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| 4. |
- Cserni, G, et al.
(författare)
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Consistency in recognizing microinvasion in breast carcinomas is improved by immunohistochemistry for myoepithelial markers.
- 2016
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Ingår i: Virchows Archiv: an international journal of pathology. - : Springer Science and Business Media LLC. - 1432-2307. ; 468:4, s. 473-481
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Tidskriftsartikel (refereegranskat)abstract
- Microinvasion is the smallest morphologically identifiable stage of invasion. Its presence and distinction from in situ carcinoma may have therapeutic implications, and clinical staging also requires the recognition of this phenomenon. Microinvasion is established on the basis of several morphological criteria, which may be difficult and not perfectly reproducible among pathologists. The aim of this study was to assess the consistency of diagnosing microinvasion in the breast on traditional haematoxylin and eosin (HE) stained slides and to evaluate whether immunohistochemistry (IHC) for myoepithelial markers could improve this. Digital images were generated from representative areas of 50 cases stained with HE and IHC for myoepithelial markers. Cases were specifically selected from the spectrum of in situ to microinvasive cancers. Twenty-eight dedicated breast pathologists assessed these cases at different magnifications through a web-based platform in two rounds: first HE only and after a washout period by both HE and IHC. Consistency in the recognition of microinvasion significantly improved with the use of IHC. Concordance rates increased from 0.85 to 0.96, kappa from 0.5 to 0.85, the number of cases with 100 % agreement rose from 9/50 to 25/50 with IHC and the certainty of diagnosis also increased. The use of IHC markedly improves the consistency of identifying microinvasion. This corroborates previous recommendations to use IHC for myoepithelial markers to clarify cases where uncertainty exists about the presence of microinvasion. Microinvasive carcinoma is a rare entity, and seeking a second opinion may avoid overdiagnosis.
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| 7. |
- In ’t Veld, Sjors G.J.G., et al.
(författare)
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Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
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Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
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Tidskriftsartikel (refereegranskat)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
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| 8. |
- Pashayan, N, et al.
(författare)
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Personalized early detection and prevention of breast cancer: ENVISION consensus statement
- 2020
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Ingår i: Nature reviews. Clinical oncology. - : Springer Science and Business Media LLC. - 1759-4782 .- 1759-4774. ; 17:11, s. 687-705
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Tidskriftsartikel (refereegranskat)abstract
- The European Collaborative on Personalized Early Detection and Prevention of Breast Cancer (ENVISION) brings together several international research consortia working on different aspects of the personalized early detection and prevention of breast cancer. In a consensus conference held in 2019, the members of this network identified research areas requiring development to enable evidence-based personalized interventions that might improve the benefits and reduce the harms of existing breast cancer screening and prevention programmes. The priority areas identified were: 1) breast cancer subtype-specific risk assessment tools applicable to women of all ancestries; 2) intermediate surrogate markers of response to preventive measures; 3) novel non-surgical preventive measures to reduce the incidence of breast cancer of poor prognosis; and 4) hybrid effectiveness–implementation research combined with modelling studies to evaluate the long-term population outcomes of risk-based early detection strategies. The implementation of such programmes would require health-care systems to be open to learning and adapting, the engagement of a diverse range of stakeholders and tailoring to societal norms and values, while also addressing the ethical and legal issues. In this Consensus Statement, we discuss the current state of breast cancer risk prediction, risk-stratified prevention and early detection strategies, and their implementation. Throughout, we highlight priorities for advancing each of these areas.
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| 9. |
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| 10. |
- Pearce, Neil E, et al.
(författare)
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IARC Monographs : 40 Years of Evaluating Carcinogenic Hazards to Humans
- 2015
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 123:6, s. 507-514
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' failures to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.OBJECTIVES: The authors of this paper are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We have examined here criticisms of the IARC classification process to determine the validity of these concerns. We review the history of IARC evaluations and describe how the IARC evaluations are performed.DISCUSSION: We conclude that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various discipline and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed.CONCLUSIONS: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.
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| 11. |
- Ahearn, Thomas U., et al.
(författare)
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Common variants in breast cancer risk loci predispose to distinct tumor subtypes
- 2022
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Ingår i: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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| 12. |
- Balmativola, D., et al.
(författare)
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Pathological non-response to chemotherapy in a neoadjuvant setting of breast cancer: an inter-institutional study
- 2014
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 1573-7217 .- 0167-6806. ; 148:3, s. 511-523
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Tidskriftsartikel (refereegranskat)abstract
- To identify markers of non-response to neoadjuvant chemotherapy (NAC) that could be used in the adjuvant setting. Sixteen pathologists of the European Working Group for Breast Screening Pathology reviewed the core biopsies of breast cancers treated with NAC and recorded the clinico-pathological findings (histological type and grade; estrogen, progesterone receptors, and HER2 status; Ki67; mitotic count; tumor-infiltrating lymphocytes; necrosis) and data regarding the pathological response in corresponding surgical resection specimens. Analyses were carried out in a cohort of 490 cases by comparing the groups of patients showing pathological complete response (pCR) and partial response (pPR) with the group of non-responders (pathological non-response: pNR). Among other parameters, the lobular histotype and the absence of inflammation were significantly more common in pNR (p < 0.001). By ROC curve analyses, cut-off values of 9 mitosis/2 mm(2) and 18 % of Ki67-positive cells best discriminated the pNR and pCR + pPR categories (p = 0.018 and < 0.001, respectively). By multivariable analysis, only the cut-off value of 9 mitosis discriminated the different response categories (p = 0.036) in the entire cohort. In the Luminal B/HER2- subgroup, a mitotic count < 9, although not statistically significant, showed an OR of 2.7 of pNR. A lobular histotype and the absence of inflammation were independent predictors of pNR (p = 0.024 and < 0.001, respectively). Classical morphological parameters, such as lobular histotype and inflammation, confirmed their predictive value in response to NAC, particularly in the Luminal B/HER2- subgroup, which is a challenging breast cancer subtype from a therapeutic point of view. Mitotic count could represent an additional marker but has a poor positive predictive value.
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| 13. |
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| 14. |
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| 15. |
- Sol, Nik, et al.
(författare)
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Tumor-Educated Platelet RNA for the Detection and (Pseudo)progression Monitoring of Glioblastoma
- 2020
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Ingår i: Cell Reports Medicine. - : Elsevier. - 2666-3791. ; 1:7
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Tidskriftsartikel (refereegranskat)abstract
- Tumor-educated platelets (TEPs) are potential biomarkers for cancer diagnostics. We employ TEP-derived RNA panels, determined by swarm intelligence, to detect and monitor glioblastoma. We assessed specificity by comparing the spliced RNA profile of TEPs from glioblastoma patients with multiple sclerosis and brain metastasis patients (validation series, n = 157; accuracy, 80%; AUC, 0.81 [95% CI, 0.74-0.89; p < 0.001]). Second, analysis of patients with glioblastoma versus asymptomatic healthy controls in an independent validation series (n = 347) provided a detection accuracy of 95% and AUC of 0.97 (95% CI, 0.95-0.99; p < 0.001). Finally, we developed the digitalSWARM algorithm to improve monitoring of glioblastoma progression and demonstrate that the TEP tumor scores of individual glioblastoma patients represent tumor behavior and could be used to distinguish false positive progression from true progression (validation series, n = 20; accuracy, 85%; AUC, 0.86 [95% CI, 0.70-1.00; p < 0.012]). In conclusion, TEPs have potential as a minimally invasive biosource for blood-based diagnostics and monitoring of glioblastoma patients.
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| 16. |
- Ahadi, Aylin, et al.
(författare)
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Implementation and evaluation of a binary mixture model and three-dimensional FE-analysis of water saturated soil
- 2006
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Ingår i: ECCOMAS CFD 2006: Proceedings of the European Conference on Computational Fluid Dynamics. - 9090209700
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Konferensbidrag (refereegranskat)abstract
- A binary mixture model for soils has been formulated and analyzed. In the model one of the constituents is soil and the other constituent an incompressible liquid. The effects of water are included by formulating a mixture model is formulated as an extension of an existing non-associated elasto-plastic material model for granular materials. This paper is focused on the balance of momentum equations of the mixture model, primarily to avoid the difficulties arising when the interaction terms between the constituents needs to be formulated and constituted. Considering the momentum balance of the mixture as an extension of the balance equation of the soil constituent, it is supplemented with body forces, stresses and flow effects from the water constituent. These supplemented terms are evaluated and analyzed. An alternative way of deriving equation of motion for the fluid is also presented. The computer algorithm for integrating the constitutive relation of dry sand is supplemented and numerical simulations with a finite element code are carried out. It is shown that although the mixture model consists of two constituents, it is possible to include the existence of voids and a system with three constituents, i.e. water unsaturated soil, can be analyzed. Results from single element tests and simulations of a flexible footing resting on a surface of water saturated sand are presented.
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| 17. |
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| 18. |
- Best, Myron G., et al.
(författare)
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RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics
- 2015
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Ingår i: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 28:5, s. 666-676
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Tidskriftsartikel (refereegranskat)abstract
- Tumor-educated blood platelets (TEPs) are implicated as central players in the systemic and local responses to tumor growth, thereby altering their RNA profile. We determined the diagnostic potential of TEPs by mRNA sequencing of 283 platelet samples. We distinguished 228 patients with localized and metastasized tumors from 55 healthy individuals with 96% accuracy. Across six different tumor types, the location of the primary tumor was correctly identified with 71% accuracy. Also, MET or HER2-positive, and mutant KRAS, EGFR, or PIK3CA tumors were accurately distinguished using surrogate TEP mRNA profiles. Our results indicate that blood platelets provide a valuable platform for pan-cancer, multiclass cancer, and companion diagnostics, possibly enabling clinical advances in blood-based "liquid biopsies".
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| 19. |
- Best, Myron G., et al.
(författare)
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Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets
- 2017
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Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 32:2, s. 238-252
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Tidskriftsartikel (refereegranskat)abstract
- Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92-0.96; p < 0.001; n = 106 early-stage validation cohort, accuracy, 81%; AUC, 0.89; 95% CI, 0.83-0.95; p < 0.001), independent of age of the individuals, smoking habits, whole-blood storage time, and various inflammatory conditions. PSO enabled selection of gene panels to diagnose cancer from TEPs, suggesting that swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources.
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| 20. |
- Cserni, Gabor, et al.
(författare)
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Distinction of isolated tumour cells and micrometastasis in lymph nodes of breast cancer patients according to the new Tumour Node Metastasis (TNM) definitions
- 2011
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 47:6, s. 887-894
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Tidskriftsartikel (refereegranskat)abstract
- Isolated tumour cells and micrometastases represent two different staging categories and are often dealt with differently when identified in sentinel lymph nodes of breast cancer patients. The reproducibility of these categories was found to be suboptimal in several studies. The new edition of the TNM (Tumour Node Metastasis) is expected to improve the reproducibility of these categories. Fifty cases of possible low-volume nodal involvement were represented by one to four digital images and were analysed by members of the European Working Group for Breast Screening Pathology (EWGBSP). The kappa value for interobserver agreement of the pN (TNM) staging categories and of the isolated tumour cells category were 0.55 and 0.56 reflecting moderate reproducibility, and the kappa of the micrometastatic category (0.62) reflected substantial reproducibility. This is an improvement over the results gained on the basis of the previous edition of the TNM. Maximal adherence to the category definitions supplemented by explanatory texts in the staging manual should result in more homogeneous nodal staging of breast cancer. (C) 2010 Elsevier Ltd. All rights reserved.
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| 21. |
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| 22. |
- Giampietro, P.G., et al.
(författare)
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Hypoallergenicity of an extensively hydrolyzed whey formula
- 2001
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Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 12:2, s. 83-86
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Tidskriftsartikel (refereegranskat)abstract
- Several different protein hydrolysate-based infant formulas have been promoted as hypoallergenic and considered suitable for the dietary management of cow's milk allergy (CMA). Accepting that none of the hydrolysate-based products is completely safe, the American Academy of Pediatrics (AAP) recommends that these formulas should be tested in a double-blind placebo-controlled setting and tolerated by at least 90% of children with proven CMA. In principle, this recommendation is also endorsed by the European Society of Paediatric Gastroenterology and Nutrition (ESPGAN) and the European Society of Paediatric Allergy and Clinical Immunology (ESPACI). In this two-center study, 32 children with proven CMA were tested with the extensive hydrolysate whey formula Nutrilon Pepti, for comparison with Profylac (extensive) and Nan HA (partial) whey hydrolysate products. Skin-prick tests (SPTs) were, respectively, positive to the three hydrolysate formulas in 19%, 15%, and 32% of children. After oral challenge it was concluded that 97% (95% CI: 85-100%) of the children tolerated Nutrilon Pepti, 94% (95% CI: 75-100%) tolerated Profylac, and 64% (95% CI: 37-81%) tolerated Nan HA. This study demonstrates that the extensive hydrolysates Nutrilon Pepti and Profylac are well tolerated in a population of children with proven CMA and that both products can be considered safe for their intended use. This study confirms that a very small number of children react even to extensively hydrolyzed formulas. SPT prior to oral exposure to the hydrolysate-based formulas can indicate whether a child is at risk of showing reactions to the product. Introduction of new products to these children should be carried out under a doctor's supervision. However, the majority of the SPT-positive children did tolerate the two extensively hydrolyzed whey-based formulas tested.
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| 23. |
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| 24. |
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| 25. |
- Marcotte, Erin L., et al.
(författare)
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Caesarean delivery and risk of childhood leukaemia : a pooled analysis from the Childhood Leukemia International Consortium (CLIC)
- 2016
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Ingår i: The Lancet Haematology. - 2352-3026. ; 3:4, s. E176-E185
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Tidskriftsartikel (refereegranskat)abstract
- Background Results from case-control studies have shown an increased risk of acute lymphoblastic leukaemia (ALL) in young children born by caesarean delivery, and prelabour caesarean delivery in particular; however, an association of method of delivery with childhood leukaemia subtypes has yet to be established. We therefore did a pooled analysis of data to investigate the association between childhood leukaemia and caesarean delivery. Methods We pooled data from 13 case-control studies from the Childhood Leukemia International Consortium done in nine countries (Canada, Costa Rica, Egypt, France, Germany, Greece, Italy, New Zealand, and the USA) for births from 1970-2013. We analysed caesarean delivery overall and by indications that probably resulted in prelabour caesarean delivery or emergency caesarean delivery. We used multivariable logistic regression models, adjusted for child's birthweight, sex, age, ethnic origin, parental education, maternal age, and study, to estimate odds ratios (ORs) and 95% CIs for the risk of ALL and acute myeloid leukaemia (AML) in children aged 0-14 years at diagnosis. Findings The studies provided data for 8780 ALL cases, 1332 AML cases, and 23 459 controls, of which the birth delivery method was known for 8655 (99%) ALL cases, 1292 (97%) AML cases, and 23 351 (> 99%) controls. Indications for caesarean delivery were available in four studies (there were caesarean deliveries for 1061 of 4313 ALL cases, 138 of 664 AML cases, and 1401 of 5884 controls). The OR for all indications of caesarean delivery and ALL was 1.06 (95% CI 0.99-1.13), and was significant for prelabour caesarean delivery and ALL (1.23 [1.04-1.47]; p= 0.018). Emergency caesarean delivery was not associated with ALL (OR 1.02 [95% CI 0.81-1.30]). AML was not associated with caesarean delivery (all indications OR 0.99 [95% CI 0.84-1.17]; prelabour caesarean delivery 0.83 [0.54-1.26]; and emergency caesarean delivery 1.05 [0.63-1.77]). Interpretation Our results suggest an increased risk of childhood ALL after prelabour caesarean delivery. If this association is causal, maladaptive immune activation due to an absence of stress response before birth in children born by prelabour caesarean delivery could be considered as a potential mechanism.
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| 26. |
- Michaut, Magali, et al.
(författare)
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Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer.
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Invasive lobular carcinoma (ILC) is the second most frequently occurring histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for around 10% of all breast cancers. The molecular processes that drive the development of ILC are still largely unknown. We have performed a comprehensive genomic, transcriptomic and proteomic analysis of a large ILC patient cohort and present here an integrated molecular portrait of ILC. Mutations in CDH1 and in the PI3K pathway are the most frequent molecular alterations in ILC. We identified two main subtypes of ILCs: (i) an immune related subtype with mRNA up-regulation of PD-L1, PD-1 and CTLA-4 and greater sensitivity to DNA-damaging agents in representative cell line models; (ii) a hormone related subtype, associated with Epithelial to Mesenchymal Transition (EMT), and gain of chromosomes 1q and 8q and loss of chromosome 11q. Using the somatic mutation rate and eIF4B protein level, we identified three groups with different clinical outcomes, including a group with extremely good prognosis. We provide a comprehensive overview of the molecular alterations driving ILC and have explored links with therapy response. This molecular characterization may help to tailor treatment of ILC through the application of specific targeted, chemo- and/or immune-therapies.
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| 27. |
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| 28. |
- Monge, P, et al.
(författare)
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Childhood leukaemia in Costa Rica, 1981-96
- 2002
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Ingår i: Paediatric and perinatal epidemiology. - : Wiley. - 0269-5022 .- 1365-3016. ; 16:3, s. 210-218
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Tidskriftsartikel (refereegranskat)
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| 29. |
- Monge, Patricia, et al.
(författare)
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Parental occupational exposure to pesticides and the risk of childhood leukemia in Costa Rica
- 2007
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Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 33:4, s. 293-303
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Parental exposure to pesticides and the risk of leukemia in offspring were examined in a population-based case-control study in Costa Rica. METHODS: All cases of childhood leukemia (N=334), in 1995-2000, were identified at the Cancer Registry and the Children's Hospital. Population controls (N=579) were drawn from the National Birth Registry. Interviews of parents were conducted using conventional and icon-based calendar forms. An exposure model was constructed for 25 pesticides in five time periods. RESULTS: Mothers' exposures to any pesticides during the year before conception and during the first and second trimesters were associated with the risk [odds ratio (OR) 2.4, 95% confidence interval (95% CI) 1.0-5.9; OR 22, 95% CI 2.8-171.5; OR 4.5, 95% CI 1.4-14.7, respectively] and during anytime (OR 2.2, 95% CI 1.0-4.8). An association was found for fathers' exposures to any pesticides during the second trimester (OR 1.5, 95% CI 1.0-2.3). An increased risk with respect to organophosphates was found for mothers during the first trimester (OR 3.5, 95% CI 1.0-12.2) and for fathers during the year before conception and the first trimester (OR 1.5, 95% CI 1.0-2.2 and OR 1.6, 95% CI 1.0-2.6, respectively), and benzimidazoles during the first, second, and third trimesters of pregnancy (OR 2.2, 95% CI 1.0-4.4; OR 2.2, 95% CI 1.0-5.0; OR 2.2, 95% CI 1.0-5.2, respectively). There was a suggestion of an exposure-response gradient for fathers as regards picloram, benomyl, and paraquat. Age at diagnosis was positively associated with fathers' exposures and inversely associated with mothers' exposures. CONCLUSIONS: The results suggest that parental exposure to certain pesticides may increase the risk of leukemia in offspring.
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| 30. |
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| 31. |
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| 33. |
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| 34. |
- Posthuma, R., et al.
(författare)
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Implementation of Bronchoscopic Lung Volume Reduction Using One-Way Endobronchial Valves: A Retrospective Single-Centre Cohort Study
- 2022
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Ingår i: Respiration. - : S. Karger AG. - 0025-7931 .- 1423-0356. ; 101:5, s. 476-484
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bronchoscopic lung volume reduction (BLVR) using 1-way endobronchial valves (EBV) has become a guideline treatment in patients with advanced emphysema. Evidence from this minimally invasive treatment derives mainly from well-designed controlled trials conducted in high-volume specialized intervention centres. Little is known about real-life outcome data in hospitals setting up this novel treatment and which favourable conditions are required for a continuous successful program. Objectives: In this study, we aim to evaluate the eligibility rate for BLVR and whether the implementation of BLVR in our academic hospital is feasible and yields clinically significant outcomes. Method: A retrospective evaluation of patients treated with EBV between January 2016 and August 2019 was conducted. COPD assessment test (CAT), forced expiratory volume in 1 s (FEV1), residual volume (RV), and 6-min walking test (6MWT) were measured at baseline and 3 months after intervention. Paired sample t tests were performed to compare means before and after intervention. Results: Of 350 subjects screened, 283 (81%) were not suitable for intervention mostly due to lack of a target lobe. The remaining 67 subjects (19%) underwent bronchoscopic assessment, and if suitable, valves were placed in the same session. In total, 55 subjects (16%) were treated with EBV of which 10 did not have complete follow-up: 6 subjects had their valves removed because of severe pneumothorax (n = 2) or lack of benefit (n = 4) and the remaining 4 had missing follow-up data. Finally, 45 patients had complete follow-up at 3 months and showed an average change +/- SD in CAT -4 +/- 6 points, FEV1 +190 +/- 140 mL, RV -770 +/- 790 mL, and +37 +/- 65 m on the 6MWT (all p < 0.001). After 1-year follow-up, 34 (76%) subjects had their EBV in situ. Conclusion: Implementing BLVR with EBV is feasible and effective. Only 16% of screened patients were eligible, indicating that this intervention is only applicable in a small subset of highly selected subjects with advanced emphysema, and therefore a high volume of COPD patients is essential for a sustainable BLVR program.
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| 35. |
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| 36. |
- Sator, Lea, et al.
(författare)
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Overdiagnosis of COPD in Subjects With Unobstructed Spirometry A BOLD Analysis
- 2019
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Ingår i: Chest. - : Elsevier BV. - 0012-3692 .- 1931-3543. ; 156:2, s. 277-288
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There are several reports on underdiagnosis of COPD, while little is known about COPD overdiagnosis and overtreatment. We describe the overdiagnosis and the prevalence of spirometrically defined false positive COPD, as well as their relationship with overtreatment across 23 population samples in 20 countries participating in the BOLD Study between 2003 and 2012.METHODS: A false positive diagnosis of COPD was considered when participants reported a doctor's diagnosis of COPD, but postbronchodilator spirometry was unobstructed (FEV1/FVC > LLN). Additional analyses were performed using the fixed ratio criterion (FEV1/FVC < 0.7).RESULTS: Among 16,177 participants, 919 (5.7%) reported a previous medical diagnosis of COPD. Postbronchodilator spirometry was unobstructed in 569 subjects (61.9%): false positive COPD. A similar rate of overdiagnosis was seen when using the fixed ratio criterion (55.3%). In a subgroup analysis excluding participants who reported a diagnosis of "chronic bronchitis" or "emphysema" (n = 220), 37.7% had no airflow limitation. The site-specific prevalence of false positive COPD varied greatly, from 1.9% in low- to middle-income countries to 4.9% in high-income countries. In multivariate analysis, overdiagnosis was more common among women, and was associated with higher education; former and current smoking; the presence of wheeze, cough, and phlegm; and concomitant medical diagnosis of asthma or heart disease. Among the subjects with false positive COPD, 45.7% reported current use of respiratory medication. Excluding patients with reported asthma, 34.4% of those with normal spirometry still used a respiratory medication.CONCLUSIONS: False positive COPD is frequent. This might expose nonobstructed subjects to possible adverse effects of respiratory medication.
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| 37. |
- Studnicka, Michael, et al.
(författare)
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COPD : Should Diagnosis Match Physiology?
- 2020
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Ingår i: Chest. - : Elsevier BV. - 0012-3692 .- 1931-3543. ; 157:2, s. 473-475
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 38. |
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| 39. |
- Wesseling, J. H., et al.
(författare)
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Exploring car manufacturers' responses to technology-forcing regulation : The case of California's ZEV mandate
- 2015
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Ingår i: Environmental Innovation and Societal Transitions. - : Elsevier BV. - 2210-4224. ; 16, s. 87-105
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Tidskriftsartikel (refereegranskat)abstract
- The ability of firms to influence environmental regulation has largely been overlooked in transition studies. We study how car manufacturers combine and change their innovation and political influence strategies in response to a technology-forcing regulation. We apply a conceptual framework on corporate responses to public innovation policy to the case of the zero emission vehicle mandate over the period 1990-2013. We use patent and sales data to operationalize the R&D and commercialization aspects of innovation strategies, while using corporate political activities data to operationalize political influence strategies. We find that first, car manufacturers used specific combinations of innovation and political influence strategies, depending on their value maintaining or value creating nature. Second, manufacturers changed their strategies and became more value creating over time, which supported socio-technical change. Third, we refine the available strategy typology by identifying subclasses in defensive (opposition and slowdown) and proactive strategies (shaping, support and progressive).
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