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With the purpose of establishing a consensus around clinical orientations for professionals involved in managing patients with sleep breathing disorders (SBD), an interdisciplinary group of scientific societies involved in this field discussed and reviewed all the published international guidelines from the American Dental Association, American Academy of Sleep Medicine, American Academy of Dental Sleep Medicine and the European counterparts. Treatment of SBD is multidisciplinary and should be made in concert with the patient, the sleep physician, and the qualified dentist to solve the individual, social, and economic burden of the disease,. This consensus document represents the current thinking of a team of Portuguese experts on managing patients with SBD based on the available evidence.
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Melanoma is one of the most severe cancers due to its great potential to form metastasis. Recent studies showed the importance of mechanical property assessment in metastasis formation which depends on the cytoskeleton dynamics and cell migration. Although cells are considered purely elastic, they are viscoelastic entities. Microrheology atomic force microscopy (AFM) enables the assessment of elasticity and viscous properties, which are relevant to cell behavior regulation. The current work compares the mechanical properties of human neonatal primary melanocytes (HNPMs) with two melanoma cell lines (WM793B and 1205LU cells), using microrheology AFM. Immunocytochemistry of F-actin filaments and phosphorylated focal adhesion kinase (p-FAK) and cell migration assays were performed to understand the differences found in microrheology AFM regarding the tumor cell lines tested. AFM revealed that HNPMs and tumor cell lines had distinct mechanical properties. HNPMs were softer, less viscous, presenting a higher power-law than melanoma cells. Immunostaining showed that metastatic 1205LU cells expressed more p-FAK than WM793B cells. Melanoma cell migration assays showed that WM73B did not close the gap, in contrast to 1205LU cells, which closed the gap at the end of 23 h. These data seem to corroborate the high migratory behavior of 1205LU cells. Microrheology AFM applied to HNPMs and melanoma cells allowed the quantification of elasticity, viscous properties, glassy phase, and power-law properties, which have an impact in cell migration and metastasis formation. AFM study is important since it can be used as a biomarker of the different stages of the disease in melanoma.
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Melanoma , Recém-Nascido , Humanos , Melanoma/patologia , Microscopia de Força Atômica , Elasticidade , Linhagem Celular Tumoral , CitoesqueletoRESUMO
Due to chlorine's ability to kill bacteria and fungi through a chemical reaction, chlorine solutions are commonly used to clean and disinfect numerous public facilities, although these actions are also dependent to the equipment present in those facilities. Accordingly, the interest in studying its effect when in contact with different materials is obvious. This study was carried out through accelerated degradation tests and various analysis methods (optical microscope, scanning electron microscope, and tensile tests). The objective was to observe the wear presented by three polymeric materials, polyvinyl chloride (PVC), high-density polyethylene (HDPE), and polypropylene (PP), when exposed to chlorine's action in swimming pools and drinking water treatment plants. The resulting effect depends on the chlorine content and the type of contact between the chemical agent and the material. The aim was to select the material less likely to be affected by chlorine through tests and analyses, allowing a longer component life. The use of certain more resistant polymeric materials can drastically reduce maintenance, reducing fundamental factors such as costs, the downtime of municipal facilities, and also the risk to public health. It was concluded that PVC has the most stable behaviour overall when in contact with chlorine solutions.
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BACKGROUND: The increased focus on quality indicators (QIs) and the use of clinical registries in real-world cancer studies have increased compliance with therapeutic standards and patient survival. The European Society of Breast Cancer Specialists (EUSOMA) established QIs to assess compliance with current standards in breast cancer care. METHODS: This retrospective study is part of H360 Health Analysis and aims to describe compliance with EUSOMA QIs in breast cancer management in different hospital settings (public vs. private; general hospitals vs. oncology centers). A set of key performance indicators (KPIs) was selected based on EUSOMA and previously identified QIs. Secondary data were retrieved from patients' clinical records. Compliance with target KPIs in different disease stages was compared with minimum and target EUSOMA standards. RESULTS: A total of 259 patient records were assessed. In stages I, II, and III, 18 KPIs met target EUSOMA standards, 5 met minimum standards, and 8 failed to meet minimum standards. Compliance with KPIs varied according to the type of hospital (particularly regarding diagnosis) and disease stage. Although small differences were found in KPI compliance among institutions, several statistical differences were found among treatment KPIs according to disease stage, particularly in stage III. CONCLUSIONS: This study represents the first assessment of the quality of breast cancer care in different hospital settings in Portugal and shows that, although most QIs meet EUSOMA standards, there is room for improvement. Differences have been found across institutions, particularly between oncology centers and general hospitals, in diagnosis and compliance with KPIs among disease stages. Stage III showed the greatest variability in compliance with treatment KPIs, probably related to the lower specificity of the guidelines in this disease stage.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/terapia , Neoplasias da Mama/diagnóstico , Indicadores de Qualidade em Assistência à Saúde , Portugal , Estudos Retrospectivos , OncologiaRESUMO
BACKGROUND: Positron emission tomography/computed tomography (PET/CT) has become in recent years a tool for breast cancer (BC) staging. However, its accuracy to detect bone metastases is classically considered inferior to bone scintigraphy (BS). The purpose of this work is to compare the effectiveness of bone metastases detection between PET/CT and BS. MATERIALS AND METHODS: Prospective study of 410 female patients treated in a Comprehensive Cancer Center between 2014 and 2020 that performed PET/CT and BS for staging purposes. The image analysis was performed by 2 senior nuclear medicine physicians. The comparison was performed based on accuracy, sensitivity, and specificity on a patient and anatomical region level and was assessed using McNemar's Test. An average ROC was calculated for the anatomical region analysis. RESULTS: PET/CT presented higher values of accuracy and sensitivity (98.0% and 93.83%), surpassing BS (95.61% and 81.48%) in detecting bone disease. There was a significant difference in favor of PET/CT (sensitivity 93.83% vs. 81.48%), however, there is no significant difference in eliminating false positives (specificity 99.09% vs. 99.09%). PET/CT presented the highest accuracy and sensitivity values for most of the bone segments, only surpassed by BS for the cranium. There was a significant difference in favor of PET/CT in the upper limb, spine, thorax (sternum) and lower limb (pelvis and sacrum), and in favor of BS in the cranium. The ROC showed that PET/CT has a higher sensitivity and consistency across the bone segments. CONCLUSION: With the correct imaging protocol, PET/CT does not require BS for patients with BC staging.
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Neoplasias Ósseas , Neoplasias da Mama , Humanos , Feminino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Estudos Prospectivos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Sensibilidade e Especificidade , Fluordesoxiglucose F18RESUMO
Genotype analysis has revealed a high genetic diversity in strains of Toxoplasma gondii, isolated from a wide range of intermediate hosts and different geographic origins. Diversity is notably striking for parasites from wild hosts in South America, generally referred as non-archetypal genotypes. Those genotypes are implicated in the etiology of severe clinical disease, multivisceral toxoplasmosis, associated with high rate of mortality in immunocompetent individuals. Can we accept specific antibodies produced during T. gondii infection as biomarkers to identify infecting genotypes? Scientific evidence supports a positive response to this question; however, the genetic diversity of T. gondii genotypes organized into 16 haplogroups and collectively defined in 6 major clades, provides a reminder of the complexity and difficulty for the purpose. This review discusses serological approaches to genotyping T. gondii.
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AIMS: the focus of this study is to evaluate if the combination of an antibiotic with a ceramic biomaterial is effective in treating osteomyelitis in an infected animal model and to define which model and protocol are best suited for in vivo experiments of local bone infection treatment. METHODS: a systematic review was carried out based on PRISMA statement guidelines. A PubMed search was conducted to find original papers on animal models of bone infections using local antibiotic delivery systems with the characteristics of bone substitutes. Articles without a control group, differing from the experimental group only by the addition of antibiotics to the bone substitute, were excluded. RESULTS: a total of 1185 records were retrieved, and after a three-step selection, 34 papers were included. Six manuscripts studied the effect of antibiotic-loaded biomaterials on bone infection prevention. Five articles studied infection in the presence of foreign bodies. In all but one, the combination of an antibiotic with bioceramic bone substitutes tended to prevent or cure bone infection while promoting biomaterial osteointegration. CONCLUSIONS: this systematic review shows that the combination of antibiotics with bioceramic bone substitutes may be appropriate to treat bone infection when applied locally. The variability of the animal models, time to develop an infection, antibiotic used, way of carrying and releasing antibiotics, type of ceramic material, and endpoints limits the conclusions on the ideal therapy, enhancing the need for consistent models and guidelines to develop an adequate combination of material and antimicrobial agent leading to an effective human application.
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Many municipal facilities, such as pools and drinking water treatment facilities, are subject to ongoing maintenance due to the corrosion of their metallic materials caused by chlorine, leading to high costs and a possible risk to public health. A proper study of the employed product's effect could lead to the use of better materials, which significantly increase the lifetime of metallic equipment more attacked by corrosion, through studies evaluating their cost-effectiveness. This paper was carried out with the objective of studying the degradation of some metallic materials (AISI 316L, AISI 321 and Duplex 14462) used in the referred facilities in order to select the one that possessed a better behavior. It was observed that the introduction of some more adequate materials can drastically reduce maintenance operations, with Duplex 14462 showing the best results, ideal for greater chlorine concentrations, followed by AISI 321, which may be employed for components in less contact with chlorine, since it is more easily affordable.
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OBJECTIVE: To evaluate the association between results from drug-induced sleep endoscopy (DISE) and computed tomography with lateral cephalometry (CTLC) of the pharynx in obstructive sleep apnea (OSA) patients, regarding the same anatomic level, in order to understand if CTLC could replace DISE in selected patients. STUDY DESIGN: Cross-sectional. SETTING: Tertiary hospital. METHODS: A total of 71 patients who attended the Sleep Medicine Consultation in the Otorhinolaryngology Department of Hospital CUF Tejo between 1.6.2019 and 30.9.2021, performed a polysomnographic sleep study and were elected to undergo DISE and CTLC of the pharynx for diagnostic purposes were selected. Obstructions at the same anatomic levels - tongue base, epiglottis and velum - were compared in both exams. RESULTS: Patients with reduction of epiglottis-pharynx space on CTLC had also a complete obstruction at epiglottis level on the VOTE classification of DISE (pâ¯=â¯0,027). Reduction of velum-pharynx space or tongue base-pharynx space were not related to complete obstruction of the velum (Pâ¯=â¯0,623) or the tongue base (pâ¯=â¯0,594) found in DISE. Those with two or more space reductions had a tendency to multilevel obstruction observed in DISE (pâ¯=â¯0.089). CONCLUSION: When evaluating the obstruction level(s) of an OSA patient, efforts should be made to perform DISE, since CTLC measures, though regarding at the same structures, don´t correlate completely with obstructions observed in DISE.
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Apneia Obstrutiva do Sono , Humanos , Cefalometria , Estudos Transversais , Apneia Obstrutiva do Sono/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Endoscopia/métodos , SonoRESUMO
The treatment for osteomyelitis consists of surgical debridement, filling of the dead space, soft tissue coverage, and intravenous administration of antimicrobial (AM) agents for long periods. Biomaterials for local delivery of AM agents, while providing controllable antibiotic release rates and simultaneously acting as a bone scaffold, may be a valuable alternative; thus, avoiding systemic AM side effects. V-HEPHAPC is a heparinized nanohydroxyapatite (nHA)/collagen biocomposite loaded with vancomycin that has been previously studied and tested in vitro. It enables a vancomycin-releasing profile with an intense initial burst, followed by a sustained release with concentrations above the Minimum Inhibitory Concentration (MIC) for MRSA. In vitro results have also shown that cellular viability is not compromised, suggesting that V-HEPHAPC granules may be a promising alternative device for the treatment of osteomyelitis. In the present study, V-HEPHAPC (HEPHAPC with vancomycin) granules were used as a vancomycin carrier to treat MRSA osteomyelitis. First, in vivo Good Laboratory Practice (GLP) toxicological tests were performed in a rabbit model, assuring that HEPHAPC and V-HEPHAPC have no relevant side effects. Second, V-HEPHAPC proved to be an efficient drug carrier and bone substitute to control MRSA infection and simultaneously reconstruct the bone cavity in a sheep model.
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The use of disinfection and cleaning chemicals in several municipal facilities, such as swimming pools and drinking water treatment plants, causes the degradation of various types of wood, which leads to failures in equipment and the corresponding need for maintenance. This degradation creates added costs for municipalities, as well as the closure of certain facilities due to curative or preventive maintenance and, in many cases, public health issues, due to the water being contaminated with deteriorating products. Through a thorough study of the degradation effect on the products, more resistant materials can be found which are able to withstand these adversities and increase the lifespan of wood in regular contact with chemical agents. This is achievable by the determination of the cost-effectiveness of the substitute material to replace these components with alternative ones, with properties that better resist the deterioration effects promoted by aggressive environments. No studies have been found so far strictly focused on this matter. The objective of this study is to evaluate the degradation presented by two types of wood, beech and oak, which are exposed to the action of chlorine in municipal facilities. This degradation varies according to the chlorine content and the materials' time of contact with the chemical agent, allowing the selection of new materials which will provide an extended lifetime of the components, reducing maintenance drastically, as well as costs for the facilities and the risk to public health. The performed experimental tests have shown that the oak wood has the best results regarding chlorine degradation resistance.
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Colorectal cancer (CRC) has been addressed in the framework of molecular, cellular biology, and biochemical traits. A new approach to studying CRC is focused on the relationship between biochemical pathways and biophysical cues, which may contribute to disease understanding and therapy development. Herein, we investigated the mechanical properties of CRC cells, namely, HCT116, HCT15, and SW620, using static and dynamic methodologies by atomic force microscopy (AFM). The static method quantifies Young's modulus; the dynamic method allows the determination of elasticity, viscosity, and fluidity. AFM results were correlated with confocal laser scanning microscopy and cell migration assay data. The SW620 metastatic cells presented the highest Young's and storage moduli, with a defined cortical actin ring with distributed F-actin filaments, scarce vinculin expression, abundant total focal adhesions (FAK), and no filopodia formation, which could explain the lessened migratory behavior. In contrast, HCT15 cells presented lower Young's and storage moduli, high cortical tubulin, less cortical F-actin and less FAK, and more filopodia formation, probably explaining the higher migratory behavior. HCT116 cells presented Young's and storage moduli values in between the other cell lines, high cortical F-actin expression, intermediate levels of total FAK, and abundant filopodia formation, possibly explaining the highest migratory behavior.
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Breast cancer (BC) is the second most cause of central nervous system (CNS) metastases. Studies report that almost one third of patients (pts) with triple-negative, one-third with human epidermal growth factor receptor 2 (HER2)-positive and 15% of those with hormone receptor-positive, HER2-negative metastatic breast cancer will develop brain metastases. It is known that the development of symptomatic brain metastases in women with advanced breast cancer is associated with poor prognosis, irrespective of local and systemic treatments. In the present study, we aim to determine the association between BC subtypes and CNS metastases occurrence and prognosis. Retrospective analysis of 309 BC patients with CNS metastases, confirmed by pathological and/or radiological methods, treated in a Cancer Center between 2003 and 2021, was obtained to identify clinicopathologic factors associated with early onset of brain metastases and survival outcomes. For analysis purposes, 3 BC subtypes were considered according to hormone receptor status and HER-2 expression: ER and/or PR positive, HER-2 positive and triple negative. The median time between diagnosis of BC and detection of CNS metastases was 43 months, and it was significantly shorter in triple negative group (8 months). Twenty-one patients (6,8%) had CNS metastases at BC diagnosis, with CNS being the first site of recurrence in 35,3%, mainly in HER2 positive. Most of the patients had parenchymal metastases (n = 245) and 37 (12%) had leptomeningeal (LM) disease, with predominance in ER and/or PR positive subtype (70,3%). In patients submitted to CNS surgery, the concordance between primary tumor and metastases subtype was higher in triple negative (76,9%) compared to 63,2% in HER-2 positive and 38,9% in ER and/or PR positive group (P < 0.05). After CNS involvement, 25,4% (n = 34) of patients with triple negative disease did not receive any systemic therapy, compared to 30,6% (n = 41) in HER-2 positive and 44% (n = 59) in ER and/or PR positive groups (P = 0.05). Median survival after CNS metastases was 9 months, but significantly longer in HER-2 positive group (16 months) and in patients submitted to surgical resection of CNS metastases, irrespectively of subtype (22 months vs 5 months in other treatment modalities). In multivariate Cox regression analysis, having HER-2 positive tumor was an independent prognostic factor for increasing survival after CNS metastases (HR 0.60, 95% CI: 0.41-0.87, P = 0.007), regardless the therapeutic strategy. Clinical behavior and prognosis of CNS metastases varies according to BC subtype. The association between LM disease and ER and/or PR positive tumors should be explored in upcoming studies. Also, these patients' prognosis depends on the availability of specific treatment options, therefore, innovative and effective therapeutic approaches are needed, in order to improve survival and quality of life of these patients.
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Neoplasias Encefálicas , Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/terapia , Prognóstico , Qualidade de Vida , Estudos Retrospectivos , Neoplasias Encefálicas/terapiaRESUMO
In this review, the mechanobiology of colorectal cancer (CRC) are discussed. Mechanotransduction of CRC is addressed considering the relationship of several biophysical cues and biochemical pathways. Mechanobiology is focused on considering how it may influence epithelial cells in terms of motility, morphometric changes, intravasation, circulation, extravasation, and metastization in CRC development. The roles of the tumor microenvironment, ECM, and stroma are also discussed, taking into account the influence of alterations and surface modifications on mechanical properties and their impact on epithelial cells and CRC progression. The role of cancer-associated fibroblasts and the impact of flow shear stress is addressed in terms of how it affects CRC metastization. Finally, some insights concerning how the knowledge of biophysical mechanisms may contribute to the development of new therapeutic strategies and targeting molecules and how mechanical changes of the microenvironment play a role in CRC disease are presented.
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Low-grade serous ovarian cancer (LGSOC) is now considered a different entity from high-grade serous ovarian cancer. The chemoresistance inherent to this type of ovarian cancer narrows the therapeutic options, especially in the recurrent setting. It is thought that the mitogen-activated protein kinase (MAPK) pathway plays a significant role in the pathogenesis of these tumours, and about 2 to 20% of LGSOC harbour a BRAF mutation. Here we present a case report of two patients with a BRAF V600E mutation that achieved sustained clinical responses with combination treatment with dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor).
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Major depressive disorder (MDD) is one of the most common mental disorders in older people. There are several biological, psychological, and social factors associated with this disorder. This study aimed to describe the depressive state to identify the associated factors and potential predictors of MDD in a population of community-dwelling older people with probable MDD. The sample consisted of 378 participants with probable dementia, with 47.3% of them presenting MDD. The factors that were found to be associated with MDD were sex, living status, mobility, and nutritional status. Knowing the factors that can predict a condition such as MDD is extremely important, both for prevention and for the customization of interventions.
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Transtorno Depressivo Maior , Idoso , Transtorno Depressivo Maior/epidemiologia , Humanos , Vida IndependenteRESUMO
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 < 0.001). Clinical staging and hormone receptors (HR) were significantly associated with pCR. ICER was 1.370 per percentage point of pCR. CONCLUSIONS: ICER was more favourable in stage III HR negative BC patients compared to other patient profiles. Innovative treatments access is critical to deliver high-quality healthcare, but sustainability must be considered. These results suggest the importance of establishing a cost-effectiveness profile of Pertuzumab in NeoT for HER2-positive BC.
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Toxoplasmosis is the most reported parasitic zoonosis in Europe, with implications in human health and in the veterinary field. There is an increasing need to develop serotyping of Toxoplasma gondii (T. gondii) in view of greater sensitivity and efficiency, through the definition of new targets and new methodologies. Nanotechnology is a promising approach, with impact in the development of point-of-care devices. The aim of this work was to develop a simple but highly efficient method for Toxoplasma gondii serotyping based on gold nanoparticles. A simple colorimetric method was developed using gold nanoparticles modified with the synthetic polymorphic peptide derived from GRA6 antigen specific for type II T. gondii. The method of preparation of the gold nanoprobes and the experimental conditions for the detection were found to be critical for a sensitive discrimination between positive and negative sera. The optimized method was used to detect antibodies anti-GRA6II both in mice and human serum samples. These results clearly demonstrate that a biosensor-based immunoassay using AuNPs conjugated with polymorphic synthetic peptides can be developed and used as a serotyping device.
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AIM: The aim of the study was to assess patient preference for the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) in patients with HER2-positive early breast cancer in PHranceSCa (NCT03674112). MATERIALS AND METHODS: Patients who completed neoadjuvant P + H + chemotherapy + surgery were randomised 1:1 to three intravenous (IV) P + H cycles followed by three cycles of PH FDC SC or vice versa (crossover) and then chose subcutaneous (SC) injection or IV infusion to continue up to 18 cycles (continuation). Assessments were via patient and healthcare professional (HCP) questionnaires. RESULTS: One hundred and sixty patients were randomised (cut-off: 24 February 2020); 136 (85.0%, 95% confidence interval: 78.5-90.2%) preferred SC; 22 (13.8%) preferred IV; 2 (1.3%) had no preference. The main reasons for SC preference were reduced clinic time (n = 119) and comfort during administration (n = 73). One hundred and forty-one patients (88.1%) were very satisfied/satisfied with SC injection versus 108 (67.5%) with IV infusion; 86.9% chose PH FDC SC continuation. HCP perceptions of median patient treatment room time ranged from 33.0-50.0 min with SC and 130.0-300.0 min with IV. Most adverse events (AEs) were grade 1/2 (no 4/5s); serious AE rates were low. AE rates before and after switching were similar (cycles 1-3 IV â cycles 4-6 SC: 77.5% â 72.5%; cycles 1-3 SC â cycles 4-6 IV: 77.5% â 63.8%). CONCLUSION: Most patients strongly preferred PH FDC SC over P + H IV. PH FDC SC was generally well tolerated, with no new safety signals (even when switching), and offers a quicker alternative to IV infusion.