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Introduction This study aims to assess safety and effectiveness of pertuzumab in combination with trastuzumab and docetaxel in the neoadjuvant treatment (NeoT) of HER2-positive breast cancer. Methods Two consecutive retrospective cohorts (n = 94, 2012–2015 and 2015–2017) of adult women with HER2-positive breast cancer, receiving NeoT at the breast clinic in Portugal (IPO-Porto), were followed. All patients had surgery and received trastuzumab as adjuvant therapy. The 2012–2015 cohort received doxorubicin, cyclophosphamide, docetaxel plus trastuzumab, whereas the 2015–2017 cohort was treated with the same protocol plus pertuzumab. Results The 2012–2015 cohort was older (median 53 years), with locally advanced tumors (48.1%), mostly hormone receptor positive (59.3%). The 2015–2017 cohort was younger (median 43 years) with 60% operable tumors. Pathologic complete response (pCR) improved in the second cohort, while maintaining a good safety profile and tolerability. Clinical staging (p = 0.001) and hormone receptor (p = 0.003) were significant predictors of pCR, but not treatment regimen (p = 0.304). Conclusion Further research with larger samples and longer follow-up is needed to understand the clinical differences. Clinical effectiveness of treatment should also be measured through overall and progression-free survival.

“Barter” consiste em uma operação em que o produtor tem a possibilidade de trocar a sua produção por insumos que serão utilizados durante o processo produtivo. Diante disso, este estudo buscou propor uma estrutura de eixos temáticos sobre o tema que poderá nortear uma agenda de pesquisas futuras. Para atingir esse objetivo, foi realizada uma revisão integrativa de literatura dos estudos que abordam sobre as operações de “Barter” no mercado como processo estratégico. Os resultados foram consistentes, sendo possível estabelecer cinco eixos temáticos que compõem a matriz conceitual e empírica sobre os estudos que abordam sobre o tema: (i) motivações para o uso de “Barter”; (ii) fatores determinantes da operação; (iii) riscos inerentes à operação; (iv) vantagens da utilização desse mecanismo; e (v) desafios e dificuldades da operação. Assim, foi identificada uma heterogeneidade temática dos estudos e recomenda-se que futuras pesquisas sejam direcionadas para melhor entendimento desses componentes temáticos, principalmente sobre os desafios e dificuldades enfrentadas pelos praticantes. Uma das características identificada na literatura é que operações de “Barter” são realizadas quando há falta de liquidez no mercado, tornando-se, portanto, uma alternativa de financiamento. Assim, os resultados encontrados podem estimular práticas dessa operação, principalmente em períodos de crises. Foi demonstrado que esse tipo de operação evoluiu nos últimos anos, mas ainda carece de estudos sobre os seus benefícios e aplicabilidade tanto para o setor produtivo quanto para as revendas de insumos.

Funding: The authors’ team wishes to acknowledge the contribution of Professor Doctor Carla Nunes for the conceptualization and formal analysis of the current study. In addition, we would like also to acknowledge the EpiDoC Unit and EpiReumaPt team for the invaluable assignment of conceptualization and operationalization of the main research project (EpiDoC), and to CHRC (UIDP/04923/2020) for supporting the current research project. Background Low back pain (LBP) is a long-Term health condition with distinct clinical courses. Its characterization together with the identification of prognostic factors for a persistent LBP course may trigger the development of personalized interventions. This study aimed to investigate the courses of chronic LBP (CLBP), its cumulative impact, and the indicators for the persistence of pain. Material and methods Patients with active CLBP from the EpiDoC, a population-based cohort study of a randomly recruited sample of 10.661 adults with prolonged follow-up, were considered. Pain, disability, and health-related quality of life (HRQoL) were assessed at three time-points over five years. According to their pain symptoms over time, participants were classified as having a persistent (pain at the baseline and at all the subsequent time-points) or a relapsing pain course (pain at the baseline and no pain at least in one of the subsequent time-points). A mixed ANOVA was used to compare mean differences within and between patients of distinct courses. Prognostic indicators for the persistent LBP course were modulated through logistic regression. Results Among the 1.201 adults with active CLBP at baseline, 634 (52.8%) completed the three time-points of data collection: 400 (63.1%) had a persistent and 234 (36.9%) a relapsing course. Statistically significant interactions were found between the group and time on disability (F (2,1258) = 23.779, p

Precise oral dosing in rodents is usually achieved by intragastric gavage. If performed incorrectly due to technical difficulties, inexperience, or animal resistance, oral gavage may have animal welfare implications such as esophageal and gastric rupture and aspiration. The stress that is induced by this procedure can also lead to confounding results. In several animal models, drug vehicles must be sugar-free, deliver drugs in a specific formulation, and sometimes supply water. Gelatin has all of these properties. The current study aimed to evaluate the use of gelatin vehicles with different sensory features as an alternative to oral gavage. We investigated the time taken by 2 different inbred mouse strains, FVB/N and C57BL/6J, to ingest sugar-free gelatin pellets of varying flavors. Results showed that FVB/N mice took more time to eat the unflavored, strawberry and diet-flavored gelatin pellets than did C57BL/6J mice. Both strains showed low preference for lemon flavor, with the same ingestion times after the second day. This study showed that the C57BL/6J mice are more likely to eat gelatin than are FVB/N mice, and that the 2 strains of mice show a lower preference for lemon flavoring as compared with other flavors. This method of voluntarily oral administration offers an alternative to gavage for studies that use oral dosing studies.

The aim of this work was to study the prevalence of hypocalcemia in cancer patients based on ionized calcium and, as a secondary aim, the influence that hypocalcemia may have on survival. For this retrospective study, a representative sample of all the records of low and normal ionized calcium measured in 2014 was studied. Patients under 18 years and patients from the bone marrow transplantation service were excluded. The number of patients included in this study was 471. The median patient age was 63 years (18 to 91), and 247 (52%) were female. The most represented cancers were thyroid, colorectal, and breast. Ionized calcium was in the normal range in 331 (70%) patients and low in 140 (30%). In a univariable analysis, there were no significant differences in survival at 4 years between normal (47%) and low-level (42%) ionized calcium (p = 0.192), but there were differences in gender, age, the primary site, the number of metastatic sites, and the level of albumin. In the multivariable analysis, only the primary cancer, the number of metastatic sites, and the albumin levels were associated with survival. In a multivariable analysis excluding thyroid cancer, hypocalcemia remained not associated with survival. Hypocalcemia occurs in a variety of cancer types, and it does not have an influence on survival.

Missing data is a common issue in epidemiological databases. Among the different ways of dealing with missing data, multiple imputation has become more available in common statistical software packages. However, the incompatibility between the imputation and substantive model, which can arise when the associations between variables in the substantive model are not taken into account in the imputation models or when the substantive model is itself nonlinear, can lead to invalid inference. Aiming at analysing population-based cancer survival data, we extended the multiple imputation substantive model compatible-fully conditional specification (SMC-FCS) approach, proposed by Bartlett et al. in 2015 to accommodate excess hazard regression models. The proposed approach was compared with the standard fully conditional specification multiple imputation procedure and with the complete-case analysis using a simulation study. The SMC-FCS approach produced unbiased estimates in both scenarios tested, while the fully conditional specification produced biased estimates and poor empirical coverages probabilities. The SMC-FCS algorithm was then used for handling missing data in the evaluation of socioeconomic inequalities in survival from colorectal cancer patients diagnosed in the North Region of Portugal. The analysis using SMC-FCS showed a clearer trend in higher excess hazards for patients coming from more deprived areas. The proposed algorithm was implemented in R software and is presented as Supplementary Material.

Background Breast cancer (BC) is largely prevalent worldwide. HER2-positive BC account for roughly 20–25% of all BC cases and has an overall survival lower than other BC. Innovation on BC therapeutics is a constant, but novel therapies have higher costs. Therefore, cost-effectiveness research is essential to provide healthcare decision-makers with solid foundations for a resource allocation. This study aims to estimate the average direct medical costs/patient and cost-effectiveness of adding pertuzumab in neoadjuvant treatment (NeoT) for HER2-positive breast cancer (BC). Methods Two retrospective real-world consecutive cohorts of ≥18yo female patients diagnosed with HER2-positive BC treated with NeoT at the Breast Clinic of IPO-Porto were studied. The AC-DH regimen (2012–2015) comprised 8 cycles of neoadjuvant therapy (4 cycles of doxorubicin + cyclosphosphamide followed by 4 cycles ofdocetaxel + trastuzumab), while the AC-DHP regimen (2015–2017) included also pertuzumab as NeoT. NeoT was followed by surgery and adjuvant trastuzumab. Micro-costing technique and a bottom-up approach was used comprising all medical direct costs from the hospital perspective. Unit costs were obtained from government official prices or from IPO-Porto costing system. Costs were adjusted to 2017 and are expressed in euros. Multivariable logistic regression models were used for effectiveness assessment, while generalized linear models with gamma distribution were used for costs. ICER was calculated using the pathological complete response (pCR) as the preferential measure of effectiveness. Sensitivity analysis was also performed. Results AC-DHP (n = 40) and AC-DH (n = 54) cohorts had heterogenous patient profiles (median age 43y/53y; 67.5%/59.3% positive HR; 60.0%/27.8% operable; 25.0%/24.1% inflammatory, respectively). The AC-DHP average total cost/patient was 56,375€, with pertuzumab accounting for 13,978€ (24.79%) and increasing in 15,982€ the average cost/patient (p, Highlights i.The results obtained in the AC-DHP cohort, which included Pertuzumab as a NeoT, suggest better clinical outcomes compared to the AC-DH group, a confirmation based on real-world data.ii.Some patient profiles seem to be more promising concerning the overall costs for pathological complete response, but the present data does not include a long-term follow-up period, which suggests that interpretations should be performed with caution.iii.Pertuzumab cost estimated represented a great proportion of overall total costs per patient, but further research (including the costs of the whole episode of care) and continuously monitoring (additional RWE) is needed for a more robust cost-effectiveness analysis. Supplementary Information The online version contains supplementary material available at 10.1186/s13561-021-00332-0.

Funding Information: The present publication was funded by Fundação Ciência e Tecnologia, IP national support through CHRC (UIDP/04923/2020). The same institution supported the first author (LAG) under an individual PhD grant (SFRH/BD/145636/2019). EpiReumaPt was supported by unrestricted grants from Direção-Geral da Saúde, Fundação Calouste Gulbenkian, Fundação Champalimaud, Fundação AstraZeneca, Abbvie, Merck, Sharp & Dohme, Pfizer, Roche, Servier, Bial, D3A Medical Systems, Happybrands, Center de Medicina Laboratorial, Germano de Sousa, Clínica Médica da Praia da Vitória, CAL-Clínica, Galp Energia, Açoreana Seguros, and individual rheumatologists. Data were provided by the EpiDoC Unit - CEDOC with permission. Publisher Copyright: © Objectives To estimate the prevalence of medical care-seeking among adults with low back pain (LBP) and to characterise and compare use of diagnostic procedures and medical management between primary and secondary care. Design Cross-sectional study. Setting Data from the EpiReumaPt, a nationwide population-based study conducted in Portugal including a representative sample of non-institutionalised adults (n=10 661) stratified by administrative territorial units was analysed. Participants Individuals who self-reported history of LBP within the previous 12 months (n=6434) and sought medical care for this problem in the same period (n=2618). Outcome measures Patients' self-reported diagnostic workup and management procedures performed by medical care for LBP collected through a structured questionnaire. Medical care procedures were stratified by level of care. Results The prevalence of medical care-seeking for LBP was 38.0% (95% CI 35.9% to 40.1%). Primary care in isolation (45.3%) was the most sought level of care. Emergency departments (25.9%) and orthopaedics (19.4%) were the most sought secondary medical specialties. Several pathoanatomical diagnoses were used, supported by laboratory or imaging tests (91.1%). Disc herniation (20.4%) and osteoarthritis (19.7%) were the most frequent diagnoses, and X-ray (63.7%) was the most frequent diagnostic procedure self-reported by individuals. Most (75.1%) reported being treated for LBP: 80.4% with oral medication and 49.9% with injectables. The mean duration of pharmacological treatment was 104.24 (SD, 266.80) days. The use of pathoanatomical diagnoses, laboratory or imaging tests, and pharmacological treatments were generally more frequent for secondary care (p

Abdominal aortic aneurysms (AAAs) secondary to Coxiella burnetii infections are rare but carry important implications. The diagnosis is difficult due to unspecific symptoms. To the authors' knowledge, this is the first AAA caused by chronic Q fever treated with an endoprosthesis.

Objective Mozambique is currently experiencing an increase in chronic diseases including cancer. There is a large unmet need for cancer surgery in Mozambique. The aim of this study was to define the content and the design of a training program for practicing surgeons in surgical oncology that would be consensually regarded as adequate to care for oncological patients requiring surgical interventions. Design & Setting A 3-round modified-Delphi approach was implemented to obtain consensus on surgical oncology training curriculum. The participants were purposefully selected experts in surgical oncology working in Mozambique. In round 1, participants answered a questionnaire with open-ended questions regarding the content of the curriculum and the timing and venue of training. In round 2, answers from the first round were presented to a purposeful selected sample of nationally recognized experts in oncology and surgical oncology, including members of the Mozambican College of Surgeons and leadership of the Ministry of Health. A final round was carried out to discuss the draft version of the training program aiming to achieve a predetermined consensus level of 80%. Participants Fifteen of 23 experts (65.2%) responded to round one.The response rate for round 1 and 3 was 80% (12 of the 15 participants in round one). Results The responses collected in the first round were analyzed and revealed that basic principles of oncology and basic principles of surgical oncology should be included in the curriculum of surgical residency in Mozambique (80% of the experts agree; Cronbach α = 0.93); a 24-months fellowship in surgical oncology should take place after residency in the surgical field (86.6% of experts agree; Cronbach α = 0.97); and should occur at Maputo Central Hospital and at comprehensive cancer centers abroad (100% agree). In round 2 the proposal for the program of surgical oncology fellowship obtained a strong agreement amongst the experts (97.3%). The final proposal for the program was divided into the following structure: (1) theoretical components; (2) duration; (3) location; (4) methodology; (5) technical skills in oncology; and (6) competency and paid particular attention to the oncological diseases prevalent in Mozambique. The agreement amongst the experts was 97.3%. Conclusions The experts reached a consensus regarding the general structure for a cancer surgery postgraduate training program in Mozambique, which should be a 24-months fellowship after residency in surgical disciplines. This fellowship should mostly take place in Mozambique, but it should also include dedicated internships in recognized cancer hospitals abroad. Such curricula embrace the Global Curriculum in Surgical Oncology including in particular the oncological nosology of Mozambique and should advance the quality of oncology surgical care provided in the country.

Aim: Characterize DNA methyltransferases/demethylases expression in testicular germ cell tumors (TGCTs). Methods: In silico analysis of TCGA database, assessment of transcript levels of most relevant enzymes in four TGCT cell lines and validation in patient cohort (real-time quantitative polymerase chain reaction; immunohistochemistry). Results: DNMT3A, DNMT3B and TET2 were the most differentially expressed between seminomas (SEs) and nonseminomas (NSs). DNMT3B was significantly overexpressed in NS-related cell lines, and the opposite was found for TET2. Significantly higher DNMT3A/B mRNA expression was observed in NS, indicating a role for de novo methylation in reprogramming. Significantly higher TET2 protein expression was observed in SEs, suggesting active demethylation contributes for SE hypomethylated state. More differentiated histologies disclosed distinct expression patterns. Conclusion: DNA-modifying enzymes are differentially expressed between TGCT subtypes, influencing reprogramming and differentiation.

Purpose To validate tools to identify patients at risk for perioperative complications to implement prehabilitation programmes in head and neck surgery (H&N). Methods Retrospective cohort including 128 patients submitted to H&N, with postoperative Intermediate Care Unit admittance. The accuracy of the risk calculators ASA, P-POSSUM, ACS-NSQIP and ARISCAT to predict postoperative complications and mortality was assessed. A multivariable analysis was subsequently performed to create a new risk prediction model for serious postoperative complications in our institution. Results Our 30-day morbidity and mortality were 45.3% and 0.8%, respectively. The ACS-NSQIP failed to predict complications and had an acceptable discrimination ability for predicting death. The discrimination ability of ARISCAT for predicting respiratory complications was acceptable. ASA and P-POSSUM were poor predictors for mortality and morbidity. Our new prediction model included ACS-NSQIP and ARISCAT (area under the curve 0.750, 95% confidence intervals: 0.63–0.87). Conclusion Despite the insufficient value of these risk calculators when analysed individually, we designed a risk tool combining them which better predicts the risk of serious complications. Electronic supplementary material The online version of this article (10.1007/s00405-020-06133-1) contains supplementary material, which is available to authorized users.

PurposeThe aim of this paper is to evaluate the use of blockchain for identity management (IdM) in the context of the Internet of things (IoT) while focusing on privacy-preserving approaches and its applications to healthcare scenarios.Design/methodology/approachThe paper describes the most relevant IdM systems focusing on privacy preserving with or without blockchain and evaluates them against ten selected features grouped into three categories: privacy, usability and IoT. Then, it is important to analyze whether blockchain should be used in all scenarios, according to the importance of each feature for different use cases.FindingsBased on analysis of existing systems, Sovrin is the IdM system that covers more features and is based on blockchain. For each of the evaluated use cases, Sovrin and UniquID were the chosen systems.Research limitations/implicationsThis paper opens new lines of research for IdM systems in IoT, including challenges related to device identity definition, privacy preserving and new security mechanisms.Originality/valueThis paper contributes to the ongoing research in IdM systems for IoT. The adequacy of blockchain is not only analyzed considering the technology; instead the authors analyze its application to real environments considering the required features for each use case.

Season of birth, a surrogate of seasonal variation of environmental exposures, has been associated with increased risk of several cancers. In the context of a Southern-Eastern Europe (SEE) consortium, we explored the potential association of birth seasonality with childhood (0-14 years) central nervous system (CNS) tumors. Primary CNS tumor cases (n = 6,014) were retrieved from 16 population-based SEE registries (1983-2015). Poisson regression and meta-analyses on birth season were performed in nine countries with available live birth data (n = 4,987). Subanalyses by birth month, age, gender and principal histology were also conducted. Children born during winter were at a slightly increased risk of developing a CNS tumor overall [incidence rate ratio (IRR): 1.06, 95% confidence intervals (CI): 0.99-1.14], and of embryonal histology specifically (IRR: 1.13, 95% CI: 1.01-1.27). The winter peak of embryonal tumors was higher among boys (IRR: 1.24, 95% CI: 1.05-1.46), especially during the first 4 years of life (IRR: 1.33, 95% CI: 1.03-1.71). In contrast, boys