Budget impact analysis of cervical cancer screening in Portugal: comparison of cytology and primary HPV screening strategies.

BACKGROUND: Primary Human Papilloma Virus (HPV) testing is the currently recommended cervical cancer (CxCa) screening strategy by the Portuguese Society of Gynecology (SPG) clinical consensus. However, primary HPV testing has not yet been adopted by the Portuguese organized screening programs. This modelling study compares clinical benefits and costs of replacing the current practice, namely cytology with ASCUS HPV triage, with 2 comparative strategies: 1) HPV (pooled) test with cytology triage, or 2) HPV test with 16/18 genotyping and cytology triage, in organized CxCa screenings in Portugal. METHODS: A budget impact model compares screening performance, clinical outcomes and budget impact of the 3 screening strategies. A hypothetical cohort of 2,078,039 Portuguese women aged 25-64 years old women is followed for two screening cycles. Screening intervals are 3 years for cytology and 5 years for the HPV strategies. Model inputs include epidemiological, test performance and medical cost data. Clinical impacts are assessed with the numbers of CIN2-3 and CxCa detected. Annual costs, budget impact and cost of detecting one CIN2+ were calculated from a public healthcare payer's perspective. RESULTS: HPV testing with HPV16/18 genotyping and cytology triage (comparator 2) shows the best clinical outcomes at the same cost as comparator 1 and is the most cost-effective CxCa screening strategy in the Portuguese context. Compared to screening with cytology, it would reduce annual CxCa incidence from 9.3 to 5.3 per 100,000, and CxCa mortality from 2.7 to 1.1 per 100,000. Further, it generates substantial cost savings by reducing the annual costs by €9.16 million (- 24%). The cost of detecting CIN2+ decreases from the current €15,845 to €12,795. On the other hand, HPV (pooled) test with cytology triage (comparator 1) reduces annual incidence of CxCa to 6.9 per 100,000 and CxCa mortality to 1.6 per 100,000, with a cost of €13,227 per CIN2+ detected with annual savings of €9.36 million (- 24%). The savings are mainly caused by increasing the length of routine screening intervals from three to five years. CONCLUSION: The results support current clinical recommendations to replace cytology with HPV with 16/18 genotyping with cytology triage as screening algorithm.

Tumor-Infiltrating T Cells in Skin Basal Cell Carcinomas and Squamous Cell Carcinomas: Global Th1 Preponderance with Th17 Enrichment-A Cross-Sectional Study.

Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are high-incidence, non-melanoma skin cancers (NMSCs). The success of immune-targeted therapies in advanced NMSCs led us to anticipate that NMSCs harbored significant populations of tumor-infiltrating lymphocytes with potential anti-tumor activity. The main aim of this study was to characterize T cells infiltrating NMSCs. Flow cytometry and immunohistochemistry were used to assess, respectively, the proportions and densities of T cell subpopulations in BCCs (n = 118), SCCs (n = 33), and normal skin (NS, n = 30). CD8+ T cells, CD4+ T cell subsets, namely, Th1, Th2, Th17, Th9, and regulatory T cells (Tregs), CD8+ and CD4+ memory T cells, and γδ T cells were compared between NMSCs and NS samples. Remarkably, both BCCs and SCCs featured a significantly higher Th1/Th2 ratio (~four-fold) and an enrichment for Th17 cells. NMSCs also showed a significant enrichment for IFN-γ-producing CD8+T cells, and a depletion of γδ T cells. Using immunohistochemistry, NMSCs featured denser T cell infiltrates (CD4+, CD8+, and Tregs) than NS. Overall, these data favor a Th1-predominant response in BCCs and SCCs, providing support for immune-based treatments in NMSCs. Th17-mediated inflammation may play a role in the progression of NMSCs and thus become a potential therapeutic target in NMSCs.

Anti-tumor necrosis factor therapy is associated with attenuated humoral response to SARS-COV-2 vaccines in patients with inflammatory bowel disease.

BACKGROUND: Immunosuppressive therapy used in the treatment of inflammatory bowel disease (IBD) is known to reduce vaccine immunogenicity. AIMS: This study aimed to 1) predict the humoral response elicited by SARS-CoV-2 vaccination in IBD patients based on their ongoing treatment and other relevant patient and vaccine characteristics and 2) assess the humoral response to a booster dose of mRNA vaccine. METHODS: We conducted a prospective study in adult IBD patients. Anti-spike (S) IgG antibodies were measured after initial vaccination and again after one booster dose. A multiple linear regression model was created to predict anti-S antibody titer following initial complete vaccination in different therapeutic groups (no immunosuppression, anti-TNF, immunomodulators and combination therapy). A two-tailed Wilcoxon test for two dependent groups was performed to compare anti-S values before and after the booster dose. RESULTS: Our study included 198 IBD patients. The multiple linear regression identified anti-TNF and combination therapy (versus no immunosuppression), current smoking, viral vector (versus mRNA) vaccine and interval between vaccination and anti-S measurement as statistically significant predictors of the log anti-S antibody levels (p < 0.001). No statistically significant differences were found between no immunosuppression and immunomodulators (p = 0.349) and between anti-TNF and combination therapy (p = 0.997). Statistically significant differences for anti-S antibody titer before and after the booster dose of mRNA SARS-CoV-2 vaccine were found, both for non-anti-TNF and anti-TNF groups. CONCLUSIONS: Anti-TNF treatment (either alone or in combination therapy) is associated with lower anti-S antibody levels. Booster mRNA doses seem to increase anti-S both in non-anti-TNF and anti-TNF treated patients. Special attention should be paid to this group of patients when planning vaccination schemes.

Measuring tourism and environmental sciences students' attitudes towards sustainable tourism.

•Tourism and environmental sciences' students are compared.•Tourism students highlight topics related to "Profit" and "People".•Sustainability literacy in tourism cannot solely depend on the interest of teachers.•Tourism academic programmes should be adapted to teach "strong sustainability".•Environmental sciences professors could be invited to lecture in tourism courses.

Evaluation of the influence of the impression technique, scanning direction and type of scanner on the accuracy of the final model / Avaliação da influência da técnica de impressão, direção de digitalização e tipo de scanner na precisão do modelo final

Objective: The purpose of this study is to evaluate the influence of the type of scanner and scanning direction on the accuracy of the final cast. Material and Methods: A partial master cast was used as a reference. A total of 128 scans were obtained and divided into two groups: the conventional method and the digital method. The digital group was divided into three groups: TRIOS 3, Omnicam and CS 3600. Each of these groups was subdivided according to the scanning direction, and each scan was overlaid on the digital reference cast to measure the trueness and precision of the procedures. Results: The overall precision values for the type of impression were 59.89 ± 13.08 µm for conventional and 13.42 ± 4.28 µm for digital; the values for trueness were 49.37 ± 19.13 µm for conventional and 53.53 ± 4.97 µm for digital; the scanning direction trueness values were 53.05 ± 4.36 µm for continuous and 54.03 ± 5.52 µm for segmented; and the precision values were 14.18 ± 4.67 µm for continuous and 12.67 ± 3.75 µm for segmented (p> 0.05). For the scanner type, the trueness values were 50.06 ± 2.65 µm for Trios 3, 57.45 ± 4.63 µm for Omnicam, and 52.57 ± 4.65 µm for Carestream; and those for precision were 11.7 ± 2.07 µm for Trios 3, 10.09 ± 2.24 µm for Omnicam, and 18.49 ± 2.42 µm for Carestream (p <0.05). Conclusions: The digital impression method is the most favorable method regarding precision; in terms of trueness, there are no differences between the types of impressions. (AU)

Objetivo: O objetivo deste estudo é avaliar a influência do tipo de técnica de moldagem, tipo de escâner intraoral e direção do escaneamento na precisão do modelo final. Material e Métodos: Um modelo parcial mestre foi usado como referência. Um total de 128 escaneamentos foi obtido e dividido em dois grupos: o método convencional (n = 32) e o método digital (n = 96). O grupo digital foi dividido em três grupos: TRIOS 3 (n = 32), Omnicam (n = 32) e CS 3600 (n = 32). Cada um desses grupos foi subdividido de acordo com a direção do escaneamento (n = 16), e cada escaneamento foi sobreposto ao modelo de referência digital para medir a veracidade e precisão dos procedimentos. Resultados: Os valores gerais de precisão para o tipo de impressão foram 59,89 ± 13,08 µm para convencional e 13,42 ± 4,28 µm para digital; os valores de veracidade foram 49,37 ± 19,13 µm para convencional e 53,53 ± 4,97 µm para digital; os valores de veracidade para a direção de digitalização foram 53,05 ± 4,36 µm para contínua e 54,03 ± 5,52 µm para segmentada; e os valores de precisão foram 14,18 ± 4,67 µm para contínua e 12,67 ± 3,75 µm para segmentada (p> 0,05). Para o tipo de scanner, os valores de veracidade foram 50,06 ± 2,65 µm para Trios 3, 57,45 ± 4,63 µm para Omnicam e 52,57 ± 4,65 µm para Carestream; e os de precisão foram 11,7 ± 2,07 µm para Trios 3, 10,09 ± 2,24 µm para Omnicam e 18,49 ± 2,42 µm para Carestream (p <0,05). Conclusões: O método de moldagem digital é o método mais favorável em relação à precisão; em termos de veracidade, não há diferenças entre os tipos de impressão (AU)

Trueness and precision of the reproduction of dental casts by the conventional, milling and 3D printing techniques / Fidelidade e precisão de modelos de trabalho reproduzidos pelas técnicas convencional, de fresagem e de impressão 3D

Objective: To compare the reproduction trueness and precision of dental casts made by the conventional, milling and 3D printing techniques. Material and Methods: From an upper right side half-arch reference model (RM), 72 models were obtained and divided into three groups: conventional (CM), milled (MM) and printed (PM). All models were scanned and converted into standard tessellation language (.STL) files. The files were superimposed using 3D analysis software, and statistical analysis was performed using the root mean square (RMS) values obtained. The Shapiro-Wilk test was used to assess normality, and the Kruskal-Wallis test was used to compare groups (ρ < ⍺; ⍺ = 0.05). The Mann-Whitney U test was used for multiple comparisons among groups (ρ < ਕ; ਕ = 0.017). Results: There were significant differences in trueness (ρ = 0.000; ρ <0.001) and precision (ρ = 0.000; ρ < 0.001) among the three dental cast groups. Regarding trueness, CM presented better results, followed by MM and PM. Regarding precision, MM showed better results, followed by PM and CM, which did not show significant differences. Conclusions: For dental cast reproduction the conventional technique has the best trueness and the milling technique has the best precision.(AU)

Objetivo: Comparar a fidelidade e precisão de reprodução de modelos de trabalho pelas técnicas convencional, de fresagem e de impressão 3D. Material e Métodos: A partir de um modelo de referência (MR) de uma hemi-arcada superior direita, foram obtidos 72 modelos divididos em três grupos: convencionais (MC), fresados (MF) e impressos (MI). Todos foram digitalizados e convertidos sob a forma de ficheiros .STL (standard tesselation language). Os ficheiros foram sobrepostos utilizando um software de análise 3D, e através dos valores RMS (raiz do valor quadrático médio) obtidos foi realizada a análise estatística. Para avaliação da normalidade foi utilizado o teste Shapiro Wilk e para a comparação entre grupos foi utilizado o teste Kruskal-Wallis (ρ < ⍺; ⍺ = 0.05). Para as comparações múltiplas entre grupos, foi utilizado o teste U de Mann-Whitney (ρ < ਕ; ਕ = 0.017). Resultados:Existem diferenças significativas de fidelidade (ρ = 0.000; ρ <0.001) e precisão (ρ = 0.000; ρ < 0.001) entre os três grupos. Em relação à fidelidade, MC apresentou melhores resultados, seguido por MF e MI. Em relação à precisão, MF apresentou melhores resultados, seguido por MI e MC, que não apresentaram diferenças significativas entre si. Conclusão: Para reprodução de modelos de trabalho, a técnica convencional é a que apresenta maior fidelidade e a técnica de fresagem a que apresenta maior precisão.(AU)