-benefit ratios and additional costs. With better follow-up, STT prevented overtreatment and improved outcomes., Discussion: For Uganda, the STT approach appears preferrable, if the screening sequences of hrHPV-based ST and STT are similar in practice. While VIA triage alone would reduce overtreatment the most, it could also result in more cancer cases. Risk stratification via genotyping could improve STT. Potential follow-up differences and resource availability should be considered by decision-makers when planning Uganda's hrHPV-based screening strategy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sultanov et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Screening with low-dose CT (LDCT) in a high-risk population, as defined by age and smoking behavior, reduces lung cancer-related mortality. However, LDCT screening presents a major challenge. Numerous, mostly benign, nodules are seen in the lungs during screening. The question is how to distinguish the malignant from the benign nodules. Various studies use different protocols for nodule management. The Dutch-Belgian NELSON (Nederlands-Leuvens Longkanker Screenings Onderzoek) trial, the largest European lung cancer screening trial, used distinctions based on nodule volumetric assessment and growth rate. This review discusses key findings from the NELSON study regarding the characteristics of screening-detected nodules, including nodule size and its volumetric assessment, growth rate, subtype, and their associated malignancy risk. These results are compared with findings from other screening studies and current recommendations for lung nodule management. By examining differences in nodule management strategies and providing a comprehensive overview of outcomes specific to lung cancer screening, this review aims to contribute to the broader discussion on optimizing lung nodule management in screening programs., (© RSNA, 2024.)

To identify older surgical cancer patients at risk of decreased postoperative recovery of physical activity (PA), this study assesses whether preoperative radiological sarcopenia (RS) is associated with a decreased ability to return to baseline PA. RS was defined as decreased psoas muscle mass or -density by gender-specific cut-offs on CT-scans at level of vertebra L3. PA was assessed as steps/day measured with PA tracker and recovery of PA was defined as >90% of preoperative steps/day at 3 months postoperatively. Of 44 included patients aged 65 and over undergoing oncologic surgery, 18 patients (41%) showed RS. Seventeen patients (39%) returned to baseline PA, of which eight patients had RS (47%). RS was not associated with a return to baseline PA (OR: 1.38, 95%CI 0.39-4.92, p = 0.61). In this exploratory study, no association was found between preoperative RS and recovery of PA postoperatively., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)