Near Infrared Biomimetic Hybrid Magnetic Nanocarrier for MRI-Guided Thermal Therapy.

Cell-membrane hybrid nanoparticles (NPs) are designed to improve drug delivery, thermal therapy, and immunotherapy for several diseases. Here, we report the development of distinct biomimetic magnetic nanocarriers containing magnetic nanoparticles encapsulated in vesicles and IR780 near-infrared dyes incorporated in the membranes. Distinct cell membranes are investigated, red blood cell (RBC), melanoma (B16F10), and glioblastoma (GL261). Hybrid nanocarriers containing synthetic lipids and a cell membrane are designed. The biomedical applications of several systems are compared. The inorganic nanoparticle consisted of Mn-ferrite nanoparticles with a core diameter of 15 ± 4 nm. TEM images show many multicore nanostructures (∼40 nm), which correlate with the hydrodynamic size. Ultrahigh transverse relaxivity values are reported for the magnetic NPs, 746 mM-1s-1, decreasing respectively to 445 mM-1s-1 and 278 mM-1s-1 for the B16F10 and GL261 hybrid vesicles. The ratio of relaxivities r2/r1 decreased with the higher encapsulation of NPs and increased for the biomimetic liposomes. Therapeutic temperatures are achieved by both, magnetic nanoparticle hyperthermia and photothermal therapy. Photothermal conversion efficiency ∼25-30% are reported. Cell culture revealed lower wrapping times for the biomimetic vesicles. In vivo experiments with distinct routes of nanoparticle administration were investigated. Intratumoral injection proved the nanoparticle-mediated PTT efficiency. MRI and near-infrared images showed that the nanoparticles accumulate in the tumor after intravenous or intraperitoneal administration. Both routes benefit from MRI-guided PTT and demonstrate the multimodal theranostic applications for cancer therapy.

Immunogenic Cell Death Photothermally Mediated by Erythrocyte Membrane-Coated Magnetofluorescent Nanocarriers Improves Survival in Sarcoma Model.

Inducing immunogenic cell death (ICD) during cancer therapy is a major challenge that might significantly improve patient survival. The purpose of this study was to develop a theranostic nanocarrier, capable both of conveying a cytotoxic thermal dose when mediating photothermal therapy (PTT) after its intravenous delivery, and of consequently inducing ICD, improving survival. The nanocarrier consists of red blood cell membranes (RBCm) embedding the near-infrared dye IR-780 (IR) and camouflaging Mn-ferrite nanoparticles (RBCm-IR-Mn). The RBCm-IR-Mn nanocarriers were characterized by size, morphology, surface charge, magnetic, photophysical, and photothermal properties. Their photothermal conversion efficiency was found to be size- and concentration-dependent. Late apoptosis was observed as the cell death mechanism for PTT. Calreticulin and HMGB1 protein levels increased for in vitro PTT with temperature around 55 °C (ablative regime) but not for 44 °C (hyperthermia), suggesting ICD elicitation under ablation. RBCm-IR-Mn were then intravenously administered in sarcoma S180-bearing Swiss mice, and in vivo ablative PTT was performed five days later. Tumor volumes were monitored for the subsequent 120 days. RBCm-IR-Mn-mediated PTT promoted tumor regression in 11/12 animals, with an overall survival rate of 85% (11/13). Our results demonstrate that the RBCm-IR-Mn nanocarriers are great candidates for PTT-induced cancer immunotherapy.

Trends, geographical variation and factors associated with the use of anti-VEGF intravitreal injections in Portugal (2013-2018): a retrospective analysis of administrative data.

AIMS: The arrival of anti-vascular endothelial growth factor (anti-VEGF) therapies represented a treatment shift for several ophthalmological disorders and led to an increasing number of patients undergoing intravitreal injections. The aims of this observational study were to assess the expansion of anti-VEGF intravitreal injections in the Portuguese National Health System (NHS) and to identify factors correlated with geographical variations in episode rates. METHODS: Administrative database on discharge from Portuguese NHS hospitals was analysed for annual values and rates of intravitreal anti-VEGF injections at a national and regional level, between 2013 and 2018. RESULTS: The number of episodes of anti-VEGF treatment and patients treated increased 16% and 9% per year, respectively, between 2013 and 2018. During the study period around 72% of patients were treated in the Metropolitan areas of Lisbon and Porto and in the Central region. Intravitreal anti-VEGF treatment rates in 2018 were 560 per 100 000 population and presented high variability between municipalities. Higher anti-VEGF treatment rates at the municipality level were associated with shorter distances between their residence and the hospital. At the hospital level, higher ratio of ophthalmologists and higher organisational level were associated with higher anti-VEGF treatment rates. CONCLUSION: The number of episodes and patients treated with anti-VEGF injections has been growing in recent years. Proximity to healthcare, more access to ophthalmologists and hospitals with higher organisational levels are associated with higher anti-VEGF treatment rates. Improving access is crucial to reduce regional discrepancies and ensure optimal treatment frequency, which may improve health outcomes.

Defining ambulatory care sensitive conditions for adults in Portugal.

BACKGROUND: Ambulatory Care Sensitive Conditions (ACSCs) are health conditions for which adequate management, treatment and interventions delivered in the ambulatory care setting could potentially prevent hospitalization. Which conditions are sensitive to ambulatory care varies according to the scope of health care services and the context in which the indicator is used. The need for a country-specific validated list for Portugal has already been identified, but currently no national list exists. The objective of this study was to develop a list of Ambulatory Care Sensitive Conditions for Portugal. METHODS: A modified web-based Delphi panel approach was designed, in order to determine which conditions can be considered ACSCs in the Portuguese adult population. The selected experts were general practitioners and internal medicine physicians identified by the most relevant Portuguese scientific societies. Experts were presented with previously identified ACSC and asked to select which could be accepted in the Portuguese context. They were also asked to identify other conditions they considered relevant. We estimated the number and cost of ACSC hospitalizations in 2017 in Portugal according to the identified conditions. RESULTS: After three rounds the experts agreed on 34 of the 45 initially proposed items. Fourteen new conditions were proposed and four achieved consensus, namely uterine cervical cancer, colorectal cancer, thromboembolic venous disease and voluntary termination of pregnancy. In 2017 133,427 hospitalizations were for ACSC (15.7% of all hospitalizations). This represents a rate of 1685 per 100,000 adults. The most frequent diagnosis were pneumonia, heart failure, chronic obstructive pulmonary disease/chronic bronchitis, urinary tract infection, colorectal cancer, hypertensive disease atrial fibrillation and complications of diabetes mellitus. CONCLUSIONS: New ACSC were identified. It is expected that this list could be used henceforward by epidemiologic studies, health services research and for healthcare management purposes. ACSC lists should be updated frequently. Further research is necessary to increase the specificity of ACSC hospitalizations as an indicator of healthcare performance.

Comparative research aspects on hospitalizations for ambulatory care sensitive conditions: the case of Brazil and Portugal / Aspectos de pesquisa comparativa em internações por condições sensíveis à atenção primária: o caso de Brasil e Portugal

Abstract Hospitalizations for ambulatory care sensitive conditions have been used to measure access, quality and performance of the primary health care delivery system, as timely and adequate care could potentially avoid the need of hospitalization. Comparative research provides the opportunity for cross-country learning process. Brazil and Portugal have reformed their primary health care services in the last years, with similar organizational characteristics. We used hospitalization data of Brazil and Portugal for the year 2015 to compare hospitalizations for ambulatory care sensitive conditions between the two countries, and discussed conceptual and methodological aspects to be taken into consideration in the comparative approach. Brazil and Portugal presented similarities in causes and standardized rates of hospitalizations for ambulatory care sensitive conditions. There was great sensitivity on rates according to the methodology employed to define conditions. Hospitalizations for ambulatory care sensitive conditions are important sources of pressure for both Brazil and Portugal, and there are conceptual and methodological aspects that are critical to render the country-comparison approach useful.

Resumo As internações por condições sensíveis à atenção primária têm sido usadas para medir o acesso, a qualidade e o desempenho da atenção primária à saúde, uma vez que o atendimento oportuno e adequado poderia evitar a necessidade de internação. A pesquisa comparativa oferece oportunidade para o processo de aprendizagem entre países. Brasil e Portugal reformaram seus serviços de atenção primária à saúde nos últimos anos, com características organizacionais semelhantes. Utilizamos dados de internação do Brasil e de Portugal para o ano de 2015 para comparar internações por condições sensíveis à atenção primária entre os dois países, e discutimos aspectos conceituais e metodológicos a serem considerados na abordagem comparativa. Brasil e Portugal apresentaram semelhanças nas causas e taxas padronizadas de internações por condições sensíveis à atenção primária. Houve grande sensibilidade nas taxas de acordo com a metodologia empregada para definir as condições. Internações por condições sensíveis à atenção primária são importantes fontes de pressão tanto para o Brasil quanto para Portugal, e há aspectos conceituais e metodológicos que são fundamentais para tornar a abordagem comparativa entre países útil.

Risk Factors and Diagnosis of Diabetic Foot Ulceration in Users of the Brazilian Public Health System.

BACKGROUND: An individual with diabetes mellitus (DM) has an approximately 25% risk of developing ulcerations and/or destruction of the feet's soft tissues. These wounds represent approximately 20% of all causes of hospitalizations due to DM. OBJECTIVE: To identify the factors for the development of diabetic foot ulceration (DFU) among individuals treated by the Brazilian public health system. METHODS: This cross-sectional study was conducted on individuals with diabetes mellitus, aged above 18 years, of both sexes, and during July-October 2018 within a public healthcare unit in Brazil. All participants were assessed based on their socioeconomic, behavioral, and clinical characteristics, along with vascular and neurological evaluations. All participants were also classified according to the classification of risk of developing DFU, in accordance with the International Working Group on the Diabetic Foot (IWGDF). Statistical analyses were conducted using the chi-squared test, chi-squared test for trend, and Fisher's exact test, with a significance level of 5% (p < 0.05). RESULTS: The study consisted of 85 individuals. The DFU condition was prevalent in 10.6% of the participants. Adopting the classification proposed by IWGDF, observed risks for stratification categories 0, 1, 2, and 3 were 28.2%, 29.4%, 23.5%, and 8.2%, respectively. A statistically significant (p < 0.05) association was observed between the development of DFU and the following variables: time since the diagnosis of diabetes and the appearance of the nails, humidity, and deformations on the feet. CONCLUSION: The present study found an elevated predominance of DM patients in the Brazilian public health system (SUS) featuring cutaneous alterations that may lead to ulcers; these individuals had elevated risks of developing DFU. Furthermore, it was revealed that the feet of patients were not physically examined during treatment.

Cadastro Nacional de Estabelecimentos de Saúde: evidências sobre a confiabilidade dos dados / National Registry of Health Facilities: data reliability evidence

Resumo O presente trabalho comparou a confiabilidade de um grupo de dados registrados junto às bases secundárias do Cadastro Nacional dos Estabelecimentos de Saúde. Para cumprir este objetivo, o trabalho foi realizado em 'survey' com 2.777 hospitais. Os hospitais visitados forneceram dados sobre equipamentos, localização geográfica, status de funcionamento e número de leitos. Quanto à concordância entre os hospitais visitados e o cadastro nacional, pode-se destacar que o status de funcionamento estava atualizado em 89% dos casos, o número de leitos em 44%, 82% mantinham o quantitativo de equipamentos correto e 63% apresentaram coordenadas geográficas precisas. Esses achados apontam para uma boa confiabilidade dos dados do Cadastro Nacional dos Estabelecimentos de Saúde, quanto às categorias comparadas, excetuando-se os dados referentes ao número de leitos cadastrados e quanto a existência de alguns equipamentos. Como desdobramento deste trabalho pesa a necessidade de discutir estratégias e incentivos para melhorar a confiabilidade dos dados que ainda apresentam inconsistências, de forma a ampliar a qualidade dos instrumentos utilizados para a formulação de políticas públicas.

Abstract This study compared the reliability of a data group registered in the secondary databases of the National Registry of Health Facilities. A survey was conducted in 2,777 with hospitals to achieve this objective. Visited hospitals provided information on equipment, geographic location, operating status and number of beds. Regarding matching data between visited hospitals and the National Registry, it can be noted that the operating status was updated in 89% of cases, the number of beds in 44%, 82% had the correct amount of equipment and 63% had accurate geographic coordinates. These findings point to a good reliability of information from the National Registry of Health Facilities, regarding the compared categories, excepting for data on the number of registered beds and for some equipment. As a further development of this work, we stress the need to discuss strategies and incentives to improve the reliability of data that still have inconsistencies, in order to improve the instruments used to formulate public policies.

Oral primary care: an analysis of its impact on the incidence and mortality rates of oral cancer.

BACKGROUND: Oral cancer is a potentially fatal disease, especially when diagnosed in advanced stages. In Brazil, the primary health care (PHC) system is responsible for promoting oral health in order to prevent oral diseases. However, there is insufficient evidence to assess whether actions of the PHC system have some effect on the morbidity and mortality from oral cancer. The purpose of this study was to analyze the effect of PHC structure and work processes on the incidence and mortality rates of oral cancer after adjusting for contextual variables. METHODS: An ecological, longitudinal and analytical study was carried out. Data were obtained from different secondary data sources, including three surveys that were nationally representative of Brazilian PHC and carried out over the course of 10 years (2002-2012). Data were aggregated at the state level at different times. Oral cancer incidence and mortality rates, standardized by age and gender, served as the dependent variables. Covariables (sociodemographic, structure of basic health units, and work process in oral health) were entered in the regression models using a hierarchical approach based on a theoretical model. Analysis of mixed effects with random intercept model was also conducted (alpha = 5%). RESULTS: The oral cancer incidence rate was positively association with the proportion of of adults over 60 years (ß = 0.59; p = 0.010) and adult smokers (ß = 0.29; p = 0.010). The oral cancer related mortality rate was positively associated with the proportion of of adults over 60 years (ß = 0.24; p < 0.001) and the performance of preventative and diagnostic actions for oral cancer (ß = 0.02; p = 0.002). Mortality was inversely associated with the coverage of primary care teams (ß = -0.01; p < 0.006) and PHC financing (ß = -0.52-9; p = 0.014). CONCLUSIONS: In Brazil, the PHC structure and work processes have been shown to help reduce the mortality rate of oral cancer, but not the incidence rate of the disease. We recommend expanding investments in PHC in order to prevent oral cancer related deaths.

Primary Health Care and Cervical Cancer Mortality Rates in Brazil: A Longitudinal Ecological Study.

Cervical cancer is a common neoplasm that is responsible for nearly 230 000 deaths annually in Brazil. Despite this burden, cervical cancer is considered preventable with appropriate care. We conducted a longitudinal ecological study from 2002 to 2012 to examine the relationship between the delivery of preventive primary care and cervical cancer mortality rates in Brazil. Brazilian states and the federal district were the unit of analysis (N = 27). Results suggest that primary health care has contributed to reducing cervical cancer mortality rates in Brazil; however, the full potential of preventive care has yet to be realized.